>>WELCOME TO THE 7th ANNUAL
VIVIAN PINN SYMPOSIUM HONORING
THE FIRST FULL-TIME DIRECTOR OF
THE NIH OFFICE OF RESEARCH ON
WOMEN'S HEALTH, VIVIAN PINN
M.D., IN RECOGNITION OF NATIONAL
WOMEN'S HEALTH WEEK.
THIS EVENT SERVES AS A CRITICAL
FORUM FOR EXPERTS ACROSS SECTORS
TO COMMUNICATE AND COLLABORATE
FOR THE ADVANCEMENT OF WOMEN'S
HEALTH AND OUR TOPIC TODAY WILL
BE MENOPAUSE AND OPTIMIZING THE
MID-LIFE HEALTH OF WOMEN.
MY NAME IS SARAH TEMKIN,
ASSOCIATE DIRECTOR FOR CLINICAL
RESEARCH AT THE NIH OFFICE OF
RESEARCH ON WOMEN'S HEALTH.
I WILL BEGIN WITH A FEW
LOGISTICS FOR TODAY'S EVENT.
THROUGHOUT THE SYMPOSIUM THOSE
IN THE VIRTUAL ENVIRONMENT CAN
USE THE Q&A FUNCTION TO SUBMIT
QUESTIONS.
IF YOU ARE VIEWING VIA VIDEOCAST
YOU MAY SUBMIT QUESTIONS SHE A
THAT PAGE AS WELL.
TODAY'S EVENT IS VIDEOCAST BY
THE NIH AND IS BEING RECORDED.
IN THE COMING WEEKS RECORDINGS
OF THE EVENT WILL BE MADE
AVAILABLE THROUGH THE ORWH WEB
SIEVMENT WE'RE EXCITED TO HAVE A
GRAPHIC REPORTER JOIN US TODAY
TO CREATE ILLUSTRATED NOTES.
SOME VISUAL NOTES WILL BE
DISPLAYED DURING THE BREAKS AND
WILL BE AVAILABLE AS WELL AFTER
THE EVENTS WITH SUMMARY OF
TODAY'S SPEAKER.
TODAY'S TALKS.
AND NOW IT IS MY PLEASURE TO
INTRODUCE OUR FIRST SPEAKER, DR.
JANINE AUSTIN CLAYTON, NIH
ASSOCIATE DIRECTOR FOR RESEARCH
ON WOMEN'S HEALTH, NIH DIRECTOR
FOR RESEARCH ON WOMEN'S HEALTH,
OFFICE OF RESEARCH ON WOMEN'S
HEALTH.
DURING HER TENURE AT ORWH DR.
CLAYTON HAS TIRELESSLY SUPPORTED
HEALTH IN A WORLD WHERE WOMEN
RECEIVE EVIDENCE-BASED HEALTH
CARE TAILORED TO THEIR
CIRCUMSTANCES.
HER BIO MAY BE FOUND IN THE
PROGRAM BOOKLET LINKED TO THE
CHAT.
WELCOME.
>> THANK YOU.
GOOD MORNING, EVERYONE.
I'M EXCITED TO BE WITH YOU ALL
TODAY TO TALK ABOUT A TOPIC THAT
IS NEAR AND DEAR TO MY HEART,
SOMETHING THAT'S SO IMPORTANT
FOR THE HEALTH OF WOMEN.
TODAY WE THINK OF MENOPAUSE AS
AN INFLECTION POINT IN WOMEN'S
MID-LIFE HEALTH.
AND YOU HEARD FROM SARAH A
PHRASE WE'VE INCORPORATED INTO
THE NIH VISION FOR THE HEALTH OF
WOMEN.
WE IMAGINE A WORLD IN WHICH
EVERY WOMAN RECEIVES
EVIDENCE-BASED DISEASE
PREVENTION AND TREATMENT,
TAILORED TO HER OWN
CIRCUMSTANCES, GOALS, AND NEEDS.
WE THINK THAT THROUGH RESEARCH
AND RESEARCH ADVANCES WE CAN GET
CLOSER TO REALIZING THIS VISION
AND BETTER ENABLING CLINICIANS
TO DELIVER INDIVIDUALIZED CARE
APPROPRIATE FOR EACH WOMAN'S AGE
AND REPRODUCTIVE STAGE.
YOU WILL HEAR OFTEN THAT ORWH
FROM ITS OUTSET AND DR. PINN'S
DIRECTION INCLUDED A LIFE COURSE
PERSPECTIVE FROM THE BEGINNING.
AND MID-LIFE IS A PART OF THE
LIFE COURSE THAT IS OFTEN NOT
CONSIDERED AS MUCH AS SOME OF
THE EARLIER STAGES.
WE KNOW OF COURSE THAT
PERIMENOPAUSE CAN BEGIN AS EARLY
AS IN OUR 40s, AND AVERAGE AGE
OF MENOPAUSE MORE IN EARLY
'50s, AND POST-MENOPAUSAL
PERIOD IS AN IMPORTANT COMPONENT
OF THE LIFE COURSE, FRAMED HERE
WITH THE THOUGHT THAT MENOPAUSE
BRINGS ITS OWN CHALLENGES BUT
ITS OWN REWARDS AS WELL.
IT'S A POTENTIALLY STRESSFUL
TIME IN TERMS OF LIFE, CAREER,
FAMILY, BUT IT'S ALSO AN
OPPORTUNITY TO MAKE LIFESTYLE
CHANGES, TALK TO A HEALTH CARE
PROVIDER, UNDERSTAND YOUR OWN
PERSONAL HEALTH RISKS, AND TO
DELAY, INTERRUPT, OR PREVENT THE
DEVELOPMENT OF CHRONIC DISEASE.
WHY IS THAT SO IMPORTANT?
HERE IS THE DATA THAT SHOW THAT
CARDIOVASCULAR DISEASE IN WOMEN
IS BOTH AGE ASSOCIATED AND AGE
SPECIFIC, AND WE KNOW THAT
THERE'S AN INCREASE IN
CARDIOVASCULAR DISEASE INCIDENCE
BY AGE IN WOMEN WITH
POST-MENOPAUSAL WOMEN HAVING TWO
TO SIX FOLD GREATER RISK FOR
CARDIOVASCULAR DISEASE UP TO 54
YEARS OF AGE.
THAT MID-LIFE PERIOD AND
MENOPAUSEALL TRANSITION WE SEE
ONSET OF CHRONIC DISEASE IN
WOMEN, WHY IT'S SO IMPORTANT TO
ADDRESS MENOPAUSAL TRANSITION
AND OPTIMIZE MANAGEMENT OF
MENOPAUSAL SYSTEMS WHICH CAN
RANGE FROM DIFFICULT TO
DEBILITATING.
IN TERMS OF CHRONIC DISEASES,
THIS IS AN AREA OF INCREASED
INTEREST BY MANY.
IN FACT, THE U.S. SENATE AND
HOUSE OF REPRESENTATIVES
APPROPRIATION BILLS IDENTIFIED
RISING CHRONIC CONDITIONS IN
WOMEN AS AN AREA OF WOMEN AS A
RESULT OF ORWH-LED ALONG WITH
ADVISORY COMMITTEE, A CONFERENCE
CALLED ADVANCING NIH RESEARCH ON
HEALTH OF WOMEN AND SUMMARIZED
THAT INFORMATION IN A REPORT
THAT'S AVAILABLE ON OUR WEBSITE.
MORE RECENTLY, DR. TEMKIN AND
OUR CO-AUTHORS IN BMC WOMEN'S
HEALTH HIGHLIGHTED CONDITIONS
AND DEVELOPMENT OF FRAMEWORK,
LAST DEFINED BY HHS MULTIPLE
YEARS AGO, IMPORTANT TO THINK
THROUGH THE LENS HOW WOMEN
EXPERIENCE THEM, WHAT MAY BE
FEMALE SPECIFIC AND HOW SEX
DIFFERENCES MIGHT PLAY OUT.
I WANT TO HIGHLIGHT THAT FOR YOU
AND I WANT TO SHARE WITH YOU
THAT THE NATIONAL ACADEMIES OF
SCIENCE, ENGINEERING AND
MEDICINE WITH SUPPORT FROM ORWH
ARE CONDUCTING A STUDY LOOKING
AT FRAMEWORK FOR CONSIDERATION
OF CHRONIC DEBILITATING
CONDITIONS IN WOMEN.
UNDERSTANDING CHRONIC CONDITIONS
IS ALSO OF IMPORTANCE IN TERMS
OF HOW ORWH HAS COLLABORATED
ACROSS THE NIH 27 INSTITUTES AND
CENTERS, PARTNERING WITH THREE
I.C.s LISTED HERE, SEVERAL
I.C.s ON AN R01 AND R21
RECENTLY RELEASED WITH FIRST
RECEIPT DATE COMING UP IN JUNE.
THIS FUNDING OPPORTUNITY ALLOWS
APPLICATIONS ON CHRONIC
CONDITIONS UNDERSTUDIED AMONG
WOMEN OR THAT DISPROPORTIONATELY
AFFECT PORTIONS OF WOMEN
UNDERSTUDIED, UNDERREPRESENTED,
AND UNDERREPORTED IN BIOMEDICAL
RESEARCH AND THAT SHOULD ALIGN
WITH GOAL 1 OF THE NIH-WIDE
STRATEGIC PLAN WHICH IS
ADVANCING RIGOROUS RESEARCH
RELEVANT TO HEALTH OF WOMEN.
WE HOPE THAT THESE FUNDING
OPPORTUNITIES WILL PROVIDE THE
SPACE FOR INVESTIGATORS TO
ADDRESS A VARIETY OF CONDITIONS,
DIFFERENCES BETWEEN MEN AND
WOMEN IN TERMS OF LIFE COURSE
TIME POINTS WHEN WE SEE DISEASES
ACCELERATE LIKE MID-LIFE AND
MENOPAUSE.
AND OF COURSE, NIH HAS FUNDED
MENOPAUSE RESEARCH FOR OVER 30
YEARS, BEGINNING IN 1991, WITH
THE LAND LANDMARK WOMEN'S HEALH
INITIATIVE AND INVESTMENT UNDER
FORMER NIH DIRECTOR BERNADINE
HEALEY, TO THE SWAN STUDY, STUDY
OF WOMEN'S HEALTH ACROSS THE
NATION, WHICH CHARACTERIZED
MENOPAUSAL TRANSITION INCLUDING
BIOLOGICAL AND PSYCHOSOCIAL
ANTECEDENTS IN AND SEQUELAE IN A
DIVERSE SAMPLE OF MID-LIFE
WOMEN, MSFLASH, INVESTIGATING
TREATMENTS FOR MENOPAUSAL
SYMPTOMS WITH A WIDE-RANGING
COLLECTION OF INTERVENTIONS AND
MS-BRAIN, EXPLORING HOW
MENOPAUSAL SYMPTOMS AFFECT
SHORT- AND LONG-TERM BRAIN
HEALTH AND MENOPAUSE AND:
CHRONOLOGICAL INFLUENCE ON THE
BRAIN.
RCDC CODE FOR MENOPAUSE RESEARCH
WILL ALLOW US TO ASSESS THE
PORTFOLIO ACCURATELY AND FOLLOW
THAT OVER TIME.
I WANT TO SHARE WITH OUR
ATTENDEES MY MENOPLAN, AN
EVIDENCE-BASED TOOL PROVIDES
WOMEN WITH SCIENCE-BASED
INFORMATION ABOUT TREATMENT
OPTIONS AND HELPS EMPOWER HIM TO
MAKE DECISIONS ABOUT MENOPAUSAL
TRANSITION THAT WILL WORK FOR
THEM.
THE OFFICE OF RESEARCH ON
WOMEN'S HEALTH HAS OPPORTUNITIES
HAS OPPORTUNITIES, THE R01, THE
FIRST EVER ON SEX AND GENDER, IS
ONE OPPORTUNITY FOR THAT.
WE HAVE ALSO SUPPORTED MENOPAUSE
RESEARCH UNDER OUR U3
ADMINISTRATIVE SUPPLEMENT
PROGRAM FOCUSING ON WOMEN OF
UNDERREPRESENTED POPULATIONS,
GENDER R25 GALVANIZING HEALTH
EQUITY THROUGH NOVEL AND DIVERSE
EDUCATIONAL RESOURCES IS ANOTHER
OPPORTUNITY TO EXPAND
UNDERSTANDING OF MENOPAUSE AND
MENOPAUSE RESEARCH, WHICH IS
IMPORTANT, AND FAIRLY RECENTLY
SUMMARIZED SOME EFFORTS THAT NIH
HAS IN RESEARCH ON MENOPAUSE IN
WOMEN'S HEALTH IN FOCUS
QUARTERLY PUBLICATION, OUTLINING
SEVERAL QUESTIONS THAT REMAIN
GAPS IN KNOWLEDGE AND TALKED
ABOUT HOW WE SHOULD ADDRESS
FUTURE RESEARCH ABOUT QUESTIONS
IN MENOPAUSE.
OUR SIGNATURE PROGRAM
SPECIALIZED CENTERS OF RESEARCH
EXCELLENCE ON SEX DIFFERENCES
HAS SEVERAL SCORE PROGRAMS THAT
ADDRESS ISSUES RELEVANT TO
RESEARCH WHETHER IT'S THE
BRIGHAM AND WOMEN'S HOSPITAL
FOCUSED ON PITUITARY GONADAL
ACCESS, PRODUCING VASOMOTOR
SYMPTOMS, AND STRESS RELATES TO
NEUROLOGIC CONSEQUENCES,
BRAIN-GUT MICROBIOME
INTERACTIONS, PERIMENOPAUSAL,
PRE AND POST MENOPAUSAL AT UCLA,
OR RESEARCH ON CARDIOMETABOLIC
HEALTH CHANGES THAT OCCUR IN THE
MENOPAUSE TRANSITION OR SCORE
THAT LOOKS AT MENOPAUSE BROUGHT
ON BY SURGICAL REMOVELY OF BOTH
OVARIES OR UCLA SCORE, OR THE
CEDARS-SINAI SCORE, DIFFERENCE
IN VASCULAR DISEASE, FROM THE
LENS OF SEX DIFFERENCES FOR MANY
YEARS AND WILL CONTINUE TO DO
SO.
I WANT TO MAKE SURE I SHARE
EXCITING NEWS.
THE OFFICE OF RESEARCH ON
WOMEN'S HEALTH HAS FORMED AN
OFFICE OF AUTOIMMUNE DISEASE
RESEARCH, IN 2022 THE NATIONAL
ACADEMIES REPORTED ON
RECOMMENDATION FOR NIH TO FORM
SUCH AN OFFICE AND FISCAL YEAR
23 THE CONSOLIDATED
APPROPRIATIONS ACT OF 2023
CONGRESS ALLOCATED $10 MILLION
TO ESTABLISH OADR IN THE OFFICE
OF RESEARCH ON WOMEN'S HEALTH,
LOOKING TOWARDS DEVELOPING
OPPORTUNITIES FOR
INTERDISCIPLINARY RESEARCH ON
AUTOIMMUNE DISEASE IN THE
CONTEXT OF A WOMAN'S LIFE COURSE
INCLUDING PERSPECTIVES RELATED
TO MENOPAUSE.
AND THE FIRST FUNDING
OPPORTUNITY ON THE EXPOSOME,
WITH OUR COLLABORATING PARTNERS,
RECEIPT DATE OF JUNE 16, 2023,
STAY TUNED FOR MORE INFORMATION.
WE WANT TO MANUAL A WORLD IN
WHICH EVERY WOMAN RECEIVES
EVIDENCE-BASED DISEASE
PREVENTION AND TREATMENT
TAILORED TO HER OWN NEEDS,
CIRCUMSTANCES, AND GOALS.
IN ORDER TO DO THAT WE HAVE TO
GENERATE THE EVIDENCE TO INFORM
SUCH CLINICAL DECISION MAKING.
AT THE BEGINNING OF MY REMARKS I
SHOWED YOU THAT QUOTE AND ASKED
THAT YOU ALL IMAGINE A WORLD
THAT WE CAN BUILD WHERE TOGETHER
THROUGH RIGOROUS RESEARCH THAT
WORKS TO EXAMINE AND UNDERSTAND
MENOPAUSE TO INCREASE RESEARCH
FINDINGS TO ADVANCE THE HEALTH
OF ALL WOMEN AT ALL STAGES.
WE THINK NOW IS THE TIME TO
CONNECT AND REDOUBLE MENOPAUSE
RESEARCH EFFORTS ACROSS NIH AND
WORK TOGETHER.
WE WANT TO HIGHLIGHT THE WAYS WE
THINK ABOUT THE HEALTH OF WOMEN,
VERSUS WOMEN'S HEALTH.
THE HEALTH OF WOMEN IS
EVERYTHING THAT AFFECTED A WOMAN
FROM HEAD TO TOE, INSIDE AND
OUT, ACROSS THE LIFE COURSE, AND
WE WANT TO CONNECT THE DOTS
ACROSS THESE EFFORTS THAT ARE
CONDUCTED IN THE INSTITUTES AND
CENTERS, ALL CHRONIC DISEASES,
CONDITIONS, THAT AFFECT MEN AND
WOMEN ACROSS THE LIFE COURSE AND
PROVIDE OPPORTUNITIES FOR GROWTH
AND SYNERGY IN THE FUTURE.
THIS IS THE WAY WE CAN PROVIDE
INDIVIDUALIZED CARE FOR WOMEN IN
THE FUTURE AS WE BETTER
UNDERSTAND THE MENOPAUSAL
TRANSITION, WE CAN IMPROVE THE
HEALTH OF ALL WOMEN.
AS RESEARCH ADVANCES WE COME
CLOSER TO REALIZING THIS VISION
AND BETTER ENABLING CLINICIANS
TO DELIVER INDIVIDUALIZED CARE
APPROPRIATE FOR EACH WOMAN'S AGE
AND REPRODUCTIVE STAGE.
AND WITH THAT, IT'S MY PLEASURE
TO OVER THREE DECADES AFTER THE
WOMEN'S HEALTH INITIATIVE WAS
STARTED, TO INTRODUCE THE 7th
ANNUAL VIVIAN PINN SYMPOSIUM
KEYNOTE SPEAKER, DR. JOANN
MANSON.
DR. MANSON IS THE PROFESSOR OF
MEDICINE AND MICHAEL AND LEE
BELL PROFESSOR OF WOMEN'S HEALTH
AT HARVARD MEDICAL SCHOOL, AND
PROFESSOR IN THE DEPARTMENT OF
EPIDEMIOLOGY AT THE HARVARD T H
CHAN SCHOOL OF PUBLIC HEALTH,
CHIEF OF THE DIVISION OF
PREVENTIVE MEDICINE AT BRIGHAM
AND WOMEN'S HOSPITAL, HAS
RECEIVED NUMEROUS HONORS
INCLUDING AMERICAN HEART
ASSOCIATION POPULATION RESEARCH
PRIZE, DISTINGUISHED SCIENTIST
AWARD, AMONG MANY OTHERS,
ELECTED INTO THE INSTITUTE OF
MEDICINE, NOW NATIONAL ACADEMY
OF MEDICINE, AND AS A MEMBER OF
THE ASSOCIATION OF AMERICAN
PHYSICIANS SHE IS A FELLOW OF
THE AMERICAN ASSOCIATION FOR THE
ADVANCEMENT OF SCIENCE,
BERNADINE HEALEY AWARD FOR
VISIONARY LEADERSHIP IN WOMEN'S
HEALTH, AND RENAISSANCE WOMAN
AWARD, JAMES BRUCE MEMORIAL
AWARD, FROM THE AMERICAN COLLEGE
OF PHYSICIANS AND SHE'S AN
ELECTED MASTER OF AMERICAN
COLLEGE OF PHYSICIANS.
DR. MANSON HAS PUBLISHED MORE
THAN 1200 PEER-REVIEWED ARTICLES
IN MEDICAL LITERATURE, AUTHOR OR
EDITOR OF SEVERAL BOOKS AND TEXT
BOOKS, AND SERVES AS EDITOR IN
CHIEF OF CONTEMPORARY CLINICAL
TRIALS.
SHE'S A PAST PRESIDENT OF THE
NORTH AMERICAN MENOPAUSE
SOCIETY, ONE OF THE MOST HIGHLY
CITED PHYSICIANS, FEATURED IN
THE NATIONAL LIBRARY OF MEDICINE
EXHIBITION CALLED CHANGING THE
FACE OF MEDICINE, I'M SO PLEASED
DR. MANSON WILL SHARE VAST
KNOWLEDGE AND RESEARCH WITH US
TODAY.
I LOOK FOR WASHED TO LEARNING
MORE FROM HER KEYNOTE SPEECH.
PLEASE JOIN ME IN WELCOMING DR.
JOANN MANSON.
>> THANK YOU SO MUCH, DR.
CLAYTON, FOR THAT VERY KIND
INTRODUCTION.
SO IT'S A TREMENDOUS HONOR TO
HAVE BEEN INVITED TO GIVE THE
KEYNOTE ADDRESS THIS MORNING AT
THE VIVIAN PINN SYMPOSIUM.
DR. PINN HAS BEEN AN
EXTRAORDINARY ROLE MODEL AND
MENTOR TO ME OVER THE DECADES AS
I KNOW SHE'S BEEN TO SO MANY
OTHERS.
I'M THRILLED THIS ANALYSIS POEM
YUM IN HER NAME CONTINUES TO
RECOGNIZE AND SERVES AS A
TRIBUTE TO DR. PINN'S ENORMOUS
CONTRIBUTION AND IMPACT.
I CAN'T THANK YOU ENOUGH, DR.
PINN, AND THANK YOU, DR.
CLAYTON, FOR YOUR GREAT WORK AND
FOR YOUR TREMENDOUS
CONTRIBUTIONS OVER THE YEARS AS
WELL.
THIS YEAR THE WHI CELEBRATES THE
30-YEAR ANNIVERSARY OF THE START
OF STUDY RECRUITMENT, AND WHAT
AN EPIC JOURNEY IT'S BEEN OVER
THESE 30 YEARS.
I'D LIKE TO SHARE SOME OF IT
WITH YOU TODAY, AT LEAST THE
LESSONS FROM THE HORMONE THERAPY
COMPONENT.
IT'S NOT ADVANCING.
OKAY.
THERE WE GO.
I HAVE NO FINANCIAL CONFLICTS OF
INTEREST RELATED TO THIS
PRESENTATION.
SO, I WANT TO START BY SAYING
THAT AN OBSCURE HISTORICAL
FIGURE ONCE SAID THINGS SHOULD
BE AS SIMPLE AS POSSIBLE, BUT
NOT ANY SIMPLER.
AND I THINK THE HORMONE THERAPY
SAGA IS A GREAT EXAMPLE OF THIS.
THE ANSWER IS NOT
ONE-SIZE-FITS-ALL IN TERMS OF
HORMONE THERAPY.
WHO IS A GOOD CANDIDATE, WHO
ISN'T A GOOD CANDIDATE?
WE REALLY NEED TO AVOID
OVERSIMPLIFICATION, AND I THINK
THAT THE TENDENCY TO
OVERSIMPLIFY THE RESULTS OF THE
VARIOUS STUDIES OF HORMONE
THERAPY TO TURN IT INTO THIS
ONE-SIZE-FITS-ALL SOLUTION IS
REALLY WHAT'S LEADING TO THE
SWINGING PENDULUM FROM HORMONE
THERAPY IS GOOD FOR ALL WOMEN,
WHICH WAS THE MESSAGE PRIOR TO
THE WHI, TO THEN HORMONE THERAPY
IS BAD FOR ALL WOMEN.
I THINK THAT THE EVIDENCE IS
SHOWING THAT HORMONE THERAPY IS
GOOD FOR SOME BUT NOT ALL WOMEN,
AND THE CHALLENGE IS REALLY TO
IDENTIFY THE WOMEN WHO WILL
BENEFIT.
AND AVOID RISK AMONG THE WOMEN
WHO DO NOT BENEFIT, OR DO NOT
HAVE A FAVORABLE BENEFIT/RATIO.
MANY PEOPLE DO NOT UNDERSTAND
WHAT THE WHI WAS ACTUALLY
DESIGNED TO ADDRESS.
ITS GOAL WAS TO ASSESS THE
BENEFIT-RISK PROFILE OF
MENOPAUSAL PROFILE IN A WIDE AGE
RANGE, 50 TO 79, MEAN AGE WAS
63.
ITS ROLE, THE ROLE OF THIS LARGE
SCALE RANDOMIZED TRIAL WAS NOT
TO EVALUATE HORMONE THERAPY'S
REAL FOR MENOPAUSAL SYMPTOM
MANAGEMENT OR FOR THE TREATMENT
OF PREMATURE OR EARLY MENOPAUSE,
FOR EXAMPLE WHEN HORMONE THERAPY
IS STARTED AMONG WOMEN IN THEIR
30s OR 40s, THAT WAS NOT ITS
PURPOSE.
LOOKING AT POST MENOPAUSAL WOMEN
AGE 50-79.
AND I WANT TO DESCRIBE RECENT
FINDINGS FROM WHI AND OTHER
RANDOMIZED TRIALS OF HORMONE
THERAPY ON CLINICAL EVENT
OUTCOMES, DESCRIBE PATIENT
CHARACTERISTICS, PARTICULARLY
AGE, NUMBER OF YEARS SINCE
MENOPAUSE, UNDERLYING RISK
FACTOR STATUS, EVEN WE'LL TALK
ABOUT SOME BIOMARKER LEVELS THAT
MODIFY HEALTH OUTCOMES ON HT AND
WILL ALSO ADDRESS THE ROLE OF
RECENT RESEARCH IN IMPROVING
CLINICAL DECISION MAKING FOR
HORMONAL VERSUS NON-HORMONAL
THERAPY.
MY COLLEAGUE DR. ANDY KAUNITZ
PUBMED FANNED
PUBMED FANNED -- PUBLISHED A
PIECE, GETTING CLINICAL CARE
BACK ON TRACK, NOTED THAT AS IS
WELL KNOWN MORE THAN 75% OF
PERIPOST MENOPAUSAL WOMEN HAVE
HOT FLASHES, NIGHT SWEATS, NOT
ALL NEED HORMONE THERAPY, MAYBE
20% OR SO WOULD HAVE REALLY
BOTHERSOME MODERATE TO SEVERE
SYMPTOMS WHERE THEY BENEFIT FROM
PRESCRIPTION MEDICATIONS, BUT
THESE SYMPTOMS CAN HAVE A
SUBSTANTIAL IMPACT ON SLEEP,
QUALITY OF LIFE, WORK
PRODUCTIVITY, AND HORMONE
THERAPY IS THE MOST EFFECTIVE
TREATMENT FOR VASOMOTOR
SYMPTOMS, MANY WOMEN ARE HAVING
DIFFICULTY FINDING A CLINICIAN
WHO HAS TRAINING IN THESE
DISCUSSIONS WITH WOMEN TO
DETERMINE IF THEY ARE A GOOD
CANDIDATE TO HAVE THE WOMEN
SHARE IN DECISION MAKING ABOUT
HORMONE THERAPY OR NON-HORMONAL
TREATMENT FOR THESE VASOMOTOR
SYMPTOMS AND OTHER MENOPAUSEALL
SYMPTOMS.
SO IN SOME WAYS MANY CLINICIANS
ARE MISSING IN ACTION FOR THIS
PATIENT POPULATION.
AND I THINK IT'S REALLY
IMPORTANT THAT WE TAKE THIS
ISSUE SERIOUSLY AND GET CLINICAL
CARE FOR MENOPAUSE BACK ON
TRACK.
WE KNOW HORMONE THERAPY IS A
VERY EFFECTIVE AND THE MOST
EFFECTIVE TREATMENT VASOMOTOR
SYMPTOMS, HOT FLASHES, NIGHT
SWEATS, AND THESE ARE RANDOMIZED
TRIALS SHOWING EFFECTIVENESS OF
HARMONY THERAPY REGARDLESS OF
DOSE, THERE'S 80 TO 90%
REDUCTION IN HOT FLASHES PER DAY
WITH ANY FORMULATION.
HORMONE THERAPY IS VERY
EFFECTIVE.
LET'S LOOK AT SOME OF THE
NON-HORMONAL TREATMENTS.
FOR NON-HORMONAL REMEDIES THERE
ARE SSRIS, GABAPENTIN, OFF
LABEL, THESE OTHERS ARE AT LEAST
AS EFFECTIVE 30 TO 50% REDUCTION
IN SYMPTOMS, AND YOU MAY HAVE
HEARD JUST LAST WEEK NK 3
RECEPTOR ANTAGONIST WAS JUST
APPROVED BY THE FDA.
NONE OF THESE TREATMENTS WOULD
BE FREE OF RISK.
WE KNOW SSRIs ARE NOT FREE OF
RISK.
NK 3 RECEPTOR AGONIST REQUIRES
LIVER FUNCTION MONITORING AT
BASELINE AND EVERY THREE MONTHS,
AT LEAST THROUGH NINE MONTHS.
THERE IS CONCERN ABOUT SOME RISK
OF ALL OF THESE MEDICATIONS.
WHAT IS IMPORTANT IS TO BALANCE
BENEFITS AND RISKS AND IDENTIFY
WOMEN WHO WILL HAVE A VERY
FAVORABLE BENEFIT/RISK RATIO
WITH TREATMENT.
YOU MAY HAVE HEARD ABOUT TIMING
HYPOTHESIS OR CRITICAL WINDOW
HYPOTHESIS, WHICH HAS GAINED A
LOT OF TRACTION OVER THE YEARS.
I'LL SHOW YOU SOME EVIDENCE
SUPPORTING IT AND SOME EVIDENCE
THAT RAISES SOME QUESTIONS ABOUT
IT.
BUT BASICALLY, WHAT THIS THEORYS
IN THE HEALTHY BLOOD VESSEL, THE
LINING OF THE CORONARY ARTERIES
AND ENDOTHELIUM IS QUITE
HEALTHY, ABLE TO RESPOND TO
ESTROGEN BY INCREASING NITRIC
OXIDE SYNTHESIS, AND HAVING
VASODILATION.
THERE'S ALSO SOME EVIDENCE THAT
ESTROGEN WHEN GIVEN TO A WOMAN
WITH HEALTHY BLOOD VESSELS WILL
HAVE AN ANTI-INFLAMMATORY
EFFECT, WILL ACTUALLY DECREASE
THE LEUKOCYTE ADHESION TO THE
BLOOD VESSEL WALL, AND MAY
DECREASE PLAQUE PRODUCTION.
THERE ARE SOME FAVORABLE EFFECTS
ON LIPIDS.
HOWEVER, QUITE A DIFFERENT
SCENARIO IS PRESENT IN A WOMAN
WITH ADVANCED ATHEROSCLEROSIS,
ADVANCED PLAQUES.
FIRST THE ESTROGEN RECEPTOR IS
NOT -- IS DOWNREGULATED AND NOT
EASILY ACCESSIBLE TO ESTROGEN,
AS A RESULT YOU DO NOT SEE
NITRIC OXIDE SYNTHESIS OR
DILATION, YOU SEE A PARADOXICAL
PRO-INFLAMMATORY RESPONSE,
INCREASED RISK IF IT'S ORAL IN
PARTICULAR OF THROMBOTIC EFFECT
THAT CAN OCCLUDE A STENOTIC
CORONARY ARTERY LEADING TO
VASOOCCLUSION, ALSO EFFECT ON
MMP WHERE THERE MAY BE EROSION
OF PLAQUES AND GREATER RISK OF
PLAQUE RUPTURE.
SO IT'S ALMOST THE OPPOSITE
EFFECT BASED ON ANIMAL STUDIES
AND LABORATORY STUDIES, REALLY
SUGGESTING THAT ESTROGEN'S
FAVORABLE EFFECTS IN EARLY
MENOPAUSE WAY NOT APPLY TO LATER
MENOPAUSE OR TO WOMEN WITH
UNDERLYING ATHEROSCLEROSIS.
WHERE DID THIS HYPOTHESIS COME
FROM THAT ESTROGEN COULD BE
CARDIO PROTECTIVE?
WELL, MANY OF US REMEMBER IN THE
1980s, 1990s, THERE WERE
MANY OBSERVATIONAL STUDIES,
THESE ARE OBSERVATIONAL
CORRELATIONAL STUDIES BEING
PUBLISHED OF HORMONE THERAPY AND
CHD WHERE THE WOMEN WHO WERE
TAKING HORMONE THERAPY, WHO
ASKED TO TAKE HORMONE THERAPY,
THEY GENERALLY HAD ABOUT 40 TO
50% LOWER RISK OF CORONARY HEART
DISEASE THAN WOMEN NEVER USERS.
THESE WERE SIGNIFICANT
DIFFERENCES SHOWED UP IN
META-ANALYSES.
AND SYSTEMIC HORMONE THERAPY WAS
INCREASINGLY BEING PRESCRIBED
FOR PREVENTION OF CHRONIC
DISEASES, SUCH AS CORONARY HEART
DISEASE, STROKE, COGNITIVE
DECLINE, OTHER CHRONIC DISEASES
IN THE 1980s, 1990s, MANY OF
US IN CLINICAL PRACTICE REMEMBER
HOW COMMONLY HORMONE THERAPY WAS
BEING PRESCRIBED BY MANY
CLINICIANS FOR THIS PURPOSE.
IT WAS AN INCREASING TREND.
THIS WAS TRUE ACROSS ALL
MENOPAUSAL AGE GROUPS, NOT ONLY
IN WOMEN WHO WERE JUST ENTERING
MENOPAUSE.
THIS WAS AMONG WOMEN, MANY WHO
WERE MORE THAN TEN YEARS PAST
ONSET OF MENOPAUSE, IN THEIR
70s AND '80s, PRESCRIBED
HORMONE THERAPY FOR CHRONIC
DISEASE PREVENTION.
LET'S LOOK AT SOME DIFFERENCES
BETWEEN THE WHI ANDS
OBSERVATIONAL STUDIES.
FIRST THERE ARE SOME BIOLOGICAL
DIFFERENCES IN TERMS OF AGE AND
TIME SINCE MENOPAUSE.
WHI FOCUSED ON WOMEN ACROSS THE
SPECTRUM OF 50 TO 79, MEAN AGE
WAS 63.
OBSERVATIONAL STUDIES WERE
GENERALLY WOMEN, MANY OF THESE
STUDIES WERE STARTED IN THE
1970s AND 1980s, WOMEN
SEEKING HORMONE THERAPY FOR HOT
FLASH, NIGHT SWEATS, IN THEIR
EARLY 50s.
THE TIME SINCE MENOPAUSE IS
QUITE DIFFERENT, IN THE WHI IT'S
MORE THAN 12 YEARS ON AVERAGE
SINCE ONSET OF MENOPAUSE.
SO ON EVERYTHING WOMEN IN WHI
ARE MORE THAN A DECADE PAST
ONSET OF MENOPAUSE, IN
OBSERVATIONAL STUDIES JUST A FEW
YEARS.
AND THE HEALTH STATUS WAS QUITE
DIFFERENT.
AS YOU KNOW, THE GOLD STANDARD
RANDOMIZED CLINICAL TRIAL, THE
BEAUTY IS THAT YOU RANDOMIZE AND
THE GROUPS, PLACEBO AND ACTIVE
TREATMENT GROUPS ARE VERY
SIMILAR IN TERMS OF HEALTH
STATUS BASELINE CHARACTERISTICS,
OBSERVATIONAL STUDIES THE USERS
TENDED TO BE HEALTHIER, HIGHER
SES, THAN NON-USERS, IT'S VERY
CHALLENGING TO ADJUST COMPLETELY
FOR VARIABLES.
LET'S TURN TO WHAT WE'VE LEARNED
FROM THE RANDOMIZED CLINICAL
TRIALS OF HORMONE THERAPY.
SO, FIRST I CAN SUMMARIZE IN ONE
SENTENCE WHAT THE SECONDARY
PREVENTION RANDOMIZED TRIALS
SHOW.
THEY DID NOT SHOW A BENEFIT OF
HORMONE THERAPY FOR REDUCING
RECURRENT CLINICAL EVENTS OR
DEATH FROM CARDIOVASCULAR
DISEASE.
IN FACT, JUST THERE WERE SO MANY
OF THESE SECONDARY PREVENTION
TRIALS EVIDENCE THERE WAS A
HYPOTHESIS THAT HORMONE THERAPY
MIGHT BE CARDIO PROTECTIVE IN
WOMEN WITH HIGHEST RISK, PRIOR
CARDIOVASCULAR DISEASE, WOMEN
WITH EVIDENCE OF
ATHEROSCLEROSIS, NOT A SINGLE
ONE SHOWED CARDIO PROTECTION, IN
FACT THEY SHOWED NEUTRAL RESULT
OR HARM IN INCREASED RISK.
THIS IS IRRESPECTIVE OF WHETHER
THEY TESTED, CONJUGATED EQUINE
ESTROGEN OR ESTRADIOL, OR OTHER
FORMULATIONS, LEAVING US WITH
PRIMARY PREVENTION TRIALS OF THE
WOMEN'S HEALTH INITIATIVE, WHICH
THERE ARE TWO SEPARATE PARALLEL
TRIALS, ESTROGEN PLUS PROGESTIN
AND ESTROGEN ALONE.
THE WHI TRIAL, THE TWO WHI
TRIALS WERE BASED ON WHETHER THE
WOMEN HAD A PRIOR HYSTERECTOMY
AT START OF THE STUDY.
IF SHE DID, AND THERE WERE MORE
THAN 10,000 WOMEN IN THAT
CATEGORY, SHE WAS RANDOMIZED TO
CONJUGATED EQUINE ESTROGENSES,
CEE, TRADITIONAL DOSE 0.65
MILLIGRAMS A DAY VERSUS PLACEBO.
IF SHE HAD INTACT UTERUS, 16,000
WOMEN IN THAT TRIAL, RANDOMIZED
TO COMBINATION OF CEE, SAME
DOSE, PLUS MPA, 2.5 MILLIGRAMS A
DAY VERSUS PLACEBO.
WERE WHY THESE FORMULATIONS
CHOSEN?
WE DON'T USE THEM VERY MUCH
ANYMORE.
WELL, THE REASON THEY WERE
CHOSEN IS THAT THESE WERE THE
MOST COMMON HORMONE THERAPY
FORMULATIONS THAT WERE USED AT
THE TIME THE WHI WAS BEING
DESIGNED IN THE VERY EARLY
1990s, AND THESE WERE THE
FORMULATIONS THAT WERE THE
PREDOMINANT ONES IN THE
OBSERVATIONAL STUDIES THAT WERE
SHOWING CARDIO PROTECTION.
SO TO HAVE TESTED A DIFFERENT
FORMULATION COULD HAVE LED TO
OTHER TYPES OF CRITICISM, WELL,
YOU NEVER TESTED THE
FORMULATIONS THAT WERE
ASSOCIATED WITH CARDIO
PROTECTION IN ALL OF THOSE
OBSERVATIONAL STUDIES AND
META-ANALYSES.
AGAIN, I WANT TO EMPHASIZE THAT
THE WHI HORMONE THERAPY TRIALS
WERE NOT ADDRESSING HT
INITIATION AT AGES LESS THAN 40
OR LESS THAN 45, PREMATURE EARLY
MENOPAUSE, AND I KNOW THERE WILL
BE TALKS ABOUT SOME ISSUES
REGARDING RISKS WITH EARLY
PREMATURE MENOPAUSE, WERE
HORMONE THERAPY SHOULD BE USED,
NOT WHAT WHI WAS DESIGNED TO
ADDRESS, ALSO NOT ADDRESSING HT
USE IN PERIMENOPAUSE OR
MENOPAUSE TRANSITION.
NOW, BOMBSHELL FINDINGS OF THE
WHI E PLUS P TRIAL SHOWN ON THIS
SLIDE.
IN JULY OF 2002, MANY PEOPLE,
MANY OF US CAN REMEMBER WHERE WE
WERE AT THAT TIME.
THESE RESULTS WERE SURPRISING.
MOST -- MOST INVESTIGATORS, MOST
VIN IDENTIFICATIONS WERE
EXPECTING THAT THE BENEFITS
WOULD OUTWEIGH THE RISK, WHI
TRIAL RESULTS WERE PUBLISHED
EARLY THE TRIAL WAS STOPPED 3.3
YEARS EARLY.
I THINK IT'S QUITE CLEAR THAT
THE RISKS DID OUTWEIGH BENEFITS.
NUMBERS MAY SOUND ALARMING.
WHEN YOU'RE TALKING ABOUT
PERCENTAGE INCREASES, IT SEEMS
VERY, VERY FRIGHTENING.
AND WE'VE LEARNED WITH SOME
SURVEYS OVER THE YEARS THAT MANY
CLINICIANS AND PATIENTS HAVE
INTERPRETED THE PERCENT INCREASE
IN RISK AS RISK THEY ARE GOING
HAVE BE A EVENT ON HORMONE
THERAPY SUCH AS YOU HAVE NOT A
29% INCREASE IN CORONARY HEART
DISEASE BUT 29% OVERALL RISK OF
HAVING A HEART ATTACK, 41% RISK
OF HAVING STROKE, THAT'S NOT
WHAT THE WHI SHOWED.
BUT IN TERMS OF RELATIVE RISKS,
HAZARD RATIOS, IT DID SHOW AT
THE TIME IT WAS STOPPED EARLY IN
JULY OF 2002 THAT CORONARY HEART
DISEASE WAS 29% INCREASE, STROKE
41%, PULMONARY EMBOLISN AND
BREAST CANCER INCREASED, 65 AND
OLDER INCREASED RISK OF
DEMENTIA, DOUBLING BUT LATER
STUDIES SHOWED NO INCREASE IN
COGNITIVE DECLINE AMONG WOMEN
WHO WERE 50 TO 55.
IN 2004 ESTROGEN ALONE TRIAL
RESULTS, CEE ALONE TRIAL,
RESULTS PUBLISHED, IT WENT ON
TWO YEARS LONGER, STOPPED ONLY
ONE YEAR EARLY.
THE REASON IT WAS STOPPED EARLY
WAS THAT INCREASED RISK OF
STROKE WAS FOUND, SIMILAR TO
INCREASED RISK WITH ESTROGEN
PLUS PROGESTIN, BUT THERE WAS A
SIMILAR MAGNITUDE REDUCTION IN
HIP FRACTURE BUT I DON'T KNOW
THAT THESE ENDPOINTS TOTALLY
BALANCE EACH OTHER OUT, CAN
LEAVE THAT UP TO WHAT A WOMAN
CONSIDERS MORE IMPORTANT.
BUT THERE WERE MANY NULL
FINDINGS THAT HAD SHOWN RISK
WITH E PLUS P BUT WERE VERY NULL
WITH ESTROGEN ALONE, INCLUDING
CORONARY HEART DISEASE, .91,
BREAST CANCER WAS TRENDING
DOWNWARD, NEUTRAL, NOT
SIGNIFICANT DIFFERENCES,
ALL-CAUSE MORTALITY, GLOBAL
INDECEMBER WERE ALL NEUTRAL, AND
DEMENTIA WAS JUST BORDERLINE
INCREASED IN WOMEN 65 AND OLDER
BUT NO INCREASE LATER FOUND WITH
COGNITIVE DECLINE IN WOMEN 50-
55.
IN JAM A IN 2013 PUBLISHED A
STUDY OF RESULTS DURING THE
INTERVENTION AND EXTENDED POST
INTERVENTION PHASES THROUGH 13
YEARS OF CUMULATIVE FOLLOW-UP,
I'LL GO THROUGH RESULTS WITH
YOU.
FIRST, I WANT TO GIVE YOU THE
BOTTOM LINE.
THE GREEN SHOWS INTERVENTION
PHASE, I'VE GONE THROUGH.
THESE RESULTS DIDN'T CHANGE MUCH
IN TERMS OF WHAT WAS INCREASED
WITH E PLUS P, BREAST CANCER
STROKE, GLOBAL INDEX, CEE ALONE,
STROKE, WHAT WAS DIFFERENT IS
THAT FURTHER EVENTS ACCRUING,
THIS IS DURING THE INTERVENTION
PHASE, CORONARY HEART DISEASE
WAS NO LONGER SIGNIFICANTLY
INCREASED.
IT WAS JUST BORDERLINE BUT NOT
SIGNIFICANT.
DURING THE POST INTERVENTION
FOLLOW-UP UP TO 13 YEARS, THERE
WERE ONLY A FEW RESULTS THAT
PERSISTED.
BASICALLY ALL OF THE
CARDIOVASCULAR EVENTS RETURNED
TO BASELINE, AND FRACTURE
EVENTS, ALL-CAUSE MORTALITY
CONTINUED TO BE NEUTRAL, ZERO IS
NO EFFECT.
VERY NEUTRAL THROUGHOUT THE
ENTIRE TRIAL AND FOLLOW-UP,
GLOBAL INDEX, SUMMATION OF ALL
OF THESE CHRONIC DISEASE
OUTCOMES, INTERESTINGLY WE DID
IDENTIFY A SIGNIFICANT
REDUCTION, ABOUT 1/3 REDUCTION
IN ENDOMETRIAL CANCER, MAYBE
BECAUSE THE FORMULATION IS GOOD
AT PROTECTING THE UTERUS, QUITE
INTERESTING.
WHAT WAS MOST SURPRISING WAS THE
BREAST CANCER RISK CONTINUED
WITH E PLUS P, CONTINUED TO BE
INCREASED AND WITH ESTROGEN
ALONE BECAME EVEN LOWER, AND
STATISTICALLY SIGNIFICANT.
I WANT TO SHOW YOU HOW THE
RESULTS FOR CEE PLUS MPA AND CEE
ALONE WERE ALMOST MIRROR, REALLY
MIRROR IMAGES OF EACH OTHER, AND
DELVED DEEPLY.
WITH E PLUS P INCIDENCE, THIS IS
A FOLLOW-UP OVER EVEN 20 YEARS,
YOU CAN SEE AROUND 4 YEARS YOU
START TO GET THE INCREASE IN
INCIDENCE OF BREAST CANCER, WITH
E PLUS P, THIS KIND OF LEVELED
OFF AT 28% INCREASE, FOR
MORTALITY IT WAS -- HAZARD RATIO
1.35, NOT QUITE A SIGNIFICANT
INCREASE FOR BREAST CANCER, THIS
IS BREAST CANCER MORTALITY.
FOR ESTROGEN ALONE, QUITE
INTERESTINGLY, THE REDUCTION WAS
22% AND IT WAS STATISTICALLY
SIGNIFICANT FOR BREAST CANCER
INCIDENCE, AND A 40% REDUCTION
IN BREAST CANCER MORTALITY.
SO VERY DIFFERENT FINDINGS FOR
ESTROGEN PLUS PROGESTIN AND
ESTROGEN ALONE, THIS IS
CONJUGATED EQUINE ESTROGEN IN
TERMS OF BREAST CANCER.
THE KEY QUESTION RIGHT NOW, IS
THIS A FINDING SPECIFIC TO
CONJUGATED ESTROGEN OR IS THIS
GOING TO BE FOUND, THIS ESTROGEN
ALONE FINDING, IS THIS GOING TO
BE FOUND WITH ALL FORMULATIONS
OF ESTROGEN AND ALSO INCREASED
RISK WITH CEE PLUS MPA, IS THIS
ALSO GOING TO BE FOUND WITH
OTHER ESTROGEN FORMULATIONS AND
OTHER PRO GESTOGINE
FORMULATIONS.
I HOPE YOU GET FROM THIS TALK
THAT THE ABSOLUTE RISK, NUMBER
OF CASES PER LET'S SAY 10,000
PERSON-YEARS ARE VERY DIFFERENT
BY AGE GROUP, WHEN YOU'RE
TALKING ABOUT THE EFFECTS OF
HORMONE THERAPY.
ACTUALLY, WHETHER YOU LOOK AT
THE ACTIVE GROUP, WHICH IS SOLID
BAR, OR PLACEBO GROUP, CROSS
HATCH, YOU CAN SEE THAT THE
TREATMENT IS MAKING VERY LITTLE
DIFFERENCE ESPECIALLY AMONG THE
YOUNGER WOMEN BUT THEIR ABSOLUTE
RISKS, NUMBER OF CASES PER
10,000 PER YEAR, IS JUST VERY
LOW, ESPECIALLY COMPARED TO
WOMEN 70 TO 79, IT'S ABOUT FOUR
TO FIVE TIMES HIGHER AMONG WOMEN
70 TO 79.
AND INTERMEDIATE IN 60 TO 69.
NOW, IN TERMS OF THE RELATIVE
RISK, WE JUST TALKED ABOUT THE
ABSOLUTE RISK, WHICH IS SO
IMPORTANT TO DISCUSS WITH
PATIENTS WHEN THEY ARE MAKING
DECISIONS, THEY WANT TO KNOW
WHAT ABSOLUTE RISKS ARE, YOU
KNOW, IF RISK IS 1 IN A MILLION
INCREASED BY 20%, IT'S STILL A
VERY LOW RISK.
PATIENTS ARE INTERESTED IN
ABSOLUTE LOW RISK BUT IN TERMS
OF THE HAZARD RATIOS IN BOTH
TRIALS THE HAZARD RATIOS WERE
SIMILAR BY AGE FOR MOST OF THE
HEALTH OUTCOMES, INCLUDING
STROKE, VENOUS THROMBOSIS,
BREAST CANCERS, OTHER CANCERS,
PULMONARY EMBOLISM, BUT MUCH
LOWER ABSOLUTE RISK IN YOUNGER
COMPARED TO OLDER WOMEN.
DIDN'T SEE MAJOR DIFFERENCES
BY -- WERE LIMITED IN POWER TO
ADDRESS THAT, AND ALSO NOT GOING
TO BE PRESENTING UPCOMING SLIDES
CHANGES IN BODY WEIGHT, WEIGHT
COMPOSITION, MANY BIOMARKERS,
THERE WILL BE OTHER
PRESENTATIONS ON THAT SUBJECT.
I DO WANT TO HIGHLIGHT THAT
THERE WERE SOME SPECIFIC
OUTCOMES, IMPORTANT OUTCOMES,
WHERE EVEN THE HAZARD RATIOS
DIFFERED, AND IT WAS NOT ONLY
THE LOWER ABSOLUTE RISK BUT IT
WAS ALSO THE LOWER RELATIVE
RISK.
AND THIS DOES INTRODUCE
ADDITIONAL NUANCES.
SO, FOR EXAMPLE, FOR TOTAL M.I.,
THE MOST RIGOROUSLY ADJUDICATED
CORONARY ENDPOINT, WE DID SEE
FOR THE 50 TO 59 YEAR AGE GROUP
.55, WHICH WAS SIGNIFICANT,
69.95, STARTED TO SEE INCREASE
WITH ESTROGEN ALONE, STARTING
WITH ESTROGEN ALONE HERE.
THE P FOR TREND BY AGE GROUP WAS
STATISTICALLY SIGNIFICANT, 0.02,
ALSO FOR ALL-CAUSE MORTALITY WE
SAW THIS SIGNAL FOR REDUCTION
WITH ESTROGEN ALONE IN ALL-CAUSE
MORTALITY, 0.70, NOT
STATISTICALLY SIGNIFICANT, VERY
NEUTRAL FOR 60 TO 69, TRENDING
UPWARD FOR WOMEN IN THEIR 70s,
AND, AGAIN, A SIGNIFICANT
P-VALUE FOR TREND BY INCREASING
AGE.
NOW, WITH ESTROGEN PLUS
PROGESTIN THE RISK OF M.I. WAS A
LITTLE MORE COMPLEX.
IN FACT, WHEN LOOKED AT BY AGE
GROUP, THERE REALLY WAS NO
SIGNAL OF DIFFERENCE, THIS MAY
BE WHY IN THE EARLY YEARS WHEN
THE TRIAL RESULTS WERE BEING
PUBLISHED THERE WASN'T A LOT OF
ATTENTION TO AGE BUT WE LATER
LOOKED AT THE NUMBER OF YEARS
SINCE MENOPAUSE AND HOW THAT
RELATED TO RISK OF M.I. ON
ESTROGEN PLUS PROGESTIN AND WE
SAW THAT THERE WAS QUITE A
STRONG TREND, NO INCREASED RISK
OF M.I. AMONG WOMEN WITHIN TEN
YEARS SINCE ONSET OF MENOPAUSE
BUT A DOUBLING IN RISK OF M.I.
AMONG WOMEN 20 OR MORE YEARS
SINCE MENOPAUSE, A STRONG TEST
FOR TREND.
NOW, WHAT OTHER EVIDENCE IS
THERE FOR THIS TIMING
HYPOTHESIS, AT LEAST AS IT
RELATES TO CARDIOVASCULAR
CORONARY DISEASE?
WELL, THE ELITE TRIAL, EARLY
VERSUS LATE WITH ESTRADIOL, THIS
WAS ACTUALLY DESIGNED
SPECIFICALLY TO TEST THE TIMING
HYPOTHESIS, VERY SMALL TRIAL.
I MEAN, YOU KNOW, WHI, WE'RE
TALKING ABOUT 10,000, AND THEN
16,000 PARTICIPANTS IN EACH OF
THE TRIALS.
THIS IS 1/10.
I MEAN, THIS IS VERY, VERY
SMALL, LESS THAN 1/10 THE SIZE,
643 HEALTHY POST MENOPAUSAL
WOMEN, LOOKING AT A SURROGATE
ENDPOINT, NOT CLINICAL EVENTS
BUT RATHER CHANGE IN CAROTID
INTERMEDIATAL THICKNESS UP TO 6
YEARS, RANDOMIZED TRIAL DESIGN
LOOKING AT ORAL ESTRADIOL VERSUS
PLACEBO IN TWO GROUPS, LESS THAN
SIX YEARS SINCE ONSET, EARLY
MENOPAUSE GROUP, AND THOSE WHO
WERE AT LEAST ONE DECADE SINCE
ONSET OF MENOPAUSE, AND THE
INTERVENTION WAS 17 BETA
ESTRADIOL 1 MILLIGRAM A DIE,
PROGRESS AT VAGINAL MICRONIZED
GEL 12 DAYS A MONTH, CAROTID TID
AS ENDPOINT.
THERE WAS A DIFFERENCE, THE TOP
TWO CURVES SHOW THE WOMEN WHO
WERE MORE THAN A DECADE PAST
MENOPAUSE, THERE'S VERY LITTLE
DIFFERENCE IN TWO CURVES IN
TERMS OF INCREASED CAROTID IMT
THICKNESS.
IN THE WOMEN WHO WERE LESS THAN
6 YEARS SINCE ONSET OF MENOPAUSE
YOU SEE VERY ALSO INCREASE IN
CAROTID IMT, MORE IN THE GROUP
RECEIVING PLACEBO, SIGNIFICANT
DIFFERENCE IN CURVES,
SIGNIFICANT INTERACTION BETWEEN
OLDER AND YOUNGER WOMEN, MORE
DISTANT FROM ONSET OF MENOPAUSE.
THIS HAS BEEN CITED AS FURTHER
EVIDENCE OF THE TIMING
HYPOTHESIS IN ADDITION TO THOSE
OBSERVATIONAL STUDIES AND
SUBGROUP FINDINGS IN WHI.
NOW, NOT ALL RANDOMIZED TRIALS
OF WOMEN IN EARLY MENOPAUSE HAVE
SHOWN DIFFERENCES IN CAROTID
IMT, LOOKED AT IN THE PREVENTION
STUDY, THE KEEPS TRIAL, IT WAS
LOOKED AT BEFORE -- THIS IS
ABOUT A FOUR-YEAR TRIAL, LOOKING
AT CAROTID IMT AS ENDPOINT,
THERE WERE NO SIGNIFICANT
DIFFERENCES ACROSS THE TREATMENT
GROUPS LOOKING AT ORAL CEE BUT
LOWER DOSE, TRANSDERMAL
ESTRADIOL OR PLACEBO, LOWER
DOSES OF ESTROGEN MAY BE A
FACTOR BUT NOT YET CLEAR HOW
IMPORTANT, ALSO BECAUSE THESE
WERE EXTREMELY HEALTHY WOMEN
HAVING LITTLE CHANGE IN THIS
ENDPOINT.
NOW, THIS SLIDE SUMMARIZES
SOMETHING THAT CAN BE HELPFUL IN
DISCUSSIONS WITH PATIENTS.
IT'S FOCUSING, THIS SLIDE, IS
FOCUS ON 50- 59 AGE GROUP WITH
THE MOST COMMON VASOMOTOR
SYMPTOMS, MOST DECISION MAKING
ABOUT USE OF HORMONE THERAPY AND
TYPICAL TREATMENT PERIOD MIGHT
BE 5 YEARS.
SO IT'S LOOKING IN A GROUP OF
POST MENOPAUSAL WOMEN 50-59,
BENEFITS AND RISKS OF HORMONE
THERAPY FOR PER 1,000 WOMEN OVER
FIVE YEARS OF TREATMENT, THIS IS
OVER THEIR FULL FIVE-YEAR COURSE
OF TREATMENT.
THIS IS THE NUMBER OF ADVERSE
EVENTS SHOWN HERE IS ENDPOINT,
CHD, STROKE, DVT, BREAST CANCER,
COLORECTAL AND OTHER CANCERS,
FRACTURE, SOME REDUCTION
FRACTURE, ALL-CAUSE MORTALITY,
DIABETES, E PLUSP IN THE TOP
PANEL COMPLEX PATTERN.
WITH CEE ALONE IT LOOKED PRETTY
GOOD FOR THE WOMEN 50-59.
THERE WAS A SLIGHT INCREASE IN
DEEP VENOUS THROMBOSIS ENDPOINT
BUT OVERALL THE STROKE LOOKED
PRETTY NEUTRAL, EVEN THOUGH WE
DON'T SEE SIGNIFICANT
INTERACTION BY AGE GROUP BUT IT
WAS NEUTRAL IN THIS PARTICULAR
AGE GROUP.
AND THERE WAS A REDUCTION IN
CORONARY DISEASE WE TALKED ABOUT
THAT, THERE WAS NO INCREASE IN
ANY OF THESE CANCERS, BREAST
CANCER TRENDING DOWNWARD,
REDUCTION IN FRACTURE, REDUCTION
IN ALL-CAUSE MORTALITY,
REDUCTION IN DIABETES, LOOKED
QUITE GOOD OVERALL BUT WE HAVE
TO BE CONCERNED ESPECIALLY WITH
ORAL ESTROGEN, VENOUS THROMBOSIS
AND STROKE.
THIS IS ANOTHER WAY OF LOOKING
AT WHAT I JUST SHOWED YOU.
SO, AGAIN, THESE ARE THE CASES
PER THOUSAND WOMEN USING HORMONE
THERAPY OVER FIVE-YEAR TREATMENT
PERIOD, THIS SHOWS ALL OF THE
AGE GROUPS FOR TWO REALLY
IMPORTANT ENDPOINTS OF ALL-CAUSE
MORTALITY, AND GLOBAL INDEX
WHICH IS A COMPOSITE OF ALL OF
THESE ADVERSE EVENTS.
AND WHAT WE FOUND BLUE IS RISK
REDUCTION, ACTUALLY SHOWING
FEWER CASES, AND RED IS SHOWING
SOME INCREASE.
WHAT WE FOUND IS THAT OVERALL
FOR THE WOMEN 50-59 IN THE E
PLUS P TRIAL THEY DID REASONABLY
WELL, FIVE FEWER DEATHS PER
THOUSAND WOMEN OVER FIVE YEARS,
GLOBAL INDEX SIX EXTRA ADVERSE
EVENTS IN TOTAL, PER THOUSAND
WOMEN OVER FIVE YEARS.
IN THE ESTROGEN ALONE, 50-59
YEAR AGE GROUP HAD SIX FEWER
DEATHS, TEN FEWER ADVERSE EVENTS
OVER FIVE YEARS, PER THOUSAND
WOMEN.
AND SO THAT LOOKS PRETTY
FAVORABLE.
BUT DO NOTICE THAT THESE RISKS,
ESPECIALLY FOR GLOBAL INDEX, ARE
GETTING QUITE SUBSTANTIAL IN THE
70 TO 79 YEAR AGE GROUP.
EVEN GETTING UP THERE, 60 TO 69
FOR THE E PLUS P TRIAL, EVEN IN
THE ESTROGEN ALONE WHERE THE
RESULTS WERE GENERALLY MORE
FLAVORRABLE THAN E PLUS P, 70 TO
79 DID HAVE 13 EXTRA DEATHS PER
THOUSAND WOMEN OVER FIVE YEARS
AND 25 EXTRA ADVERSE EVENTS PER
THOUSAND WOMEN OVER FIVE YEARS.
WE DELVED MORE DEEPLY INTO
MORTALITY FINDINGS IN JAMA IN
2017, OVER 18 YEARS OF
FOLLOW-UP, AND WE DID SEE PRETTY
FAVORABLE RESULTS IN THE 50-59
YEAR AGE GROUP FOR ALL-CAUSE
MORTALITY, PULLING THE TWO
TRIALS SIGNIFICANT 31%
REDUCTION, CBD AND CANCER
MORTALITY ON THE SIDE OF
BENEFIT, IN THE 50-59 YEAR AGE
GROUP AND OTHER NON-CBD
NON-CANCER MORTALITY ON THE SIDE
OF BENEFIT.
WE WERE INTERESTED IN THE
QUESTION OF IN THE ESTROGEN
ALONE TRIAL THIS BENEFIT SEEN
FOR ALL-CAUSE MORTALITY AND SOME
OUTCOMES, DID IT DIFFER FOR
WOMEN WITH BILATERAL
OOPHORECTOMY AND WOMEN ARE
CONSERVED OVARIES?
AND WE ACTUALLY DID SEE A
DIFFERENCE.
KEEP IN MIND THIS IS NOT
STARTING ESTROGEN AT THE TIME
THEY HAD THE BILATERAL BILATERL
OOPHORECTOMY, SOMETIMES IT WAS
MORE THAN TEN YEARS.
NONETHELESS, WE SAW THAT THE
REDUCTION THAT WE'RE SEEING IN
ALL-CAUSE MORTALITY WITH
ESTROGEN ALONE, THAT SIGNAL FOR
REDUCTION IS ALMOST ENTIRELY IN
THE WOMEN WITH BILATERAL
OOPHORECTOMY, AND OVER 18 YEARS
OF FOLLOW-UP THIS BECAME A
SIGNIFICANT 32% REDUCTION IN
WOMEN WITH BSO, OTHER FINDINGS,
OTHER AGE GROUPS DID NOT HAVE
THESE SIGNIFICANT REDUCTIONS,
ALSO WOMEN WITH CONSERVED
OVARIES DID NOT HAVE A
SIGNIFICANT REDUCTION.
FOR EXAMPLE, THEIR HAZARD RATIO
FOR ALL-CAUSE MORTALITY WAS
0.93.
I MEAN STILL TO THE LEFT OF
UNITY BUT IT WAS NOTHING TO
WRITE HOME ABOUT.
>> I'M LETTING YOU KNOW ABOUT
TIME.
>> OKAY.
I WILL RUSH THROUGH.
LDL, WE LOOKED AT BIOMARKERS TO
SEE WHETHER THEY MADE A
DIFFERENCE, GENERALLY WOMEN WITH
GOOD BIOMARKER STATUS TENDED TO
DO BETTER WITH HORMONE THERAPY
IN TERMS OF CHD RISK THAN WOMEN
WITH ADVERSE BIOMARKER RATIO.
TRANSDERMAL ESTRADIOL, NO
RANDOMIZED TRIAL ASSESSING
RELATIVE SAFETY OR CLINICAL
EVENTS, THESE ARE OBSERVATIONAL
STUDIES.
ARE LOWER DOSES SAFER FOR BLOOD
PRESSURE, SOME EVIDENCE FROM
OBSERVATIONAL VERSUS HEALTH
STUDY THAT .3 MILLIGRAMS MAY NOT
INCREASE STROKE THE WAY .65 DOES
BUT OTHER STUDIES HAVE SHOWN
MIXED RESULTS.
I'LL MENTION QUICKLY THAT ONE OF
THE CONCERNS ABOUT NON-PROVIDING
THE CLINICAL CARE TO WOMEN WHO
ARE SEEKING TREATMENT FOR THEIR
HOT FLASHES AND MENOPAUSAL
SYMPTOMS IS THAT THEY ARE
TURNING TO CUSTOM COMPOUNDED
HORMONE THERAPY WHICH IS NOT FDA
REGULATED.
THIS USE HAS SKYROCKETED,
BILLION DOLLAR HEAVILY MARKETED
INDUSTRY.
NO DATA ON EFFICACY, SAFETY,
QUALITY CONTROL.
WE DO HAVE FDA APPROVED
BIOIDENTICAL HORMONE THERAPY
FORMULATIONS SUCH AS ESTRADIOL,
YOU'LL HEAR MORE IN OTHER TALKS.
AND BUT MANY WOMEN THINK
COMPOUNDED HORMONE THERAPY IS
SAFER BECAUSE IT'S WITHOUT A
PACKAGE INSERT OR WARNING.
OTHERS WILL TALK ABOUT DECISION
MAKING.
WE PUBLISHED IN JAMA A FEW YEARS
AGO, CRANDALL AND SCHIFRIN AND
I, THAT STILL THE DECISION
SHOULD BE BASED ON VASOMOTOR
SYMPTOM, PRIMARILY THIS IS THE
INDICATION FOR TREATMENT,
CONFIRM HOT FLASHES ARE NIGHT
SWEATS ARE ADVERSELY AFFECTING
SWEET, DAYTIME FUNCTION, QUALITY
OF LIFE, ASSESS FOR
CONTRAINDICATIONS, ASSESS FOR
UNDERLYING RISK, GREEN LIGHT FOR
WOMEN LESS THAN 60 YEARS OLD,
MENOPAUSE ON SET WITHIN 10
YEARS, LOW RISK OF BREAST
CANCER, CARDIOVASCULAR DISEASE.
OTHER GROUPS COULD CONSIDER
TRANSDERMAL, OF COURSE AN OPTION
FOR ALL WOMEN, AND OTHERS SHOULD
PROBABLY AVOID HORMONE THERAPY.
TRANSDERMAL WITH DIABETES,
INCREASED RISK OF THROMBOSIS,
SOME EVIDENCE THAT IT'S
PREFERABLE WITH LOWER LIBIDO
ISSUES OR SEXUAL FUNCTION ISSUES
BECAUSE IT DOESN'T HAVE AS MUCH
EFFECT IN LOWERING
TESTOSTERONE,, MIGRAINES.
HORMONE THERAPY HAS AN IMPORTANT
ROLE IN MANAGE OF SYMPTOMS.
THIS IS NOT REFUTED OR EVEN
ADDRESSED BY THE WHI.
THE CURRENT EVIDENCE DOES NOT
SUPPORT USE OF HORMONE THERAPY
FOR PREVENTION OF CVD OR CHRONIC
DISEASES BECAUSE IT'S NOT A GOOD
TRADEOFF DUE TO AN INCREASED
RISK OF ETE, POSSIBLY STROKE,
WITH E PLUS P BREAST CANCER
ACROSS AGE GROUPS.
BEST CANDIDATES FOR SYSTEMIC
HORMONE THERAPY ARE RECENTLY
MENOPAUSAL, SYMPTOMATIC WOMEN IN
GENERALLY GOOD HEALTH WITH LOW
ABSOLUTE RISK, GREATER QUALITY
OF LIFE BENEFITS.
AND FOR PREVENTION PURPOSES, WE
HAVE A LARGE NUMBER OF
MODALITIES AND OPTIONS,
LIFESTYLE MODIFICATION,
GUIDELINE-DIRECTED CARE,
STATINS, ET CETERA.
RISK STRATIFICATION IS IMPORTANT
FOR APPROPRIATE DECISION MAKING
ABOUT HORMONE THERAPY AND SO
IMPORTANT TO HAVE SHARED
DECISION MAKING WITH THE
PATIENT.
WE DO NEED ADDITIONAL RESEARCH
ON DIFFERENT FORMULATION, ROUTES
OF DELIVERY, NON-HORMONAL
OPTIONS.
I WANT TO THANK ALL OF THE WOMEN
WHO PARTICIPATED IN THE WHI WHO
OVER THE 30 YEARS HAVE BEEN SO
DEDICATED TO THE WHI, ALL OF THE
INVESTIGATORS AND STAFF WHO HAVE
BEEN INVOLVED WITH WHI AND SO
MANY OTHER RESEARCH STUDIES OVER
THE YEARS.
AND THANK YOU FOR YOUR
ATTENTION.
I'LL END THERE.
>> THANK YOU SO MUCH FOR THAT
TALK, DR. MANSON.
IT WAS TERRIFIC TO HEAR YOUR
THOUGHTS ABOUT THE FOLLOW-UP
FROM THE WOMEN'S HEALTH
INITIATIVE.
I'D LIKE TO NOW INTRODUCE DR.
HADINE JOFFE, PROFESSOR OF
PSYCHIATRY AND BRIGHAM AND
WOMEN'S HOSPITAL IN BOSTON,
MODERATING THE NEXT SESSION AND
WILL INTRODUCE THE NEXT
SPEAKERS.
WE'RE GOING TO HOLD THIS Q&A
UNTIL THE Q&A WITH ALL OF THE
SPEAKERS IN THE INTEREST OF
TIME.
WELCOME, DR. JOFFE.
>> THANK YOU.
WHAT A GREAT START TO THE
PROGRAM.
THANK YOU, DR. MANSON.
AND DR. TEMKIN.
IT'S A PLEASURE TO INTRODUCE THE
NEXT SET OF SPEAKERS.
FIRST DR. GREENDALE, SHE CAN PUT
HER SCREEN ON AND JOIN ME HERE.
PROFESSOR OF MEDICINE AND
OBSTETRICS AND GYNECOLOGY, DAVID
GEFFIN SCHOOL OF MEDICINE, UCLA.
HER TALK IS ON MENOPAUSE
TRANSITION DEFINITIONS, HEALTH
IMPLICATIONS, FUTURE DIRECTIONS.
>> GOOD MORNING, EVERYONE.
THANK YOU FOR ALLOWING ME TO
SHARE INSIGHTS ABOUT DEFINITION,
HEALTH IMPLICATION, GAIN FROM
WORK IN THE STUDY OF WOMEN'S
HEALTH ACROSS THE NATION, AND TO
SHARE A FEW IDEAS ABOUT WHERE WE
THINK THIS WILL INFORM FUTURE
INVESTIGATIONS.
OUR AGENDA FOR THE NEXT 20
MINUTES IS AS FOLLOWS.
FIRST, A VERY BRIEF DESCRIPTION
OF THE STUDY OF WOMEN'S HEALTH
ACROSS THE NATION, AND NEXT
ENCAPSULATED TRANSLATIONAL
ADVENTURE, IN WHICH I'LL DISCUSS
SOME NEW CONCEPTUALIZATIONS OF
THE TRANSITION, HOW A VERY FEW
SELECTED BIOLOGICAL OUTCOMES
CHANGE DURING MENOPAUSE
TRANSITION, AND HONE IN ON
EXAMPLE OF ONE OUTCOME THAT CAN
INFORM OPPORTUNITIES FOR
MAINTAINING HEALTH.
SWAN IS A MULTI-CENTER,
MULTI-HETEROGENEITY NICK
COMMUNITY -- MULTI-ETHNIC STUDY
TO STUDY EFFECTS ON HEALTH BEING
AND LATER LIFE.
OVERARCHING AND HIGHLY IMPORTANT
GOAL IS TO DESCRIBE NATURAL
HISTORY OF MENOPAUSE IN ORDER TO
DRAW CLINICALLY RELEVANT
THERAPEUTIC TARGETS.
THE SWAN LONGITUDINAL COHORT
WHICH WAS INCETTED IN THE
1990s, 42 TO 52, PRE-OR EARLY
PERIMENOPAUSAL, A MEMBER OF EACH
SITE'S RACIAL OFFER ETHNIC
GROUP, WHICH WERE WHITE, BLACK,
HISPANIC, CHINESE, JAPANESE.
JAPANESE, CHINESE AND HISPANIC
WOMEN AT ONE SITE, BLACK AT FOUR
SITES, AND WHITE WOMEN AT ALL
SEVEN CLINICAL SITES, AND THE
NUMBERS OF INITIALLY ENROLLED
WOMEN BY EACH ETHNIC GROUP ARE
SHOWN ON THE SLIDE.
NOW, I SAID WE'RE GOING TO TALK
ABOUT CONCEPTUALIZATIONS OF THE
MENOPAUSE AND MENOPAUSE
TRANSITION, SO STARTING FROM
PRIOR TO MENOPAUSE TRANSITION
ORIENTED STUDIES MEDICAL
COMMUNITY USED TO CONCEIVE OF
MENOPAUSE AS BINARY CONDITION,
YOU'RE PRE OR POST MENOPAUSAL,
AND POST WAS JUST DEFINED AS 12
MONTHS WITHOUT A PERIOD.
WITH THE ADVENT OF MENOPAUSE
TRANSITION-BASED THINKING IN THE
1980s INVESTIGATORS NEEDED A
WAY TO CATEGORIZE, USING
MENSTRUAL PATTERNS.
EARLY PERIMENOPAUSE WAS DEFINED
AS LESS PREDICTABLE CYCLES BUT
NO GAPS, LATE PERIMENOPAUSE WAS
DEFINDS AS OVERT GAP OF LESS
THAN OR EQUAL TO 3 MONTHS.
THESE CATEGORIZATIONS HAVE BEEN
REFINED A BIT OVER THE LAST
COUPLE DECADES BUT I WILL NOT GO
INTO MORE DETAIL ABOUT THE
MENSTRUALLY DEFINED STAGES IN
THE INTEREST OF TIME.
I AM GOING TO CONCENTRATE ON THE
FINAL MENSTRUAL PERIOD TIME
FRAMEWORK, WHICH IS ONE OF THE
LARGE SHIFTS IN HOW WE THINK
ABOUT THE MENOPAUSE TRANSITION.
AND THIS SLIDE ILLUSTRATES HOW
TO THINK ABOUT FMP TIME.
FMP TIME IS DEFINED AS TIME
ZERO, THE DATE WHEN YOU'VE HAD
YOUR FINAL MENSTRUAL PERIOD.
YEARS PRIOR TO THE FMP ARE GIVEN
NEGATIVE NUMBERS.
YEARS AFTER THE FMP ARE GIVEN
POSITIVE NUMBERS.
OBVIOUSLY, WE CANNOT DATE A
WOMAN'S FMP TIME UNTIL SHE HAS
HAD HER FMP.
SO WE DID THIS IN SWAN AFTER
WOMEN HAD GONE THROUGH THEIR
MENOPAUSE TRANSITION AFTER 12
MONTHS OF AMENORREAH BACKED UP
12 MONTHS AND SAID THAT'S YOUR
FMP DATE.
NOW, WHY WOULD WE WANT TO BOTHER
TO DO THIS?
WHY DO WE HAVE TO THINK ABOUT
TIME TO FMP?
ONE GOOD REASON TO REDEFINE THE
MENOPAUSE TRANSITION OR ADD IT
TO OUR CADRE OF DEFINITIONS IS
MENSTRUALLY DEFINED STAGES ARE
NOT STRONG INDICATORS OF TIME TO
FINAL MENSTRUAL PERIOD.
SHOWN ON THIS SLIDE WE HAVE
NUMBER OF MONTHS BEFORE THE FMP,
OR FMP TIME ON THE Y-AXIS.
AND MENOPAUSE STAGES BY BLEEDING
PATTERNS ON THE X-AXIS.
AND I CALL YOUR ATTENTION TO THE
LAST ROW.
WOMEN IN THIS LAST ROW ARE
WITHIN 12 MONTHS OF THEIR FMP,
SO FMP TIME MINUS 12 TO ZERO,
68.7% CLINICAL DEFINED BY
BLEEDING PATTERNS AS EARLY
PERIMENOPAUSAL, THERE'S NOTHING
EARLY ABOUT BEING ONE YEAR PRIOR
TO YOUR FMP I WOULD ARGUE.
SO WHAT?
DOES KNOWING HOW FAR AWAY YOUR
FMP IS MATTER?
I THINK THE ANSWER TO THAT
QUESTION IS YES.
AND HERE IS SOME EVIDENCE TO
SUPPORT MY CONTENTION.
SHOWN HERE IS A LOESS PLOT OF
TRAJECTORY BY FMP TIME, WITH
BASELINE NORMALIZED LUMBAR SPINE
BMD, EVERY WOMAN NORMALIZED TO
HER OWN BASELINE, AND FMP TIME
ON THE X-AXIS WITH OUR FRIEND
FMP TIME ZERO SHOWN BY SOLID
LINE, MINE MINUS YEARS ARE YEAS
BEFORE.
IF YOU LOOK AT THE LOWEST PLOT
YOU'LL SEE WOMEN'S BONE DENSITY
IS STABLE UNTIL THEY HIT ABOUT A
YEAR PRIOR TO THEIR FMP, WHERE
THERE IS A STRIKING ACCELERATION
IN THE RATE OF BONE LOSS,
THERE'S THE ONSET OF BONE LOSS,
FROM MINUS 1 TO PLUS 2 FMP
YEARS.
AND THEN THIS RATE SLOWS BUT
DOES NOT CEASE AT ABOUT 2 YEARS
AFTER THE FMP.
AND TO DR. CLAYTON'S POINT ABOUT
INFLECTION, IF THIS ISN'T AN
INFLECTION, I DON'T KNOW WHAT
IS.
NOW, THAT'S A LOESS PLOT, THOSE
OF YOU THAT ARE FAMILIAR WILL
KNOW THOSE ARE BASED ON
CROSS-SECTIONAL DATA, NOT
PARAMETRIC BUT WHAT YOU CAN DO
IS YOU CAN GENERATE A PIECE-WISE
LINEAR MODEL THAT CAPTURES BE ON
VACCINATIONS IN THE LOESS PLOT
AND DIVIDE FMP INTO
PRE-MENOPAUSE TRANSITION, MINUS
1, AND PLUS 2 TO PLUS 5.
AGAIN, I'M GOING TO UNDERSCORE
THE FACT THAT THESE ARE
FMP-BASED DEFINITIONS, DO NOT
CORRESPOND TO MENSTRUAL CATEGORY
DEFINITION.
AT THE LUMBAR SPINE, AS
SUGGESTED BY THE PLOT, THERE IS
NO BONE LOSS, THESE ARE MEAN
RATES, THERE'S NO BONE LOSS
PRIOR TORE FMP MINUS 1 AT EITHER
BONE SITE, LUMBAR SPINE OR
FEMORAL NECK.
DURING THE TRANSITION WHEN
THINGS TAKE OFF RATE OF LOSS AT
LUMBAR SPINE IS 2.5% PER YEAR,
FEMORAL NECK 1.78% PER YEAR WITH
DECREASE IN THAT LOSS RATE
DROPPING DOWN TO ABOUT A PERCENT
PER YEAR IN EARLY POST
MENOPAUSE.
AS I MENTIONED, THESE ARE MEAN
VALUES, AND I'D LIKE TO CALL
YOUR ATTENTION TO A VERY
STRIKING ESTIMATE.
IF WE CONSIDER WHO IS IN THE TOP
QUARTILE OF LUMBAR SPINE BONE
LOSS RATE, THESE ARE WOMEN WHOSE
BONE LOSS RANGE FROM MINUS 3.6
TO MINUS 10.8% A YEAR,
ASTRONOMICALLY HIGH RATES OF
BONE LOSS.
THIS SLIDE IS A BIT OF A
DIGRESSION, BUT I WANTED TO
UNDERSCORE THE NOTION THAT THE
ACCELERATED CHANGES IN BIOLOGY
THAT OCCUR DURING THE MENOPAUSE
TRANSITION ARE NOT ISOLATED TO
BONE DENSITY ALONE.
BUT BEING A BONE HEAD I CAN'T
HELP MYSELF, I HAVE A LOSS OF
TRABECULAR BONE SCORE, A MEASURE
OF BONE STRENGTH AND APPROXIMATE
ESTIMATE OF BONE
MICROARCHITECTURE.
AND AS YOU CAN SEE FROM LOOKING
AT THIS FIRST PANEL, IT IS
STABLE UP TO FMP MINUS 1 1/2.
LET ME POINT OUT FOR MANY
BIOLOGICAL OUTCOMES THESE
INFLECTION POINTS DIFFER A BIT,
IF I SHOWED YOU OTHER SLIDES YOU
WOULD FIND DIFFERENT INFLECTION
POINTS.
MINUS 1 1/2 TO PLUS 2 THERE'S A
SHARP ACCELERATION IN THE LOSS
OF TRABECULAR BONE SCORE OR BONE
STRENGTH, AND SLOWING IN THE
POST-MENOPAUSE.
SWITCHING OVER TO ANOTHER
BIOLOGICAL SYSTEM, THE AMOUNT OF
FAT MASS AS MEASURED BY DUAL
ENERGY X-RAY ABSORBTOMETR, IT'S
STATISTICALLY SIGNIFICANT
POSITIVE LINE, BUT ACCELERATING
IN THE MENOPAUSE TRANSITION AND
LEVELING OUT AFTER MENOPAUSE
TRANSITION, I WILL MENTION THESE
DO DIFFER BY BIOLOGICAL OUTCOME,
FOR BONES THEY CONTINUE TO TREND
DOWN AFTER MENOPAUSE TRANSITION,
FOR FAT MASS WE HAVE SEEN
STABILIZATION.
IF YOU'RE INTERESTED IN THE
PIECE-WISE LINEAR REGRESSIONS
YOU CAN LOOK UP THE JOURNAL OF
CLINICAL AND ENDOCRINOLOGY OR
JCI INSIGHT REFERENCES TO GET
THOSE EXACT ESTIMATES.
SO THIS BRINGS US TO A
TRANSLATIONAL OPPORTUNITY, AND I
AM GOING TO HONE IN ON BONE
BECAUSE IT'S VERY, VERY
DEVELOPED BIOLOGICAL OUTCOME IN
SWAN AND IT'S BECAUSE I KNOW A
LOT ABOUT BONE RELATIVE TO OTHER
THINGS, SO THAT'S WHAT I SHOULD
TALK ABOUT.
THE QUESTION OF GOING TO POST,
SHOULD WE TRY TO STOP MENOPAUSE
TRANSITION-RELATED BONE LOSS?
AGAIN, MY RESPONSE TO THIS
QUESTION IS YES.
WE SHOULD TRY TO STOP MENOPAUSE
TRANSITION-RELATED BONE LOSS AND
THIS SUMMARIZES THE THREE
REASONS I RESPOND WITH A YES
ANSWER.
ONE, MORE BONE IS BETTER THAN
LESS BONE.
WE DID NOT DISCOVER THIS IN
SWAN.
MANY, MANY, MANY OTHER COHORTS
HAVE SHOWN THAT THE STRONGEST
PREDICTOR OF FUTURE FRACTURE IS
YOUR ABSOLUTE BONE DENSITY.
I DID SHOW YOU THAT DURING THE
MENOPAUSE TRANSITION BONE IS
LOST AT ABOUT TWICE THE AGING
RATE, IF YOU CONSIDER THE AGING
RATE TO BE THE ONE THAT I SHOWED
YOU IN EARLY POST MENOPAUSE,
WHICH IS A REASONABLE ESTIMATE.
AND BONE ARCHITECTURE IS DAMAGED
DURING THE MENOPAUSE TRANSITION.
NOW, HERE IS THE REALLY STRIKING
PART AND UNIQUE PART ABOUT THE
MENOPAUSE TRANSITION.
INDEPENDENT OF STARTING LEVEL,
SO INDEPENDENT OF ABSOLUTE BMD,
MORE MENOPAUSE
TRANSITION-RELATED BONE LOSS
PREDICTS GREATER FRACTURE RISK.
FASTER YOU LOSE, MORE RISK YOU
HAVE.
GREATER TURNOVER LEADS TO
GREATER RISK INDEPENDENT OF BMD
LOSS.
SO INDEPENDENT OF YOUR LOSS
RATE, YOU ARE AT HIGHER RISK IN
YOU HAVE HIGHER BONE TURNOVER.
I DON'T HAVE TIME TO EXPLAIN
BONE TURNOVER BUT IF YOU WOULD
LIKE TO ASK ME ABOUT WHAT THAT
MEANS, PLEASE DO SO IN THE Q&A.
SO, A FEW STATISTICS TO SUPPORT
POINTS 2 AND 3, FOR STANDARD
DEVIATION, THERE'S 78% INCREASE
IN FRACTURE HAZARD,
DEMONSTRATING THAT THIS RELATION
BETWEEN ABSOLUTE BONE DENSITY
AND RISK OF FRACTURE HOLDS IN
PRE AND POST MENOPAUSE, AND
IMPORTANTLY PER 1% PER YEAR OF
FASTER DECLINE IN LUMBAR SPINE
BMD THERE'S 56% INCREASE IN
FRACTURE HAZARD.
IN SUPPORT OF POINTS 3, FASTER
INCREASE PREDICTS FRACTURE
INDEPENDENT OF BMD LOSS RATE,
THAT FRACTURE HAZARD IS 24%
GREATER PER STANDARD DEVIATION
INCREMENT IN THE RATE OF
INCREASE OF NTX IN TRANSITION,
AND THIS HAZARD IS IMPERVIOUS TO
ADJUSTMENT.
IF YOU ACCEPT IT MIGHT BE A GOOD
IDEA TO TRY TO PREVENT MENOPAUSE
TRANSITION-RELATED BONE LOSS
THEN YOU NEED TO ASK YOURSELF
CAN WE PREVENT MENOPAUSE
TRANSITION-RELATED BONE LOSS?
THAT'S A DIFFICULT PROPOSITION
BECAUSE THE FIRST THING WE NEED
TO DO IS IDENTIFY THE ONSET OF
BONE LOSS, AND AS I SHOWED IN
PRIOR SLIDES THE DECLINE OF BONE
DENSITY AND TRABECULAR BONE
SCORE STARTS AT 1 TO 2 YEARS
PRIOR TO FMP AND THAT IS A
CLINICALLY OCCULT PHENOMENON.
AND IT IS NOT WELL MARKED BY
YOUR MENSTRUAL CHARACTERISTICS.
SO HOW DO WE KNOW WHEN WOMEN ARE
STARTING TO LOSE BONE?
WELL, WE CAN LOOK TO SOME
SIGNALS THAT PRECEDE THE ONSET
OF BMD LOSS AS POTENTIAL
CANDIDATES FOR THINGS THAT COULD
PREDICT IT.
SO HERE I'VE SHOWN A SCHEMATIC
OF THE BMD PIECE-WISE LINEAR
REGRESSION, REMEMBER THAT FOR
LUMBAR SPINE BMD THIS IS AVERAGE
OF 2.4% PER YEAR, AND THIS IS
MINUS 1 AND PLUS 2 FOR BRACKETS.
HERE IS NTX ON Y-AXIS, A MARKER
OF BONE TURNOVER, LOW S PLOT
SHOWS THAT IT STARTS TO
ACCELERATE ABOUT MINUS 2, SO WE
HAVE THIS WINDOW OF OPPORTUNITY
WHERE AN ACCELERATING NTX
PROFILE MIGHT TELL US THAT THE
ONSET OF BMD LOSS IS IMMINENT
AND MIGHT ALSO TELL US WHAT THE
RATE OF LOSS WOULD LOOK LIKE.
AND ANALOGOUS SITUATION HOLDS
FOR ANTI--MULLERIAN HORMONE,
DECLINES IN YEARS LEADING TO
FMP, SO IT IS A LOVELY CANDIDATE
FOR A WARNING SIGNAL THAT BMD IS
GOING TO START TO BE LOST OR ITS
RATE OF LOSS.
WE'VE DONE STUDIES, EARLY
PERIMENOPAUSAL NTX IS SHOWN
HERE, HAZARD OF STARTING TO LOSE
BONE FOR STANDARD DEVIATION
INCREMENT IN NTX HIGHER IS
WORSE, IS SHOWN HERE 1.18 IS
HAZARD RATIO, 1.2 AT FEMORAL
NECK.
ONSET OF BONE LOSS IS THRESHOLD,
WE USE A THRESHOLD OF MINUS --
OF 1.23% PER YEAR IN THIS STUDY,
REMEMBER THAT NUMBER.
WE THINK THAT NUMBER IS A LITTLE
BIT TOO TIGHT.
WE'RE HARD ON OURSELVES.
AND ALSO THIS MODEL PREDICTS
ONSET OF BONE LOSS IN THE NEXT
TWO TO THREE YEARS, AND WE THINK
WE NEED TO WORK ON THAT A LITTLE
BIT.
I'LL GET TO THAT AT THE END.
THE SAME BASIC PARADIGM IS SHOWN
HERE, PRE-OR EARLY
PERIMENOPAUSAL ANTI-MULLERIAN
HUER --
HORMONE.
HERE A THRESHOLD, RELATED TO
DOUBLING OF THE RISK THAT YOU'RE
GOING TO START TO LOSE BONE AT
THE FEMORAL NECK, AND ABOUT A
1.68 HAZARD THAT YOU'RE GOING TO
LOSE BONE AT THE FEMORAL NECK,
WITHIN THE NEXT TWO TO THREE
YEARS, AT THAT SAME 1.23% PER
YEAR THRESHOLD.
WHICH BRINGS US TO FUTURE
DIRECTIONS.
THE INFORMATION WE'VE GAINED SO
FAR I BELIEVE PROVIDES A STRONG
IMPETUS FOR US TO STRONGLY
CONSIDER TRYING TO PREVENT
MENOPAUSE TRANSITION-RELATED
BONE LOSS.
WE'VE SHOWN IN PRINCIPLE AMT
BONE TURNOVER MARKER, NTX,
CLINICAL FEATURES CAN PREDICT
THE ONSET AND RATE OF MENOPAUSE
TRANSITION RELATED BONE LOSS, WE
NEED TO WORK ON THIS MODEL OF
PREDICTION TO GET IT SUITABLE
FOR CLINICAL PREDICTION, WE'RE
STARTING TO DO THAT NOW BY
COMBINING PREDICTORS, BY
CONSIDERING NEWER BONE TURNOVER
MARKERS THAT ARE CURRENT
REFERENCE REPRESENTS STANDARDS,
BY SHORTENING THIS WINDOW OF
PREDICTION DOWN TO ABOUT 1 TO 2
YEARS FROM 2 TO 3 YEARS, AND BY
PLAYING WITH OUR THRESHOLD A
LITTLE TO MAKE IT WHAT WE THINK
IS MORE APPROPRIATE.
IF WE CAN SUCCEED AT THAT, THEN
WE COULD TEST A PREVENTIVE AGENT
AND THERE ARE -- THERE'S ONE
CANDIDATE BEING BANDIED AROUND
FOR THAT, WHICH IF GIVEN WHEN
BONE LOSS IS IMMINENT BEFORE IT
STARTS WHICH IS WHY WE NEED THIS
PREDICTION MODEL COULD TRANSFORM
THIS BLUE LINE INTO THIS PINK
LINE.
THERE BY ALLOWING WOMEN TO BEGIN
THEIR POST MENOPAUSAL YEARS WITH
HIGHER ABSOLUTE BMD AND ALSO
OBVIATING UNIQUE TRANSMENOPAUSAL
NEGATIVE CONSEQUENCES OF RAPID
BONE LOSS AND HIGH BONE TURNOVER
WHICH ARE INDEPENDENTLY RELATED
TO POST MENOPAUSAL FRACTURE RISK
APART FROM ABSOLUTE BMD.
THANK YOU FOR YOUR ATTENTION.
>>THANK YOU, DR. GREENDALE.
>> REALLY IMPORTANT TALK, DR.
GREENDALE.
I'M GOING TO ASK PEOPLE TO
CONTINUE TO PUT QUESTIONS IN THE
Q&A, WE'LL HAVE A SESSION AFTER
THE NEXT THREE SPEAKERS.
SO NOW IT'S MY PLEASURE TO
INTRODUCE DR. GENEVIEVE
NEAL-PERRY, ROBERT ROSS
DISTINGUISHED PROFESSOR AND
CHAIR AT THE DEPARTMENT OF
OB/GYN AT UNC-CHAPEL HILL, HER
TALK ABOUT ON IS IT'S HOT IN
HERE, UNDERSTANDING BASIC
BIOLOGY OF MENOPAUSE TRANSITION.
>> THANK YOU FOR THAT
INTRODUCTION.
THANK YOU FOR THE OPPORTUNITY TO
TALK ABOUT MENOPAUSE, SOMETHING
I AM REALLY INTERESTED IN
LEARNING MORE ABOUT AS WELL AS
HEARING INFORMATION.
MY GOAL TODAY IS REALLY TO HELP
YOU UNDERSTAND SOME OF THE
THINGS THAT WE NOW KNOW ABOUT
THE -- WHAT LEADS TO MENOPAUSE
AND THE CAUSE OF HOT FLASHES.
I DON'T HAVE ANY SPECIFIC
DISCLOSURE RELATED TO THIS TALK
BUT I AM ON THE ASTELASS
ADVISORY BOARD.
YOU SHOULD BE ABLE TO UNDERSTAND
BASIC PHYSIOLOGY OF MENOPAUSE
AND SYMPTOMS.
DATA PRESENTED TODAY REFLECT
CLINICAL DATA FROM PEOPLE WHO
IDENTIFY AS WOMEN AND WHO WERE
BORN WITH OVARIES.
PHYSIOLOGY AND NATURAL HISTORY
OF MENOPAUSE, IMTHINK WHEN WE
THINK ABOUT MENOPAUSE, WE TEND
TO THINK ABOUT THE OVARY, WE
KNOW THAT THERE ARE
(INDISCERNIBLE) AND CHANGES IN
LOSS OF OVARIAN HORMONES, SUCH
AS ESTROGEN, DRIVING SOME
SYMPTOMS.
SOME THINGS HAPPEN AT THE LEVEL
OF AX IT DIFFERENT THAN ELEVATED
RISE.
CHANGES IN THE WAY NEURONS
RESPOND TO ESTROGEN AND THIS MAY
OR MAY NOT CONTRIBUTE TO
FOLLICULAR DEVELOPMENT,
FOLLICULAR DEPLETION, BUT
THERE'S MORE EVIDENCE IN TERMS
OF HOW HORMONAL CHANGES ACTUALLY
TRIGGER HOT FLASHES.
THAT'S WHAT I'M GOING TO TALK
ABOUT TODAY.
THERE ARE A NUMBER OF MODIFIERS
IN TERMS OF AN INDIVIDUAL
EXPERIENCING TRANSITION.
AUTOIMMUNE DISORDERS WHICH
INVOLVES THE OVARY THAT MAY HAVE
IMPACT ON TIMING OF MENOPAUSE,
THERE'S FAMILY GENES OF
POLYMORPHISMS, WE KNOW SMOKING
HAS AN EARLIER IMPACT ON TIME OF
MENOPAUSE, EARLIER SPECIFICALLY,
CHEMOTHERAPY, AND INDUSTRIAL
EXPOSURES.
IN ADDITION THERE ARE GENETIC
DEFECTS SUCH AS TURNER SYNDROME,
FRAG
FRAGILE X.
WHEN WE THINK ABOUT VASOMOTOR
SYMPTOMS I THINK THEY ARE ONE OF
THE SYMPTOMS OF MENOPAUSE,
TYPICALLY WHY INDIVIDUALS MAY
PRESENT TO ME.
WE KNOW TO SOME DEGREE IT'S
RELATED TO HYPO ESTROGENNISM,
BUT IF YOU MEASURE AROUND A TIME
OF WHEN SOMEONE IS HAVING A HOT
FLASH TO PREDICT, IT'S NOTE BEEN
DEMONSTRATED.
WE KNOW UP TO 75% OF WOMEN WILL
ACTUALLY REPORT HOT FLASHES,
OFTEN THE REASON THEY SEEK HELP.
THEY CAN LAST FROM SIX MONTHS TO
MORE THAN SEVEN YEARS, AND
YOU'LL HEAR SOME OTHER
DISCUSSIONS LATER ABOUT SOME
RACIAL DISPARITIES IN TERMS OF
THE SYMPTOMS AND DURATION OF
SYMPTOMS.
GENERALLY WHEN WE THINK ABOUT
BOTHERSOME HOT FLASHES WE THINK
ABOUT MODERATE TO SEVERE.
TYPICALLY 7 TO 8 PER DAY, 50 TO
60 PER WEEK, YOU CAN IMAGINE HOW
DISRUPTIVE THIS MIGHT BE.
WHAT ARE SOME GENETIC MODIFIERS
OF HOT FLASHES?
WHAT WE KNOW IS THERE IS
NEUROREGULATORY SYSTEMS ARE
AFFECTED, AND SPECIFICALLY WE
KNOW SEROTONERGIC, H
ISTAMINEERGIC AND OTHERS.
WE KNOW THESE AS WELL AS CYP 3A4
CAN AFFECT SEVERITY OF HOT
FLASHES, FREQUENCY, AND
UDP-UGT1A 1 ASSOCIATED WITH
FEWER HOT FLASHES.
THERE ARE GENETIC POLYMORPHISMS
IN TERMS OF HOW HORMONES ARE
METABOLIZED THAT RECEPTORS
FUNCTION THAT WILL HAVE THE
SIGNIFICANT IMPACT ON THE
EXPERIENCE OF THOSE EXPERIENCING
HOT FLASHES.
WHAT IS THE BLACK BOX BEHIND HOT
FLASHES?
IT'S A NEURAL DERIVED
PHENOMENON.
AND WHAT WE ALSO KNOW IS THAT
ESTROGEN CAN REDUCE HOT FLASHES.
YOU'VE SEEN SOME DATA FROM OUR
TWO PREVIOUS SPEAKERS.
BUT IS IT ACTUALLY ESTROGEN THAT
IS SOLELY LOSS THAT EXPLAINS THE
HOT FLASH?
I ALWAYS LIKE TO REVIEW AND GO
BACK TO THIS STUDY DONE LOOKING
AT DAILY HORMONAL LEVELS IN
INDIVIDUALS WHO WERE
REPRODUCTIVE AGE, PERIMENOPAUSE,
TO LOOK AT WHAT WAS HAPPENING
WITH ESTRADIOL, PROGESTERONE,
BECAUSE WE DID THINK THAT IT WAS
A REDUCTION IN ESTROGEN
TRIGGERING THESE.
SHE SHOWED WE DO SEE INCREASE IN
FSH WE WERE NOT SEEING
REDUCTIONS IN ESTROGEN OR
ESTRADIOL.
IT RAISED QUESTIONS WHAT'S
HAPPENING WITHIN THE BRAIN, ARE
THERE SOME CHANGES IN THE WAY
THE BRAIN IS RESPONDING TO
ESTROGEN.
THIS LED TO ANOTHER STUDY THAT
WAS DONE WITH THE STUDY OF WOMEN
ACROSS THE NATION THAT ACTUALLY
LOOKED AT THE LIKELIHOOD OF
SURGE, WHAT THEY DID WAS TO
ORGANIZE HORMONE LEVELS RELATIVE
TO HIGHEST LEVEL OF ESTROGEN AND
Y-AXIS IS DAY OF CYCLE, ZERO
REFLECTS HIGHEST LEVEL OF
ESTROGEN, AND Y-AXIS RECOMMENDS
URINARY ESTRONES.
ALTHOUGH WE HAVE TWO GROUPS OF
INDIVIDUALS WHO REACH RELATIVELY
SIMILAR ESTROGEN LEVELS, THAT
DID NOT MEAN THEY WOULD EACH
HAVE A SURGE.
THE GROUP ON THE LEFT HAD A
SURGE BUT THE GROUP ON THE RIGHT
DID NOT IMPLYING THE
HYPOTHALAMIC AXIS WAS NOT
RESPONDING AS THE UPPER
REPRODUCTIVE AGE WOMEN.
WE HAVE DONE SOME STUDIES
LOOKING AT WHETHER IT'S
PITUITARY OR HYPOTHALAMIC
RESPONSE.
PITUITARY RESPONSE ROBUSTLY
GENERATES AGONIST OR CHALLENGE,
AT THE LEVEL OF HYPOTHALAMUS.
WHAT ARE THE KNOWLEDGE GAPS?
FOR MANY YEARS WHILE WE KNEW HOT
FLASHES OCCURRED, WE KNOW
ESTROGEN COULD REDUCE THEM, WE
DIDN'T UNDERSTAND WHAT THE BASIC
BIOLOGY WAS.
AND IN MY OPINION SOME OF THE
SEMINAL WORK THAT HELPED US
UNDERSTAND WHAT'S DRIVING HOT
FLASHES AND REALLY HELP US
UNDERSTAND A MORE SPECIFIC WAY
THEY APPROACH WAS BORN OUT OF
WORK COMING FROM NAOMI RANCE,
SHE LOOKED AT THE BRAINS OF PRE
ANDS POST MENOPAUSAL WOMEN,
SPECIFICALLY FOUND
PRE-MENOPAUSAL WOMEN COMPARED TO
POST-MENOPAUSAL THERE WAS THIS
BIG CHANGE IN THE DENSITY OF
THESE NEURONS HERE LOCATED RIGHT
HERE.
SHE WENT ON TO DO A SIMILAR
STUDY A FEW YEARS LATER IN
MONKEYS WHERE SHE REMOVED
OVARIES, WAS ABLE TO SEE THE
SAME NEURONS IN THE BRAIN, THEY
HAVE COME FATTER AND MORE ROBUST
IN ANIMALS THAT DID NOT HAVE
ESTROGEN AND DID A SIMILAR STUDY
INFUSED ESTROGEN AND WAS ABLE TO
REDUCE THE SIZE OF THESE NEURONS
AND WITH THE ADVENT OF BETTER
HISTOCHEMISTRY WERE ABLE TO
IDENTIFY THE NEURONS.
THEY WERE KNDY NEURONS.
THEY EXPRESS A PEPTIDE KISSPEP
TIN, NEUROKININ B AND DNYORPHIN.
THEY ACTUALLY COMMUNICATE WITH
ONE ANOTHER, AND SO IN THE
ABSENCE OF ESTROGEN THEY
ACTUALLY STIMULATE EACH OTHER
WITH THIS NKB, PROJECTING TO
AREAS OF THE BRAIN, IMPORTANT
FOR SENSING.
IN THE ABSENCE OF ESTROGEN THEY
ARE PRETTY MUCH RELEASED FROM
ESTROGEN NEGATIVE FEEDBACK,
HYPERACTIVE, STIMULATE EACH
OTHER AND STIMULATE NEURONS THAT
ARE IMPORTANT FOR DEGENERATION
OF HOT FLASHES.
AND SO THE HYPOTHESIS WAS THAT
THESE NEURONS WERE WHAT WERE
DRIVING HOT FLASHES, AND SEVERAL
STUDIES HAVE SHOWN THAT IF YOU
INFUSE AN AGONIST WITHIN THE
BRAIN AND TRIGGER SOME SIMILAR
SYMPTOMS, IN MICE.
AND I'M GOING TO SHOW WORK IN
THE LAB TO ACTUALLY TEST THIS
HYPOTHESIS, THE AGONIST FOR THE
NEUROKININ.
ONE THING THAT'S IMPORTANT TO
KNOW HOT FLASHES ARE NOT EASY
TO -- WE DEVELOPED A
THERMOCLINE, WERE ABLE TO CREATE
A WARM PORTION AND COOL PORTION,
AND WE COULD USE THIS TO SEE
WHICH DIRECTION, WITH THE
ANIMALS, REFERRED IF THEY ARE
GIVEN INJECTION THAT CAUSES THEM
TO FEEL HOT.
AND THIS IS A STUDY WHERE WE
SHOW THAT YOU HAVE YOUR MICE
LINED UP ON THE WARM SIDE.
YOU SEE NONE PREFERRED COOL
SIDE.
WHEN WE ACTUALLY INJECT THEM
WITH SENK, A NEUROKININ AGONIST,
THIS IS THE EXPERIMENT WE DID.
IN ADDITION TO SEEING THEM MOVE
TO THE COOLER SIDE WE ALSO
EVALUATED THEIR TAIL, BECAUSE
MICE USE THE TAIL TO DISSIPATE
HEAT TO SEE WHETHER ANIMALS HAD
HOT FLASHES.
AND WHAT YOU SEE HERE IS AN
EXPERIMENT WHERE ANIMALS WERE
INJECTED WITH VEHICLE, PREFERRED
WARMER SIDE, ALSO INJECTED WITH
NK3 AGONIST WHICH INDUCES
SENSATION OF FEELING WARM AND
THEY MOVED TO THE COOLER SIDE.
SIMILARLY, ANIMALS THAT RECEIVED
OF THE SENKTIDE HAD HIGHER
TEMPERATURE IN TAIL, AGAIN
DISTATING HEAT.
WE HAVE THIS DATA IN NON-HUMAN
PRIMATE THAT SUGGESTS THAT IF
YOU TRIGGER -- USE THIS NK3
AGONIST YOU CAN TRIGGER HOT
FLASHES.
CAN WE DO THIS IN HUMAN?
IT WAS INJECTED IN
PRE-MENOPAUSAL WOMEN, IN
INDIVIDUALS WHO HAD THE NKB
AGONIST, FELT HOT, RECEIVED
VEHICLE AND RECEIVED NKB AND
ALSO FELT HOT.
WHAT WAS IMPORTANT IS THEY WERE
ABLE TO SHOW OTHER SYMPTOMS THAT
ARE REPORTED WITH HOT FLASHES,
HEART RATE CHANGE, THERE WAS
ALSO A CHANGE IN TERMS OF
TEMPERATURE, BUT ALSO IN TERMS
OF PEOPLE FEELING ANXIOUS.
WHAT IS THE CURRENT MODEL?
WELL, IN A NORMAL STATE THE
MODEL IS KNDY NEURONS IN AN
ESTROGEN RICH ENVIRONMENT FIRE,
THERE'S NEGATIVE FEEDBACK,
NEURONS ARE KIND OF BEHAVING
DOING WHAT THEY SHOULD BE DOING.
IN THE ABSENCE OF ESTROGEN OR
LOSS OF ESTROGEN NEGATIVE
FEEDBACK THESE NEURONS BECOME
HYPERTROPHIED, RELEASING NKB
WHICH WILL STIMULATE OTHER KNDY
NEURONS, AS WELL AS THEY ARE
PROJECTING TO AREAS WITHIN THE
MEDIAL PRE-OPTIC AREA WHERE
THERMOREGULATION OCCURS, TRIGGER
THIS SENSATION OF HOT FLASHES.
WOMEN SWEAT TO DISSIPATE THE
SENSATION OF FEELING WARM.
BECAUSE OF THEIR OVERACTIVATION
AND KIND OF ALTERED
RESPONSIVENESS TO ESTROGEN.
NOW, I THINK THERE WAS -- JOANN
MENTIONED ABOUT THE NKB
ANTAGONIST THAT WAS RECENTLY
NOTED TO REDUCE -- RECENTLY
APPROVED BY THE FDA, IT WORKS AS
ANTAGONIST, BOTH AT THE LEVEL
OF -- NEURONS WITHIN THE MEDIAL
PRE-OPTIC AREA THAT EXPRESS NK3
RECEPTOR TO BLOCK THE HOT
FLASHES.
SO, IS THIS REALLY RELEVANT IN
TERMS OF WHEN WE THINK ABOUT
HUMANS, THIS IS A STUDY THAT I
WOULD LIKE TO SHARE WITH YOU
THAT WAS PART OF WHI, AND WHAT
THEY SHOWED WAS THAT INDIVIDUALS
WHO HAD MORE INTOLERABLE HOT
FLASHES ALSO HAD POLYMORPHISMS
OF THE TACK 3 RECEPTOR THAT
RESPONSE TO NEUROKININ B.
WE KNOW THE KNDY NEURONS UNDER
NORMAL ESTROGEN STATE ARE NOT AS
ACTIVE AND THEY ARE NOT
PROJECTING AND STIMULATING THE
HEAT SENSING REGION OF THE BRAIN
IN AN ABNORMAL WAY.
IN ABSENCE OF ESTROGEN FEEDBACK
WE KNOW THESE NEURONS HERE WITH
OVERSTIMULATED FROM KNDY
NEURONS.
WE DON'T KNOW WHETHER THE
NEURONS HAVE IMPACT ON SOME OF
THE METABOLIC AND DYSREGULATION
WE SEE REPORTED DURING
MENOPAUSE, AS WELL AS THERE'S
NOT AS MUCH INFORMATION, THERE
SEEMS TO BE SOME SUGGESTION THAT
THESE NATIONAL HURRICANE CENTER
MAY ALSO PROJECT AND AFFECT
AREAS WITHIN THE BRAIN THAT ARE
IMPORTANT FOR SLEEP.
SO, I WANT TO SAY THANK YOU FOR
THE NUMBER OF PEOPLE WHO HELPED
AS WELL AS FUNDING, SUPPORTED
MUCH OF THIS WORK.
AND THANK YOU FOR BEING PRESENT
>> THANK YOU FOR THAT REALLY
FASCINATING TALK.
I LOVE THOSE LITTLE MICE
CRAWLING BACK ACROSS THEIR BOX.
AND THE NEXT SPEAKER IS
PRE-RECORDED, DR. WALTER ROCCA
FROM THE MAYO CLINIC IS GOING TO
GIVE A TALK ABOUT THE
ACCUMULATION OF MORBIDITY
FOLLOWING MENOPAUSE.
>> I'LL BE PLAYING THE
RECORDING AND HE WILL BE AT THE
Q&A AT THE END.
DR. ROCCA IS PROFESSOR OF
EPIDEMIOLOGY AND NEUROLOGY AT
MAYO CLINIC COLLEGE OF MEDICINE
AND SCIENCE, WE LOOK FORWARD TO
HEARING HIS PRESENTATION.
>> LADIES AND GENTLEMEN, GOOD
MORNING.
I WOULD LIKE FIRST TO THANK THE
ORGANIZERS OF THE SYMPOSIUM FOR
THE KIND INVITATION, IT IS OF
COURSE A GREAT PLEASURE AND
HONOR TO TALK TO YOU TODAY.
I WILL BE TALKING ABOUT
PREMATURE OR EARLY MENOPAUSE AND
ACCELERATED ACCUMULATION OF
MULTI-MORBIDITY.
AND I DO NOT HAVE ANY FINANCIAL
RELATIONSHIP TO DISCLOSE.
I WILL TALK FOR 20 MINUTES,
FOCUSING ON STUDIES OF WOMEN
WITH BILATERAL OOPHORECTOMY
BECAUSE IT'S BEEN AND REMAINS
THE MOST COMMON CAUSE OF
PREMATURE EARLY MENOPAUSE IN THE
GENERAL POPULATION.
I WILL REVIEW SOME EVIDENCE FROM
CLINICAL RESEARCH.
I WILL REVIEW EVIDENCE THAT IS
AGAINST THE POSSIBILITY OF
CAUSE-EFFECT INVERSION, AND THEN
MOVE INTO EVIDENCE FROM
BIOMARKER RESEARCH IN ANIMAL
STUDIES.
AT THE END OF THE PRESENTATION
YOU WILL DRAW CONCLUSIONS AND
PRESENT GENERAL THEORY AND GIVE
BRIEF CLINICAL RECOMMENDATIONS.
MANY OF THE DATA THAT I'M
PRESENTING TODAY HAVE BEEN
PUBLISHED, AND YOU WILL SEE AT
THE BOTTOM OF MY SLIDES THE
NUMBER OF KEY REFERENCES.
LET US BEGIN WITH THE EVIDENCE
FROM CLINICAL RESEARCH.
AND I WILL FOCUS PRIMARILY ON
DATA THAT CAME FROM WORK DONE BY
OUR GROUP AT THE MAYO CLINIC.
WE PUBLISHED A NUMBER OF DATA
UNDER THE LABEL OF THE MAYO
CLINIC COHORT STUDY OF
OOPHORECTOMY AND AGING NUMBER 2
THAT WE CALL MOA-2.
THIS IS NUMBER 2 BECAUSE THERE'S
BEEN A NUMBER 1 IN THE PAST AND
THIS IS A NEW COHORT OF WOMEN
WHO UNDERWENT BILATERAL
OOPHORECTOMY IN MINNESOTA
BETWEEN 1988 AND 2007.
SO WE'RE DEALING WITH 20 YEARS
OF RECRUITMENT.
WE WERE ABLE TO RECRUIT 1653
WOMEN, THAT HAD THE OOPHORECTOMY
AT AGE 50, BELOW AGE 50, AND
MATCHED 1:1 TO THE SAME BE IN
WHO HAD NOT UNDERGONE
OOPHORECTOMY.
OF THESE 1653, APPROXIMATELY
1,000 HAD OOPHORECTOMY AT
PARTICULARLY YOUNG AGE, THAT IS
AT THE AGE 45 OR YOUNGER, AND
THEY WERE MEASURED WITH EQUAL
ENOUGH OF REFERENT.
REAR WE FOLLOWED OVER TIME,
APPROXIMATELY 14 YEARS, COHORTS
ARE STILL RELATIVELY YOUNG BUT
FORTUNATELY WE'RE CONTINUING TO
FOLLOW THESE WOMEN AND WE WILL
BE ABLE IN THE FUTURE TO REPORT
DATA WITH THE MORE MATURE
COHORT.
THE OUTCOMES OF THE STUDY WERE
18 CHRONIC CONDITIONS, WHICH
WERE PICKED BY U.S. DEPARTMENT
OF HEALTH AND HUMAN SERVICES AS
BEING THE MOST IMPORTANT CHRONIC
DISEASES IN THE UNITED STATES.
AND THEY WERE SELECTED TO BE
USED TO DEFINE MULTI-MORBIDITY.
WE STUDIED FIVE MENTAL HEALTH,
FIVE CARDIOVASCULAR OR
METABOLICS, SIX OTHER SOMATIC
CONDITIONS.
YOU WILL SEE EACH ONE OF THESE
CONDITIONS IN THE COMING SLIDES.
HOWEVER, IN ADDITION TO LOOKING
AT THEM INDIVIDUALLY, WE ALSO
COMBINED THE CHRONIC CONDITIONS
INTO A CONCEPT MULTI-CHRONIC
CONDITION OR MULTI-MORBIDITY AND
CONSIDER THAT AS A CLINICAL
MARKER OF ACCELERATED AGING.
HOWEVER, BECAUSE THE TWO GROUPS,
TWO COHORTS WERE DIFFERENT AT
BASELINE IN A NUMBER OF
CHARACTERISTICS WE USED
STATISTICAL METHOD OF INVERSE
POP -- PROBABILITY WEIGHTS TO
MAKE SIMILAR AT TIME OF SURGERY
FOR 18 CHRONIC CONDITIONS
ALREADY PRESENT AT THE SURGERY,
BY EDUCATION, RACE, BODY MASS
INDEX, SMOKING, AGE, CALENDAR
YEAR.
LET'S START BY LOOKING AT
RESULTS, LOOKING AT DISEASES ONE
BY ONE.
FIRST SLIDE, FIVE MALTED
MENTAL HEALTH
CONDITIONS.
VERTICAL DOTTED LINE MEANS TWO
INCREASE OR DECREASE RISK.
AND ON THE RIGHT SIDE YOU HAVE
INCREASED RISK, LEFT SIDE
DECREASED RISK.
FOR EACH DISEASE WE HAVE THREE
MEASURES, ONE IN BLUE IS EFFECT
ON THE GROUP OVERALL.
IN RED WE HAVE THE EFFECT IN
WOMEN WHO HAD THE YOUNGER
OOPHORECTOMY.
IN BLACK RESULT FOR WOMEN WITH
LATER OOPHORECTOMY.
WHEN THE RESULT WAS SIGNIFICANT,
I ADDED A RED ARROW.
SO AS YOU CAN SEE MANY OF THE
RESULTS WERE SHIFTED TO THE
RIGHT SIDE OF THE VERTICAL LINE
AND SOME REACHED STATISTICAL
SIGNIFICANCE, CERTAINLY FOR NOW
THE DEPRESSION AND ANXIETY.
IF YOU LOOK AT CARDIOVASCULAR
AND METABOLIC CONDITIONS, AGAIN
WE HAVE A LOT OF FINDINGS
SHIFTED TO THE RIGHT OF THE NULL
RISK, AND SOME REACHED
STATISTICAL SIGNIFICANCE EVEN IN
RELATIVELY YOUNG WOMEN,
HYPERLIPIDEMIA, DIABETES,
CARDIAC ARRHYTHMIA, CORONARY
ARTERY DISEASE.
THERE WAS ONE ESTIMATION,
ESTIMATE THAT WAS IN THE
OPPOSITE DIRECTION, AND THIS WAS
CONGESTIVE HEART FAILURE, AND
THIS IS AN ARTIFACT DUE TO THE
FACT THAT WOMEN AT HIGH RISK OF
CONGESTIVE HEART FAILURE HAVE A
CONTRAINDICATION TO SURGERY AND
THEY WERE NOT -- DID NOT UNDERGO
SURGERY, THIS IS AN ARTIFACT OF
THE SELECTION FOR THE SURGERY.
LOOK AT OTHER SOMATIC CONDITIONS
AGAIN YOU HAVE A LOT OF FINDINGS
SHIFTED TO RIGHT SIDE INDICATING
INCREASE IN RISK, AND SOME WERE
SIGNIFICANT SUCH AS ARTHRITIS,
CANCER IN OLDER WOMEN, ASTHMA,
CHRONIC OBSTRUCTIVE PULMONARY
DISEASE AND OF COURSE AS
EXPECTED OSTEOPOROSIS.
THE KIDNEY FINDINGS WERE VERY
INTERESTING, SUGGESTIVE, BUT DID
NOT REACH SIGNIFICANCE BECAUSE
THE NUMBER OF COURSE WERE STILL
RELATIVELY SMALL.
AS YOU CAN SEE WE HAVE VERY
IMPORTANT FINDINGS IN THESE
WOMEN IN THE DIRECTION OF
INCREASED RISK LOOKING AT
DISEASES ONE BY ONE, BUT IF WE
NOW PUT TOGETHER ALL OF THESE
DISEASES, CAN GIVE TO EACH WOMAN
A SCORE WHICH CAN STUDY
ACCUMULATION OF 18 CONDITIONS
OVER TIME.
AND I'M SHOWING ANALYSIS
RESTRICTED TO WOMEN AGE 45 OR
YOUNGER AT OOPHORECTOMY BECAUSE
THIS IS THE GROUP THAT SHOWS THE
MORE EXTREME RESULTS.
ON THE X-AXIS, YOU HAVE THE
TIME, ZERO IS TIME OF
OOPHORECTOMY.
AND WE HAVE TEN YEARS BEFORE
OOPHORECTOM AND 15 YEARS AFTER.
ON THE Y-AXIS YOU HAVE THE
NUMBER OF CHRONIC CONDITIONS.
IN BLACK IS THE CURVE OF WOMEN
THAT ARE REFERENT, REPRESENTING
THE GENERALLY POPULATION OF
WOMEN, SLOPE OF INCREASE OF
MORBIDITY WITH AGE IN NORMAL
WOMEN.
THE WOMEN THAT UNDERWENT
OOPHORECTOMY WERE ALREADY
ACCUMULATING DISEASES IN
ACCELERATED FASHION BUT AT THE
TIME OF SURGERY THEY FURTHER
INCREASED ACCELERATION AND
REACHED SIGNIFICANT ACCELERATION
IN FOLLOW-UP.
THERE WAS DIFFERENCE EVEN AT THE
TIME OF SURGERY, WE TRIED TO
ADDRESS THIS DIFFERENCE USING
WEIGHTING, BUT WE ALSO DID SOME
ADDITIONAL ANALYSIS TO MAKE SURE
THERE WAS NOT A CAUSE-EFFECT
INVERSION.
WHAT DOES A CAUSE-EFFECT
INVERSION MEAN?
IT MEANS THAT WE ARE
INTERPRETING THE RESULTS AS
SUGGESTING THAT BILATERAL
OOPHORECTOMY OR THE SURGERY
CAUSED ACCELERATION OF AGING BUT
NEED TO MAKE SURE AND TO RULE
OUT THAT IT'S NOT THE OPPOSITE,
THAT THE WOMEN WERE ALREADY
HAVING UNDERGOING PROBLEMS WITH
AGING AND THEN THEY DEVELOPED
GYNECOLOGICAL SYMPTOMS WHICH
PROMPTED HYSTERECTOMY THAT
PROMPTED OOPHORECTOMY.
IN THIS CASE, SURGERY WOULD BE A
CONSEQUENCE OR EFFECT, INNOCENT
AS TO THE PROCESS.
WE HAVE SOME VERY INTERESTING
DATA TO ADDRESS THIS QUESTION,
THE MOST INTERESTING DATA
COMMENTS FROM ANALYSIS PUBLISHED
IN 2017, WHERE WE RESTRICTED OUR
ANALYSIS TO WOMEN WHO HAD ZERO
CONDITIONS AT BASELINE, SO THESE
WOMEN WERE ONLY THE ONES WHO THE
DAY BEFORE THE SURGERY HAD ZERO
DISEASES, NO HYPERTENSION OR
HYPERLIPIDEMIA, NO DEPRESSION,
NO DISEASES.
IF YOU TAKE THIS GROUP OF WOMEN
AND SEE THE ONE REFERENT, YOU
SEE ACCUMULATION OF
MULTI-MORBIDITY AND WHAT
HAPPENED TO THE WOMEN THAT
UNDERWENT SURGERY, OOPHORECTOMY.
THEY HAVE ACCELERATION OF
ACCUMULATION FOR FIRST FIVE, SIX
YEARS, REACH MORE PARALLEL
CONTINUING GROWTH OVER TIME WITH
SIGNIFICANT EFFECT.
SO, THIS IS A VERY IMPORTANT
PIECE OF EVIDENCE, SUGGESTING
THAT THE OOPHORECTOMY ITSELF IS
CAUSAL AND NOT SIMPLY A MARKER
OF AGING.
THERE ARE OTHER DATA THAT
SUPPORT A DIRECT CAUSALITY, ONE
SET OF ANALYSIS IS BY INDICATION
FOR OOPHORECTOMY.
WHEN WE DIVIDED OUR COHORT IN
WOMEN WHO HAD A BENIGN OVARIAN
CONDITION, PRIMARILY
ENDOMETRIOSIS, AND DID NOT HAVE
BENIGN INDICATION, RESULTS WERE
VERY SIMILAR AND THEY WERE BOTH
SIGNIFICANT SUGGESTING THAT THE
INDICATION WAS NOT EXPLAINING
THE OUTCOME.
BUT VERY IMPORTANTLY, WE ALSO
DID AN ANALYSIS, STRATIFYING
COHORT IN WOMEN WHO WERE TREATED
WITH ESTROGEN UP TO AGE 45, AND
WOMEN WHO WERE NOT TREATED.
AND YOU CAN SEE THE WOMEN WHO
ARE TREATED AT LITTLE INCREASED
RISK, WOMEN NOT TREATED WERE
CARRYING ALL OF THE RISK.
THIS MEANS THAT THIS IS AN
INDIRECT PROOF THAT IT IS THE
OOPHORECTOMY THAT CAUSES AGING
THROUGH DEPRIVATION OF ESTROGEN
AND IF YOU PUT IT BACK WITH
THERAPY YOU ELIMINATE AT LEAST
IN PART THE NEGATIVE EFFECT.
AGAIN, VERY IMPORTANT EVIDENCE.
WE ALSO STRATIFIED BY CALENDAR
YEAR DECADES AND FOUND NO
DIFFERENCE SUGGESTING THAT
EFFECT WE OBSERVED WERE NOT DUE
TO SURGICAL TECHNIQUE, THEY WERE
NOT DUE TO ANESTHESIA OR ANY
OTHER ISSUE RELATED TO THE
PERFORMANCE OF THE SURGERY.
LET US MOVE TO EVIDENCE FROM
BIOMARKER RESEARCH IN ANIMAL
MODEL MAL -- ANIMAL STUDIES.
A GROUP LOOKED AT EFFECT OF
BILATERAL HORMONE THERAPY ON
ACCELERATED AGING, DEFINED BY
COMPARING BIOLOGICAL AGE AT
CELLULAR AND TISSUE LEVEL
TO: CHRONOLOGICAL AGE.
IF A WOMAN HAS BIOLOGICAL AGE
THAT CORRESPONDS TO
CHRONOLOGICAL AGE IS AGING
NORMALLY.
IF HAS OLDER BIOLOGICAL AGE SHE
IS ON ACCELERATED TRACT, IF
BETTER SHE'S AGING SUCCESSFULLY.
THE PROBLEM IS YOU NEED TO
MEASURE BIOLOGICAL AGE AND THERE
ARE A NUMBER OF WAYS OF
MEASURING BIOLOGICAL AGE AT THE
CELLULAR, TISSUE, ORGAN LEVEL,
USING EPIGENETIC CLOCK, AND THIS
IS BASED ON DNA METHYLATION.
SIMPLE IDEA IS THAT THE OLDER IS
A CELL, THE MORE DNA METHYLATION
THERE WILL BE.
AND SO THAT'S A VERY SIMPLE
RELATIONSHIP.
NOW, THEY SHOWED THAT WOMEN WHO
UNDERWENT OOPHORECTOMY ARE
HIGHER LEVELS OF METHYLATION IN
BLOOD AND SALIVA, TWO DIFFERENT
TISSUES SHOWED ACCELERATION OF
AGING, THEY ALSO SHOWED IF THE
AGE AT MENOPAUSE WAS YOUNG BUT
NOT CAUSED BY THE SURGERY, BUT
CAME NATURALLY, IF A WOMAN HAD
PREMATURE OR EARLY SPONTANEOUS
OR NATURAL MENOPAUSE, THERE WAS
ACCELERATION OF THE AGING
PROCESS, IF THEY RECEIVED
ESTROGEN THERAPY THERE WAS
ACCELERATION, SHOWING
OOPHORECTOMY IS LEAVED TO
ACCELERATION OF AGING PROCESS
MEASURED BY BIOMARKERS RATHER
THAN CLINICAL OUTCOMES.
ALSO WE HAVE A LOT OF VERY
IMPORTANT STUDIES FROM ANIMALS,
AND IN MICE OOPHORECTOMY HAS
USED FOR DECADES, SO A LOT OF
WORK IS BEING DONE ON AGONIST
AND ANTAGONIST AND MODULATION OF
THE EFFECT OF ESTROGEN, USING
HORMONE THERAPY -- OOPHORECTOMY
IN THE ANIMALS.
WITH MONKEYS, REMOVAL OF OAF
RILLS CAN CAUSE AC -- OVARIES
CAN CAUSE ACCELERATION WITH
PLAQUES.
IN RODENTS AND MONKEY WE HAVE
EVIDENCE THAT REMOVING OVARIES
WILL ACCELERATE DEGENERATION OF
THE BRAIN, THIS IS VERY
IMPORTANT FOR BRAIN RESEARCH, IN
DOGS AND MICE WE HAVE EVIDENCE
SUGGESTING REMOVAL OF THE
OVARIES THAT IN ANIMAL IS CALLED
CASTRATION CAUSES REDUCTION IN
LIFESPAN.
BUT FASCINATING ARE EXPERIMENTS
THAT HAVE BEEN DONE IN MICE
WHERE IF YOU TRANSPLANT THE
OVARIES FROM YOUNG MICE TO OLD
MICE, YOU WILL OBSERVE THAT THE
OLD MICE WILL BEHAVE LIKE YOUNG
MICE, AND WILL HAVE INCREASED
LIFESPAN.
BASICALLY YOU CAN SAY THAT
SURVIVAL CAN BE TRANSPLANTED BY
THE TRANSPLANTATION OF OVARY AND
TISSUE, THIS IS A VERY DIRECT
FASCINATING DEMONSTRATION OF THE
ROLE OF OVARIAN FUNCTION ON
AGING AND LIFESPAN.
LET'S REACH CONCLUSIONS AND GIVE
SOME BRIEF CLINICAL
RECOMMENDATIONS, CONCLUSION
FIRST OF ALL, AN ATTEMPT OF
PUTTING TOGETHER A GENERAL
THEORY OF WHAT HAPPENS AFTER
OOPHORECTOMY.
AND THIS WAS PUBLISHED BY OUR
GROUP IN PHYSIOLOGY IN 2018.
SO IF YOU START FROM THE LEFT
YOU CAN SAY PREMATURE LOSS OF
ESTROGEN OR OTHER OVARIAN
HORMONES WILL CAUSE AN
ACCELERATION OF AGING PROCESS IN
GRAY BOX, AT THE CELLULAR TISSUE
ORGAN AND SYSTEM LEVEL.
THIS PROCESS CAN BE ACCUMULATION
MUCH SENESCENT CELL,
INFLAMMATION IN ABSENCE OF
INFECTION, PROTEIN AGGREGATION
AND MISFOLDING, MITOCHONDRIAL
DYSFUNCTION, EPIGENETIC
ALTERATION WE'VE SEEN THE
EXAMPLE OF METHYLATION, TELOMERE
INFILL RATION AND SO ON, WE HAVE
A SERIES OF AGING PROCESS --
TELOMERE ATTRITION.
AND THESE CHANGES WILL MANIFEST
CLINICALLY AT THE CLINICAL
LEVEL, EITHER AS
MULTI-MORBIDITY, WE'VE SEEN
ACCELERATION OF MENTAL HEALTH
CONDITION, CARDIOVASCULAR AND
METABOLIC AND SOMATIC OR AS
FRAILTY WHICH IS DECLINE IN
PHYSICAL FUNCTION OR DECLINE IN
COGNITIVE FUNCTION.
NOW, MULTI-MORBIDITY AND FRAILTY
CAN BE INTERRELATED,
INTERDEPENDENT BUT CAN BE
CONSIDERED -- CONVENIENT TO
CONSIDER THEM IN PARALLEL.
NOW, MULTI-MORBIDITY AND FRAILLY
WILL LEAD TO REDUCED HEALTH SPAN
AND OF COURSE THE ACCELERATION
OF REACHING DEATH.
THIS IS THE MAIN CAUSAL AX IS BT
ESTROGEN REPLACEMENT THERAPY CAN
REDUCE OR ATTENUATE SOME OF THE
HARMFUL EFFECT OF OOPHORECTOMY.
ALSO, THERE ARE GENETIC VARIANTS
THAT CAN INFLUENCE EITHER
POSITIVELY OR NEGATIVELY EFFECT
OF OOPHORECTOMY, AND THERE ARE
OTHER VARIABLES THAT ARE
BEHAVIORAL AND ENVIRONMENTAL,
SUCH AS DIET, PHYSICAL ACTIVITY,
SMOKING, ADVERSE CHILDHOOD
EVENTS, ENVIRONMENTAL TOXINS.
THESE VARIABLES SHOWED IN THE
BLUE BOX CAN EITHER WORSEN THE
EFFECT OF OOPHORECTOMY OR
ATTENUATE THE EFFECT.
SO WE CAN SAY THAT NOT ALL WOMEN
WHO UNDERGO OOPHORECTOMY AT THE
SAME AGE WILL HAVE THE SAME
NEGATIVE EFFECT, THIS WILL BE
MODIFIED OR MODULATED BY
ESTROGEN REPLACEMENT THERAPY AND
BY OTHER VARIABLES THAT ARE
INTERACTING WITH ESTROGEN
DEPRIVATION.
THE CONCLUSION IS THAT
OOPHORECTOMY IN YOUNGER WOMEN
CONTRIBUTES TO ACCELERATED AGING
WHICH WILL LEAD TO INCREASED
MORBIDITY AND MORTALITY.
THE CLINICAL DATA, DATA COMING
FROM CLINICAL RESEARCH, ARE
CONSISTENT WITH DATA COMING FROM
STUDIES OF DNA METHYLATION, AND
THEY ARE CONSISTENT WITH THE
VERY LARGE BODY OF ANIMAL
STUDIES, INCLUDING PRIMATES.
SO WE CAN CONCLUDE OOPHORECTOMY
IS A DISRUPTOR OF THE ENDOCRINE
CONTROL OVER AGING, AND THE
WOMEN WHO HAVE UNDERGONE
BILATERAL OOPHORECTOMY IN THE
LAST 20, 30, 40 YEARS PROVIDE US
A UNIQUE NATURAL EXPERIMENT AND
THEY SHOULD BE STUDIED BECAUSE
BY STUDYING THESE WOMEN WE WILL
LEARN A LOT ABOUT THE AGING
PROCESS.
WE THINK THE EFFECT OF
OOPHORECTOMY IS MEDIATED BY
ESTROGEN, POSSIBLY BY OTHER
OVARIAN HORMONES AND MAY BE
MEDIATED BY CHANGES IN
HYPOTHALAMIC OVARIAN AXES. --
AXIS.
THERE ARE GENETIC VARIANTS,
DEVELOPMENTAL FACTORS, EARLY
LIFE EVENTS.
THESE ARE EFFECT MODIFIERS OF
THE PRIMARY CHAIN OF CAUSALITY.
IN TERMS OF CLINICAL
RECOMMENDATION AND BRIEFLY
BECAUSE WE DO NOT HAVE TIME TO
GO INTO THE CLINICAL
RECOMMENDATION, WE WOULD SAY
THAT IN 2023, IT SHOULD BE ONLY
PERFORM WHEN THERE'S A CLEAR
INDICATION, BECAUSE THERE ARE
IMPORTANT HARMFUL SEQUELAE.
AND THE CLEAR INDICATION IS
RESTRICTED TO WOMEN WHO CARRY
HIGH RISK GENETIC VARIANT SUCH
AS BRCA1 OR BRCA2, FOR THESE IT
IS CORRECTLY BUT EVEN IF THEY
UNDERGO THE SURGERY SHOULD
RECEIVE ESTROGEN REPLACEMENT
THERAPY TO PREVENT HARMFUL
EFFECTS.
THANK YOU FOR YOUR ATTENTION.
>> THANK YOU.
I'M THRILLED TO INTRODUCE THE
'40s SPEAKER, DR. WENDY KOHRT,
PROFESSOR OF MEDICINE,
UNIVERSITY OF COLORADO ANSCHUTZ
MEDICAL CAM THUS, TO E OR --
CAMPUS, TO E OR NOT TO E,
METABOLIC ACTIONS OF ESTROGENS.
>> THANK YOU FOR INVITING ME TO
BE PART OF THIS OUTSTANDING
SYMPOSIUM.
I HAVE NO FINANCIAL DISCLOSURES.
AND WHAT I'D LIKE TO TALK ABOUT
TODAY IS WORK THAT HAS COME FROM
OUR SPECIALIZED CENTER OF
RESEARCH EXCELLENCE ON SEX
DIFFERENCES WHICH IS FOCUSED ON
BIOENERGETIC AND METABOLIC
CONSEQUENCES OF THE LOSS OF
GONADAL FUNCTION.
THIS SLIDE SHOWS OUR WORKING
MODEL THAT GUIDES OUR THINKING
AND OUR RESEARCH THAT WE
DEVELOP.
SO, BECAUSE THE OVARIES AND
TESTES ARE ENDOCRINE ORGANS IF
THERE'S LOT OF GONADAL FUNCTION
IT HAS POTENTIAL TO IMPACT MANY
SYSTEMS.
WE BELIEVE THAT THIS COULD
MODIFY FACTORS IN A WAY THAT
WOULD INCREASE DISEASE RISK.
THIS IS PARTICULARLY IMPORTANT
FOR WOMEN BECAUSE GONADAL AGING
OCCURS DURING MID-LIFE, AVERAGE
AGE OF MENOPAUSE IS 51.
AND IF THERE IS A SIMILAR AGE
TRIGGERED LOSS OF GONADAL
FUNCTION IN MEN, IT HAPPENS MUCH
LATER IN LIFE POTENTIALLY 20 TO
30 YEARS LATER.
SO, WOMEN HAVE TO DEAL WITH THE
LOSS OF THIS, POTENTIAL IMPACT
ON HEALTH STATUS, ON FUNCTIONAL
STATUS, AND ON QUALITY OF LIFE.
AS DR. GREENDALE POINTED OUT
EARLIER THIS MORNING, WE HAVE AN
EXCEPTIONALLY WELL STUDIED
EXAMPLE OF THIS WHEREBY LOSS OF
OVARIAN FUNCTION ACCELERATES
BONE LOSS AND LEADS TO INCREASED
RISK OF OSTEOPOROSIS.
BUT IT'S NOT LIMITED TO EFFECT
ON BONE.
THE LOSS OF OVARIAN FUNCTION
COULD IMPACT OTHER TISSUES LIKE
THE BRAIN OR SKELETAL MUSCLE IN
A WAY THAT COULD INCREASE RISK
FOR DEMENTIAS OR SARCOPENIA.
IT COULD ALSO AFFECT REGULATORY
SYSTEMS, SOMETHING LIKE THE
REGULATION OF ENERGY BALANCE IN
A WAY THAT PROMOTES FAT GAIN AND
LEADS TO INCREASED RISK OF
CARDIOVASCULAR DISEASE,
DIABETES, AND OTHER
OBESITY-RELATED DISEASES.
IT'S THIS SIDE OF THE WORKING
MODEL OUR SCORE HAS BEEN HEAVILY
FOCUSED ON.
SOMETHING THAT I'LL TRY TO
IMPRESS UPON YOU DURING MY TALK
IS EXCESS FAT GAIN THAT OCCURS
DURING THE MENOPAUSAL TRANSITION
AND POTENTIALLY AFTER IS NOT
JUST MORE FAT IN THE SAME
PLACES.
THERE'S A CHANGE IN THE
DISTRIBUTION OF FAT, SO RATHER
THAN STORING IT IN THE HIPS AND
THIGHS WHERE PRE-MENOPAUSAL
WOMEN TEND TO GAIN FAT IT'S
SHIFTED TO ABDOMINAL, ASSOCIATED
WITH METABOLIC DYSFUNCTION, AND
CHANGE IN CELLULAR COMPOSITION
OF ADIPOSE TISSUE, I'M GOING TO
TOUCH BRIEFLY ON THAT AT THE END
OF MY TALK.
AND THEN ADDING ONE MORE
COMPONENT TO THIS MODEL IS
SOMETHING THAT IS I THINK VERY
WELL APPRECIATED IN THE BASIC
AND PRE-CLINICAL SCIENCE
COMMUNITY BUT LESS SO IN THE
CLINICAL SCIENCE COMMUNITY.
AND THAT'S THAT STEROID HORMONES
HAVE WHAT SEEMS TO BE A POTENT
REGULATORY EFFECT ON PHYSICAL
ACTIVITY.
SO WITH THE LOSS OF GONADAL
FUNCTION THERE'S A DECREASE IN
SPONTANEOUS PHYSICAL ACTIVITY,
AND BECAUSE WE KNOW PHYSICAL
ACTIVITY HAS MANY BENEFITS TO
HEALTH, THAT COULD EXACERBATE
ALL OF THESE OTHER FACTORS THAT
I'VE PUT WITHIN THIS
ENCAPSULATION ON THIS SLIDE.
WITH THAT AS THE WORKING MODEL,
I WANT TO FIRST POINT OUT SOME
PRE-CLINICAL DATA BEFORE I GET
TO THE CLINICAL DATA BECAUSE
THIS CAN BE CONTROLLED EASIER IN
ANIMALS THAN IN HUMANS.
SO THE OUTCOMES ARE MORE
CONSISTENT.
SO, THIS IS USING A MODEL, I
PICKED THIS BECAUSE IT INCLUDES
MICE AND RATS TO SHOW
CONSISTENCY ACROSS THESE TWO
SPECIES, HOW BODY WEIGHT CHANGES
IN RESPONSE TO THE REMOVAL OF
THE OVARIES.
SO YOU CAN SEE WHEN BOTH THE
MICE AND RATS RECOVER FROM THEIR
SURGERIES, THOSE THAT HAD
OVARIES REMOVED COMPARED TO
THOSE WHOSE OVARIES ARE LEFT
INTACT HAVE A VERY ACCELERATED
RATE OF WEIGHT GAIN, DISRUPTION
IN ENERGY BALANCE THAT PROMOTES
FAT, WEIGHT GAIN, PROBABLY FAT
GAIN.
THESE INVESTIGATORS FOUND THAT
THERE WAS INCREASE IN ENERGY
INTAKE, BUT LOOKING AT THE RATS
HERE, EVEN IF THEY PAIR FED OF
GROUP WITH THE SHAM OPERATED
RATS, EATING THE SAME AMOUNT OF
FOOD, OOPHORECTOMY RATS STILL
HAD ACCELERATED RATE OF WEIGHT
GAIN.
IF IT'S NOT ENERGY INTAKE SIDE
THAT'S AFFECTED IT MUST ALSO BE
THE ENERGY EXPENDITURE SIDE OF
THINGS.
IN FACT, WHEN THEY LOOKED AT
LOCOMOTOR ACTIVITY, HOW MUCH
ANIMALS WERE MOVING AROUND THEIR
CAGES, YOU CAN SEE THE SHAM
OPERATED ANIMALS ONCE THEY
RECOVERED FROM THEIR SURGERY
WERE ESSENTIALLY BACK TO THEIR
PRE-SURGERY LEVELS OF ACTIVITY.
SAME THING FOR THE RATS.
BUT THE OOPHORECTOMIZED ANIMALS
HAD DECREASE IN HOW MUCH THEY
WERE MOVING THAT WAS ABOUT 30%.
THIS STUDY FROM UNIVERSITY OF
MINNESOTA MAKES AN EVEN GREATER
VISUAL IMPACT ABOUT THE
CONSEQUENCE OF OOPHORECTOMY,
MICE HAD RUNNING WHEELS IN THEIR
CAGES, MICE ARE VERY ACTIVE.
THEY RUN ALMOST 10 KILOMETERS A
DAY, YOU CAN SEE THESE ARE THE
SHAM-OPERATED ANIMALS WHO
MAINTAINED THIS LEVEL OF
ACTIVITY WEEKS AFTER THEIR
SURGERIES.
THERE'S TWO GROUPS OF
OOPHORECTOMIZED, DECREASES OF 70
TO 90% IN RUNNING.
ANIMALS TREATED WITH PLACEBO
ADDBACK THERAPY THERE WAS NO
SPONTANEOUS RECOVERY OF THEIR
PHYSICAL ACTIVITY.
BUT IN ANIMALS GIVEN ESTRADIOL
IMPLANTS, THEY WERE RIGHT BACK
IN THEIR RUNNING WHEELS AND
ACHIEVING LEVELS OF ACTIVITY
THAT WERE NOT DIFFERENT FROM THE
SHAM CONTROLS.
SO, THIS SAYS THAT WHEN YOU
REMOVE THE OVARIES THERE ARE A
LOT OF THINGS SECRETED BY
OVARIES BUT IT SEEMS
SPECIFICALLY LOSS OF ESTRADIOL
THAT IS MODIFYING THIS
PHENOTYPE.
TO MAKE MORE OF AN IMPACT THAT
IT IS SPECIFICALLY LOSS OF
ESTRADIOL FROM OVARIES THAT
INFLUENCES MANY OUTCOMES, THIS
STUDY SHOWS CHANGES IN BODY MASS
WITH OOPHORECTOMY SHOWING THIS
INCREASED BODY WEIGHT AND IT IS
PREVENTED BY ESTRADIOL ADD-BACK.
THE IMPACT ON ADIPOSITY AS
PERCENT OF BODY WEIGHT IS
REMARKABLE, TWO TO THREE-FOLD
GREATER LEVELS OF ADIPOSITY IN
OOPHORECTOMIZED VERSUS SHAM,
PREVENTED BYES THAT DIOL
TREATMENT.
THIS IS AN INDICATOR OF RESTING
METABOLIC RATE IN MICE.
IF INCREASED ENERGY INTAKE AND
DECREASED PHYSICAL ACTIVITY
ISN'T ENOUGH OF A DISRUPTION TO
ENERGY BALANCE, HERE'S ANOTHER
FACTOR.
EVEN AT REST, THE LOSS OF
OVARIAN FUNCTION SEEMS TO
SOMEHOW MAKE ANIMALS MORE
EFFICIENT SO THEY HAVE TO EXPEND
LESS ENERGY AT REST TO MAINTAIN
FUNCTION.
THAT IS PREVENTED BYES THAT --
BY ESTRADIOL TREATMENT.
THIS IS INSULIN SIMULATED
GLUCOSE DISPOSAL, INDICATOR OF
INSULIN RESISTANCE AND RISK FOR
DIABETES, DECREASE IS INDICATOR
OF INSULIN RESISTANCE PREVENTED
BY ESTROGEN TREATMENT.
THERE ARE MANY STUDIES IN THE
LITERATURE THAT ARE CONSISTENT
WITH THESE RESULTS.
OOPHORECTOMY IN RODENTS CAUSES
DECREASE IN PHYSICAL ACTIVITY,
DECREASED RESTING METABOLIC
RATE, THERE'S INCREASE IN ENERGY
INTAKE ALTHOUGH THIS IS NOT
CONSISTENT ACROSS SPECIES, ONE
OF THE CONSEQUENCES OF THIS IS
AN INCREASE IN ABDOMINAL FAT
GAIN IN ADDITION TO TOTAL BODY
FAT LEVELS, AND THE EXPECTED
METABOLIC DYSFUNCTION THAT WOULD
RESULT FROM THAT.
I HAVEN'T SHOWN ANY STUDIES
REGARDING EXERCISE.
I DID SHOW THAT ESTROGEN
PREVENTS THIS.
BUT TREADMILL EXERCISE IN
ANIMALS HAS ALSO BEEN SHOWN TO
BE EFFECTIVE AS PREVENTING MOST
OF THESE CHANGES.
AND THIS IS GREAT FOR MICE AND
RATS.
BUT WHAT'S THE RELEVANCE TO
WOMEN?
IN OUR STUDIES, BECAUSE THE
MENOPAUSE IS A PROCESS, NOT AN
EVENT, THAT HAPPENS OVER MANY
YEARS IT'S VERY DIFFICULT TO
ISOLATE THE EFFECTS OF MENOPAUSE
FROM THOSE OF AGING AND OTHER
FACTORS THAT CHANGE OVER MANY
YEARS.
SO, WE'VE GONE TO THE APPROACH
OF USING A PHARMACOLOGIC MODEL
OF MENOPAUSE, WHEREBY WE GIVE
GONAD OH TROPIN ANALOGS TO
PRE-MENOPAUSAL WOMEN, PUT THEM
IN A TEMPORARY POST MENOPAUSAL
STATE FOR 20 WEEKS, TO ISOLATE
EFFECTS OF ESTRADIOL
SPECIFICALLY, WE EITHER ADD BACK
A PLACEBO TRANSDERMAL PATCH OR
AN ESTRADIOL TRANSDERMAL PATCH.
IN THIS STUDY RANDOMIZED 70
WOMEN TO THESE TWO ARMS, I'M
GOING TO CALL YOUR ATTENTION TO
THE AVERAGE AGE.
THESE WERE ALL-COMEERS FOR
PRE-MENOPAUSAL REGARDLESS OF AGE
SO AVERAGE AGE WAS 35.
WE LOOK AT BODY COMPOSITION
CHANGES THAT OCCURRED.
THIS IS SOMETHING THAT WE'VE
SEEN REPEATEDLY IN OUR STUDIES
THAT WE KNOW THE LOSS OF
ESTROGEN CAUSES DECREASE --
ACCELERATED RATE OF BONE LOSS
BUT ALSO SEEMS TO CAUSE
ACCELERATED LOSS OF LEAN MASS.
SO THIS IS .6 KILOGRAM DECREASE
IN TOTAL BODY LEAN PASS
PREVENTED IN ESTROGEN-TREATED
GROUP.
ESTROGEN IS A HYDRATING HORMONE,
SO WATER IS PART OF THE LEAN
COMPONENT OF THE BODY.
SO THIS COULD JUST BE A LOSS OF
WATER.
BUT TO LOOK AT THIS MORE
CAREFULLY, WE DID CTs OF THE
MID-THIGH AND MEASURED THE
MID-THIGH MUSCLE AREA, AND YOU
CAN SEE THAT THE PATTERNS OF
CHANGE REFLECT THE CHANGES AT
THE WHOLE BODY LEVEL SUGGESTING
THIS IS INDEED A DECREASE IN
MUSCLE MASS, NOT JUST A LOSS OF
BODY WATER.
WHEN WE LOOK AT CHANGES IN FAT
MASS IN THIS STUDY TOTAL BODY
FAT MASS THIS WAS A SURPRISING
OUTCOME.
WE EXPECTED A SIGNIFICANT
INCREASE IN FAT MASS WHICH WE
DID NOT SEE.
BUT DESPITE THE FACT THAT THERE
WAS NO INCREASE IN TOTAL BODY
FAT, THERE WERE SIGNIFICANT
INCREASES IN ABDOMINAL FAT AREAS
MEASURED BY CT, IN BOTH THE
SUBCUTANEOUS BUT MORE ROBUSTLY
IN ABDOMINAL VISCERAL
COMPARTMENT, INCREASE IN
VISCERAL FAT AREA OF 12% AND
THAT WAS PREVENTED BY ESTRADIOL
TREATMENT.
WE ALSO ASKED WOMEN IN THE STUDY
TO WEAR AN ACCELEROMETER ONE
WEEK OUT OF EVERY MONTH OF THE
STUDY, AND QUANTIFIED MODERATE
TO I VIGOROUS DATA.
IT'S THE WOMEN TREATED WITH
ESTRADIOL THAT MAINTAIN HIGHER
PHYSICAL ACTIVITY LEVELS THAN
THE WOMEN WHO HAVE THEIR OVARIAN
FUNCTION SUPPRESSED, ABOUT 20 TO
30 MINUTES PER DAY LESS PHYSICAL
ACTIVITY.
HERE IN COLORADO WE HAVE THE
GOOD FORTUNE OF HAVING A ROOM
CALORIMETE, MEASURING 24 HOUR
EXPENDITURE OR LONGER.
BASED ON THOSE STUDIES WE FOUND
THAT WOMEN WHO WE SUPPRESS
OVARIAN FUNCTION IN HAVE
DECREASE IN RESTING ENERGY
EXPENDITURE IN THE NEIGHBORHOOD
OF 50 TO 70 K CALS PER DAY,
DECREASE IN TOTAL ENERGY
EXPENDITURE, ESTRADIOL DID NOT
AFFECT THAT OUTCOME WHEREBY DID
PREVENTS DECREASE IN RESTING
ENERGY EXPENDITURE.
THIS IS THE SLIDE GOING BACK, I
TOLD YOU WE WERE SURPRISED WE
DIDN'T SEE INCREASE IN TOTAL
BODY FAT MASS IN THIS STUDY.
THAT'S BECAUSE THIS SLIDE SHOWS
IN ADDITION TO OUR STUDY ALL OF
THE OTHER STUDIES THAT HAD USED
GnRH ANALOGS IN WOMEN, LOOKING
AT CHANGES IN BODY COMPOSITION,
THESE WERE DIFFERENT DURATIONS
OF STUDIES FROM 12 TO 24 WEEKS,
YOU CAN SEE THIS GENERAL TREND
FOR FAT MASS TO INCREASE GIVEN
POSITIVELY RELATED TO THE
DURATION OF THERAPY.
SO WE WERE EXPECTING A 1
KILOGRAM INCREASE THAT DIDN'T
OCCUR BUT IN THE NEXT STUDY I'LL
SHOW YOU, MOST RECENT STUDY THAT
WE'VE COMPLETED UNDER OUR SCORE,
WE DID SEE THIS INCREASE IN FAT
MASS THAT WE HAD PREDICTED.
AND IN THIS STUDY WE DIDN'T HAVE
AN ESTRADIOL ADD-BACK GROUP BUT
HAVE ENDURANCE EXERCISE ARM IN
THIS STUDY, WE CARRIED THIS ONE
OUT FOR 24 WEEKS, SO WE HAVE
PLACEBO-TREATED WOMEN, WOMEN
SUPPRESSED, WOMEN WHO WERE
SUPPRESSED AND THEN ALSO ENGAGED
IN ENDURANCE EXERCISE PROGRAM.
SMALL NUMBERS OF WOMEN IN THIS
STUDY BUT IN THIS ONE UNIQUE
ASPECT WE ENROLLED WOMEN
APPROACHING THE MENOPAUSE
TRANSITION SO THEY WERE ALL AT
LEAST 40 YEARS OF AGE, SO
AVERAGE AGE IN THIS STUDY IS
ABOUT TEN YEARS MORE THAN THE
PREVIOUS STUDY.
AGAIN LOOKING AT CHANGES IN BODY
COMPOSITION WE SEE DECREASE IN
LEAN MASS WE'VE OBSERVED
REPEATEDLY AND ENDURANCE
EXERCISE DID NOT SEEM TO MODIFY
THAT AT ALL.
ENDURANCE EXERCISE IS NOT MUSCLE
BUILDING.
I WAS HOPING IT MIGHT BE
PRESERVE BUG
PRESERVING BUT DOES IN ESTRADIOL
DEFICIENCY DOES NOT SEEM TO BE
THE CASE.
WE SEE CRE DECREASE OF 1.6
KILOGRAMS OVER 26 WEEKS, A
DISRUPTION IN ENERGY BALANCE OF
MORE THAN 80 K-CALS A DAY, WHAT
WOULD ACCOUNT FOR THAT
MAGNITUDE, CONSISTENT WITH
MAGNITUDE OF DISRUPTION IN
VARIOUS ASPECTS.
WE SAW MOST INCREASE IN FAT MASS
WAS IN THE TRUNK REGION, THIS IS
MEASURED BY DEXA.
WE DON'T HAVE CT FROM THIS
STUDY.
AND IN THIS CASE EXERCISE SEEMED
TO PREVENT HALF.
THIS IS A WAY TO EVALUATE THIS
UNDER FREE LIVING CONDITIONS,
AND WE DO SEE THIS TREND FOR --
SUPPRESSED GROUP TO HAVE
DECREASE OF ABOUT 100 K-CALLS
PER DAY IN TOTAL ENERGY
EXPENDITURE, ABOUT A THIRD WAS
ATTRIBUTABLE TO LESS ENERGY
EXPENDITURE FROM PHYSICAL
ACTIVITY BUT BULK ATTRIBUTED TO
DECREASE IN RESTING ENERGY
EXPENDITURE AND RESTING
METABOLIC RATE.
JUST TO SUMMARIZE HERE, WHAT WE
FOUND IN THESE AND OTHER
STUDIES, I DIDN'T SHOW ANY BASIC
RESEARCH, GENETIC MANIPULATIONS,
SUCH AS ESTROGEN RECEPTOR
KNOCKOUT MICE BUT ACROSS BASIC
PRE-CLINICAL AND CLINICAL
STUDIES THERE IS CONSISTENT
EVIDENCE THAT REGULATION OF
ENERGY BALANCE IS STRONGLY
INFLUENCED BY ESTRADIOL.
THE LOSS OF ESTROGENS OR
ESTROGEN SIGNALING PROMOTES FAT
GAIN THROUGH MULTIPLE SYSTEM
LEVEL MECHANISMS INCLUES
DECREASED METABOLIC RATE AND
THIS DISRUPTION OF ENERGY
BALANCE DOES NOT SIMPLY RESULT
IN THE SAME TYPE OF FAT GAIN, IN
THE SAME PLACES.
THERE'S A SHIFT IN ABDOMINAL FAT
ACCUMULATION, AND IN MICE
THERE'S A CHANGE IN THE CELLULAR
COMPOSITION OF IN THAT.
MY COLLEAGUE DISCOVERED THESE
UNIQUE WHITE ADIPOCYTES,
HEMATOPOIETIC STEM CELL DERIVED
WITH A UNIQUE SIGNATURE, HIGHLY
INFLAMMATORY WHEN COMPARED TO
CONVENTIONAL ADIPOCYTES BY GENE
EXPRESSION AND DO NOT PRODUCE
LEPTIN.
AND HE HAS DETERMINED THAT THE
PROLIFERATION OF THESE CELLS IN
FEMALE MICE ARE STRONGLY
INFLUENCED BY ESTRADIOL, SO IN
OOPHORECTOMIZED MICE THERE'S A
HUGE PROLIFERATION, ESPECIALLY
IN GONADAL VISCERAL REGION OF
FAT, THAT'S ENTIRELY PREVENTED
BY ESTRADIOL TREATMENT BUT NOT
BY PROGESTERONE TREATMENT, ALSO
IS OBSERVED IN ESTROGEN RECEPTOR
KNOCKOUT MICE.
WE THINK THERE ARE IMPORTANT
MOLECULAR SIGNALS THAT WE NEED
TO UNDERSTAND FOR HOW THE LOSS
OF ESTROGEN CONTRIBUTES BOTH TO
THE SHIFT IN FAT DISTRIBUTION
TOWARD ABDOMINAL ADIPOSITY AND
METABOLIC DYSFUNCTION.
I WOULD POINT THAT THIS REVIEW
ARTICLE WE PUBLISHED RECENTLY
THAT SUMMARIZES A LOT OF OUR
WORK IN THIS AREA.
AND THEN I WANT TO THANK ALL THE
PEOPLE IN MY GROUP AND SPONSORS
THAT CONTRIBUTED TO THIS
RESEARCH.
THANK YOU.
>> THANK YOU FOR THAT GREAT
PRESENTATION.
I THINK ONE HOUSEKEEPING THING,
WE'RE BEHIND TIME BUT WE WANTED
TO LET PEOPLE KNOW WE WILL BE
STARTING THE NEXT SESSION AT
1:05 BUT WE WILL EXTENDS THE Q&A
UNTIL 12:45.
IF THE SPEAKERS FROM THE FIRST
SESSION WANT TO TURN ON THEIR
CAMERAS THEN I'M GOING TO TURN
THIS OVER TO DR. JOFFE TO START
WITH THE FIRST QUESTION.
>> OUTSTANDING PRESENTATIONS.
I THANK THE SPEAKERS FOR
PRESENTING THOUGHTFUL AND
IMPORTANT WORK.
THERE ARE SO MANY QUESTIONS IN
THE Q&A.
WE WON'T BE ABLE TO GET TO ALL
BUT I WANT TO PUT SOME FORWARD.
I'LL DIRECT THEM TO EACH BUT
PLEASE ADD IN IF YOU HAVE OTHER
COMMENTS BEYOND THE FIRST.
I WANT TO MAKE SURE WE
DISTRIBUTE THEM SO EVERY TOPIC
IS COVERED.
DR. MANSON, A QUESTION HAS COME
UP WITH NEWLY POSTMENOPAUSAL
WOMEN, YOUNG WOMEN USING ORAL
CONTRACEPTIVES COMBINED ESTROGEN
AND PROGESTERONE AND
RISK/BENEFIT DECISION IN TERMS
OF USING THAT MEDICATION VERSUS
MENOPAUSE ESTROGEN AND PROGESTIN
COMBINATIONS..
>> SOME ARE SIMILAR.
ORAL CEE PLUS MPA, THERE ARE
SOME INCREASED RISKS OF VENOUS
THROMBOSIS, VENOUS
THROMBOEMBOLISM AND STROKE, WITH
BOTH ORAL CONTRACEPTIVES AND
ORAL MENOPAUSAL HORMONE THERAPY.
AGAIN, TRANSDERMAL ESTRADIOL IS
INOBSERVATIONAL STUDIES SHOWING
LESS INCREASE IN STROKE BUT NOT
YET TESTED IN RANDOMIZED TRIAL.
WE'RE SEE WITH MENOPAUSAL
HORMONE TRIALS THERE'S A
REDUCTION IN TYPE 2 DIABETES,
WITH CEE PLUS MPA, PLUS MPA
ALONE.
THE BREAST CANCER FINDINGS THAT
WE SEE WITH CEE ALONE HASN'T
BEEN FOUND, THIS REDUCTION IN
BREAST CANCER RISK WITH CEE
ALONE, HAS NOT BEEN FOUND WITH
ORAL CONTRACEPTIVES, THERE'S
BEEN A SMALL INCREASE WHEN ORAL
CONTRACEPTIVES ARE LONG DURATION
OR STARTED BEFORE FIRST
PREGNANCY, MORE RESULT SIMILAR
TO CEE PLUS MPA.
WE WERE INTERESTED IN THE
INTERACTION WITH CIGARETTE
SMOKING ORAL CONTRACEPTIVES HAVE
A STRONG ADVERSE INTERACTION, IT
QUADRUPLES, RISK.
WE HAD FEW HEAVY SMOKERS, IN THE
WHI OR BECAUSE MENOPAUSAL
HORMONE THERAPY TENDS TO BE
WEAKER CEE, WEAKER ESTROGEN
THAN ESTRADIOL BUT DO NOT SEE
ADVERSE INTERACTIONS WITH
CIGARETTE SMOKING, I THINK
OVERALL IT'S A COMPLEX QUESTION,
AND WILL DEPEND ON THE
FORMULATION, DOSE OF THE HORMONE
THERAPY, DEPENDING ON DOSE THERE
MAY BE DIFFERENCE, UNDERLYING
HEALTH STATUS OF THE WOMAN BUT
MANY SIMILARITIES WITH RISK OF
ORAL CONTRACEPTIVES.
>> THANK YOU FOR THAT.
I'M GOING TO CHANGE AND ASK DR.
GREENDALE A QUESTION, SOME
COMMENTS AND QUESTIONS HAVE COME
UP ABOUT THRESHOLDS, GIVEN THE
CONCERN ABOUT BONE LOSS STARTING
IN THE YEAR BEFORE FINAL
MENSTRUAL PERIOD, WHAT IS KNOWN
IN TERMS OF PREDICTABILITY ON
NTX, AT WHAT POINT WOULD YOU
RECOMMEND BONE SCANS FOR
BASELINE GIVEN THAT WE'RE
STARTING TO SEE (INDISCERNIBLE)
BEFORE FMP?
>> IF I WON'T GOBBLE UP THE
ENTIRE TIME I'LL PICK ONE AND
ANSWER.
WHAT ABOUT THRESHOLDS?
A THRESHOLD IS AN ARBITRARILY
CHOSEN NUMBER, AND IT'S BASED IN
LARGE PART, ONE OF THE WAYS IS
WHAT NUMBER DO YOU THINK IS
CLINICAL RELEVANT?
THE AVERAGE LOSS RATE IS ABOUT 2
1/2% AT THE LUMBAR SPINE SO 50%
OF WOMEN WILL HAVE THAT RATE OF
LOSS OR GREATER, AND SO IF YOU
WANT TO TRY TO PREVENT
TRANSMENOPAUSAL BONE LOSS YOU
HAVE TO ASK YOURSELF IN WHOM DO
I WANT TO PREVENT IT, HOW MUCH
PEOPLE.
DO I WANT TO PREVENT IT IN
PEOPLE WHO ARE ABOVE AVERAGE?
YOU USE A THRESHOLD OF 2 1/2%.
DO I WANT TO PREVENT ANYTIME
PEOPLE WHO ARE AT THE MOST
EXTREME QUARTILE OF RISK?
USE A THRESHOLD MINUS 3.6%
BECAUSE THAT DEFINES LOWER BOUND
OF THE HIGHEST QUARTILE.
SO IT'S A VERY GOOD QUESTION,
THRESHOLD ONE WOULD USE WOULD
DEPEND ON WHO YOU WANT TO TARGET
FOR RISK PREVENTION, AND THOSE
ARE SOME OF THE BENEFIT-RISK
QUESTIONS WE ASK OURSELVES NOW.
>> A LOT OF PEOPLE WAITING FOR
RESULTS, SO MUCH MORE NEEDS TO
BE DONE.
DR. NEAL-PERRY, QUESTIONS ABOUT
OTHER ROLES OF THE KNDY NEURONS
BESIDES RESPONSIVITY TO ESTROGEN
IN TERMS OF THERMOREGULATION.
>> THANK FOR THE QUESTION.
KNDY NEURONS ARE IMPORTANT IN
PUBERTY, IMPORTANT IN TERMS OF
TIMING OF PUBERTY, THEY ALSO
PARTICIPATE, I DIDN'T SHOW THIS
IN MY PRESENTATION BECAUSE OF
TIME, BUT REGULATE GNH NEURONS
IN TERMS OF THEY HAVE IMPORTANCE
IN LIKE STRESS AND NUTRITIONAL
SURVEILLANCE AND SO PROVIDE
FEEDBACK IN TERMS OF ENVIRONMENT
TO NUTRITIONAL ENVIRONMENT AND
STRESS ENVIRONMENT.
SO THEY HAVE MULTIPLE ROLES, AND
IT SEEMS TO BE RELATED TO THE
NEUROPEPTIDE PREDOMINANT AT THAT
TIME.
>> THANK YOU.
LET ME MOVE TO DR. ROCCA.
AND QUESTION ABOUT WHY ESTROGEN
CONTRIBUTES TO OR LACK OF
ESTROGEN CONTRIBUTES TO
ACCELERATED AGING, BIOLOGICAL
EXPLANATIONS FOR THAT.
>> I DON'T THINK WE KNOW
EXACTLY WHICH MECHANISM.
I LIST THE A NUMBER OF POSSIBLE
MECHANISMS, THE CELLULAR TISSUE
ORGAN OR SYSTEM LEVEL THAT
CHARACTERIZES AGING SO THAT THE
THEORY IS ESTROGEN WOULD HAVE
EFFECT ON THESE MECHANISMS BUT
SPECIFIC LEVEL OF CHEMICAL LEVEL
WE DO NOT KNOW YET.
OF COURSE WE KNOW THERE'S
ACTIVITY DIRECTLY ON THE CELLS
BUT SPECIFIC STEPS ARE NOT YET
CLEAR SO IT'S MORE LIKE A SERIES
OF -- WE HAVE PIECES OF THE
PUZZLE THAT LINE UP BUT WE DON'T
KNOW ALL OF THE INTERMEDIATE, IF
THAT IS THE QUESTION.
>>A LOT OF WORK TO BE DONE AS
WELL.
DR. KOHRT, I'LL COME BACK TO
YOU.
THERE'S QUESTIONS FOR EVERYBODY
ELSE.
IF I COULD ASK YOU TO TAKE YOUR
WORK AND TRANSLATE TO THE
CLINICAL RECOMMENDATION FOR
ACTIVITY FOR WOMEN GIVEN THAT
YOU'RE SEEING SO MANY PROFOUND
CHANGES IN ANIMAL AND
NON-PRIMATE AND HUMANS WITH
REGARD TO ENERGY EXPENDITURE AND
PHYSICAL ACTIVITY WHAT WOULD YOU
RECOMMEND WOMEN THIS AGE TO BE
DOING?
>> THANKS.
YEAH, OUR WORK IS FOCUSED ON
TRYING TO UNDERSTAND EXACTLY
WHAT THE METABOLIC CONSEQUENCES
ARE OF THE LOSS OF OVARIAN
FUNCTION SO THAT WE CAN TRY TO
DESIGN LIFESTYLE OR OTHER TYPES
OF INTERVENTIONS TO HELP
MITIGATE SOME CHANGES.
WE'VE DONE SMALL STUDIES LOOKING
AT THE POTENTIAL BENEFITS OF
EITHER RESISTANCE TYPE EXERCISE
OR ENDURANCE EXERCISE,
RESISTANCE IS WEIGHT LIFTING
MUSCLE BUILDING, THAT DOES SEEM
TO BE EFFECTIVE AND
PREVENTING -- NOT PREVENTING,
SLOWING THE LOSS OF LEAN MASS,
BONE AND MUSCLE DURING THE
MENOPAUSE TRANSITION, IT DOESN'T
SEEM TO PREVENT INCREASE IN
ABDOMINAL ADIPOSITY OR EVEN
BEGIN TO TOUCH THAT.
ENDURANCE EXERCISE, CARDIO TYPE
OF EXERCISE, GENERALLY INCREASES
ENERGY EXPENDITURE MORE SO THAN
RESISTANCE EXERCISE SO DOES SEEM
TO HAVE A BENEFICIAL EFFECT TO
PREVENT SOME OF THE INCREASE IN
ADIPOSITY THAT OCCURS ACROSS THE
MENOPAUSE TRANSITION, BUT,
AGAIN, DOESN'T FULLY PREVENT IT
BUT WE DEFINITELY NEED MORE WORK
IN THIS AREA SO I THINK THE
TAKEHOME MESSAGE IS THAT THE
MENOPAUSE TRANSITION IS A
CRITICAL TIME WHERE EITHER
MAINTAINING OR INCREASING YOUR
PHYSICAL ACTIVITY LEVEL IS VERY
IMPORTANT FOR HAVING BENEFICIAL
EFFECTS ON HEALTH.
>> GOOD TO HAVE POSITIVE
MESSAGES LIKE THAT.
WINDOW OF OPPORTUNITY IN TERMS
OF PHYSICAL ACTIVITY AS YOU SAY.
SO, BACK TO DR. MANSON, A
QUESTION ABOUT STATINS, WHAT'S
KNOWN IN TERMS OF ANY IMPACT OF
REVERSING OR PREVENTING ADVERSE
EFFECTS OF ENP THERAPY.
>> THEY HAVE BEEN LOOKED AT IN
WHI AND RANDOMIZED TRIALS.
THEY HAVE NOT SHOWN A REALLY
STRONG INTERACTION WITH HORMONE
THERAPY IN TERMS DECREASING
RISK, I DON'T THINK ANY TRIALS
ARE WELL POWERED TO ADDRESS THAT
QUESTION BUT STATINS SHOULD BE
USED ACCORDING TO GUIDELINES,
GUIDELINE DIRECTED CARE,
STARTLING THEM IF A WOMAN IS
GOING ON HORMONE THERAPY, I
DON'T THINK THERE'S A STRONG
EVIDENCE BASE FOR THAT AT THIS
TIME.
AND ASPIRIN HAS ALSO BEEN LOOKED
AT BECAUSE THEY HAVE ALMOST THE
OPPOSITE EFFECTS, ORAL ESTROGEN
IS GOING TO INCREASE THROMBOSIS,
ASPIRIN DECREASE PLATELET
AGGREGATION, DECREASE
THROMBOSIS, COULD ASPIRIN
POSSIBLY COUNTERACT SOME OF THE
INCREASED THROMBOTIC RISK?
THERE'S BEEN A VERY, VERY SUBTLE
SIGNAL THAT IT MIGHT HAVE A ROLE
DOING THAT BUT IT'S NOT STRONG
ENOUGH TO ACTUALLY BECOME A
CLINICAL RECOMMENDATION, AND I
THINK NOW WITH THE TREND TOWARD
USING TRANSDERMAL RATHER THAN
ORAL, IN ORDER TO AVOID SOME OF
THE THROMBOTIC RISKS ESPECIALLY
VENOUS THROMBOSIS, EMBOLISM,
THAT MAY BE LESS OF AN ISSUE.
>>TO DR. GREENDALE, TRANSLATING
TO RECOMMENDATION OF BONE SCANS
AND MONITORING.
>> THEY DON'T.
IT WOULD BE CLINICAL VASTLY
PREMATURE TO RECOMMEND ANY
CHANGE TO CURRENT SCREENING
RECOMMENDATIONS BASED ON SWAN
DATA.
AS ENTHUSIASTIC AS I AM ABOUT
FINDING OUT THAT BONE LOSS
BEGINS BEFORE THE FMP COMES, I
AM APPROPRIATELY CONSERVATIVE
WITH SAYING THAT WE DON'T HAVE
ANY PROVEN EFFECTIVE THERAPY TO
INITIATE AT THAT POINT IN TIME
AND WE DON'T EVEN YET KNOW HOW
TO TARGET THE WOMEN WHO WILL
LOSE BONE IN AN AMOUNT THAT'S
RELEVANT NOR EVEN DO WE HAVE OUR
CLINICAL PREDICTION MODEL
COMPLETELY TOGETHER.
SO PERHAPS I GAVE AN OVERLY
ENTHUSIASTIC PICTURE WHICH I
WANTED TO DO TO SHOW HOW MUCH
PROGRESS WE MADE.
THAT'S VERY IMPORTANT.
BUT WE STILL NEED TO DO A LOT OF
HEAVY LIFTING BEFORE WE CAN GET
TO CLINICAL RECOMMENDATIONS
BASED ON SWAN DATA.
>> BALANCING WHERE WE ARE WITH
THE FINDINGS WE HAVE.
I APPRECIATE THAT.
SO DR. NEAL-PERRY ANOTHER
QUESTION ABOUT OTHER HYPO
ESTROGENIC STATES LIKE
AMENORREAH, POSTPARTUM, OTHER
CONDITIONS WHERE THERE'S
ESTROGEN WITHDRAWAL, LOW
ESTROGEN STATE, AND WHAT'S KNOWN
ABOUT THAT ACTIVITY IN TERMS OF
THE KNDY NEURONS AND ALSO
VASOMOTOR SYMPTOMS.
>> THERE ARE SOME WOMEN AND
PEOPLE WHO EXPERIENCE HOT
FLASHES AROUND THE TIME OF
ESTROGEN WITHDRAWAL AND
POSTPARTUM PERIOD.
THERE HAVEN'T BEEN STUDIES TO
SPECIFICALLY LOOK AT THE PERIOD,
I IMAGINE THE BIOLOGY IS
SIMILAR.
THERE IS ACTUALLY SOME DATA
LOOKING AT KNDY NEURONS IN PCOS,
THERE'S SOME DATA TO SUPPORT
THAT.
AND POSTPARTUM PERIOD, OH,
ACTUALLY TACHYKININ DEFICIENCY
ASSOCIATED WITH HYPO GONADISM,
THERE'S REAL BIOLOGY THERE THAT
I FEEL HAS REALLY JUST BEEN A
GAME CHANGER IN TERMS OF HOW WE
UNDERSTAND KIND OF THE BIOLOGY
THERE.
>> IS THERE ANYTHING KNOWN
HYPOTYLAMIC AMENORREAH?
>>DATA IN ANIMAL MODELS SUGGEST
KNDY NEURONS MAY REGULATE PRO
ACTIN, MORE SO AROUND
TACHYTACHYKININ RECEPTOR,
HYPOGONADISM.
>> QUESTIONS ABOUT THE
PREMATURE MENOPAUSE RELATED TO
BILATERAL, SINGLE REMOVAL OF
ONE, ONE OR MORE BUT NOT TWO,
AND HOW TO TRANSLATE AND HAVE
EQUIVALENCIES ACROSS TO NATURAL
MENOPAUSE.
>> WELL, THANK YOU.
THE QUESTION IS A VERY GOOD ONE.
AND TOUCHES ON OUR LACK OF
KNOWLEDGE.
OF COURSE IF YOU REMOVE TWO
OVARIES AT THE SAME TIME, OR THE
SECOND OF TWO, YOU GET INTO A
CLEAR PICTURE, IF YOU WANT, OF
COMPLETE ABSENCE OF OVARY
PRODUCTION.
IF YOU REMOVE ONE OVARY ONLY,
FOR EXAMPLE IN TERMS OF
FERTILITY, BUT IN TERMS OF
ENDOCRINE ACTIVITY WE ARE NOT
SURE THERE IS ADEQUATE FUNCTION
OF SINGLE OVARY.
AND SHOWN, FOR EXAMPLE, THE
SECOND OVARY SEEMS TO GO INTO A
PHASE OF ANTICIPATED
INSUFFICIENCY AND THAT MAY BE AS
A RESULT OF A SINGLE OVARY
HAVING TO PRODUCE A FULLY
(INDISCERNIBLE) EVERY CYCLE OR
CAN BE SOME SECONDARY SUFFERING
OF THE REMAINING OVARY.
SO I THINK WE KNOW VERY LITTLE
ABOUT THE SITUATION OF A SINGLE
OVARY REMOVAL COMPARED TO TWO.
ALSO THE QUESTION BECOMES EVEN
MORE COMPLICATED WHEN YOU TRY TO
SAY IS A PREMATURE BELOW 40 OR
EARLY BETWEEN 40 AND 45
MENOPAUSE EQUIVALENT IF IT IS
INDUCED BY THE SURGICALLY OR
CHEMOTHERAPY OR SOME OTHER WAY
VERSUS OCCURRING SPONTANEOUSLY,
WELL, WE DON'T KNOW.
CLEARLY IF YOU DO IT SURGICALLY
OR CHEMICAL IT'S MORE ABRUPT,
RAPID, INSANE THANOUS --
INSTANTANEOUS, A WOMAN GOES FROM
FULL LEVEL TO ZERO, DAY OF
SURGERY, SO ONE WOULD GUESS THEY
ARE NOT EQUIVALENT BUT
UNFORTUNATELY WHAT WE KNOW UNTIL
TODAY IS PRIMARILY BASED ON WHAT
WE KNOW FROM OOPHORECTOMY SO
MANY OF THE CURRENT CONCEPTS
COME FROM WHAT WE HAVE LEARNED
USING COHORT OF WOMEN WITH
OOPHORECTOMY BUT IF IT'S
POSSIBLE WITH SPONTANEOUS
BECAUSE OF SLOWER DECLINE MAY BE
DIFFERENT, LESS DRAMATIC, MANY
OF THE CURRENT GUIDELINES FROM
SOCIETIES BASICALLY RECOMMEND
THE SAME APPROACH TO PREMATURE
OR EARLY MENOPAUSE REGARDLESS
WHERE IT CAME FROM BUT THIS BE
OVERSIMPLIFICATION, THE IDEA IS
TREAT THESE WOMEN AND MAKE SURE
THEY HAVE RECEIVING ESTROGEN ROW
PLACEMENT ADEQUATELY BECAUSE IF
THEY DON'T THEY WILL HAVE
SEQUELAE BUT IF DOSE IS
DIFFERENT WE DON'T KNOW.
WE HAVE NO CLINICAL TRIALS, NO
EXPERIMENTAL EVIDENCE, THE
EVIDENCE IS OBSERVATIONAL, WHICH
IS THE BEST WE HAVE.
AND I THINK THERE'S A TREMENDOUS
NEED FOR RESEARCH IN THIS AREA,
PREMATURE AND EARLY MENOPAUSE
SHOULD BE A FOCUS OF HIGH
PRIORITY BECAUSE IT'S NOT
UNCOMMON AND IT'S A BIG UNKNOWN
AREA OF TREATMENT.
>> THANK YOU.
WE'RE REALLY AT TIME.
I HOPE TO ASK DR. K OHRT A QUICK
QUESTION.
IN THE HUMAN CONDITION MOST
WOMEN WHO AFTER MENOPAUSE IF
THEY ARE GOING TO GO ON ESTROGEN
WILL BE ON PROGESTIN AS WELL, IS
THERE ANYTHING KNOWN FROM MODELS
WHERE YOU ARE HAVE E E ADD-BACK
HAS THE SAME OR E ALONE?
>> WE'RE STARTING TO DO THOSE
IN ANIMAL WORK BUT THESE DNRH
ANALOG STUDIES ARE CHALLENGING
SO WE HAVEN'T -- IT WOULD
REQUIRE ADDING ANOTHER ARM AND
WE JUST HAVEN'T GONE THERE.
>> THANK YOU ALL FOR YOUR
THOUGHTFUL ANSWERS TO SO MANY
IMPORTANT QUESTIONS, AND THERE'S
STILL MORE IN THE Q&A, IF PEOPLE
HAVE TIME TO ANSWER THEM.
>> THANK YOU, EVERYONE.
WE WILL RETURN AT 1:05 FOR THE
AFTERNOON SESSIONS.
>>WELCOME BACK.
I THANK EVERYONE WHO HAS SPOKEN
SO FAR.
IT'S MY PLEASURE TO WELCOME DR.
REBECCA THURSTON, PITTSBURGH
FOUNDATION CHAIR IN WOMEN'S
HEALTH AND DEMENTIA UNIVERSITY
OF PITTSBURGH.
>> I'M THRILLED TO BE HERE.
>> WE CAN'T HEAR YOU.
>> I CAN HEAR YOU.
I'LL BE PRESENTING DR. BARBARA
NORQUIST, ASSOCIATE PROFESSOR,
DEPARTMENT OF OBSTETRICS,
UNIVERSITY OF WASHINGTON.
>> CAN EVERYBODY HEAR ME OKAY?
>> THANK YOU.
I'M SO HONORED TO BE HERE.
I'M A GYNECOLOGIC ONCOLOGIST,
UNIVERSITY OF WASHINGTON, WHILE
I DO RESEARCH IN THESE AREAS,
IT'S INFORMED BY MY CLINICAL
CARE OF PATIENTS WHO ARE THE
RISK FOR OVARIAN CANCER, A LARGE
PART OF MY CLINICAL PRACTICE.
I HAVE NO FINANCIAL DISCLOSURES.
I'M GOING TO SPEAK ABOUT WHO IS
AT RISK FOR OVARIAN CANCER.
I'LL GO THROUGH WHAT OPTIONS
PATIENTS HAVE TO PREVENT
CANCERS.
WHAT ARE POTENTIAL HARMS OF
INTERVENTIONS WE HAVE TO OFFER
THEM AND FINALLY WHAT ARE SOME
UNANSWERED QUESTIONS ABOUT
HORMONE REPLACEMENT THERAPY OR
HRT IN THESE PATIENTS AT RISK
FOR BOTH OVARIAN AND BREAST
CANCER.
FIRST PATIENTS AT RISK OF
OVARIAN CANCER, SPRINKLED IN
SOME RANDOM PHOTOS OF PACIFIC
NORTHWEST HIKING, JUST TO
INDICATE TOPIC CHANGES.
SO WE KNOW WITH MUTATIONS IS
HIGH FOR OVARIAN AND BREAST
CANCER.
THIS PAPER IN JAMA, UPDATED RISK
INFORMATION, OVARIAN ON THE
RIGHT SIDE OF THE FIGURE.
BRCA1 CARRIERS HAVING HIGHEST
RISK, AND BRCA2 HAVING ELEVATED
RISK BUT NOT AS HIGH AS BRCA1.
THESE LOOKED HIGH TO ME, I DON'T
KNOW IF THEY LOOK HIGH TO
EVERYONE WATCHING, BUT OVARIAN
CANCER IS SUCH A SERIOUS CANCER
AND MOST PATIENTS WHO ARE
DIAGNOSED WITH OVARIAN CANCER
WILL DIE FROM THEIR CANCERS.
THERE ARE MANY OTHER PATIENTS
WHO ARE ALSO AT RISK FOR OVARIAN
CANCER.
MUCH OF THE TALK ABOUT FOCUS ON
THE BRCA1 AND 2 CARRIERS, THE
LARGEST GROUP, AND THE GROUP WE
HAVE THE MOST INFORMATION ON BUT
I DIDN'T WANT TO LEAVE OUT THESE
OTHER POPULATIONS SUCH AS
MUTATIONS IN HOMOLOGOUS
RECOMBINATION GENES AND
MUTATIONS IN GENES LEADING TO
LYNCH SYNDROME WITH RISKS OF
OVARIAN AND END MEDIAL CANCER.
WHY DON'T THESE PATIENTS GET
MORE SCREENING?
MANY ON THIS SYMPOSIUM
UNDERSTAND SCREENING HAS BEEN
NOT EFFECTIVE FOR THESE
PATIENTS.
PART IS THE NATURE, IDENTIFYING
A PRECURSOR TO A CANCER THAT CAN
BE SUCCESSFULLY TREATED.
AND THE BEST WE CAN HOPE FOR
WITH OVARIAN CANCER IS FOR
EARLIER DISEASE DETECTION THAT
MIGHT BE EASIER TO TREAT.
BUT WE'VE NOT AFTER ABLE TO
IMPROVE EARLY DETECTION IMPROVES
MORTALITY OR HELPS PATIENTS LIVE
LONGER.
AND PART IS THIS PHOTO HERE OF
THESE CANCERS MICROSCOPICALLY
STARTING IN THE FALLOPIAN TUBE,
EVEN THE SMALLEST CLINICAL
RECOMMENDATION IS LARGE SURGERY,
SIX CYCLES OF CHEMOTHERAPY WITH
HIGH RECURRENCE RATES EVEN WHEN
DETECTED EARLY.
FOR MOST PATIENTS THEY WOULD
AGREE THAT IS NOT AN ACCEPTABLE
SUBSTITUTE FOR OUTRIGHT
PREVENTION.
SO THE CURRENTLY AVAILABLE
OVARIAN CANCER SCREENINGS
METHODS ARE JUST NOT SENSITIVE
ENOUGH TO FIND THOSE SMALL
LESIONS.
WE HAVE BLOOD TEST MONITORING
AND TRANSVAGINAL ULTRASOUND TO
LOOK AT OVARIES, THESE HAVE BEEN
STUDIED EXTENSIVELY IN THE
LANDMARK PLCO TRIAL AND UKCTOCS
TRIALS, NEITHER HAS BEEN ABLE TO
SHOW IMPROVED MORTALITY FROM
OVARIAN CANCER.
THIS IS NOT TO SAY PELVIC
ULTRASOUND IS NOT THE TEST OF
CHOICE TO ALLEVIATE SYMPTOMS BT
NOT A GREAT ASYMPTOMATIC
SCREENING TEST.
IN PATIENTS WITH HIGH RISK, U.K.
FOX TRIAL DID A TREMENDOUS
EFFORT WITH 4,000 PATIENTS WITH
GREATER THAN 10% LIFETIME RISK
OF OVARIAN CANCER.
THEY HAD A CA-125 EVERY 4 MONTHS
USING ROCAA ALGORITHM.
18 INCIDENT CANCERS DETECTED, 12
SCREENING, 6 OCCULT CANCERS,
UNRELATED TO SCREENING THEY HAD.
OF THOSE 12 SCREEN DETECTED HALF
WERE STILL ADVANCED STAGE
DESPITE BEING SCREEN DETECTED.
THEY WERE EASIER TO OPERATE ON
WITH GREATER RATES OF COMPLETE
GROSS RESECTION WHICH CAN BE
IMPORTANT PROGNOSTICALLY BUT WE
HAVEN'T BEEN ABLE TO PROVE THIS
HELPED PEOPLE LIVE LONGER.
SO, WHAT ACTUALLY WORKS FOR
THESE PATIENTS?
THE INTERVENTION THAT'S
EFFECTIVE IS WHAT I SOMETIMES
REFER TO AS NUCLEAR OPTION, THE
ONLY WAY WE HAVE TO EFFECTIVELY
REDUCE RISK AS MUCH AS POSSIBLE
IS SURGICALLY REMOVE THE AT RISK
ORGANS, RECOMMENDED IN NCCN
GUIDELINES WITH REMOVAL OF TUBES
AND OVARIES WITH INCREASED RISK
OF OVARIAN CANCER.
RISK REDUCING
SALPINGO-OOPHORECTOMY IS
RECOMMENDED BETWEEN 35 TO 40 FOR
BRCA1, AND 40 TO 45 FOR BRCA2.
YOU'LL NOTICE AGES ARE DIFFERENT
FOR THE TWO GENES BECAUSE RISK
PROFILE IS DIFFERENT.
THE RISK IS HIGHER AND EARLIER
ONSET FOR BRCA1, THIS TABLE JUST
SHOWS OBSERVATIONAL DATA IN A
LARGE COHORT OF PATIENTS WITH
BRCA1 AND 2 MUTATIONS AND
LEFT-HAND SIDE LOOKS AT BRCA1
CARRIERS SHOWING SOME OVARIAN
CANCERS IN PATIENTS BELOW AGE OF
40.
AND THIS PAPER WAS ABLE TO
ESTIMATE A RISK OF AROUND 4% OF
DEVELOPING OVARIAN OR FALLOPIAN
TUBE CANCER BETWEEN 35 TO 40 FOR
BRCA1 CARRIERS, AND BRCA2
CARRIERS VERY FEW MALIGNANCIES
PRIOR TO AGE 40.
THERE ARE GUIDELINES FOR OTHER
GENES I MENTIONED, FOR PURPOSES
OF TIME I WON'T GO INTO THIS,
THERE ARE AN EXPANDED NUMBER OF
PATIENTS WITH GUIDELINES FOR
OVARIAN CANCER PREVENTION.
IS THIS EFFECTIVE?
WE HAVE QUITE A BIT OF
ACCUMULATED DATA FOR BRCA1 AND 2
MUTATION CARRIERS, RISK
REDUCING, REASSURING IN LIGHT OF
THE DATA SHOWN EARLIER BY DR.
ROCCA AND DR. MANSON LOOKING AT
MORTALITY CHANGES WITH
MENOPAUSE.
WE KNOW SCREENING IS NOT
EFFECTIVE, AND SURGERY IS THE
INTERVENTION THAT IS LIFE
SAVING.
AND THERE ARE GUIDELINES THAT
SHOULD MAKE THIS RELATIVELY
SIMPLE WHEN TAKING CARE OF
PATIENTS BUT WHAT ARE PEOPLE
ACTUALLY DOING LIKE WHAT IS
ACTUALLY HAPPENING?
AT THESE INSTITUTIONS, WE LOOKED
AT OUR EXPERIENCE OVER THE PAST
20 YEARS OR SO, AND OUT OF 371
BRCA1 AND 2 CARRIERS, OVER HALF,
57%, HAVE RISK REDUCTION
SURGERIES AFTER GUIDELINE
RECOMMENDED AGES, WHICH WOULD BE
GREATER THAN 40, FOR BRCA1
CARRIERS, OVER 45 FOR BRCA2.
WE FOUND 16 OCCULT NEOPLASMS IN
THIS COHORT, WITH EIGHT BEING
PRE-CANCEROUS LESIONS, AND EIGHT
BEING INVASIVE CANCERS, 81% WERE
OVER THE GUIDELINE-RECOMMENDED
AGES, OR IF YOU LOOK ANOTHER
WAY, IF YOU WERE PAST GUIDELINE
RECOMMENDED AGES THERE WAS 6%
RISK OF FINDING OCCULT NEOPLASIA
VERSUS 2% RISK IF SURGERY WAS
DONE WITHIN THE
GUIDELINE-RECOMMENDED AGES.
NOW IN THIS STUDY WE WERE NOT
ABLE TO TELL WHY PEOPLE WERE
WAITING FOR SURGERY, AND THERE'S
A NUMBER OF THINGS THAT COULD BE
CONTRIBUTING TO THAT.
ONE IS THAT MANY OF THESE
PATIENTS FIND OUT THEY HAVE THE
RISK BECAUSE THEY HAVE DEVELOPED
A CANCER AND HAD TESTING, SO
THOSE POPULATIONS MAY BE OLDER.
AND BUT AT LEAST SOME COULD BE
FROM PATIENTS WAITING TO HAVE
SURGERY FOR A VARIETY OF
REASONS.
SO IS HORMONE REPLACEMENT
THERAPY RECOMMENDED FOR PRE-MEN
PAUSAL CHARACTERS AFTER RISK
REDUCING OOPHORECTOMY?
THERE ARE NO SPECIFIC
GUIDELINES.
THE NORTH AMERICAN MENOPAUSE
SOCIETY HAS THIS STATEMENT ON
BASIS OF LIMITED STUDIES,
CONSIDERING OFFERING SYSTEMIC
HORMONE THERAPY UNTIL MEDIAN AGE
OF MENOPAUSE, AND AMERICAN
COLLEGE OF OBSTETRICS AND
GYNECOLOGY SAYS WOMEN UNAFFECTED
SHOULD BE OFFERED HORMONE
REPLACEMENT THERAPY TO MITIGATE
EARLY EFFECTS OF MENOPAUSE.
NOT A LOT OF SPECIFICS THERE.
ONE OF THE PRIMARY CONCERNS IN
THIS POPULATION, SPECIFICALLY
RISK OF DEVELOPING BREAST
CANCER, WHILE TAKING HORMONE
REPLACEMENT THERAPY, AS THESE
ARE PATIENTS WHO ARE AT RISK FOR
BOTH OVARIAN AND BREAST CANCER,
AND THERE'S NOT A TON OF DATA IN
THIS SETTING BUT WE DO HAVE SOME
GOOD PROSPECTIVE COHORT STUDIES
THAT HAVE BEEN QUITE REASSURING
IN TERMS OF BREAST CANCER RISK
WITH HORMONE REPLACEMENT THERAPY
AFTER PRE-MENOPAUSAL
OOPHORECTOMY WITH THE PRO STUDY
SHOWN HERE AND THEN THIS MORE
RECENT PAPER SHOWING
PARTICULARLY IN BRCA1 CARRIERS
THERE WAS NO INCREASED RISK
AFTER OOPHORECTOMY.
EACH STUDY WAS TOO SMALL TO SEE
IF DIFFERENT TIMES OF HRT WERE
ASSOCIATED WITH RISK.
WE KNOW FROM WHI DESCRIBED BY
DR. MANSON THAT THE ESTROGEN
ALONE ARM OF THE TRIAL DID NOT
HAVE AN INCREASED RISK OF BREAST
CANCER COMPARED TO THE GROUP
GETTING ORAL E PLUS P.
WE HAVE PATIENTS WHO WILL DECIDE
TO HAVE RISKIER SURGERY WITH
HYSTERECTOMY TO FIT THIS
PARADIGM WHEN THEY TAKE HRT
AFTER SURGERY.
WHAT DO WE KNOW GOOD QUALITY OF
LIFE AFTER RISK REDUCING
OOPHORECTOMY?
WE'RE ACCUMULATING STUDIES.
MARTHA HICKEY LED THE WHAM
STUDY, AS A CHILD OF THE '80s
THAT WAS ONE OF THE BEST-NAMED
STUDIES THAT I'VE COME ACROSS.
LOOKING AT WHAT HAPPENS TO
PEOPLE AFTER MENOPAUSE.
AND THE TWO PUNCHLINES FROM THE
PUBLICATION, MORE DATA TO COME,
HRT REDUCES BUT DOES NOT RESOLVE
VASOMOTOR SYMPTOMS AFTER
OOPHORECTOMY AND HRT IMPROVES
MENOPAUSE RELATED QUALITY OF
LIFE BUT NOT TO PRE-SET LEVELS,
A RECURRING THEME IN THESE
STUDIES.
I SEE THEY ROUTINELY.
34-YEAR-OLD PRESENTING WITH A
BRCA1 MUTATION.
LIFETIME RISK OF OVARIAN CANCER
IS QUITE SUBSTANTIAL.
BASED ON THAT I COUNSEL HER
ABOUT THE GUIDELINES INDICATING
THAT RISK-REDUCING REMOVAL OF
TUBES AND OVARIES IS RECOMMENDED
BETWEEN 35 TO 40.
THE WHOLE REASON SHE KNOWS SHE
HAS THIS BRCA1 MUTATION IS
BECAUSE SHE WAS DIAGNOSED WITH A
HORMONE RECEPTOR NEGATIVE BREAST
CANCER, WHICH WAS TREATED WITH
CHEMOTHERAPY AND BILATERAL
MASTECTOMY.
SO HOW SHOULD WE MANAGE THIS
PATIENT?
SHE'S NOT ON HORMONE
SUPPRESSION, AND ONE MEDICAL
ONCOLOGIST SHE SPOKE WITH TOLD
HER IT WAS OKAY, ANOTHER TOLD
THEY ARE ABSOLUTELY NOT, NO WAY
THEY WOULD CONSIDER GIVING IT,
AND WE ARE CAUGHT IN THE MIDDLE,
THERE'S NOT A LOT OF DATA TO
GUIDE THIS SCENARIO BUT PEOPLE
HAVE A LOT OF FEELINGS ABOUT IT.
THE TRIAL SHOWING HORMONE
REPLACEMENT THERAPY INCREASED
RISK OF BREAST CANCER RECURRENCE
WAS UNDERPOWERED TO LOOK AT
SUBGROUP WITH HORMONE RECEPTOR
NEGATIVE CANCERS, AND ALSO
INCREASED RISK WITH LOCAL OR
CONTRALATERAL RECURRENCE, AND
MANY OF THESE PATIENTS HAD
BILATERAL MASTECTOMIES, WE DON'T
KNOW HOW THAT CHANGES OUR
RECOMMENDATIONS FOR THESE
PATIENTS BUT THIS IS A TIGHT
SPOT TO BE IN FOR THESE WOMEN.
A FEW MORE SCENARIOS IN MY OWN
PRACTICE, SO A 40-YEAR-OLD BRCA2
CARRIER COMES IN WHO ALREADY HAD
TUBES AND OVARY REMOVED IN
GUIDELINE RECOMMENDED AGES FOR
RISK OF OVARIAN CANCER BUT HAS
BEEN TOLD HORMONE REPLACEMENT
THERAPY ISN'T SAFE BECAUSE SHE'S
AT INCREASED RISK OF BREAST
CANCER, DESPITE THE DATA AND
OTHER FINDINGS.
AND SO SHE IS HAVING VERY POOR
QUALITY OF LIFE AND FEELS
CONFLICT AND GUILTY AND DOESN'T
KNOW WHAT TO DO.
ANOTHER SCENARIO I SEE, A
35-YEAR-OLD BRCA1 CARRIER WITH
HISTORY OF ESTROGEN RECEPTOR
POSITIVE BREAST CANCER,
PRESCRIBED VAGINAL ESTROGEN FOR
DYSPAREUNIA, THE PHARMACIST SAID
IT WAS CONTRAINDICATED BECAUSE
OF HISTORY OF BREAST CANCER AND
REFUSED TO FILL THE
PRESCRIPTION.
ANOTHER SCENARIO 42-YEAR-OLD
BRCA1 CARRIER WITH HISTORY OF
NON-INVASIVE DCIS OF THE BREAST,
HAD A BILATERAL MASTECTOMY,
PLANNING RISK REDUCING
SALPINGO-OOPHORECTOMY WANTS TO
GO ON HORMONE REPLACEMENT
THERAPY BUT DOCTORS CANNOT AGREE
THIS IS SAFE.
AND THE FINAL, 45-YEAR-OLD BRCA2
CARRIER, HAVING BOTHERSOME HOT
FLASHES AND NIGHT SWEATS, UNABLE
TO FIND A PHYSICIAN TO ADDRESS
HER CONCERNS, COMES TO ME PRIOR
TO SURGERY, ALREADY ON A REGIMEN
OF COMPOUNDED HORMONES WHICH SHE
IS PAYING A LARGE SUM OF MONEY
FOR EACH MONTH, BECAUSE SHE
COULDN'T FIND A PHYSICIAN WHO
WOULD PRESCRIBE HER FDA-APPROVED
THERAPYIES IN THE HIGH RISK
SCENARIO.
I EXPECT THIS TO GET WORSE IN
LIGHT OF THE DOBBS DECISION AND
OB/GYNS LEAVING STATES IN WHICH
THEY FIND IT UNSAFE TO PRACTICE
THEIR FIELD.
SO WHAT ABOUT THE FALLOPIAN
TUBES?
IT WILL BE ADDRESSED LATER BY
SUE FRIEDMAN BUT THE MAJORITY OF
OVARIAN CANCERS WE THINK MAY
COME FROM THE FALLOPIAN TUBE,
THIS HAS LED TO INTEREST IN
REMOVING THE FALLOPIAN TUBES
FIRST RATHER THAN OVARIES WHICH
LEADS TO STERILIZATION WITH
UNCERTAIN DEGREE OF RISK
REDUCTION, PATIENTS NEED TWO
SURGERIES.
BUT THERE ARE A NUMBER OF
REASONS TO WAIT ON OOPHORECTOMY.
I SEE DR. TEMKIN AND I'M CLOSE
TO TIME.
A COUPLE MORE SLIDES.
WE CAN MITIGATE CONSEQUENCES CAN
HORMONE REPLACEMENT THERAPY,
PATIENTS HAVE REAL CONCERNS,
SUBSTANTIAL ENOUGH TO DRIVE
MULTIPLE CLINICAL TRIALS OF
PATIENTS CONSIDERING HAVING SAL
PINGECTOMY FOLLOWED BY
OOPHORECTOMY COMPARED WITH
BILATERAL SALPINGO-OOPHORECTOMY,
PATIENTS ARE CHOOSING WHAT TYPE
OF SURGERY THEY WILL HAVE, THESE
ARE NOT RANDOMIZED.
I WAS INVOLVED WITH THE WISP
STUDY IN THE UNITED STATES
LOOKING AT HOW PEOPLE DID AFTER
THESE OPERATIONS IN TERMS OF
SEXUAL FUNCTION AND MENOPAUSAL
SYMPTOMS.
HERE ARE SOME OF THE FINDINGS.
THE STUDY HAS NOT BEEN PUBLISHED
BUT SHOULD BE COMING OUT
HOPEFULLY SOON.
WHICH I THINK WILL ADD TO THESE
DATA.
THE TUBA STUDY IN THE
NETHERLANDS CONFIRMED WHAT WHAM
SHOWED, MENOPAUSE-RELATED
QUALITY OF LIFE WAS WORSE AFTER
RISK REDUCING
SALPINGO-OOPHORECTOMY EVEN WITH
HORMONE REPLACEMENT THERAPY AND
SEXUAL FUNCTIONING WAS BETTER
WITH HRT BUT NOT BACK TO
BASELINE.
THERE ARE PENDING STUDIES
LOOKING AT CANCER OUTCOMES.
OVARIAN CANCER IS A
LIFE-THREATENING DISEASE,
SCREENING IS NOT EFFECTIVE.
SURGERY IS THE LIFE SAVING
INTERVENTION BUT LEADS TO
SURGICAL MENOPAUSE.
AND DESPITE HRT QUALITY OF LIFE
AND SEXUAL FUNCTIONING ARE NOT
THE SAME AFTER PRE-MENOPAUSAL
RISK REDUCING
SALPINGO-OOPHORECTOMY, MORE DATA
IS NEEDED TO MITIGATE SIDE
EFFECTS.
THANK YOU FOR YOUR TIME.
>> THANKS YOU FOR INFORMATIVE
PRESENTATION.
THE NEXT SPEAKER, DR. SARA
LOOBY, HARVARD MEDICAL SCHOOL,
WILL BE TALKING TO US ABOUT
MENOPAUSE IN WOMEN WITH HIV.
>> THANK YOU.
IF YOU COULD START MY SLIDES.
CAN EVERYBODY HEAR ME OKAY?
GOOD AFTERNOON.
THANK YOU VERY MUCH FOR THE
OPPORTUNITY TO PRESENT AT THIS
PRESTIGIOUS SYMPOSIUM.
I'M SARA LOOBY, WITH THE
PRIVILEGE OF SHARING RESEARCH,
RICH PERSPECTIVES, EXPERIENTIAL
CLINICAL DATA FROM MY WORK, THAT
OF MY COLLEAGUES FROM AROUND THE
WORLD, AND FROM THE EXPERTS,
WOMEN LIVING WITH HIV.
ON THE TOPIC OF MENOPAUSE,
EMERGING KNOWLEDGE, SPECIAL
CONSIDERATIONS.
NO DISCLOSURES.
NEXT SLIDE PLEASE.
THIS SHARES AN OVERVIEW OF
SELECT TOPICS I WILL PRESENT IN
THE NEXT 20 MINUTES, BUILDING ON
THE INCREDIBLE PRESENTATIONS
WE'VE HEARD FROM THE EXPERTS
TODAY, IT'S MY GOAL TO PROVIDE A
MINI STATE OF THE SCIENCE,
RESEARCH, VOICES OF WOMEN,
CLINICAL CONSIDERATION FOR THIS
GROWING POPULATION OF WOMEN
EXPERIENCING MENOPAUSE.
ONE OF THE MOST IMPORTANT THINGS
I'VE LEARN IN TWO DECADES OF
CLINICAL RESEARCH, IS THAT
FINDINGS FROM THE MOST RIGOROUS
SCIENCE AND MOST SEMINAL
PUBLICATIONS AND MOST REPUTABLE
JOURNALS ARE ONLY AS EFFECTIVE
AS THE PATIENT'S ABILITY TO
UNDERSTAND, TRUST, AND OPT TO
USE THESE FINDINGS TO HELP
ENHANCE THEIR OWN HEALTH.
AS PROVIDERS, RESEARCHERS,
EDUCATORS AND PEERS, A CRITICAL
FIRST STEP IN FACILITATING
UPTAKE OF EVIDENCE-BASED
TREATMENT IS NOT ASSESSING AND
TREATING A PARTICULAR CONDITION
BASED ON EVIDENCE ALONE, IT'S
UNDERSTANDING THE PATIENT AS A
WHOLE, INCLUDING FACTORS SUCH AS
SOCIAL DETERMINANTS OF HEALTH,
PSYCHOLOGICAL HEALTH, COMORBID
CONDITIONS, HOW A PATIENT MAY
EXPERIENCE A MEDICAL CONDITION
OR SYMPTOM OR HOW PROVIDERS MAY
ASSESS AND TREAT THE SAME
SYMPTOM OR CONDITION IS STRONGLY
INFLUENCED BY SOCIODEMOGRAPHIC
AND BIOPSYCHOSOCIAL
CHARACTERISTICS AND DIFFER
ACROSS PATIENT POPULATIONS.
LET'S LOOK IN THE CONTEXT OF
MENOPAUSE AND WOMEN WITH HIV.
13 YEARS AGO I WAS ASKED BY A
WOMAN WITH HIV IN HER MID-40s
HOW SHE COULD TELL IF THE NIGHT
SWEATS SHE STARTED EXPERIENCING
WERE RELATED TO A LOW CD4 COUNT,
HIGH HIV VIRAL LOAD VERSUS
MENOPAUSE?
THIS NEW ONSET OF NIGHT SWEATS
ABSOLUTELY TERRIFIED HER.
HAVING LIVED 15 YEARS WITH
STABLE HIV ON MEDICATION, SHE
WAS CONCERNED HER HIV
MEDICATIONS WERE NO LONGER
WORKING AND NOW HAD AIDS OR
ANOTHER HIV-ASSOCIATED
CONDITION.
NEXT SLIDE PLEASE.
HER STORY IS NOT ISOLATED.
IN HIV PATIENT PUBLICATION, HELL
IN A HOT FLASH, SHARED SIMILAR
ACCOUNTS ABOUT HOT FLASHES
EXPERIENCED BY WOMEN WITH HIV.
AND PERHAPS THE MOST INSIGHTFUL
QUOTE FROM THE ARTICLE, WAS
AFTER A WEEK OF WAKING UP IN THE
MIDDLE OF THE NIGHT WERE
DRENCHING NIGHT SWEATS, I RAN TO
MY DOCTOR IN AEN PAIC, REMINISCE
OF OF DAYS T CELL COUNT WAS 8, I
KNEW SOMETHING MAJOR WAS WRONG
WITH ME.
THESE QUOTES REVEAL SOME WOMEN
WITH HIV PERCEIVE MENOPAUSE
SYMPTOMS TO BE HIV SYMPTOMS, AND
THIS MAY BE DUE TO LACK OF
KNOWLEDGE REGARDING MENOPAUSE
AND ITS ASSOCIATED SYMPTOMS OR
OVERLAP BETWEEN SYMPTOMS OF HIV
AND SYMPTOMS OF MENOPAUSE.
THIS CLEARLY CAUSES
PSYCHOLOGICAL DISTRESS AMONG
MID-LIFE WOMEN WITH HIV,
HIGHLIGHTING THE NEED FOR
PATIENT AND PROVIDER EDUCATION.
NEXT SLIDE PLEASE.
WOMEN EXPERIENCE TRAUMA.
SEXUAL ASSAULT, RAPE, TEEN
PREGNANCY, DOMESTIC VIOLENCE,
PERHAPS HAVING A FIRST MENSTRUAL
PERIOD IN THE ABSENCE OF AN
ADULT CARETAKER.
IN MANY CULTURE AND FAMILIES
DISCUSSION OF WOMEN'S HEALTH AND
MENOPAUSE CAN CONTRIBUTE TO
KNOWLEDGE GAP TRAUMA, STIGMA,
ISOLATION, THUS EDUCATING WOMEN
WITH HIV, A TRAUMA INDUCED
APPROACH CONSIDERATE IN A MANNER
WITH CULTURAL BACKGROUND, AGE,
HEALTH LITERACY AND CLINICAL
FACTORS.
NEXT SLIDE.
OF GREAT CONCERN IS
PSYCHOLOGICAL WELL BEING AND
QUALITY OF LIFE OF WOMEN WITH
HIV IN THE TRANSITION MAY BE
FURTHER COMPOUNDED WITH SOCIAL
CONCERNS EXPERIENCED BY MANY
WOMEN WITH HIV THAT ARE SHARED
ON THIS SLIDE.
WHETHER MENOPAUSE WILL OFFSET
THIS PRECARIOUS HEALTH STATE IN
THIS POPULATION IS NOT FULLY
UNDERSTOOD.
A LARGE PORTION OF THE
LITERATURE ON HIV AND MENOPAUSE
TO DATE FOCUSED ON DETERMINING
AGE OF ONSET AND WHETHER IT IS
EARLIER IN WOMEN WITH HIV.
NEXT SLIDE.
CRITERIA TO HELD GUIDE
CLINICIANS WITH ASSESSMENT OF
REPRODUCTIVE AGING AND ONSET IN
WOMEN DO EXIST, AS WE'VE LEARNED
FROM PRESENTERS THIS MORNING.
HOWEVER, THEY ARE NOT
ONE-SIZE-FITS-ALL AND EXISTING
GAP IN LITERATURE TO DATE
IDENTIFIED AT THE STAGES OF
REPRODUCTIONING AGE WORKSHOP IN
2012 IS EVALUATING STAGING OF
REPRODUCTIVE AGING IN WOMEN WITH
CHRONIC ILLNESSES INCLUDING HIV
NEEDED.
PRIOR STUDIES SUGGEST WOMEN WITH
HIV EXPERIENCE EARLIER ONSET OF
MENOPAUSE OCCURRING BETWEEN AGES
OF 46 AND 50, VERSUS 51 OR 52,
MEDIAN AGE OF ONSET COMMONLY
OBSERVED IN WOMEN WITHOUT HIV.
HOWEVER, SOME FINDINGS IN
STUDIES HAVE BEEN LIMITED DUE TO
ASSESSMENT IN METHODOLOGICAL
CONCERNS WITH CLASSIFYING
MENOPAUSE STAGE OR STATUS IN
RESEARCH STUDIES.
NEXT SLIDE.
IT CAN BE CHALLENGING TO
DECIPHER IF CESSATION OF MENSES
IS RELATED TO TRUE MENOPAUSE DUE
TO AMENORREAH DUE TO SUBSTANCE
USE DISORDER, LOW WEIGHT, AND
MIGHT BE RELATED TO HIV-SPECIFIC
CHARACTERISTICS AS SHOWN ON THIS
SLIDE.
NEXT SLIDE PLEASE.
THERE HAVE BEEN STUDIES AMONG
WOMEN WITH HIV THAT HAVE
DESCRIBED HYPOTHALAMIC
AMENORREAH, AND INVESTIGATORS
FOUND THAT AMONG EVALUATED
STUDIES A SIGNIFICANT
ASSOCIATION BETWEEN HIV STATUS
AND AMENORREAH EXISTED THAT MAY
BE INDEPENDENT OF SUBSTANCE USE
AND COMMONLY RELATED TO LOW
WEIGHT IN THIS POPULATION.
THUS IT IS GREAT VALUE TO
CONDUCT COMPREHENSIVE EVALUATION
OF PSYCHOSOCIAL LIFESTYLE,
CLINICAL, HIV FACTORS,
MEDICATION WHEN DETERMINING THE
ORIGIN OF AMENORREAH IN THIS
POPULATION.
TAKEN TOGETHER SOME LITERATURE
CONFLICTS REGARDING AGE AND
ONSET AND ITS RELATIONSHIP TO
HIV IF IT MAY ENTER MENOPAUSE
EARLY, THERE IS GREAT POTENTIAL
TO DETRIMENTAL IMPACT ON
CONDITIONS AND SYMPTOMS
ASSOCIATED WITH MENOPAUSE AS
WELL AS HIV-SPECIFIC FACTORS
INCLUDING IMMUNE HEALTH,
ADHERENCE TO RETROVIRAL THERAPY,
OVERALL SYMPTOM BURDEN.
NEXT SLIDE PLEASE.
BODY OF RESEARCH EXPLORING
MENOPAUSE SYMPTOMS AND
ASSOCIATED CLINICAL CONDITIONS
IN WOMEN WITH HIV IS GROWING
THINKS HYPOTHESIS-GENERATING
STUDIES AND LARGE COHORT STUDIES
INCLUDING WOMEN'S INTERAGENCY
HIV STUDY, POSITIVE TRANSITION
THROUGH MENOPAUSE PRIME STUDY,
CANADIAN HIV WOMEN'S COHORT
STUDY AND VASCULAR EVENTS IN HIV
OR REPRIEVE TRIAL.
MORE RESEARCH IS NEEDED.
NEXT SLIDE.
GIVEN OUR COLLECTIVE
UNDERSTANDING OF THE INTERPLAY
AND RISK FOR COMORBID CONDITIONS
THERE'S CONCERN REGARDING
ADDITIONAL BURDEN OF ESTROGEN
LOSS AND DEVELOPMENT OF SIMILAR
CHRONIC DISEASES, HIGHLIGHTED ON
THE RIGHT, THAT MAY POTENTIATE
EXISTING DISEASE PROCESSES.
IN OTHER WORDS, MANY
PRE-MENOPAUSAL WOMEN WITH HIV
EXPERIENCE THESE CONDITIONS
ALREADY, AND WHAT WILL HAPPEN
WHEN THEY LOSE PROTECTIVE
EFFECTS OF ESTROGEN?
THIS SLIDE SHARES FOUR FACTS OR
SUMMARIES GLEANED ON MENOPAUSE
SYMPTOMS IN WOMEN WITH HIV.
FIRST, WOMEN WITH HIV
PERIMENOPAUSAL IN PARTICULAR
APPEAR TO HAVE MORE SEVERE
DEPRESSIVE SYMPTOMS AND ANXIETY
COMPARED TO WOMEN WITHOUT HIV
DURING PERIMENOPAUSE.
INDEED MOOD SYMPTOMS MAY VARY BY
MENOPAUSE TRANSITION STATUS, AND
CAN FLUCTUATE AMONG ALL WOMEN,
WOMEN WITH HIV TEND TO HAVE
HIGHER PREVALENCE OF DEPRESSION
AND ANXIETY DURING PRE-MENOPAUSE
COMPARED TO WITHOUT HIV.
WOMEN WITH HIV MAY REPORT OR
EXPERIENCE WORSE DEPRESSIVE
SYMPTOMS AND ANXIETY DURING THE
MENOPAUSE TRANSITION, COMPARED
TO AGE, RATE, MENSTRUAL STATUS
MATCHED WOMEN WITHOUT HIV.
IN ONE STUDY THEY REMAIN
SIGNIFICANT WHEN EVALUATED AT
BASE LINE AT 12 MONTHS LATER,
ONE YEAR.
SECOND, PRIOR STUDIES REPORTED
THAT WOMEN WITH HIV EXPERIENCE
INCREASED HOT FLASH PREVALENCE
AND SEVERITY.
THERE IS CONFLICTING DATA,
POSSIBLY DUE TO METHODOLOGICAL
CHALLENGES.
REGARDLESS, WOMEN WITH HIV
EXPERIENCE THINGS I WILL SHARE
IN A SUBSEQUENT SLIDE.
SYMPTOMS IN WOMAN ACROSS
TRANSITION OCCUR, INCLUDING
VAGINAL DRYNESS, SEXUAL
DYSFUNCTION, DYSPAREUNIA,
UNCLEAR IF WORSE IN WOMEN
WITHOUT HIV.
AND VERY FEW STUDIES EVALUATED
HORMONE THERAPY USE IN THE
CONTEXT OF MENOPAUSE.
CURRENT STUDIES HAVE BEEN
HELPFUL.
HOWEVER THEY HAVE BEEN
RETROSPECTIVE CHART REVIEWS AND
QUALITATIVE INQUIRY.
BECAUSE OF THIS UPTAKE OF
HORMONE THERAPY IS LOW IN THIS
POPULATION, DUE TO THIS LACK OF
DATA.
WOMEN WITH HIV HAVE A DIFFICULT
TIME DISTINGUISHES SYMPTOMS OF
MENOPAUSE FROM SYMPTOMS OF HIV,
DUE TO POTENTIAL FOR OVERLAP AND
THIS IS AN IMPORTANT
CONSIDERATION FOR BOTH
ASSESSMENT AND TREATMENT OF THIS
POPULATION.
THERE IS A GREAT ARTICLE IN THE
JOURNAL OF MENOPAUSE ON THIS
DISTINCTION WHICH IS DEFINITELY
WORTH READING WHEN YOU HAVE
TIME.
NEXT SLIDE PLEASE.
IN CONTEXT OF HOT FLASHES, GRET
PAPERS HAVE BEEN PUBLISHED
LOOKING AT CHARACTERISTICS
ASSOCIATED WITH HOT FLASHES IN
WOMEN WITH HIV.
SPECIFICALLY, HOT FLASHES HAVE
BEEN SHOWN TO NEGATIVELY IMPACT
ADHERENCE TO LIFE-SAVING
MEDICATION, OR ANTIRETROVIRAL
THERAPY.
IMPAIRED DOMAINS OF FUNCTION AND
ELEVATED DEPRESSIVE SYMPTOMS,
ALL IMPORTANT CONSIDERATIONS.
NEXT SLIDE.
THERE'S BEEN RESEARCH EXPLORING
RELATIONSHIP BETWEEN MENOPAUSAL
HOT FLASHES AND CARDIOVASCULAR
DISEASE RISK AMONG WOMEN WITHOUT
HIV LED BY DR. REBECCA THURSTON.
A RECENT SAMPLE DETERMINED AN
ASSOCIATION WITH HOT FLASH
FREQUENCY AND HIGHER LEVELS OF A
DISTINCT BIOMARKER OF
INFLAMMATION THAT'S BEEN
ASSOCIATED WITH CARDIOVASCULAR
DISEASE AND OTHER CONDITIONS IN
PEOPLE WITH HIV.
AND AMONG WOMEN WITH HIV YEARS
SINCE ONSET OF HOT FLASHES
RELATED TO DECREASE THE DIE A
STOLIC FUNCTION.
IN TERMS OF BONE HEALTH, THERE
HAVE BEEN SEMINAL STUDIES
EXPLORING CARDIOVASCULAR INDICES
IN WOMEN WITH HIV DURING THE
MENOPAUSE TRANSITION.
RELEVANT FINDINGS SUGGEST IN
WOMEN WITH HIV INCREASED WAIST
CIRCUMFERENCE IS ASSOCIATED WITH
ADVANCED OVARIAN AGING AND MAY
ASSOCIATE WITH CLINICAL CVD AND
INCREASED MARKERS OF IMMUNE
ACTIVATION.
WOMEN WITH HIV ARE AT INCREASED
RISK FOR OSTEOPENIA AND
OSTEOPOROSIS RELATED TO
HIV-RELATED FACTORS AND HAVE
HIGHER PREVALENCE OF THESE
INDICES IN THE MENOPAUSE
TRANSITION, AND HIV FACTORS THAT
RELATE AND ASSOCIATE WITH
REDUCED BONE MINERAL DENSITY IN
THIS POPULATION INCLUDE A LOW CD
4 COUNT, HISTORY OF LOW WEIGHT,
CERTAIN ANTIRETROVIRAL
MEDICATION THAT MAY IMPACT BONE
TURNOVER AND VITAMIN D
ABSORPTION.
BOTH ARE ASSOCIATED WITH HIV AND
MENOPAUSE PARTICULAR ATTENTION
ON RISK REDUCING BEHAVIOR AND
ASSESSMENT AND TREATMENT AMONG
THE GROWING NUMBER OF WOMEN WITH
HIV APPROACHING OR EXPERIENCING
MENOPAUSE IS WARRANTED.
NEXT SLIDE.
SO, I PROVIDED A SURFACE LEVEL
UNDERSTANDING.
WHAT ARE THE NEXT STEPS?
INDEED MORE RESEARCH IS NEEDED
TO EXPLORE ALL ASPECTS OF THE
TRANSITION IN THIS SPECIAL
POPULATION, ESPECIALLY RESEARCH
LOOKING AT TREATMENT MODALITIES
SUCH AS HORMONE REPLACEMENT
THERAPY USE, OTHER THERAPIES TO
ENHANCE THE WELLNESS OF WOMEN
WITH HIV DURING THE MENOPAUSE
TRANSITION, IMPROVING CONDITIONS
ASSOCIATED WITH ESTROGEN LOSS
AND SYMPTOM BURDEN.
ALSO, INNOVATIVE EDUCATION
STRATEGIES ARE NEEDED FOR BOTH
PATIENTS AND PROVIDERS.
ESPECIALLY DUE TO THE MYRIAD
SOCIAL CONCERNS THAT THIS
POPULATION EXPERIENCES AS I
OUTLINED IN THE BEGINNING OF
THIS PRESENTATION.
PROVIDERS MUST PAY ATTENTION TO
SOCIAL CONCERNS INCLUDING
SUBSTANCE USE DISORDER, DOMESTIC
VIOLENCE, WHICH MAY VARY, TO
PROVIDE CARE.
DRAWING FROM THE STORY I SHARED
AT THE BEGINNING, IT'S IMPORTANT
TO ASK PATIENTS IF THEY
UNDERSTAND WHAT MENOPAUSE IS,
COMMON SYMPTOMS, ESPECIALLY MOOD
FLUCTUATION AND DISTURBANCE, HOT
FLASHES, WHY THEY OCCUR, HAVE AN
OPEN DISCUSSION WITH WOMEN WITH
HIV ABOUT TRADITIONAL AND
ALTERNATIVE INTERVENTION FOR
SYMPTOM MANAGEMENT.
FOR MOOD SYMPTOMS IF A PATIENT
IS ALREADY RECEIVING TREATMENT
FOR DEPRESSION, ANXIETY, SLEEP,
RECOGNIZING THAT IN THIS
POPULATION TREATMENT MAY NEED TO
BE MODIFIED OR ENHANCED DURING
THE MENOPAUSE TRANSITION WHEN
SYMPTOMS MAY INTENSIFY.
PROVIDER EDUCATION IS NEEDED TO
ENHANCE KNOWLEDGE AND IMPROVE
DELIVERY OF CARE AND EDUCATION
FOR WOMEN WITH HIV.
THERE IS AN EVOLVING NEED TO
EDUCATE INFECTIOUS DISEASE
PROVIDERS REGARDING CARE OF
MID-LIFE WOMEN, PARTICULARLY
ASSESSMENT OF MENOPAUSE SYMPTOMS
AND COMORBID CONDITIONS DURING
MENOPAUSE AND SUPPORT EDUCATION
FOR WOMEN WITH HIV.
WOMEN'S HEALTH PROVIDERS MAY
NEED SUPPORT AND EDUCATION ON
HIV SPECIFIC FACTORS IMPORTANT
TO CONSIDER AND UNIQUE TO
NON-HIV INFECTED WOMEN AT
MID-LIFE, OCCURRING THROUGH
SYMPOSIA LIKE THIS AND CREATION
OF INNOVATIVE EDUCATION
OPPORTUNITIES TO BRING
CLINICIANS TOGETHER WITH WOMEN
WITH HIV TO ENHANCE LEARNING.
MORE WORK NEEDS TO BE DONE.
IT'S ALREADY STARTED TODAY
THROUGH THIS AMAZING SYMPOSIUM
BRINGING US TOGETHER TO SHARE
KNOWLEDGE TO IMPROVE HEALTH OF
ALL WOMEN.
NEXT SLIDE PLEASE.
I'D LIKE TO THANK YOU FOR YOUR
TIME AND ATTENTION.
I SHARED MY PERSONAL E-MAIL AND
WOULD BE HAPPY TO HEAR FROM
ANYONE AT THE END OF THE PANEL
DISCUSSION AND OFFLINE WHEN THIS
IS COMPLETED.
THANK YOU VERY MUCH.
>> THANK YOU FOR THE EXCELLENT
PRESENTATION.
DR. HARLOW FROM UNIVERSITY OF
MICHIGAN.
>> THANK YOU.
TODAY I'LL TALK ABOUT THE SOCIAL
DETERMINANTS OF DISPARITIES IN
MENOPAUSE AND MID-LIFE HEALTH,
GROWING INSIGHT FROM STUDY OF
WOMEN'S HEALTH ACROSS THE NATION
IN RELATIONSHIP TO BLACK/WHITE
HEALTH DISPARITIES.
IT'S NOT MOVING DOWN.
INITIALLY I WOULD LIKE TO BEGIN
WITH DISCUSSION OF THE SOCIAL
HISTORICAL CONTEXT OF SWAN AND
LIFE CONTEXT OF BLACK AND WHITE
SWAN PARTICIPANTS BECAUSE
ALTHOUGH STUDIES ARE CONDUCTED
IN SPECIFIC GEOGRAPHIES,
SPECIFIC CONTEXTS, THEY OFTEN
FAIL TO PROPERLY SITUATE AND
CONSIDER IMPLICATIONS OF LIFE
CONTACTS FOR THOUGHTS AND
RESEARCH FINDINGS.
I WILL NEXT PRESENT SOME OF THE
DATA ON BLACK-WHITE DISPARITIES
FROM SOMEONE RELATED TO
MENOPAUSE AND MID-LIFE HEALTH
AND SUGGEST THREE CRITICAL GAPS
IN SCIENTIFIC UNDERSTANDING OF
MENOPAUSE THAT SHOULD INFORM OUR
FUTURE RESEARCH AGENDA.
AS PREVIOUSLY STATED, WOMEN IN
SWAN WERE 42 TO 52 WHEN ENROLLED
IN THE COHORT.
THEREFORE THEY WERE BORN BETWEEN
1944 AND 1954.
AT THAT TIME IN THE UNITED
STATES JIM CROWE LAWS SANCTIONED
RACIAL DISCRIMINATION LEADING TO
SEGREGATION IN HOUSING, HEALTH
CARE.
WHICH ALSO LED TO DIFFERENTIAL
ACCESS TO QUALITY HOUSING, FEWER
EMPLOYMENT OPPORTUNITIES, POOR
QUALITY EDUCATION, AND BARRIERS
TO HEALTH CARE FOR BLACK
CITIZENS, ALSO CREATING A
CLIMATE OF TERROR.
IN 1964 THE CIVIL RIGHTS LAW
OUTLAWED THIS.
DISPARITIES IN EDUCATION WERE
OPPORTUNITIES AND ACCESS TO
HEALTH CARE CONTINUED, CONTINUED
TO EXIST.
TO PERSIST.
WE DID KNOT DIRECTLY MEASURE
STRUCTURAL RACISM IN SWAN WE CAN
EXAMINE BLACK-WHITE DIFFERENCES
THAT REFLECT PERVASIVE AND
PERSISTENT INEQUITIES STEMMING
FROM SYSTEMIC RACISM IN THE
UNITED STATES.
SO IN THIS SLIDE, DOCUMENTING
SOCIOECONOMIC DISADVANTAGE OF
BLACK WOMEN AT BASELINE, LESS
LIKELY TO HAVE A COLLEGE DEGREE,
MORE LIKELY TO REPORT FINANCIAL
STRAIN, LESS LIKELY TO BE
EMPLOYED, MORE LIKELY TO REPORT
CHILDHOOD DISADVANTAGE
CHARACTERIZED BY GREATER
PREVALENCE OF LOW PARENTAL
EDUCATION, HAVING RECEIVED
PUBLIC ASSISTANCE, HAD
DIFFICULTIES PAYING FOR FOOD OR
RENT.
BLACK WOMEN WERE LESS LIKELY TO
BE MARRIED, MORE LIKELY TO HAVE
CHILDREN.
MORE CURRENT SMOKERS.
WE ASSESSED ENVIRONMENTAL
ESTROGENS IN A SUBSET OF SWAN
PARTICIPANTS AND EXPOSURE
DIFFERS BY GEOGRAPHY AND
RACE/ETHNICITY.
IN SWAN, BLACK WOMEN IN THE
SOUTHEAST MICHIGAN, PITTSBURGH
AND BOSTON SIDES HAD HIGHEST
PFOS CONCENTRATIONS, AND THIS
GRAPH SHOWS SPECIFICALLY BLACK
WOMEN REPRESENTED BY THE ORANGE
BARS HAD HIGHER BLOOD
CONCENTRATIONS OF THE PFOS THAN
WHITE WOMEN IN THE GREEN BARS.
AS WELL AS TROUBLE WITH THE
EXPERIENCE, EXPERIENCE OF
VIOLENCE, SWAN WAS AN EARLY
ADOPTER OF MEASURES OF
DISCRIMINATION, WE USE THE
10-ITEM EVERYDAY DISCRIMINATION
SCALE THAT FRAMES EXPERIENCE
WITHOUT REFERENCE TO RACE, WITH
EACH ITEM ON THE 4-POINT SCALE.
AVERAGE IS HIGHER FOR BLACK
WOMEN AT EACH ITEM, TOTAL SCORE
HIGHER IN BLACK THAN WHITE
WOMEN.
WHEN ASKED THE REASON THE MOST
COMMON REPORTED BY BLACKS WAS
RACE, 57%.
FOR WHITE IT WAS GENDER, 23% OF
WHITE WOMEN.
MOVING ON TO DISCUSS DISPARITIES
WE'VE SEEN, ONE QUESTION SWAN
ADDRESSED IS WHETHER
RACE/ETHNICITY IMPACTS AGE AT
FINAL MENSTRUAL PERIOD.
THIS INDICATES WHEN 50% OF GROUP
APPEARED FINAL PERIOD.
HISPANICS AND AFRICAN AMERICANS
REACHED FINAL MENSTRUAL PERIOD
AT EARLIER AGE THAN WOMEN IN
OTHER GROUPS.
IMPORTANTLY COMPARED TO WHITE
PARTICIPANTS BLACK PARTICIPANTS
HAVE LESS EDUCATION, GREATER
FINANCIAL STRAIN, GREATER
CIGARETTE USE, MORE
UNEMPLOYMENT, HIGHER EXPOSURE TO
PFOS ASSOCIATED WITH EARLIER AGE
OF MENOPAUSE AS WELL AS DIABETES
WHICH I'LL SHOW DATA ON SHORTLY.
AFTER ADJUSTMENTS FOR THE
LIFESTYLE AND SES, ETHNICITY WAS
NOT INDEPENDENTLY ASSOCIATED
WITH AGE AT MENOPAUSE BUT THESE
DO CLUSTER IN THE AFRICAN
AMERICAN POPULATION.
WHEN WE LOOK AT MEDIAN AGE AT
MENOPAUSE WE HAVE TO UNDERSTAND
BLEAK WOMEN EXPERIENCE EARLIER
MENOPAUSE, 52.2 VERSUS 52.9,
REDUCED IF ONE TAKES INTO
ACCOUNT LIFE AND SOCIAL CONTEXT,
LIFE CONTEXT AND SOCIAL
DISADVANTAGE AND OBESITY
EXPERIENCED BY BLACK AND WHITE
WOMEN.
BLACK WOMEN TWICE AS LIKELY TO
HAVE SURGICAL MENOPAUSE, AN
IMPORTANT CAUSE FOR SELECTION
BIAS INTO THE SWAN COHORT.
A RECENT ANALYSIS BY ALEXIS
REEVES, IN ADDITION TO LIFE
CONTEXT AND SOCIAL DISADVANTAGE
VARIABLES, DOCUMENTED ACCOUNTING
FOR THESE VARIABLES, BLACK WOMEN
HAVE A SEVEN-MONTH EARLIER AGE
OF MENOPAUSE.
MOVING ON TO LOOK AT HOT
FLASHES, THE SWAN MENSTRUAL
CALENDAR COLLECTED REPORTS
MONTHLY WHETHER WOMEN
EXPERIENCED HOT FLASHES FOR TEN
YEARS.
THIS GRAPH SHOWS PERCENT OF
WOMEN REPORTING HOT FLASH INDEX
ON FMP TIME WITH RED BAR BEING
TIME OF FMP.
RED VERTICAL BAR.
AS YOU CAN SEE, ABOUT 10 TO 20%
OF WOMEN REPORT HOT FLASHES LONG
BEFORE ONSET OF MENOPAUSAL
TRANSITION, 8 YEARS BEFORE,
REPORTING INCREASE AS WOMEN MOVE
ACROSS MENOPAUSAL TRANSITION,
JUMPS AFTER FMP, WOMEN WERE
UNAWARE.
THE SAME GRAPH SORTED BY RACE
AND ETHNICITY.
BLACK WOMEN IN GREEN REPORTED
HIGHER PROBABILITIES ACROSS
TIME, PRE-MENOPAUSEALLY, DURING
TRANSITION, AND
POST-MENOPAUSEALLY.
WITH EVEN PRE-MENOPAUSAL, 20 TO
30% PROBABILITY OF REPORTING HOT
FLASH.
SWAN HAS LOOKED AT THIS QUESTION
EXTENSIVELY AND DOCUMENTED
SEVERAL WAYS WHICH BLACK WOMEN
SEE BURDEN EXCEEDING THAT OF
WHITE WOMEN.
INCIDENTS OF VASOMOTOR SYMPTOMS
GREATER IN BLACK WOMEN, GREEN
LINE, THAN WHITE PARTICIPANTS IN
THE BLACK LINE OR OTHER WOMEN AT
ANY STAGE OF THE TRANSITION.
WE'VE LEARNED FROM SWAN HOT
FLASHES LAST MUCH LONGER THAN
PREVIOUSLY BELIEVED.
BLACK WOMEN EXPERIENCE ON
AVERAGE 10 YEARS, COMPARED TO
6.5 IN WHITE WOMEN.
LOWER EDUCATIONAL ATTAINMENT,
GREATER PERCEIVED STRESS WERE
RELATED TO LONGER DURATION OF
VMS, DESPITE SYMPTOM BURDEN
BLACK WOMEN, HALF AS LIKELY AS
WHITE WOMEN TO USE HT.
IN THIS LONGITUDINAL TRAJECTORY
ANALYSIS WOMEN ARE GROUPED BY
PATTERNS THEY REPORT.
AGAIN, INDEXED ON FMP TIME, TWO
GROUPS.
SYMPTOMS INCREASE AS WOMEN REACH
FMP, AND DECLINE, ONE WITH
LOWER, ONE WITH HIGHER LEVEL OF
SYMPTOMS.
HOWEVER, 26% OF WOMEN HAVE
CONSISTENTLY HIGH PROBABILITY OF
SYMPTOMS FROM LONG BEFORE TO
LONG AFTER THE FINAL MENSTRUAL
PERIOD WITH FOURTH GROUP HAVING
SYMPTOMS HIGH BEFORE, RAPID
DECLINE POST.
BLACK WOMEN THREE-FOLD HIGHER
ODDS THAN WHITE WOMEN.
WE LOOKED AT CHRONIC
DISCRIMINATION, AVERAGE
DISCRIMINATION ACROSS THE SWAN
VISITS.
THIS SHOWS INCREASED RISK OR
ODDS OF VMS, TRAJECTORIES AFTER
ADJUSTMENT FOR AGE, RACE,
ETHNICITY, BMI, SMOKING.
COMPARED TO WOMEN WHO HAD LOW
LEVEL WITH FMP ONSET, WOMEN WITH
CONTINUOUSLY HIGH AND DECLINE
POST FMP HIGH FMP ON SET WERE
MORE LIKELY TO REPORT BEING IN
THOSE CATEGORIES WHEN THEY
REPORTED HIGHER LEVELS OF
CHRONIC DISCRIMINATION.
ANOTHER EXAMPLE, SLEEP.
WHEN WE ASSESS SLEEP USING
ACTIGRAPHY, WE OBSERVED
DISPARITIES IN SLEEP QUALITY.
BLACK WOMEN HAD SHORTER SLEEP,
40% VERSUS 19% OF WHITE WOMEN.
BLACK WOMEN HAVE MORE
INTERRUPTED SLEEP AND TOOK
LONGER TO FALL ASLEEP.
WITH EVERYDAY DISCRIMINATION
ASSOCIATED WITH INCREASED WAKE
AFTER SLEEP ONSET.
AND THESE DIFFERENCES PERSIST
AFTER ADJUSTMENT FOR AGE, USE OF
SLEEP MEDICATIONS, MEASURES OF
SOCIAL DISADVANTAGE, INCLUDING
EDUCATION AND EMPLOYMENT, AND
WERE MEDIATED BY FINANCIAL
HARDSHIP, STRESSFUL LIFE EVENTS,
ACTIVITY, VMS.
BLACK WHIM ENTERED THE
TRANSITION WITH A MORE ADVERSE
CARDIOVASCULAR --
CARDIOMETABOLIC HEALTH BURDEN.
AT ENROLLMENT BLACK WOMEN WERE
MORE LIKELY TO REPORT POOR
SELF-REPORTED HEALTH, MORE
LIKELY TO BE OBESE, MORE LIKELY
TO HAVE DIABETES, METABOLIC
SYNDROME, HYPERTENSION, HIGHER
ALLOSTATIC LOAD, HIGHER
INCIDENCE AND EARLIER ONSET OF
CARDIOMETABOLIC DISEASE.
WE FOUND EVIDENCE OF RISK
FACTORS BY RACE/ETHNICITY.
WITH DEPRESSION INCREASED, LOADS
OF DIABETES IN BLACK BUT NOT
WHITE WOMEN, DISCRIMINATION
INCREASED ODDS OF CORONARY
ARTERY DISEASE IN BLACK WOMEN.
BLACK WOMEN ONLY DEATHS OF
FAMILY AND FRIENDS RELATED TO
CRUET IT IMT.
WE'VE DOCUMENTED DISPARITIES IN
TIMING OF REPRODUCTIVE AGING,
BURDEN OF VMS, OTHER SYMPTOMS,
AND TIMING AND BURDEN OF
CARDIOMETABOLIC DISEASE.
IN SOME INSTANCES THESE
DISPARITIES COULD BE ACCOUNTED
FOR BLACK-WHITE DIFFERENCE,
CLUSTERING OF RISK FACTORS WITH
SOCIAL DISADVANTAGE, AMONG BLACK
PARTICIPANTS.
IN OTHERS, BLACK WOMEN WERE
DIFFERENTIALLY VULNERABLE TO
IMPACTS OF DEPRESSION AND
PSYCHOSOCIAL RISK FACTORS ON
CARDIOMETABOLIC DISEASE, TO SOME
EXTENT REFLECTING DIFFERENCE IN
EXPOSURE PROFILES, AS WELL AS
SUGGESTING A NEED FOR WITHIN
RACE ANALYSES TO BE CONDUCTED.
I'D LIKE TO ADDRESS SOME
CRITICAL GAPS IN SCIENTIFIC
KNOWLEDGE.
FOLLOWING UP ON DR. GREENDALE'S
COMMENTS, KNOWING YOUR FMP AGE
DOES MATTER.
AND WE HAVE UNFINISHED BUSINESS.
TO UPDATE THE CRITERIA,
INCORPORATE THE LARGE BODY OF
INFORMATION WE NOW HAVE ABOUT
AMH AS CRITICAL MARKER OF THE
APPROACH OF MENOPAUSE IN THE
STAGING SYSTEM FOR REPRODUCTIVE
AGING IN WOMEN.
CRITICAL FOR UNDERSTANDING WOMEN
WITH HYSTERECTOMY, AND COULD BE
QUITE CRITICAL FOR WOMEN WITH
CHRONIC DISEASE AND HIV.
AND IN ADDITION, WE DO NEED TO
DEVELOP A VALIDATED
QUESTIONNAIRE THAT CAN IDENTIFY
ONSET OF EARLY AND LATE
TRANSITION.
SECOND, WE NEED TO HAVE MORE
DISCUSSION AND INVESTIGATION
INTO WHETHER HOT FLASHES WOMEN
ARE REPORTING ARE INDEED
MENOPAUSAL.
WE NEED TO ASK ARE THESE WOMEN
WITH SUSTAINED HIGH HOT FLASHES
EXPERIENCING MENOPAUSAL HOT
FLASHES OR DO THEY BEGIN BEFORE
AND CONTINUE AFTER HAVE A
DIFFERENT ETIOLOGY?
WE SEE THE SAME GRAPH OF
MULTI-REPORTS OF HOT FLASHES, IN
RED, NO USE IN BLUE.
NOTABLY HT USERS ARE LESS LIKELY
TO REPORT HOT FLASHES AFTER FMP,
HT HAD MUCH LESS OR LITTLE
EFFECT ON REPORT OF HOT FLASHES
PRIOR TO FMP.
THAT RAISES THE QUESTION WERE
HOT FLASHES IN EARLY TRANSITION
STAGE ARE MENOPAUSAL OR DO THEY
HAVE DIFFERENT ETIOLOGY?
IT RAISES THE QUESTION TO WHAT
EXTENT IS HORMONE THERAPY
EFFECTIVE TREATMENT FOR
PRE-MENOPAUSAL VMS, IF NOT DO
RISKS OUTWEIGH THE BENEFITS.
I WOULD LIKE TO ADDRESS THE
QUESTION, WHERE IS THE SCIENCE
ON BLEEDING AND MENOPAUSE IN OUR
STUDIES?
IT WAS INTERESTING TO ME IN THE
MANY, MANY JOURNALISTS I'VE
SPOKEN TO SINCE THE PUBLICATION
OF OUR ARTICLE ON THE
BLACK-WHITE DISPARITIES, NOT ONE
HAS ASKED ABOUT OR EXPRESSED
INTEREST IN WHEN I MENTIONED THE
PROBLEM OF EXCESSIVE BLEEDING OR
ISSUE OF THE IMPACT OF BLEEDING
CHANGES IN THE MENOPAUSAL
TRANSITION, ON WOMEN'S QUALITY
OF LIFE OR HEALTH.
WE'VE KNOWN SINCE THE 196 4
WOMEN APPROACHING MENOPAUSE ARE
LIKELY TO EXPERIENCE HEAVY
BLEEDING, AND WE'VE DOCUMENTED
INCREASE IN THE EPISODES OF
PROLONGED GREATER THAN 10 DAYS
OR VERY HEAVY BLEEDING FOR THREE
OR MORE DAYS IN SWAN IN THE
MENOPAUSAL TRANSITION.
THREE OR MORE EPISODES OF
PROLONGED BLEEDING WERE REPORTED
BY THREE IN FOUR WOMEN, ONE IN
FIVE REPORTED THOSE THREE
EPISODES WITHIN A SIX-MONTH
PERIOD CONSISTENT WITH
DEFINITIONS.
THREE OR MORE OF VERY HEAVY
BLEEDING REPORTED BY ONE IN
THREE, DESPITE EXCLUSION OF MANY
WOMEN WHO HAVE A HYSTERECTOMY
BEING INELIGIBLE.
ONE IN SEVEN HAD THREE-PLUS
EPISODES IN A SIX-MONTH PERIOD.
ABNORMAL BLEEDING IS ASSOCIATED
WITH HIGHER RISK OF HYSTERECTOMY
AND CONSEQUENCES BUT WHY ARE WE
NOT CONNECTING IMPACT OF HEAVY
BLEEDING TO RISKS OF ANEMIA AND
ITS CONSEQUENCES, COGNITIVE FOG.
I RAN THESE IN PREPARATION FOR
TODAY'S TALK, ADJUSTMENT OF
FATIGUE AND HEAVY BLEEDING IN
SIX MONTHS.
WOMEN WITH THREE OR MORE DAYS OR
THREE PLUS TIMES IN SIX MONTHS
MORE LIKELY TO REPORT BEING
TIRED OR WORN OUT, EDUCATIONAL
EFFORTS ARE NEEDED TO
INCORPORATE INFORMATION ON RISK
OF EXCESSIVE BLEEDING DURING
THIS LIFE STAGE, AND WOMEN NEED
THIS INFORMATION TO KNOW WHAT TO
EXPECT AS WELL AS TO SEEK
APPROPRIATE CARE FOR BLEEDING
AND ITS MYRIAD CONSEQUENCES.
I WOULD URGE RESEARCHERS TO
FOCUS ON BLEEDING AND
RELATIONSHIP TO SYMPTOMS AND
HEALTH CARE OUTCOMES.
I'D LIKE TO ACKNOWLEDGE GRANT
SUPPORT.
I DO NOT HAVE FINANCIAL
DISCLOSURES.
AND THANK YOU VERY MUCH.
>> THANK YOU FOR THE
PRESENTATION.
I HAVE THE PLEASURE OF
INTRODUCING OUR NEXT SPEAKER,
YAMNIA CORTES, ASSISTANT
PROFESSOR UNIVERSITY OF NORTH
CAROLINA AT CHAPEL HILL SCHOOL
OF NURSING SHARE HER WORK AROUND
EXPERIENCES IN SOCIAL
DETERMINANTS OF MENOPAUSE AMONG
LATINAS.
>> GOOD AFTERNOON.
THANK YOU.
IT'S A PLEASURE TO JOIN YOU AND
DISCUSS EXPERIENCES AND SOCIAL
DETERMINANTS OF MENOPAUSE AMONG
LATINAS.
AN OVERVIEW OF MY PRESENTATION,
BEGINNING WITH DEFINITIONS OF
KEY TERMS AND BACKGROUND, THEN
MOVE TO DISCUSSING EXPERIENCES,
DISPARITIES WE'VE NOTED, AND KEY
FACTORS OF SOCIAL DETERMINANTS
OF HEALTH AND MENOPAUSE,
CONCLUDING WITH FUTURE
DIRECTION.
I WILL USE THE TERM HISPANIC AND
LATINA INTERCHANGEABLY TO REFER
TO PERSONS LIVING IN THE UNITED
STATES AND HAVING ROOTS
PRIMARILY IN SPANISH-SPEAKING
PARTS OF LATIN AMERICA AND THE
CARIBBEAN, BUT WE ALSO KNOW
PEOPLE WITH ROOTS IN SPAIN AND
NON-SPANISH-SPEAKING PARTS OF
LATIN AMERICA AND CARIBBEAN MAY
ALSO IDENTIFY AS HISPANIC AND
LATINO.
TERMINOLOGY IS IMPORTANT.
AS YOU CAN SEE BY RESEARCH IN
THE PEW RESEARCH CENTER
HISPANICS HAVE A MIXED VIEW HOW
THEY DESCRIBE THEIR IDENTITY,
WITH A PREFERENCE, OR NO
PREFERENCE BETWEEN HISPANIC OR
LATINO, SO IT'S ALWAYS IMPORTANT
TO GET AN IDEA HOW PEOPLE PREFER
TO IDENTIFY.
IT'S IMPORTANT TO THINK ABOUT
THE FACT LATINOS ARE NOT A
HOMOGENOUS GROUP.
THE HETEROGENEOUS GROUP WITH
DIFFERENT NATIONALITY, LANGUAGE,
SOCIAL AND HISTORIC CONTEXT, AND
IMMIGRATION AND -- SORRY,
MIGRATION POLICIES THAT IMPACT
MENOPAUSE EXPERIENCE AND HEALTH.
LATINAS REMAINED
UNDERREPRESENTED IN MENOPAUSE
RESEARCH.
THEY CONSTITUTE 20% OF MID-LIFE
PEOPLE IN THE U.S., MAKE UP LESS
THAN 10% OF PARTICIPANTS IN MOST
STUDIES, WITH THE EXCEPTION
BEING THE SAN FRANCISCO MID-LIFE
WOMEN'S HEALTH STUDY.
IT'S IMPORTANT TO NOTE HISPANIC
COMMUNITY HEALTH STUDY IS NHLBI
BUT NOT A MENOPAUSE STUDY.
IN ORDER TO PROVIDE CULTURALLY
RELEVANT EDUCATION AND CLINICAL
CARE IT'S NECESSARY TO
UNDERSTAND THEIR EXPERIENCE,
THEIR DEFINITION, SO HERE I
PROVIDE EXAMPLES FROM SEVERAL
QUALITATIVE STUDIES, THREE, EACH
REPRESENT THREE THEMES THAT WE
SEE IN THE LITERATURE.
ONE IS CAMBIO DE VIDA,
DESCRIBING MEN TAUS AS --
MENOPAUSE AS A CHANGE OF LIFE.
IT'S LIKE ENTERING A NEW PHASE
IN YOUR LIFE, YOUR BODY IS GOING
TO CHANGE, IRREGULARITY, SOME
SUBTHEMES THAT ALSO COME ALONG
WITH IT, NOT ONLY IS IT THAT
LATINOS VIEWS IT AS A NORMAL
STAGE OF LIFE BUT WE KNOW FOR
THIS REASON MENOPAUSE AND
THINKING ABOUT MENOPAUSE
SYMPTOMS AND SEEKING MENOPAUSE
CARE IS NOT REALLY A PRIORITY.
AND YOU'RE TOLD TO BEAR IT
BECAUSE THAT'S LIFE, AND YOU
JUST HAVE TO MOVE ON.
AND ANOTHER IMPORTANT THING THAT
WE ACTUALLY SEE IS EMERGENCE OF
ISSUES, HEALTH ISSUES DURING
MENOPAUSE TRANSITION.
AND ONE OF THE QUOTES IS I WENT
THROUGH THIS, MEN MENOPAUSE, TD
50, EVERYTHING CHANGED.
BEGINNING TO NOTE THERE ARE
CHANGES BEING ASSOCIATED WITH
MENOPAUSE BUT NOT TRULY
UNDERSTANDING WHAT IS AND IS NOT
MENOPAUSE SYMPTOM.
OR HOW TO MANAGE THESE SYMPTOMS.
AND MOST RECENTLY IN FOCUS
GROUPS WE CONDUCTED IN NORTH
CAROLINA, WE ALSO NOTED
PARTICIPANTS WANTED MORE
INFORMATION ABOUT MENOPAUSE
ESPECIALLY FROM HEALTH PROVIDERS
BECAUSE INFORMATION IS POWER.
NOW I'M ASKING QUESTIONS ABOUT
MENOPAUSE PERHAPS BECAUSE WE'VE
COME TO THIS COUNTRY, IN HOME
COUNTRY PEOPLE ARE RESERVED,
WOMEN MOVE TO THE U.S. AND IT
CHANGES THEIR THOUGHT PROCESS.
THEY FEEL IN THE UNITED STATES
CONVERSATION IS MORE OPEN.
OF COURSE IT'S IMPORTANT TO NOTE
THESE EXPERIENCES DIFFER BY
GEOGRAPHIC SETTING, LATINO
SUBGROUP, ACCULTURATION,
EDUCATION LEVEL, AND MENOPAUSE
KNOWLEDGE.
OUR FOCUS GROUPS IN NORTH
CAROLINA, THEY WERE CONDUCTED
AMONG WOMEN WHO WERE BETWEEN 35
AND 60, WHO HAD EXPERIENCED
MENOPAUSE OR THOSE THAT WERE
THINKING THROUGH WHAT WOULD BE
QUESTIONS OR EXPECTATIONS.
WE CONDUCTED A SURVEY AND FOUND
THAT 79% OF PARTICIPANTS VIEWED
MENOPAUSE POSITIVELY, IT MEANS
NO MORE PERIODS, NO MORE WORRY
ABOUT CONTRACEPTION, 60% VIEW
HORMONE THERAPY NEGATIVELY.
55% REPORT LITTLE KNOWLEDGE
ABOUT MENOPAUSE AND ONLY 24%
SAID THEY GET INFORMATION FROM A
HEALTH PROVIDER.
WHICH IS AN IMPORTANT GAP I'LL
DISCUSS LATER.
FOLLOWING UP ON DR. HARLOW, WE
FIND LATINAS DO EXPERIENCE
MENOPAUSE AT YOUNGER AGE, 50.9
VERSUS 52.9 AND 53.1, AND A
LONGER DURATION OF VASOMOTOR
SYMPTOMS.
SO 8.9 YEARS VERSUS 6.5, AND 4.8
IN JAPANESE WOMEN.
HOWEVER DR. HARLOW MENTIONED
THESE APPLIED ONCE WE ADJUST FOR
LIFESTYLE AND SOCIOECONOMIC
SUGGESTING IMPORTANCE IN
MID-LIFE HEALTH.
IN TERMS OF SYMPTOMS, A SURVEY
FOUND 50% OR MORE LATINAS REPORT
WEIGHT GAIN, FEELING
HOT-CONTROLLED, FATIGUE, SLEEP
DIFFICULTY SLEEPING.
NOW, THIS COULD BE BECAUSE THIS
IS A CROSS-SECTIONAL SURVEY,
MORE DIFFERENCE NOTED WHEN
LOOKING AT SEVERITY OF SYMPTOM,
OR INDIVIDUALS SUGGEST THIS IS
EVIDENCE OF THE LATINO HEALTH
PARADOX.
LATINO HEALTH PARADOX SUGGESTS
DESPITE SOCIOECONOMIC
DISADVANTAGES LATINOS DISPLAYED
HEALTH OUTCOMES COMPARABLE TO
NON-LATINO WHITE PERSONS.
IF YOU THEN BEGIN TO LOOK AT
LATINOS INSTEAD OF AS A GROUP,
AND DISAGGREGATE THAT
INFORMATION, THE PICTURE BECOMES
CLEARER.
THIS IS EVIDENCE WHEN WE LOOK AT
DATA FROM SWAN NEW JERSEY, THE
STUDY SITE THAT RECRUITED
LATINAS.
THE GRAPH ON THE LEFT COMPARED
SYMPTOMS BETWEEN LATINAS AS A
GROUP TO NON-LATINA WHITE WOMEN.
GRAPH ON THE RIGHT LOOK AT
LATINA DISAGGREGATED.
ON LEFT SMALL OR NO DIFFERENCE
ESPECIALLY SLEEP DISTURBANCE.
ON THE RIGHT THOUGH WE BEGIN TO
SEE DIFFERENCES IN TERMS OF
VAGINAL DRYNESS, VASOMOTOR
SYMPTOMS, AND THEN FOR SLEEP
DISTURBANCES, WHEN YOU LOOK AT
LATINO AS A WHOLE, 50%,
DISAGGREGATE AMONG DOMINICANS
AND PUERTO RICAN 66.1, 64%
COMPARED TO 49.7.
AND SO THIS IS SUGGESTING
IMPORTANCE OF LOOKING, COMPARING
ACROSS SUBGROUPS, BUT THEN ALSO
THINKING THROUGH THE DIFFERENT
FACTORS THAT MIGHT IMPACT THESE
DIFFERENCES.
IN A RECENT REVIEW WE DEVELOPED
CONCEPTUAL FRAMEWORK, BASED ON
THE NIMHD MINORITY HEALTH AND
HEALTH DISPARITIES RESEARCH
FRAMEWORK, HIGHLIGHTING DRIVERS
HEALTH INEQUITIES, SOME HAVE
BEEN DISCUSSED IN PRESENTATIONS
TODAY.
AND THE FOLLOWING SLIDE I'M
GOING TO FOCUS ON THE
SOCIOCULTURAL ENVIRONMENT AND
HEALTH CARE SYSTEM DUE TO TIME.
AND SO ONE FACTOR MOST STUDIES
HAVE EVALUATED TO EXPLAIN
DIFFERENCES BETWEEN LATINAS IS
ACCULTURATION.
ACCULTURATION IS PROCESS BY
WHICH INDIVIDUALS ADAPT TO A NEW
LIVING ENVIRONMENT AND ADAPT
VALUES, BELIEFS, NORMS OF THAT
SOCIETY.
ACCULTURATION HAS BEEN RELATED
TO MENOPAUSE, LOWER
ACCULTURATION RELATED TO MORE
POSITIVE OUTCOMES, LONGER TIME
IN THE U.S. IT'S BEEN RELATED TO
MORE SLEEP DISTURBANCE BUT AT
THE SAME TIME BEING BORN OUTSIDE
THE UNITED STATES HAS BEEN
ASSOCIATED WITH MORE SLEEP
DISTURBANCES.
ONE REASON WE MIGHT SEE THESE
INCONSISTENCIES IS BECAUSE A LOT
OF THE STUDIES ARE USING LINEAR
OR UNIDIMENSIONAL MEASURES OF
ACCULTURATION.
AND SO THE ASSUMPTION IS THAT IF
WE JUST USE LENGTH OF TIME IN
THE UNITED STATES, IT'S LINEAR,
EVERYONE ACCULTURATES THE SAME
WITH EACH YEAR, AMOUNT OF
DURATION IN THE UNITED STATES,
THAT DOESN'T TAKE INTO ACCOUNT
GEOGRAPHIC SETTING, WHETHER OR
NOT YOU HAVE RESOURCES IN
SPANISH OR YOU'RE ONE OF A FEW
LATINOS IN A COMMUNITY VERSUS
LIVING IN A COMMUNITY WHERE
THERE ARE A LOT OF RESOURCES AND
OTHER PEOPLE THAT ARE ALSO
LATINO, SPEAK SPANISH, SO YOU
MIGHT HAVE A DIFFERENT
ACCULTURATION EXPERIENCE.
THE OTHER THING I WANTED TO
MENTION ABOUT THIS AS WELL IS
THAT ACCULTURATION SOMETIMES IS
ALSO RELATED TO, IN OUR STUDIES,
WITH BEHAVIOR.
AND IT CAN SHIFT AWAY -- IT'S
IMPORTANT TO LOOK AT BUT CAN
SHIFT AWAY THE FOCUS FROM SOME
OF THE SOCIAL AND STRUCTURAL
FACULTIORS ALSO RELATED TO
MENOPAUSE SYMPTOMS AND FOR
EXAMPLE AS I MENTIONED
IMMIGRATION STATUS IS SOMETIMES
USED AS A PROXY FOR
ACCULTURATION BUT IMMIGRATION
WITHIN ITSELF IS A SOCIAL
DETERMINANT OF HEALTH,
EXISTING -- BEING --
IMPLICATIONS OF IMMIGRATION
STATUS ARE THAT IT DETERMINES
WHAT KIND OF EMPLOYMENT YOU GET,
WHAT KIND OF HOUSING, ACCESS TO
CARE AND HEALTH CARE, FEAR OF
DEPORTATION, TENSION, FEELING
SOCIAL ISOLATION AND
IMPORTANTLY, IN TERMS OF ACCESS
ISSUE WE'VE SEEN LATINOS HAVE
HIGHEST RATE OF UNINSURANCE IN
THE U.S., ABOUT 18%.
IN NORTH CAROLINA, IT'S 40%,
AMONG WOMEN IN THE STUDY I
CONDUCTED IT'S 60%.
THESE ARE NOT INDIVIDUALS THAT
WE'RE ALSO SEEING IN OUR HEALTH
CARE PRACTICES, OR IN OUR
RESEARCH STUDIES, WHICH IS ONE
OF THE GAPS THAT I WANTED TO
HIGHLIGHT.
AS WE KNOW, UNINSURED WOMEN HAVE
LESS ACCESS TO SCREENING,
COMPARED TO WOMEN WITH HEALTH
INSURANCE UNINSURED WOMEN REPORT
MORE BOTHERSOME MENOPAUSE
SYMPTOMS.
SOME ARE ANXIETY AND DEPRESSION,
TRANSITIONING TO THE NEXT SLIDE,
IN SWAN, YOU'RE ALL FAMILIAR
WITH THIS STUDY BY NOW, BASELINE
SWAN SHOWED 43% OF LATINAS HAD
DEPRESSIVE SYMPTOMS COMPARED TO
14 TO 27 OF WOMEN IN OTHER
GROUPS.
WHEN EVALUATING DEPRESSION
SYMPTOMS ACROSS 50 YEARS LATINAS
FOLLOWED A HIGH TRAJECTORY OF
SYMPTOMS, AND FACTORS WERE
HAVING MORE FINANCIAL HARDSHIP,
MORE FREQUENT VASOMOTOR
SYMPTOMS, MORE STRESSFUL LIFE
EVENTS, SLEEP DISTURBANCE, LOWER
SOCIAL SUPPORT.
ALL OF THESE WE ACTUALLY KNOW
ARE RELATED TO ADDITIONAL
CONDITIONS SUCH AS
CARDIOVASCULAR DISEASE.
IN OUR PILOT WORK DURING THE
MENOPAUSE TRANSITION,
PERIMENOPAUSAL, EXPERIENCED
HIGHER EVERYDAY DISCRIMINATION,
MORE SLEEP DISTURBANCE, HIGHER
SYSTOLIC BLOOD PRESSURE, HIGHER
BLOOD PLY COAST, HIGHER
EDUCATION, CONSISTENT WITH OTHER
STUDIES.
THE EDUCATION WAS SURPRISING,
BUT WE ALSO FOUND WOMEN WITH
HIGHER EDUCATION WERE ALSO
INDIVIDUALS WHO REPORTED MORE
EVERYDAY DISCRIMINATION.
THESE ARE FINDINGS THAT
UNDERSTORE NEED TO REEVALUATE
ROLE OF THE SOCIAL ENVIRONMENT
IN MENOPAUSE.
IN THE BEGINNING OF THE
PRESENTATION I PRESENTED
FINDINGS FROM OUR FOCUS GROUPS
WHICH INDICATED 24% OF LATINAS
SOUGHT INFORMATION ABOUT
MENOPAUSE FROM HEALTH CARE
PROVIDER.
AND I'VE DISCUSSED ACCESS MAY BE
ONE REASON.
EVEN AMONG INDIVIDUALS WITH
ACCESS WE SEE THE EXPECTATIONS
ARE NOT BEING MET, OR THERE'S
THIS DISCORDANCE.
ONE QUOTE IS, FOR ME, IT WOULD
HAVE BEEN BETTER IF THE DOCTOR
TOLD ME ABOUT ALL THIS,
MENOPAUSE, BEFORE I WENT TO ASK
ABOUT MY SYMPTOMS.
PROVIDER EXPECT PATIENTS WILL
ASK QUESTIONS, COMMENT, ASK
ABOUT MENOPAUSE, DISCUSS
SYMPTOMS THEY ARE HAVING AND
PATIENTS, ACCORDING TO SOME
FOCUS GROUPSR EXPECTING THE
PROVIDER WILL BE THE ONES TO
BRING UP THE TOPIC BUT ONLY 6.8%
OF RESIDENTS FEEL PREPARED.
AND HEALTH CARE PROVIDERS ARE
RELUCTANT TO PROVIDE INFORMATION
TO IMMIGRANT WOMEN DUE TO LACK
OF TIME, LACK OF KNOWLEDGE, LACK
OF CONFIDENCE IN CULTURALLY
COMPETENT COMMUNICATION.
WE HAVE LACK OF ACCESS TO
PROVIDERS, CULTURALLY
APPROPRIATE CARE, AND THIS
CONTRIBUTES TO THIS CONFUSION
ABOUT MENOPAUSE, WHAT TO EXPECT,
AND WHAT ARE MANAGEMENT
STRATEGIES, WHETHER THIS
MISTRUST IS APPROPRIATE FOR AN
INDIVIDUAL.
LATINAS ARE UNDERREPRESENTED IN
MENOPAUSE RESEARCH.
WE KNOW DISPARITIES EXIST
BETWEEN LATINAS AND WHITE WOMEN
AND WITHIN THE SUBGROUPS.
ACCULTURATION IS ONE IMPORTANT
FACTOR BUT IT ONLY SCRATCHES THE
SURFACE.
WE NEED MORE ADDITIONAL MEASURES
OF ACCULTURATION BUT ALSO NEED
TO GO BENEATH THAT TO LOOK
CLOSER AT THE CONTEXT,
GEOGRAPHIC SETTING, IMMIGRATION,
EDUCATION, EMPLOYMENT.
THERE'S A NEED FOR GREATER
ACCESS TO CULTURALLY RELEVANT
HEALTH CARE INFORMATION FOR
LATINAS AND TO FURTHER EVALUATE
SOCIAL AND COMMUNITY CONTEXT,
HOW THAT IMPACTS MENOPAUSE
EXPERIENCE, SO SOCIAL SUPPORT,
SOCIAL ISOLATION, HOW DOES YOUR
FAMILY VIEW MENOPAUSE?
FUTURE DIRECTIONS, WE NEED
RECRUITMENT IN RESEARCH, MOVING
BEYOND INDIVIDUAL LEVEL FACTORS
AND BEHAVIORS, TO GET AT SOME
MECHANISMS IN TERMS OF SOCIAL
DETERMINANTS OF HEALTH,
INCREASING ACCESS TO HEALTH
CARE, INCREASING AVAILABILITY OF
CULTURALLY RELEVANT EDUCATION
FOR PATIENTS AND PROVIDERS, AND
THINKING THROUGH HOW WE'RE
DISSEMINATING AND IMPLEMENTING
KNOWLEDGE.
ARE WE DISSEMINATE NATURING OUR
RESEARCH INFORMATION IN
LOCATIONS WHERE THE PUBLIC WILL
HAVE ACCESS IN A FORMAT THAT'S
AVAILABLE AND EASY TO
UNDERSTAND, LANGUAGE THAT IS
PREFERRED BY INDIVIDUALS WHO WE
WANT TO IMPACT?
THANK YOU TO EVERYONE AND ALSO
JUST SHOW A FEW PICTURES OF MY
RESEARCH TEAM AND ALL THE WORK
THEY ARE DOING.
SO THANK YOU.
>> THANK YOU, DR. CORTES, FOR
THAT IMPORTANT WORK.
WE APPRECIATE IT.
I HAVE THE PLEASURE OF
INTRODUCING DR. SUSAN FRIEDMAN,
FACING OUR RISK OF CANCER
EMPOWERED, AND SHE WILL BE
GIVING US A PATIENT PERSPECTIVE.
>> TOUGH ACTS TO FOLLOW.
I'M GOING TO SWITCH GEARS AND
TALKING MORE ABOUT MY OWN
EXPERIENCE WITH EARLY ONSET
MENOPAUSE, SURGICAL MENOPAUSE,
SO THE POPULATION THAT DR.
NORQUIST WAS TALKING ABOUT
EARLIER AND EXPERIENCE AT FORCE,
A NATIONAL NON-PROFIT
ORGANIZATION.
HERE IS OUR QR CODE.
IT'S AN ORGANIZATION FOR PEOPLE
AT RISK OF HEREDITARY CANCER.
MANY PEOPLE IN OUR COMMUNITY
THAT WE SERVE ARE PEOPLE WHO ARE
LOOKING AT RISK FOR OVARIAN AND
GYNECOLOGIC CANCER AND MAKING
THESE DECISIONS.
MY PERSONAL EXPERIENCE, THIS WAS
ME BEFORE CANCER.
I WAS A VETERINARIAN, EARLY IN
MY CAREER I WAS A NEW MOM, JUST
STARTING OUT.
I DIDN'T HAVE A FAMILY HISTORY
OF CANCER, DIDN'T EXPECT IT.
IT HIT ME OUT OF THE BLUE I
DIDN'T HAVE RESOURCES EARLY IN
MY CAREER, FOCUSING ON MY
FAMILY, AND NOT THINKING ABOUT
CANCER, NONE OF MY PEERS WERE
EXPERIENCING IT.
I WAS GETTING READY TO HAVE A
SECOND CHILD WHEN I WENT DOWN
THE LIST OF THINGS TO DO WITH
YOUR HEALTH AND BECAUSE OF A
PRIOR LUMP I FELT I WAS HAVING
MAMMOGRAMS AND SO A MAMMOGRAM
RIGHT BEFORE I GOT PREGNANT
SHOWED ABNORMALITIES THAT LED TO
DIAGNOSIS OF CANCER.
I ENDED UP WITH A QUESTIONING
RECURRENCE, COMPREHENSIVE CANCER
CENTER, A FEW OTHER THINGS
HAPPENED WHERE I DIDN'T
NECESSARILY GET THE TYPE OF CARE
THAT I NEEDED.
AND EVEN THOUGH I WAS PRIVILEGED
TO HAVE MEDICAL KNOWLEDGE AND
MEDICAL BACKGROUND THERE WAS
STILL A LOT I DIDN'T KNOW.
THIS WAS PRETTY HARD TO
NAVIGATE.
I LEARNED FROM A MAGAZINE
ARTICLE ABOUT HEREDITARY
CANCERS, BACK IN 1997 WHEN I WAS
FIRST DIAGNOSED, TESTING FOR
BRCA WAS EARLY BUT I FOUND OUT I
HAD MANY OF THE RED FLAGS FOR A
HEREDITARY CANCER SYNDROME.
SO AFTER MY RECURRENCE, AFTER
LEARNING ABOUT HEREDITARY CANCER
RISK, I ENDED UP AT A CANCER
CENTER.
HALF WHICH THROUGH CHEMOTHERAPY
I FOUND I HAD A BRCA2 MUTATION.
SO, AFTER I FINISHED TREATMENT,
AFTER CHEMOTHERAPY AND
RADIATION, I HAD A UNILATERAL
MASTECTOMY, MY THOUGHTS TURNED
TOWARD MY REMAINING RISK FOR
OVARIAN CANCER, FOR BREAST
CANCER, AT THE TIME THAT I
FINISHED TREATMENT I WAS 35.
I DIDN'T WANT TO BE DIAGNOSED
WITH BREAST CANCER OR ANY CANCER
AGAIN.
IN TALKING TO MY DOCTORS IT WAS
REALLY AGAIN PRETTY EARLY IN
GENETIC TESTING, WHAT WE KNEW,
THE KNOWLEDGE DR. NORQUIST WAS
TALKING ABOUT WITH LONG-TERM
OUTCOMES, IMPROVED SURVIVAL,
EVEN THINGS LIKE THAT WOMEN WITH
BRCA2 MUTATIONS MIGHT BE ABLE TO
DELAY OOPHORECTOMY, WE DIDN'T
KNOW THAT.
I HAD TO MAKE DECISIONS IN A
VACUUM.
IN A DATA-FREE ZONE.
I FELT FAIRLY UNPREPARED TO MAKE
THAT DECISION.
I KNEW THAT I WOULD BE ENDING MY
FERTILITY BUT NOBODY HAD OFFERED
ME ANY FERTILITY PRESERVATION
OPTIONS.
I KNEW I WOULD GO THROUGH
MENOPAUSE AT 35 IF I WENT
THROUGH WITH SURGERY.
I WAS TOLD I COULD NEVER HAVE
HORMONES BECAUSE OF BREAST
CANCER, IT ENDED UP BEING AN
ER+, WE DIDN'T KNOW THAT AT THE
TIME, THERE WAS NO LONG-TERM
DATA.
AS AN ASIDE, THIS PHOTO WAS
TAKEN FROM THE CHAPEL AT THE
HOSPITAL WHERE I HAD MY SURGERY.
I REMEMBER THE NIGHT BEFORE
SURGERY, ADMITTED EARLY, THE
NIGHT BEFORE, NOT PARTICULARLY A
RELIGIOUS PERSON BUT I REMEMBER
GOING TO THE CHAPEL AND PRAYING
BECAUSE I WAS TERRIFIED ABOUT
WHAT THIS SURGERY WOULD MEAN FOR
ME.
AS I SAID, MY DOCTOR DIDN'T
PREPARE ME.
THIS WAS EARLY IN THE DAYS OF
INTERNET, DIDN'T HAVE A
COMPUTER.
I WENT TO THE BOOK STORE, FOUND
THIS BOOK, LIGHT-HEARTED
APPROACH TO MENOPAUSE, WRITTEN
BY AN AUTHOR WHO WAS GOING
THROUGH REALLY MENOPAUSE AT AN
AVERAGE AGE, AND SHE WAS TALKING
ABOUT HER EXPERIENCE.
I QUOTE FROM THE BOOK, JUST TO
POINT OUT HOW SHE WAS TRYING TO
MAKE IT LIGHT HARDED BUT IT WAS
REALLY HARD TO HEAR.
SAYING NOW SEX HAS ALL THE
EROTICISM AND PLEASURE OF A FULL
BODY WAX.
PARENTS ARE THE GHOSTS OF
CHRISTMAS FUTURE, FROM WHAT I'VE
SEEN MY FUTURE LOOKS SHORT AND
POROUS, TALKING ABOUT BONE
HEALTH.
I REMEMBER THROWING THIS BOOK
ACROSS THE ROOM.
AT THE END THE CONCLUSION WAS
SHE EXPERIENCED A LOT OF
NEGATIVE SIDE EFFECTS OF
MENOPAUSE, AND DECIDED TO GO ON
HORMONE REPLACEMENT AND HER LIFE
WAS WONDERFUL.
AND THAT WAS NOT GOING TO BE ME.
AT THE END OF THE DAY THE BOOK
WASN'T VERY HELPFUL.
I DIDN'T HAVE MUCH IN THE WAY OF
GUIDANCE OR ANY PEERS THAT I
KNEW GOING THROUGH THIS
EXPERIENCE.
SO I WENT THROUGH THIS
THREE-YEAR EXPERIMENT OF NO
HORMONES, AND I WENT TO A LOT OF
HEALTH CARE PROFESSIONALS.
THE BIGGEST SYMPTOMS WERE
FATIGUE, NO LIBIDO, JOINT PAIN,
DEPRESSION, HOT FLASHES, BONE
LOSS, BUT THE FATIGUE WAS SUCH A
QUALITY OF LIFE CONCERN.
I REMEMBER TALKING TO WHATEVER
EXPERTS, WHOEVER WOULD TALK TO
ME.
I WAS A CONFERENCE, I ASKED A
QUESTION OF A SPEAKER TALKING
ABOUT SEXUALITY, SPECIFICALLY
FOR WOMEN WITH BRCA MUTATION WHO
HAD OOPHORECTOMY, HAVE YOU SEEN
A CONNECTION BETWEEN SURGICAL
MENOPAUSE AND LACK OF LIBIDO,
NO, SHE HAD NOT SEEN THAT.
I WAS FATIGUED BECAUSE I WAS
DEPRESSED, I KNEW THIS WAS
DIFFERENT, HAVING EXPERIENCED
DEPRESSION.
NO, I'M DEPRESSED BECAUSE I'M
FATIGUED BUT I HAD MY
EXPERIENCES INVALIDATED BY THE
HEALTH CARE COMMUNITY.
AROUND THIS THREE-YEAR MARK I
HAD AN APPOINTMENT AT A
DEDICATED FATIGUE CLINIC, CANCER
CENTER WHERE AFTER EXAMINING ME
AND HEARING MY HISTORY THEY SAID
YOU HAVE CANCER FATIGUE.
I'M THREE YEARS OUT OF
TREATMENT!
THE EXPERT SAID WE SEE IT.
I ASKED, COULD THIS BE MENOPAUSE
RELATED?
THEY SAID NO.
I WAS FRUSTRATED BUT ALSO I WAS
CONVINCED MY SYMPTOMS WERE
MENOPAUSAL.
AN ENDOCRINOLOGIST AGREED, BUT
NO HORMONES, BREAST CANCER THAT
WAS ER+.
AROUND THE THREE-YEAR MARK, AGE
38, I REACHED MY LIMIT, WENT
THROUGH ALL THESE SURGERIES AND
GENETIC TESTING, CHEMO,
RADIATION, TREATMENT, TO TRY AND
NOT JUST LIVE LONGER BUT IMPROVE
QUALITY OF LIFE.
I TOLD A LOCAL DOCTOR IF HE DID
NOT PRESCRIBE HORMONES, NOT
BEING FACETIOUS, THAT I WOULD
PERSONALLY HOLD HIM ACCOUNTABLE
WHEN I FLUNG MYSELF OFF THE TOP
OF MY OFFICE BUILDING.
I LITERALLY SAID THAT, I
LITERALLY MEANT IT.
HE PRESCRIBED ME HORMONES THAT
DAY.
I HAVE OTHER ONCOLOGISTS TELLING
ME I WAS CRAZY, TO GO ON
HORMONES WITH EVERYTHING ELSE I
HAD DONE.
FOR ME IT WAS QUALITY OF LIFE
DECISION.
I DON'T ENDORSE THIS FOR OTHER
PEOPLE.
I WENT INTO THIS WITH FULL
KNOWLEDGE I TRIED EVERYTHING
ELSE.
INCLUDING I HAD BEEN PUT ON THIS
MEDICATION USED FOR PEOPLE WITH
NARCOLEPSY AND THAT DID NOT
HELP.
AFTER STARTING HORMONES, I WAS
AT A CONFERENCE, RUNNING FULL
TIME, I WAS AT A CONFERENCE, A
FOR
YOUNG WOMEN WITH BREAST CANCER,
RUNNING ON A TREADMILL AND
FEELING GOOD FOR THE FIRST TIME
IN THE LAST THREE YEARS.
ENERGY AND LIBIDO RESTORED, I
RECOGNIZED MYSELF FOR THE FIRST
TIME IN THREE YEARS.
NOT AN ENDORSEMENT BUT I'M STILL
ON ESTROGEN TO THIS DAY, AT AGE
60.
THIS IS THE EXPERIENCE OF THE
FORCE COMMUNITY.
WE'VE DONE SURVEYS AND
DOCUMENTED, EARLY SURGICAL
MENOPAUSE.
I HAD MEMBERS COME TO ME, I HATE
TO MAKE THIS DECISION WHETHER OR
NOT TO REMOVE MY OVARIES, MORE
WORRIED ABOUT MY DAUGHTER.
I REMEMBER WITH NAIVE CONFIDENCE
BACK THEN, I STARTED FORCE IN
2000, THIS IS OUR 25th YEAR,
WE'VE COME SO FAR THERE WILL BE
BETTER DECISIONS WHEN YOUR
DAUGHTER HAS TO MAKE THIS
DECISIONS WHICH THERE AREN'T.
WE'RE JUST NOT THERE YET.
THIS QUOTE ENCAPSULATES THE
WOMAN WHO IS 38 WITH BRCA1
MUTATION, THERE ARE INCREASED
RISK FOR OSTEOPOROSIS, HEART
DISEASE FROM PREMATURE REMOVAL,
AT LEAST THIS ACKNOWLEDGE THIS,
THIS WOMAN SAYING THIS IS A
HORRIBLE HARD THING BECAUSE NO
MATTER WHAT I DO THERE SEEMS TO
BE SUBSTANTIAL RISK.
SO DR. NORQUIST TALKED ABOUT THE
IDEA OF THE FALLOPIAN TUBES,
EXCITING RESEARCH, THE FIRST
PUBLICATION I SAW WAS IN 2007,
LED TO THIS IDEA PERHAPS MOST OF
THESE CANCERS ARE STARTING IN
THE FALLOPIAN TUBES COULD WE
REMOVE THOSE BEFORE MENOPAUSE
AND WAIT TILL PEOPLE ARE CLOSER
TO MENOPAUSE BEFORE REMOVING THE
OVARIES.
AND WE DID A SURVEY IN 2011,
ASKED WOMEN WHO WERE HIGH RISK
AND HAD NOT REMOVED THEIR
OVARIES YET, HOW THEY FELT ABOUT
POTENTIALLY PARTICIPATING IN A
STUDY WHERE WE HADN'T PROVEN SAL
PINGECTOMY WOULD LOWER RISK,
WOULD THEY PARTICIPATE KNOWING
THEY WOULD NEED ANOTHER SURGERY
LATER, A THIRD SAID YES, A THIRD
UNSURE, A THIRD SAID NO.
THIS WAS A STUDY THAT OUR
COMMUNITY WOULD BE VERY
INTERESTED IN.
AND SOME OF THE QUOTES, WILL YOU
HAVE COPIES, THESE HAD SOMETHING
LIKE 107 WRITE-IN COMMENTS,
PEOPLE HAD STRONG OPINIONS.
WE'VE-CHAMPIONS OF THE SOROCK
STUDY.
THIS IS PROSPECTIVE STUDY
LOOKING AT CANCER OUTCOMES FOR
SALPINGECTOMY, REMOVAL OF
FALLOPIAN TUBES FOLLOWED BY
OOPHORECTOMY CLOSER TO
MENOPAUSE, WE WILL NOT -- THIS
WILL NOT CLOSE UNTIL 2037 SO WE
HAVE A LONG HAUL BEFORE WE HAVE
THESE ANSWERS.
IT COULD BE ANOTHER 25 YEARS IF
WE DON'T DO THE STUDY AND STILL
MAY BE TELLING PEOPLE WE DON'T
KNOW.
YOUR DAUGHTERS HAVE TO MAKE THE
SAME DECISIONS SO WE'RE VERY
INVESTED.
THERE ARE CHALLENGES TO SOROCK,
IT'S UNPROVEN AS PREVENTION IN
HIGH RISK WOMEN, SALPINGECTOMY
IS AVAILABLE OUTSIDE
CONTRACEPTION, PEOPLE WITH GOING
TO OB/GYNs BECAUSE THEY DIDN'T
KNOW SOROCK, AND HAVING SURGERY.
WE DON'T HAVE PROOF THIS IS
GOING TO BE COMPARABLE TO
OOPHORECTOMY, AND SO IF WE CAN
GET EVERYBODY ON BOARD, ANYONE
WHO WOULD QUALIFY FOR SURGERY,
WE CAN FINISH ENROLLMENT AND GET
LONG-TERM OUTCOMES.
WE'RE ASKING PEOPLE TO COMMIT, A
LONG TIME, A LOT OF PEOPLE TO
COMPLETE THIS.
THAT THREATENS OUR CHANCE TO GET
ENOUGH PEOPLE ENROLLED TO GET
ANSWERS.
THAT'S ALL I'M GOING TO SAY.
HAPPY TO ANSWER QUESTIONS AFTER.
FINAL THOUGHTS THAT PEOPLE AT
HIGH RISK FOR GYNECOLOGIC
CANCERS NEED BETTER OPTIONS,
THEY ARE MOTIVATED TO
PARTICIPATE IN RESEARCH.
BETTER OPTIONS ARE NEEDED FOR
MANAGING SIDE EFFECTS OF EARLY
MENOPAUSE ESPECIALLY FOR THOSE
FOR WHOM HORMONE REPLACEMENT IS
NOT CONSIDERED SAFE, THAT
INCLUDES ME.
I'M ON HORMONE REPLACEMENT BUT
IT'S NOT CONSIDERED SAFETY.
QUALITY OF LIFE DECISIONS.
HEALTH CARE PROFESSIONALS SHOULD
HAVE HONEST CONVERSATIONS.
WE HEAR THIS FROM OUR COMMUNITY,
MEDICAL GAS LIGHTING WE
SOMETIMES HEAR, CONCERNS ARE
REAL BECAUSE THEY ARE HEALTH
CARE PROFESSIONALS DON'T HAVE
ANYTHING TO OFFER THEM.
IT'S CRITICAL TO INVEST IN
STUDIES LIKE SOROCK AND
TUBA/WISPII SEE WE HAVE BETTER
OPTIONS FOR HIGH RISK WOMEN
TOMORROW.
THANK YOU VERY MUCH.
I'LL STOP SHARING.
>> THANK YOU SO MUCH FOR THAT
WONDERFUL PERSPECTIVE.
WE APPRECIATE IT.
NOW WE HAVE OUR FINAL SPEAKER,
DORCAS BAKER, THE CO-FOUNDER OF
OLDER WOMEN EMBRACING LIFE.
>> THANK YOU.
I WANT TO THANK DR. TEMKIN AND
THE ORGANIZING MEAT FOR THE
OPPORTUNITY TO PRESENT.
THANK YOU FOR THE AMAZING
SYMPOSIUM, AN HONOR TO SHARE
WITH YOU TODAY ABOUT AN AMAZING
GROUP OF WOMEN WHO HAVE THE
LIVED EXPERIENCE, LIFE WITH HIV,
MANY WERE DIAGNOSED MORE THAN 25
YEARS AGO, YOU SEE SOME LADIES
ON THE SCREEN, SOME 38 YEARS
PLUS IN THEIR QUOTE/UNQUOTE
GOLDEN YEARS.
ONE NOT ON THE HOME PAGE OF OUR
WEBSITE, SHE IS ONE OF THE
FOUNDERS, THE MAIN FOUNDER NOT
ON THAT PAGE, SHE WILL BE 80 IN
JULY.
AND DOING VERY WELL.
THIS IS A VERY IMPORTANT GROUP.
I'M GLAD WE WERE ABLE TO SHARE
ABOUT OLDER WOMEN EMBRACING
LIFE.
FOUNDED IN 2004, THE ACRONYM IS
PRONOUNCED "OH WELL," OLDER
WOMEN THAT PROVIDE FOR WOMEN
WITH HIV.
OUR VISION IS TO HAVE A
COMMUNITY OF WOMEN WHO ARE
LIVING FULL PRODUCTIVE LEVELS IN
SPITE OF THE CHALLENGE OF HIV.
OUR MISSION PLAN, DEVELOP THE
IMPLEMENT PROGRAM, PROJECTS, NOT
ONLY THAT AFFECT PHYSICAL HEALTH
BUT MEDICAL, SPIRITUAL,
EMOTIONAL HEALTH, BUILD STRONG
CONNECTIONS WITH ONE ANOTHER AND
ADVOCATES, WITH SERVICE
AGENCIES, HEALTH CARE PROVIDERS,
AND THEY BUILD FOUNDATION OF
SUPPORTING AND MAKING
CONFIDENCE, MAKING WOMEN FEEL
CONFIDENT AND BEING PRO-ACTIVE
IN THEIR CARE AND PARTICIPATION.
AS YOU SEE ON THIS SCREEN, THESE
WOMEN JUST TO POINT OUT THE
CURRENT FOUNDER IN RED AND BLACK
DRESS, MELANIE, THE CURRENT
EXECUTIVE DIRECTOR, NOT FOUNDER.
THE WOMEN WITH GLASSES ON HER
HEAD IS 77 YEARS OLD, WITH THE
YELLOW VEST, SHE'S 70, AND THE
ONE TO THE OTHER SIDE OF MELANIE
REESE WITH THE RED DRESS IS ONE
OF OUR LADIES, LIVING WITH HIV A
LONG TIME, AND THE LAST WOMAN IS
NOT LIVING WITH HIV BUT SHE'S
ONE OF OUR CO-FOUNDERS ALONG
WITH US.
THIS GROUP OF WOMEN, THEY ARE
ADVOCATES, EDUCATORS, MENTORS,
GRANDMOTHERS, CAREGIVERS,
COMMUNITY BOARD ADVISORS,
MEMBERS, PARTICIPANTS IN CENTERS
FOR AIDS RESEARCH, CFARs, FOR
FOUR YEARS WE'VE BEEN DOING A
BREAKOUT SESSION FOR THE JOHNS
HOPKINS GERIATRIC CONFERENCE AND
THEY INSERT THEMSELVES WITH SUCH
GRACE, IF YOU'RE NOT INCLUDING
THEM AND THEY SHOULD BE PART OF
THE CONVERSATION, WHETHER A NEW
COMMITTEE OR HIV PLANNING GROUP
OR WHATEVER, THEY ARE INVOLVED
AND HAVE BEEN SINCE 2004.
THEY ARE PRECEPTORS FOR STUDENTS
TO LEARN ABOUT HIV AND AGING AND
ESPECIALLY IN WOMEN SO THEY
MENTORED QUITE A FEW WOMEN, AND
FROM WALDEN INSTITUTE AND OTHER
PLACES.
THEY SHARE THEIR STORIES,
STRENGTHEN SO MANY INDIVIDUALS,
WHETHER THEY ARE YOUNG WOMEN,
EVEN YOUNG MEN, OLDER, DOESN'T
MATTER.
WHEN THEY TALK ABOUT THE JOURNEY
WITH LIVING WITH HIV DOESN'T
MATTER WHO THEY ARE ADDRESSING
BUT EVERYONE LISTENS AND THEY
HAVE THAT GRACE TO SHARE THEIR
STORY GOING THROUGH MENOPAUSE,
SOME ARE NOW 10 TO 20 YEARS PAST
WHEN THEY FIRST WENT THROUGH
MENOPAUSE AND QUITE A FEW STILL
DEALING WITH HOT FLASHES.
THEY ADDRESS ISOLATION AND
DEPRESSION, ESPECIALLY DURING
COVID.
WE MEET MONTHLY.
THEY HAVE A RESILIENCE THAT YOU
CAN'T SEE IT ON A SCREEN.
YOU WOULD HAVE TO HEAR THEM
SHARE THEIR STORIES AND THEIR
STRONG CONNECTIONS.
THE AVERAGE AGE MOSTLY IS IN
THEIR 60s NOW, LIVING FOR MORE
THAN, AS I SAID, UP TO 38, 39
YEARS, ENGAGED COMPLETELY IN
UNDERSTANDING MULTI-MORBIDITIES
AS ALREADY ROCCA TALKED ABOUT
AND HAS COME ACROSS IN THIS
AWESOME SYMPOSIUM WITH MENOPAUSE
AND HIV WHICH IS NOW A CHRONIC
DISEASE, DECLARED SO IN 2012,
EVEN THOUGH WE KNEW IT SOONER.
DOUBLE WHAMMY, MORE PRONE TO
HAVE AND HAVE MULTI-MORBIDITIES,
DIABETES, CARDIOVASCULAR
DISEASE, COGNITIVE CHANGES,
COPD, KIDNEY DISEASE, FRAILTY
AND POLYPHARMACY.
SOME HAVE BEEN EXPOSED TO
EARLIER YEARS OF HIV TREATMENT,
ANT RETROVIRAL THERAPY THAT
IMPACTED BONES AND SO FORTH.
NOW THERAPY IS WAY BETTER.
THESE WOMEN ARE EPITOME OF
ADHERENCE AND WE DO KNOW THAT
ADHERENCE IS ONE OF THE
QUALITIES OF AGING POPULATION OF
INDIVIDUALS, AGING REGARDLESS OF
GENDER WITH HIV.
IT'S NOT THE HIV BUT IT'S
EVERYTHING ELSE, THEY SAY THAT
IS A SHORT VISIT BUT AGING
ISSUES AND AGING ISSUES THAT
CONCERN THE WOMEN, SOME HAD HIP
REPLACEMENTS, KNEE REPLACEMENTS,
SHOULDER REPLACEMENTS.
AND ARE DOING WELL, EXTREMELY
RESILIENT.
OWEL EMBRACES COMMUNITY
ENGAGEMENT, INITIATING, IN
EARLIER YEARS GOING TO SENIOR
CENTERS OR SENIOR ACTIVITIES
WHERE WE COULD ASK CAN WE BE
INVITED SO WOMEN CAN TALK ABOUT
SEXUAL HEALTH AS OLDER WOMEN,
REMARKABLE BECAUSE THEY ALSO ARE
INTO PREVENTION.
A FEW WERE DIAGNOSED IN 50s,
NOW IN THEIR 70'S BUT WERE
SEXUALLY ACTIVE, NOT ALL, SOME
HAVE CHOSEN NOT TO, IT'S THE
LEAST OF THEIR CONCERNS AND THEY
DEAL WITH IT IN OTHER WAYS.
IF YOU WANT TO TALK ABOUT SEXUAL
ACTIVITY, THAT DOES NOT STOP AS
THEY AGE, THAT'S ANOTHER
CONVERSATION.
THEY PARTICIPATE WITH SISTER
ORGANIZATIONS ACROSS THE UNITED
STATES, EXECUTIVE DIRECTOR IS
INVOLVED INTERNATIONALLY AS
WELL.
AND LOCALLY WE WERE INVOLVED
WITH DOING OUR COVID VACCINE
CLINICS, SO IN SPITE OF WHAT
THEY HAVE GOING ON, THEY ARE
RESILIENT WITH COMMUNITY
PARTICIPATION.
WE DO THE ANNUAL SIGNATURE
CONFERENCE, LEGENDS FOR 18
YEARS, IT BROUGHT TOGETHER WOMEN
REGIONALLY, THOSE THAT CANNOT
ATTEND INTERNATIONALLY WE PAY
GREETINGS, AS FAR AS AFRICA AND
KENYA, AND THERE'S A GROUP THERE
THAT DEALS WITH HIV IN OLDER
WOMEN.
THEY ARE ACTIVE PARTICIPANTS IN
RESEARCH AND ADVOCATE FOR
RESEARCH TO BE DONE THAT
INCLUDES OLDER WOMEN AS WELL.
WE'VE BEEN RECOGNIZED.
WE RECEIVED HENRIETTA LACKS
AWARD IN 2018 FOR ONGOING
PARTICIPATION IN THE CHECKUP
STUDY, A STUDY THAT TALKED ABOUT
EDUCATING WOMEN, THE NEED TO
MAKE SURE THEY ARE GETTING THEIR
PAP SMEARS AND UNDERSTAND
CERVICAL CANCER AND HOW TO
PREVENT THAT BECAUSE, AGAIN,
WITH HIV, WHICH IS A CHRONIC
DISEASE, ALSO INFLAMMATION, BUT
WOMEN ARE MORE PRONE TO HAVE
OTHER ISSUES WITH CERVICAL
CANCER AND SO FORTH BUT THEY
WERE RECOGNIZED.
WE APPLIED FOR THREE YEARS, AND
IN THE THIRD YEAR WE DID GET IT
BECAUSE WE COLLABORATED WITH A
FACULTY AT THE SCHOOL OF NURSING
THAT WAS DOING THE CERVICAL
CANCER STUDY.
I COULD GO ON AND ON.
THERE'S SO MANY OTHER THINGS
THAT THIS UNIQUE GROUP OF WOMEN
HAVE DONE.
WE MAY BE ABOUT 100 STRONG WHEN
IT COMES TO PARTICIPANTS, WE
DON'T SAY MEMBERSHIP.
YOU DON'T HAVE TO JOIN BUT YOU
CAN JUST ATTEND AND YOU WILL SEE
YOU'LL BECOME PART OF IT.
WE PARTICIPATED IN THE FOLLOW
YOUR HEART STUDY WITH DR. LOOBY
IN 2017.
THEY PARTICIPATED IN COGNITIVE
CHANGES IN WOMEN STUDY, IN ONE
OF THE LADIES, WITH GLASSES ON
HER HEAD, IN 1985, IN 1989,
PARTICIPATED IN NEW THERAPIES
FOR HIV TREATMENT, WAY BACK
THEN.
AND EVEN NOW A PARTICIPANT IN
THE CLINICAL TRIALS FOR
TREATMENT USING INJECTABLE ANT
RETROVIRAL.
WE'VE COME SO FAR WITH HIV
TREATMENT THAT IT'S WAY
TOLERABLE, ADHERENCE IS NOT A
PROBLEM.
BUT AGING IS.
MENOPAUSE IS AN ISSUE.
BUT I WANTED YOU TO SEE THAT
THERE IS A GROUP OF OLDER WOMEN
WHICH WAS NOT A GROUP BEFORE
2004.
I COULD NOT FIND A GROUP FOR
OLDER WOMEN.
AND THIS WAS FORMED, THE
ATTITUDE WAS, OH WELL, WE HAVE
HIV BUT WE'RE GOING TO EMBRACE
LIFE, MAKE THE MOST OF IT, WE'RE
GOING TO MAKE SURE WHOEVER WE
COME IN CONTACT WITH, THEY WILL
NOT FORGET THAT THEY HAVE BEEN
TALKING TO AN OLDER WOMAN WITH
HIV THAT'S SURVIVING.
THEY ARE MOTIVATED EVEN MEN AND
LIKE I SAID YOUNG MEN,
REGARDLESS OF GENDER.
YOU TAKE YOUR THERAPY.
AND SEE HOW LONG YOU LIVE.
LOOK AT ME.
I'M AN EXAMPLE.
AND THE LAST THING I WOULD LIKE
TO SAY IS WE DID NOT KNOW THAT
FOLKS WOULD BE LIVING LONG WITH
HIV IN THE EARLIER YEARS, AND
NOW THIS IS THE FIRST COHORT,
MEN AND WOMEN, THAT ARE LIVING
LONGER RESILIENT, BASICALLY
DOING WELL BUT THERE ARE
CHALLENGES.
IT'S AGING THAT'S THE CHALLENGE,
ALL THAT GOES WITH IT.
IF YOU WANT TO HEAR FROM WOMEN
THAT HAD MENOPAUSE 10 OR 20
YEARS AGO THIS IS A GREAT GROUP
TO TALK TO.
I THANK YOU.
I DON'T WANT TO DETAIN THE TIME
ANY LONGER BECAUSE WE WANT
QUESTIONS.
THANK YOU SO MUCH.
>> THANK YOU FOR THAT VALUABLE
PERSPECTIVE.
NOW, WE ARE ENTERING INTO THE
QUESTION-AND-ANSWER PERIOD.
SO I ENCOURAGE PEOPLE TO --
ATTENDEES TO PUT THEIR QUESTIONS
INTO THE QUESTION AND ANSWER
AREA AND WE WILL HAVE THE
PANELISTS AND SPEAKERS ANSWER
THEM.
WE HAVE SOME THAT CAME IN DURING
THE TALKS.
ONE IS, ANECDOTALLY WOMEN I KNOW
IN PERIMENOPAUSE AND MENOPAUSE
DISCUSS DIETARY APPROACHES TO
MITIGATE SYMPTOMS.
I.E. EAT MORE PROTEIN,
INCORPORATE FLAX SEED, TAKE
MATCHA POWDER, ET CETERA.
ARE THERE SIGNIFICANT MEDICAL
RECOMMENDATIONS ABOUT DIET FOR
PEOPLE IN THESE STAGES OF LIFE?
DO ANY SPEAKERS WANT TO ADDRESS
THE DIET QUESTION?
>> MAYBE ONE OF THE PHYSICIANS
FROM THE PRIOR SESSION MIGHT
GIVE THE MEDICAL
RECOMMENDATIONS.
>> I CAN PROBABLY ADDRESS A
LITTLE OF THE DATA.
TYPICALLY DIETARY APPROACHES
HAVE NOT BEEN HELPFUL TREATING
VASOMOTOR SYMPTOMS, ONE
EXCEPTION HAD A STRICT VEGAN LOW
FAT AND I BELIEVE HIGH SOY DIE
THAT -- DIET THAT SHOWED COME
EFFICACY BUT NOT THE BULK OF THE
LITERATURE.
>> DR. CORTES?
DR. LOOBY?
>> SORRY.
YES, I CAN ONLY SPEAK IN THE
CONTEXT OF MID-LIFE WOMEN'S
HEALTH, NUTRITION, SPECIFICALLY
CARDIOVASCULAR HEALTH AND BONE
LOSS.
CHARACTER FOR WOMEN AT THIS
PHASE OF LIFE IT'S VERY
IMPORTANT FOR WOMEN TO RECONNECT
WITH THEIR DIET AND MAKE SURE IT
IS HEART HEALTHY, OBVIOUSLY,
ALSO NUTRIENT RICH PARTICULARLY
WITH REGARD TO VITAMIN D AND
CALCIUM, AND RAISE THE QUESTION
BECAUSE IT DOESN'T HAPPEN TO
FALL ON THE LIST OF THINGS.
SO CHECKING IN WITH YOUR HEALTH
CARE PROVIDERS OR PROVIDERS
BEING SENSITIVE TO RAISE
AWARENESS TO ASKING SPECIFICALLY
ABOUT CARDIOVASCULAR HEALTH,
DIET, EXERCISE, AND ALSO BONE
HEALTH IN THAT REGARD.
WHAT COMES HAND IN HAND IS
EXERCISE.
MAKING SURE THAT FOLKS ARE AWARE
OF RISK REDUCTION BEHAVIORS IN
THE CONTEXT OF NUTRITION BUT
ALSO INCREASING PHYSICAL
ACTIVITY AS ABLE.
AND THEN I ALSO WOULD REALLY BE
CAREFUL ABOUT ADVISING OR
PARTICIPATING IN ANY FAD BASED
DIETS THAT GET HYPE NATIONWIDE
AND INTERNATIONALLY.
THERE'S A NEW ONE EVERY WEEK.
SOME MAY BE VERY EFFECTIVE FOR
CERTAIN POPULATIONS BUT I THINK
IT'S A GREAT THING TO CHECK IN
WITH YOUR HEALTH CARE PROVIDER
TO MAKE SURE THAT DIET, ANY
SUPPLEMENTS, HERBAL REMEDIES OR
DRASTIC CHANGES ATED MY LIVE
WHERE SO MUCH IS CHANGE -- AT
MID-LIFE, IT'S A GREAT
OPPORTUNITIES TO MAKE SURE IT'S
SAFE FOR YOU.
>> I WOULD SAY, FOLLOWING UP
THAT WE'RE NOT FOCUSING ENOUGH
ON IMPACT OF BLEEDING, WOMEN ARE
LOSING A LOT OF IRON.
DIETS THAT -- DIETS OR
SUPPLEMENTS THAT ADDRESS GETTING
ADEQUATE IRON MIGHT BE SOMETHING
THAT WOULD WANT TO BE MONITORING
WITH THEIR HEALTH PROFESSIONALS.
>> THANK YOU.
THANKS FOR THE ANSWERS.
WE ALSO HAVE ANOTHER QUESTION
HERE FROM OUR ATTENDEES, ARE
THERE UNIQUE MENOPAUSAL SYMPTOMS
OF WOMEN LIVING WITH HIV?
>> I WOULD SAY THAT ONE OF THE
THINGS THAT CAN BE DIFFICULT IS
DIFFERENTIATING BETWEEN WHAT IS
A SYMPTOM OF HIV AS WE MENTIONED
IN MY PRESENTATION, AND WHAT IS
A SYMPTOM OF MENOPAUSE BECAUSE
THERE IS A LOT OF OVERLAP.
IN MY EXPERIENCE, BASED ON
RESEARCH THAT I HAVE READ IN
THIS AREA, THEY SEEM TO BE
GENERALLY SIMILAR, ALTHOUGH
WOMEN WITH HIV PARTICULARLY IN
THAT LATE PERIMENOPAUSE PHASE
APPEAR TO EXPERIENCE MORE SEVERE
SYMPTOMS OR REPORT MORE SEVERE
SYMPTOMS WITH HOT FLASH, MOOD,
ANXIETY, HAS TO DO WITH
INTERPLAY BETWEEN HAVING THESE
CONDITIONS PRE-MENOPAUSEALLY.
I WILL SHARE ONE OF THE THINGS
THAT I ENCOUNTERED IN WOMEN WITH
HIV, TO MY KNOWLEDGE THERE'S
BEEN NOTHING WRITTEN UP ABOUT
THIS, IS THAT THE DISTRESS THAT
MID-LIFE SYMPTOMS CAUSE AS I
SHARED IN MY PRESENTATION
PARTICULARLY HOT FLASHES AND
MOOD SWINGS, THAT HAPPEN DURING
THIS TIME, WITH THE LACK OF
KNOWLEDGE AND UNDERSTANDING THAT
THIS IS ACTUALLY A PHYSIOLOGIC
PROCESS CAN TRIGGER SUCH MOOD
AND PTSD CHANGES THAT I HAVE
SEEN WOMEN WHO CONTRACTED HIV
THROUGH INTRAVENOUS DRUG USE
RELAPSE BECAUSE THEY ARE SO
SCARED ABOUT WHAT'S HAPPENING TO
THEM OR FEELING A LACK OF
CONTROL OR HAVING SOME PTSD OR
FORM OF TRAUMA.
SO I WOULD SAY THAT THAT IS NOT
NECESSARILY A UNIQUE SYMPTOM BUT
IF THERE IS A PATIENT UNDER YOUR
CARE WHO EXPERIENCES SUBSTANCE
USE DISORDER, WHO IS IN
RECOVERY, PARTICULARLY AT
MID-LIFE, IN ADDITION TO
CHECKING IN ON MOOD AND MENTAL
HEALTH STATUS IF THEY HAVE THAT
HISTORY, I THINK IT'S A
TREMENDOUS IDEA TO MAKE SURE
THEY ARE OKAY IN THEIR RECOVERY.
>> FOR DR. FRIEDMAN, WHAT DO
YOU THINK HEALTH CARE
PROFESSIONALS CAN DO TO RAISE
AWARENESS AND ACCELERATE OVARIAN
CANCER PREVENTION INDIVIDUALS
FOR HIGH RISK INDIVIDUALS?
>> GREAT QUESTION.
THANK YOU FOR THAT.
IT GIVES ME THE OPPORTUNITY TO
PROMOTE TWO STUDIES, I PUT THEM
IN THE CHAT.
IF SOMEONE CAN SHARE WITH
EVERYONE.
I THINK A LOT OF TIMES PATIENTS
ARE NOT TOLD ABOUT STUDIES THEY
MAY QUALIFY FOR, ESPECIALLY
PREVENTION STUDIES, WE THINK OF
CLINICAL TRIALS OFTEN AS
TREATMENT BASED, AND SO
OFTENTIMES IF THE STUDY IS
HAPPENING AT AN INSTITUTION
OUTSIDE OF YOUR OWN, THAT
THERE'S BARRIERS TO LETTING
PATIENTS KNOW ABOUT IT.
BE AWARE OF THE STUDIES THAT ARE
AVAILABLE OUT THERE,
PARTICULARLY SOROCK, AND
TUBA-II, BUT THERE ARE STUDIES,
THE FORCE WEBSITE HAS A LOT OF
THOSE BUT ALSO
clinicaltrials.gov.
AND SHARE IN PLAIN LANGUAGE ALL
STUDIES WITH PATIENTS SO THEY
KNOW THEIR OPTIONS.
>> THANK YOU.
ANOTHER QUESTION, WE'VE TALKED
ABOUT SOCIAL DETERMINANTS OF
HEALTH, AND DIFFERENCES IN
ACCESS TO TREATMENT FOR
VASOMOTOR SYMPTOMS, BLEEDING, ET
CETERA.
DO ANY PANELISTS HAVE THOUGHTS
ABOUT HOW WE CAN START TO BEGIN
TO TACKLE SOME OF THE BARRIERS
TO TREATMENT THAT WOMEN MAY
FACE, AND THIS PIGGYBACKS ON A
QUESTION IN THE CHAT ABOUT
HELPING TO ALERT WOMEN EARLY,
BEFORE THEY ENTER MENOPAUSE
TRANSITION ABOUT WHAT TO EXPECT.
IT'S A TWO-PRONGED QUESTION, HAS
TO DO WITH ACCESS TO TREATMENT
AND HOW WE'RE STRUCTURAL OUR
MENOPAUSE CARE.
>> I THINK IT'S LIKE A TWO-PART
ISSUE, ONE BEING -- PROVIDING
MORE PUBLIC INFORMATION THAT'S
READILY AVAILABLE SO THAT
INDIVIDUALS FEEL EMPOWERED TO
ASK QUESTIONS, DURING CLINICAL
ENCOUNTERS, HAVE THAT
INFORMATION AVAILABLE.
BUT THEN EVEN THROUGH OUR FOCUS
GROUPS AND EVERYTHING,
PARTICIPANTS WANT TO KNOW
EARLIER.
AGE 35, BEFORE AGE 40.
THEY WANT TO JUST KNOW WHAT TO
EXPECT, WHAT AGE, AROUND WHAT
AGE WILL I EXPECT CHANGES, WHAT
KINDS OF CHANGES.
I WAS TOLD WHAT TO EXPECT DURING
PUBERTY WHEN I ENTERED MENARCHE,
DURING PREGNANCY, WHY AM I NOT
TOLD WHAT TO EXPECT IN THE
MENOPAUSE TRANSITION?
DURING ANNUAL VISITS OR CLINICAL
ENCOUNTERS BRINGING IT UP AS WE
DO FOR OTHER STAGES OF LIFE.
>> I WANT TO ADD TO THAT,
EMPOWERING YOUNGER WOMEN OR
THOSE MID-LIFE WITH GROUPS SUCH
AS OH WELL, THEY DO TALK ABOUT
THAT.
DON'T DO LIKE I DID.
YOU NEED TO KNOW THESE ARE THE
WEST YOU WANT TO THINK ABOUT
ASKING AT YOUR NEXT VISIT, VERY
EMPOWERING, THAT'S WHY I
APPRECIATE OWEL SO MUCH BUT THEY
DO HAVE CONVERSATIONS TO HELP
EMPOWER WOMEN THAT MAY NOT BE
ASKED BUT KNOW, YOU GO IN
PREPARED TO ASK QUESTIONS.
IT MEANS A LOT, ESPECIALLY FOR
BLACK WOMEN, AND THEY REALLY GO
INTO THAT.
THANK YOU.
>> I'M CONSCIOUS OF TIME.
I SEE YOU'RE READY TO MOVE US
ALONG.
>> I WAS GOING TO SAY IF ANYONE
HAS A LAST ANSWER, WE'RE STILL
GOING TO START THE NEXT SESSION
AT 3:10.
I'LL OPEN IT IF ANYONE ELSE HAS
ANYTHING TO SAY OR WE'LL TAKE A
SHORT BREAK.
>> I'LL JUST ADD THAT'S
SOMETHING THAT FORCE PROVIDES,
THAT PEER EXPERIENCE.
SO THAT EVEN IF YOUR HEALTH CARE
PROFESSIONALS DOES PREPARE YOU
THERE'S NOTHING LIKE TALKING TO
SOMEONE ELSE WHO HAS BEEN
THROUGH THE EXPERIENCE.
>> THANK YOU.
>> IN TERMS OF DISPARITIES
QUESTION, ONE OF THE ISSUES, NOT
BEING A HEALTH CARE PROVIDER
MYSELF, THAT THERE IS A CONCERN
ABOUT THE LEVEL OF KNOWLEDGE AT
THE PRIMARY CARE LEVEL, NOT
EVERYONE HAS ACCESS TO
GYNECOLOGICAL CARE OR SPECIALTY
WOMEN'S HEALTH CENTERS NEAR
RESEARCH CENTERS.
I THINK ONE BIG ISSUE HAS TO DO
WITH IMPROVING THE LEVEL OF
KNOWLEDGE AT THE PRIMARY CARE
LEVEL ABOUT CRITICAL ISSUES IN
MENOPAUSE CARE.
AND WE NEED TO HAVE A LOT MORE
INFORMATION IN MULTIPLE
LANGUAGES, SO THERE'S VERY GOOD
WEBSITES BEING DEVELOPED, NEED
TO MAKE SURE THEY ARE AVAILABLE
IN MULTI-LANGUAGES FOR VARIOUS
COUNTRIES THAT WE NEED HAVE.
>> ONE COMMENT AS A GYN
ONCOLOGIST, THIS HAS TO BE A
MULTI-PRONGED APPROACH TO GET
THIS INFORMATION OUT THERE, AND
THERE'S A LACK OF KNOWLEDGE AT
EVERY LEVEL ON HOW TO TAKE CARE
OF THIS PROBLEM, AND IT HAS BEEN
SYSTEMATICALLY IGNORED AND
UNDEREMPHASIZED, WOMEN ARE OKAY
WITH SUFFERING, IT'S SOMETHING
THAT'S EXPECTED OF THEM, AND
THIS MENTALITY BLEEDS INTO EVERY
ASPECT OF HEALTH CARE AND WITH
OB/GYNs BEING LESS AVAILABLE
IN DIFFERENT AREAS, OTHER
SPECIALTIES ARE GOING TO NEED TO
LEARN SOME GYNECOLOGY, AND WE
ALL HAVE TO WORK TOGETHER TO
HELP TAKE CARE OF THESE
PATIENTS.
>> I COULDN'T AGREE MORE.
EVERY PANELIST HAS ECHOED ALL
THE THOUGHTS THAT CROSSED MY
MIND.
NOTHING MORE TO ADD.
THANK YOU.
>> I WANT TO THANK EVERYONE.
WE'RE GOING TO TAKE A VERY SHORT
BREAK AND WE'RE GOING TO SEE
SOME GRAPHIC REPORTING THAT HAS
BEEN BEING DONE DURING THIS
SESSION.
WE'LL RECONVENE IN FIVE
SHORT
MINUTES.
THANK YOU.
>> I WANT TO THANK EVERYONE FOR
JOINING US TODAY.
AS WE ENTER THE END OF THE DAY,
7th ANNUAL SYMPOSIUM, I WANT
TO THANK ANGELIQUE FOR HER
DRAWINGS AND GRAPHIC REPORTING
DURING THE DAY.
IT'S MY PLEASURE TO INTRODUCE
DR. NANETTE SANTORUM, TAILOR
CHAIR IN DEPARTMENT OF
OBSTETRICS, UNIVERSITY OF
COLORADO SCHOOL OF MEDICINE.
>> IT'S PLEASURE TO BE HERE.
WE'RE GOING TO BEGIN WITH THE
WHO, WHEN, WHAT OF THERAPY WITH
DR. VIRGINIA MILLER, SHE'S
PROFESSOR EMERITA OF SURGERY
MAYO CLINIC, HAD GREAT IMPACT ON
THE FIELD.
I'M GOING TO KEEP US ON STRICT
TIME LIMIT, I'LL THE LOW YOU
KNOW WHEN YOU HAVE THREE MINUTES
LEFT.
>> PERFECT.
I DON'T HAVE TO START MY TIMER.
THANKS TO THE ORGANIZERS.
WE'VE HEARD A LOT ABOUT
INDIVIDUALIZING HORMONE
TREATMENT TODAY.
MY FUNDING SOURCES ARE HERE, I'M
GRATEFUL TO THE GRANTS FROM NIH
THAT SUPPORTED US OVER THE YEARS
AS WELL AS FROM THE KRONOS
INSTITUTE FROM THE AURORA
FOUNDATION WHICH SUPPORTED THE
KEEPS TRIAL.
I HAVE NO CONFLICTS OF INTEREST.
FIRST OBJECTIVE TO RENEW
MECHANISM OF ACTION, WITHOUT
UNDERSTANDING OR REFRESHER WE
WON'T UNDERSTAND SOME
IMPLICATIONS OF THE
RISK/BENEFITS OF HORMONE
TREATMENT.
I'M GOING TO LEVEL INTO THE
PHARMACOGENETICKIC APPROACHES
USED TO UNDERSTAND EFFICACY OF
HORMONE TREATMENTS, ESPECIALLY
AS THEY RELATE TO
INDIVIDUALIZING TREATMENTS BASED
ON PERHAPS GENOTYPE OR
METABOLISM OF ESTROGEN AND LEAVE
YOU WITH CHALLENGES SCIENCE
FACES PERSONALIZING HORMONE
TREATMENTS AND LOOKS TO THE
FUTURE OF WHAT NEEDS TO BE DONE.
MOST OF THE ONES TODAY HAVE BEEN
ESTRADIOL, AND ORAL CONJUGATED
EQUINE ESTROGEN.
YOU CAN SEE FROM THE SLIDE, ORAL
EQUINE CONJUGATED CONTAINS
ESTRADIOL IT CONTAINS OTHER
PRODUCTS.
WHAT ARE THESE EFFECTS IN THE
CELL?
COMPOUNDS CAN ENTER AND BIND TO
HORMONE RECEPTORS, IN THIS CASE
ESTROGEN RECEPTOR, GO INTO
NUCLEUS, AFFECT GENE
TRANSCRIPTION AND TRANSLATION.
THESE ARE CALLED GENOMIC
REGULATION OF HORMONE
TREATMENTS, AND THROUGH THE
REGULATION OF THE GENOME CAN
AFFECT PROTEIN SYNTHESIS, MANY
CELL FUNCTIONS, LONG TERM, AND
LONG LASTING.
AND TAKE A WHILE TO ACTUALLY BE
OBSERVED.
ON THE OTHER HAND THEY BIND TO
RECEPTORS IN THE CELL MEMBRANE,
AND ALSO CAUSE SEVERAL VERY
RAPID CHANGES IN ION REGULATION,
SIGNAL PATHWAYS, RELEASE OF
NITRIC OXIDE WHICH YOU HEARD
FROM DR. MANSON'S TALK EARLIER
THIS MORNING, AND AGAIN THESE
PATHWAYS CAN AFFECT CELL
FUNCTION.
THESE RESPONSES ARE PRESENT WHEN
HORMONES ARE THERE, GONE WHEN
THE HORMONES ARE REMOVED.
REVERSIBLE EFFECTS OF TREATMENT.
YOU HAVE KEEP IN MIND LOOKING AT
BENEFITS AND RISKS, LONG TERM
CONSEQUENCES.
AS MODE OF DELIVERY AFFECT THEIR
EFFICACY, ORAL COMPOUNDS MUST GO
THROUGH OR BE TAKEN INTO THE
LIVER AND METABOLIZED.
I SHOWED ESTROGEN AND
METABOLITES, THOSE OCCUR IN THE
LIVER AND AFFECT INFLAMMATORY
FACTORS AND COAGULATION FACTORS
WHICH GIVES US SOME BIOLOGICAL
BASIS FOR THE FACT THAT ORAL
COMPOUNDS MAY BE THROMBOGENIC
THAN THOSE USE TRANSDERMALLY
THAN THOSE WITHOUT BEING
METABOLIZED BEFORE ENTERING THE
LIVER AND BROKEN DOWN AND
ELIMINATED.
WHEN WE'RE TALKING ABOUT EFFECTS
OF HORMONES AND INDIVIDUALIZING
TREATMENT, YOU HAVE TO KEEP IN
MIND THESE TWO IMPORTANT
FACTORS.
WHAT IS THE FORMULATION AND HOW
ARE THEY DELIVERED, AFFECTING
OUTCOMES OF CHOICE.
HOW CAN WE LOOK AT GENETICS
AFFECTING OUTCOME.
I'M GOING TO TALK ABOUT THE
KEEPS STUDY.
WHICH WAS BEGUN AS A
MULTI-CENTER STUDY, NINE SITES
ACROSS THE UNITED STATES IN 20,
FIRST OF ALL THE AGE OF THE
PARTICIPANTS WERE WITHIN AVERAGE
AGE OF MENOPAUSE.
WE WERE KEEN TO ASSURE THE WOMEN
WERE WITHIN CLOSE RANGE, THREE
YEARS, OF THEIR LAST MENSTRUAL
PERIOD.
YOU REMEMBER SOME WOMEN WHY TEN
YEARS PAST FINAL MENOPAUSE SO
MENOPAUSAL AGE IS ONE OF THE
QUESTIONS CAME FROM THE
AUDIENCE, AND WE WERE KEEN TO
ASSURE WE WERE WITHIN A
REASONABLE RANGE CLOSE TO THE
FINAL MENOPAUSE.
WOMEN WERE METABOLICALLY
HEALTHY.
HERE IS THEIR BMI, BLOOD
PRESSURE, SCREENED FOR CORONARY
CALCIFICATION, BLOOD PRESSURE
UNDER CONTROL, AIRED YO
METABOLIC PARAMETERS WITHIN THE
NORMATIVE RANGE.
WHAT DID WE USE TO TREAT?
TWO FORMULATIONS, FIRST
TRANSDERMAL 17 BETA ESTRADIOL
AND HERE IS DOSAGE AND ORAL
CONJUGATED EQUINE ESTROGEN, 0.4
MILLIGRAMS PER DAY, A LOWER
CONCENTRATION THAT WAS USED IN
THE WHI, BECAUSE WE WERE BASED
ON OUTCOMES OF THE WHI CHOSE TO
USE LOWER DOSE.
IN CONTRAST TO WHI USED NATURAL
PROGESTERONE, GIVEN NOT
CONTINUOUSLY BUT FOR FIRST 12
DAYS OF THE MONTH.
SO WHEN WE THINK ABOUT THE
METABOLISM OF THESE TWO
COMPOUNDS, WE NEED KEEP IN MIND
ESTROGEN METABOLISM IS COMPLEX.
IT'S HIGH DOCKS LATE -- HYDROXY
LATED.
THERE ARE GENETIC VARIANTS IN
THE GENES THAT ENCODE THIS
ENZYME, WE WERE CURIOUS TO SEE
IF THIS THAT ANY EFFECT ON ANY
OUTCOMES.
YOU CAN SEE THIS IS A COMPLEX
GENETIC VARIATION.
YOU CAN HAVE ONE COPY OF THE
VARIATION, TWO OF THE VARIATION,
THREE OR FOUR.
THE MORE COPIES THE FASTER YOU
METABOLIZE TO THE SULFYNATED
FORM.
DOES THIS A SUBSEQUENT
CONSEQUENCE IF A WOMAN CARRIES A
LARGE NUMBER?
WE FOUND IT DID.
IF WE LOOK AT WOMEN WHEN THEY
ENROLLED IN THE TRIAL, AND THE
AGE WHICH THEY EXPERIENCED THEIR
FINAL MENSTRUAL PERIOD, WE FOUND
THE WOMEN THAT HAD NUMBER OF
ALLELES WITH THIS VARIANT, THE
MORE COPIES OF THE VARIANT THEY
HAD, THE EARLIER WAS THEIR ONSET
OF MENOPAUSE.
IN OTHER WORDS, THE NUMBER OF
THESE PARTICULAR VARIANT ALLELES
INCREASED THE ACTIVITY WHICH
WOULD REMOVE THE ACTIVE FORM OF
ESTROGEN FROM CIRCULATING POOL
REDUCING THE AMOUNT OF HORMONE
THAT WAS AVAILABLE TO BIND TO
THE RECEPTORS FOR ITS CELLULAR
EFFECTS.
WHAT ABOUT VARIABILITY AND
RESPONSE?
THIS WAS BASED ON WOMEN WHEN
THEY CAME INTO THE TRIAL, PRIOR
TO HAVING -- RECEIVING THEIR
DRUG, PRIOR TO RANDOMIZATION,
WAS THERE ANY RELATIONSHIP TO
ESTROGEN METABOLISM AND AGE OF
MENOPAUSE, YES, THERE WAS.
KNOWING THERE'S VARIATIONS IN
THESE ENZYMES THAT AFFECT
ESTROGEN METABOLISM WOULD THAT
AFFECT RESPONSE TO THE HORMONE
TREATMENTS?
LET'S SEE WHAT HAPPENED.
FIRST WE NEED TO ESTABLISH THAT
THESE HORMONE TREATMENTS DID
RAISE THE LEVEL, CIRCULATING
LEVELS OF HORMONES IN THE BLOOD.
WOMEN RANDOMIZE TO TRANSDERMAL
17 BETA ESTRADIOL, THEIR HORMONE
LEVELS WERE INCREASED AND THEY
STAYED PRETTY SUBSTANTIALLY THE
SAME THROUGHOUT THE FOUR YEARS
OF THE TRIAL.
THE WOMEN THAT RECEIVED THE
CONJUGATED ESTROGEN LEVELS WERE
NOT HIGH BUT GIVEN THE NATURE OF
THE COMPOUND THEY WERE GIVEN,
AND HOW THIS METABOLIZED IN THE
LIVER WE SEE INDEED ESTRONE WAS
HIGHER THAN THOSE THAT RECEIVED
ESTRADIOL PATCH.
EACH OF THESE ACTIVE TREATMENTS
DID INDEED INCREATES CIRCULATING
LEVEL OF A PHARMACO EFFECTIVE
TREATMENT STEROID BUT WHAT CAN
WE SAY ABOUT THESE DIFFERENCES
IN HORMONE LEVELS ON THE
SYMPTOMS OF MENOPAUSE AND OTHER
PARAMETERS OF THE KEEPS TRIAL?
LET'S LOOK.
WE'VE HEARD ABOUT VASOMOTOR
SYMPTOMS, HOT FLASHES, NOT THE
ONLY SYMPTOMS WHICH WOMEN ARE
CONCERNED ABOUT.
THEY ARE CONCERNED ABOUT
IRRITABILITY, INSOMNIA, I CAN'T
READ BECAUSE THERE'S A THING ON
TOP.
>> NIGHT SWEATS.
>> THANK YOU VERY MUCH.
SO THESE ARE TERRIBLE.
WE TALKED ABOUT THE WOMAN WHO
THOUGHT SHE WAS IN A SAUNA IN
THE NIGHT, OKAY?
THE IMPORTANT THING IS TO LOOK
AT THESE SCALE OF THESE
SYMPTOMS, WOMEN IN PLACEBO,
COMPARED TO THOSE ON THE ACTIVE
TREATMENT, INDEED FOR HOT
FLASHES, NIGHT SWEATS, INSOMNIA
THE TREATMENTS BOTH OF THEM EVEN
THOUGH CONTAIN DIFFERENT
CONCENTRATIONS OF ACTIVE
HORMONES THEY SIGNIFICANTLY
REDUCED THESE SYMPTOMS AS
REPORTED BY THE WOMEN IN THE
STUDY.
IRRITABILITY, NOT MUCH RESPONSE
THERE.
THERE WAS NOT MUCH DIFFERENCE
BETWEEN THE GROUP AND NUMBER OF
WOMEN THAT REPORTED IRRITABILITY
WAS ALSO QUITE SMALL.
IN SPITE OF DIFFERENCES IN
CIRCULATING LEVELS OF HORMONES
AND TYPE, THE ABILITY TO REDUCE
THESE SYMPTOMS OF MENOPAUSE WERE
COMPARABLE.
THESE ARE THE COLLECTIVE DATA.
IS THERE ANY INFORMATION THAT
CAN BE RELATED TO THIS OF
INDIVIDUAL VARIATION AND
RESPONSE TO THESE SYMPTOMS?
AGAIN, WE TRIED TO LOOK AT THE
GENETIC COMPOSITION OF THE
METABOLITES, AND GENETIC
VARIATION OF THE ENZYMES.
THESE ARE PHARMACOGENOMIC
EFFECTS, THAT IS GENETIC VARIANT
OR SNP INFLUENCES THE EFFECT OF
THE TREATMENT ON THE OUTCOME.
SO IF WE HAVE A GENETIC
VARIATION OF SOMETHING, WHICH IN
THIS CASE WE WERE LOOKING AT
ENZYMES THAT METABOLIZE, DOES IT
HAVE EFFECT OF THE TREATMENT ON
THE OUTCOME WHICH WOULD BE HOT
FLASHES, NIGHT SWEATS, SO ON.
SO LET'S LOOK AT THIS.
AGAIN, KEEP IN MIND THAT THIS IS
A CELL, METABOLISM OF ESTROGEN
IS COMPLEX.
WE HAVE SHULFINATION,
HYDROXYLATION AND METHYLATION
FOR ELIMINATION BUT THERE'S A
TRANSPORTER WHICH IS INVOLVED
WHICH TAKES ESTROGEN OR ESTRONE
INTO THE CELL, WHERE IT BEGINS
THIS JOURNEY THROUGH THE
METABOLIC PATHWAYS.
SO, WE DECIDED TO LOOK AT THIS
TRANSPORTER, IS THERE ANY
GENETIC VARIATION IN THIS
TRANSPORTER RELATED TO
INDIVIDUAL WOMAN TO HORMONE
TREATMENTS AS RELATED TO
MENOPAUSAL SYMPTOMS?
THIS IS NOT THE SLIDE I'M MOST
PROUD OF.
HOW CAN WE FOLLOW IT?
BEAR WITH ME.
THE VISUALS, YOU'LL SEE, PROVE
TO BE EASY TO SEE.
THESE ARE THE CONCENTRATIONS OF
ESTRONE MEASURED, 17 BETA
ESTRADIOL, THIS IS THE -- THESE
ARE THE SAME THROUGH ALL THE
PANELS, PLACEBO GROUP,
TRANSDERMAL, ORAL CONJUGATED
GROUP.
AT THE BOTTOM ARE THE GENOTYPES.
THIS WOULD BE HOMOZYGOUS FOR CC
ALLELE, HETEROZYGOUS FOR CT
ALLELE, AND HOMOZYGOUS FOR TT
ALLELE.
IN PLACEBO GROUP THESE VARIANTS
DIDN'T HAVE MUCH OF A RESPONSE
ON HORMONE CONCENTRATIONS
BECAUSE THERE WAS NO HORMONE
THERE, RIGHT?
WHEN YOU LOOK AT THOSE
RANDOMIZED TO THE TRANSDERMAL 17
BETA ESTRADIOL COMPARED TO
CONJUGATED ESTROGEN, YOU SEE
DIFFERENCES IN THE SIZE OF THE
BARS AND DIRECTION THEY GO.
LET'S LOOK AT THIS.
THERE'S A BIGGER RESPONSE WHEN
THEY ARE ON ORAL -- TRANSDERMAL
ESTROGEN COMPARED TO CONJUGATED
ESTRONE COMPARED TO ESTRADIOL.
HETEROZYGOUS RESPONSE IS LARGER
FOR THE CONCENTRATIONS OF THE
HORMONES THAN THE HOMOZYGOUS IN
ORAL CONJUGATED -- TRANSDERMAL
AND ORAL CONJUGATED ESTROGEN IN
TERMS OF LEVEL OF HORMONES.
>> THREE MINUTE WARNING.
>> OKAY.
WE'RE GOOD.
IN OTHER WORDS, WHAT WE HAVE IS
IF YOU HAVE MORE OF THE T
ALLELES, HOMOZYGOUS, LOWER
CONCENTRATIONS OF THESE
EFFECTIVE HORMONES.
WHAT DOES THAT TRANSLATE OUT TO
IN TERMS OF SYMPTOMS?
WITH TREATMENT THE WOMEN WITH CT
ALLELE, THAT IS THE
HETEROZYGOUS, HAD GREATER
DECREASES IN NIGHT SWEATS THAN
WOMEN WITH HOMOZYGOUS TT ALLELE.
THE MORE ESTROGEN IN THE BLOOD,
THE BETTER YOUR TREATMENT OF
SYMPTOMS, IN OTHER WORDS NOT
TRANSPORTED INTO THE CELL FOR
METABOLISM.
WE LOOKED AT ANOTHER
CHARACTERISTIC, THIS IS THE
DEPOSITION OF AMYLOID IN THE
BRAIN, CARRIERS FOR APOE4 MORE
LIKELY TO HAVE AMYLOID LAID
DOWN, A CHARACTERISTIC OF
ALZHEIMER'S DISEASE, WITH
ESTROGEN TREATMENT AMOUNT OF
AMYLOID WAS DETECTED IN BRAINS
OF THESE WOMEN LOWER THAN THOSE
IN EITHER CONJUGATED EQUINE OR
COMPARED TO PLACEBO, AGAIN THESE
ALLELES FOR ANOTHER
CHARACTERISTIC EXPRESSION OF IT,
LAYING DOWN OF AMYLOID WAS BEING
INFLUENCED BY THE PRESENCE OF
THE HORMONES.
WHAT ARE THE CHALLENGES GOING
FORWARD?
WE HAVE SIMILAR STUDY
POPULATIONS, WE TALKED
THROUGHOUT THIS TALK, WE HAVE
DISSIMILAR STUDY POPULATIONS,
KEEPS TRIAL, DISSIMILAR STUDY
POPULATIONS.
THERE'S NOT THE SAME TYPE OF
TREATMENT REGIME.
THE DOSE IS DIFFERENT, DURATION
IS DIFFERENT.
ONE OF THE PARTICIPANTS ASKED
CAN'T WE HAVE REGISTRIES WHERE
EVERYBODY REGISTRIES?
THESE ARE KIND OF QUESTIONS AND
TYPES OF INFORMATION THAT NEED
TO BE COLLECTED, AND UNLESS
COLLECTED ACCURATELY YOU WON'T
BE ABLE TO MAKE SOUND
CONCLUSIONS.
THERE'S ALSO DIFFERENCES IN THE
ASSESSMENTS AND CLASSIFICATION
OF SYMPTOMS AND OUTCOMES.
EVERYBODY USES NOT THE SAME
SCALE, SOME IS REALLY
QUALITATIVE RATHER THAN
QUANTITATIVE AND HOW DO YOU
ASSESS SEVERITY OF SYMPTOMS?
AND IT'S EASIER WHEN YOU MEASURE
SOMETHING LIKE BONE MINERAL
DENSITY OR CORONARY CALLS IF
CALCIFICATION BECAUSE YOU HAVE A
STAND ART QUALITATIVE OR
QUANTITATIVE MEASURE.
AND THEN YOU HAVE TO KEEP IN
MIND THERE'S INTERACTIONS AMONG
DIFFERENT GENETIC VARIANTS.
AND SO WE WOULD LIKE TO SAY HERE
IS OUR SEQUENCE AND GIVE ME THE
DRUG THAT'S RIGHT FOR ME, IT
DEPENDS ON THE GENETIC
COMPOSITION OF MULTIPLE ENZYMES
INVOLVED IN ESTROGEN METABOLISM
LET ALONE RECEPTORS AND OTHER
GENETIC VARIANTS AND THE
OUTCOMES THAT WE'RE LOOKING AT.
WE SAY MEDICINE IS A SCIENCE OF
UNCERTAINTY, IT IS AN ART, AN
ART OF PROBABILITY, AND MANY OF
THE PHYSICIANS IN THE AUDIENCE
I'M SURE SAY THAT THEY USE THOSE
IN TERMS OF ADJUSTING HORMONE
TREATMENTS FOR INDIVIDUAL
PATIENTS.
THAT'S PRETTY MUCH WHERE WE ARE
IN TERMS OF PHARMACOGENOMICS,
THE PRICE OF DOING GENETIC
TESTING ON EVERYONE IS NOT
REASONABLE, LET ALONE THE
INTERPRETATION IS NOT
STRAIGHTFORWARD FOR THOSE WHO
AREN'T USED TO LOOKING AT
COMPLICATED ANALYSIS.
>> THANKS, DR. MILLER.
WE'RE OUT OF TIME.
>> I WOULD LIKE TO SAY NONE
WOULD HAPPEN WITHOUT VIVIAN
PINN, THIS TAKEN IN 2016 WHEN
SHE WAS GUEST SPEAKER AT MAYO
AND WITHOUT HER WE WOULDN'T KNOW
ANY OF THIS INFORMATION TODAY.
THANK YOU VERY MUCH.
>> THANK YOU GREAT START TO THE
SESSION.
WE'RE GOING TO MOVE TO OUR NEXT
SPEAKER DR. ANDREW KAUNITZ, HE'S
PROFESSOR AND ASSOCIATE CHAIR,
UNIVERSITY OF FLORIDA, TALKING
ABOUT NOT SYSTEMATIC BUT I
IMAGINE SYSTEMIC HORMONE
THERAPY.
BALANCING EVIDENCE WITH CLINICAL
JUDGMENT.
I'M SETTING MY TIMER.
>> ANDY, I DON'T KNOW IF YOU'RE
MUTED.
>> I NEED TO GO TO PRESENTATION
MODE.
>> YOU'RE ALMOST THERE.
WE WOULD LOVE TO SEE YOUR FACE
IF YOU WANT TO TURN YOUR VIDEO
ON.
I CAN DO THAT FOR YOU ACTUALLY.
>> THANKS, DR. TEMKIN.
>> YOU'RE NOT IN PRESENTATION
MODE.
>> LET ME TRY AGAIN.
>> PERFECT.
>> GREAT.
HERE ARE MY DISCLOSURES.
AS YOU HEARD FROM DR. MANSON
FIRST THING IN THE MORNING,
SINCE PUBLICATION OF INITIAL WHI
FINDINGS OVER 20 YEARS AGO
THERE'S BEEN A TREMENDOUS DROP
IN PRESCRIPTION OF SYSTEMIC
HORMONE THERAPY BY U.S.
CLINICIANS.
THAT'S TRUE BOTH FOR PRIMARY
CARE PHYSICIANS, CLINICIANS, BUT
ALSO FOR OB/GYNs, PARTICULARLY
YOUNGER OB/GYNs.
DESPITE THAT HEALTHY WOMEN WITH
BOTHERSOME SYMPTOMS WITHIN 10
YEARS OF ONSET OF MENOPAUSE THAT
HORMONE THERAPY IS SAFE, MOST
CLINICIANS IN THE U.S. REMAIN
RELUCTANT TO PRESCRIBE IT
BECAUSE THEY ARE CONCERNED ABOUT
THE SAFETY OF HORMONE THERAPY.
WHAT WE'VE SEEN IS THAT THE
PENDULUM HAS SWUNG IN THE
DIRECTION OF AWAY FROM EVIDENCE
BASE AND TOWARDS FEAR-BASED
DECISION-MAKING ABOUT HORMONE
THERAPY LEAVING MANY WOMEN WHO
MIGHT OTHERWISE BE GOOD
CANDIDATES --
[ NO AUDIO ]
I'LL SPEND A FEW MINUTES
DEMAILING MY WISH LIST IN TERMS
OF FUTURE TRIALS THEY MIGHT
CONSIDER SPONSORING.
WE'VE HEARD FROM DR. MANSON,
ALSO FROM DR. MILLER ABOUT THE
DIFFERENCES BETWEEN ORAL AND
TRANSDERMAL ESTROGEN.
THERE'S NO RANDOMIZED DATA
COMPARING ONE WITH THE OTHER,
WE
HAVE A WEALTH OF OBSERVATIONAL
DATA, IF YOU ONLY WANT TO LOOK
AT ONE SUCH STUDY, THE BRITISH
EPIDEMIOLOGIST, HER WAS A
PARTICULARLY LARGE AND WELL
CONTROLLED STUDY BUT ALL OF THE
OBSERVATIONAL LITERATURE SHOWS
THAT IN CONTRAST TO ORAL
ESTROGEN, SHOWING RISK,
TRANSDERMAL ESTROGEN SEEMS NOT
TO HAVE ANY IMPACT ON RISK OF
VTE.
(INAUDIBLE) WHEN YOUR PATIENTS
HAD HIGH BMI OR OTHER RISK
FACTORS FOR VTE ARE PRESENT,
APPROPRIATE FOR WOMEN WITH
BASELINE HYPER TRIGLYCERIDEEMIA,
WE KNOW ORAL ESTROGEN IN
CONTRAST TO PATCH, CAN CAUSE
TRIGLYCERIDE LEVELS TO SKYROCKET
IN PATIENTS WITH ELEVATED
BASELINE LEVELS.
WE HAVE NO RANDOMIZED TRIALS
COMPARING BREAST SAFETY, THERE
IS ONE LARGER RECENTLY PUBLISHED
STUDY AND A SMALLER ONE, WITH
THE PROGESTIN USED IN WOMEN'S
HEALTH INITIATIVE, IN THE 16,000
WOMEN WITH INTACT UTERUS, AND
ANOTHER SYNTHETIC PROGESTIN USED
IN THE U.S., THE LARGE UK-BASED
STUDY WITH 40,000 CASES OF
BREAST CANCER, USING MPA IN THE
U.K. RELATIVE RISK OF BREAST
CANCER WAS 1.28, REMARKABLY
SIMILAR TO WHAT WE FOUND WITH
WOMEN'S HEALTH INITIATIVE WITH
EQUINE ESTROGEN.
WOMEN WHO USED ESTROGEN WITH
MICRONIZED PROGESTERONE, THERE
WAS NO DIFFERENCE BETWEEN
HORMONE USERS AND NON-HORMONE
USERS, RISK ESSENTIALLY
IDENTICAL.
OLDER FRENCH COHORT STUDY
LOOKING AT FRENCH TEACHERS, MUCH
SMALLER THAN THE U.K. STUDY,
FOUND ESSENTIALLY IDENTICAL
FINDINGS.
BREAST CANCER SAFETY WITH
RESPECT TO PROGESTERONE WITH
ESTROGEN, SMALL ELEVATED RISK
WITH ESTROGEN PLUS MPA.
LET'S MOVE ON TO SOME MORE
PRACTICAL ISSUES WHEN WOMEN ARE
INITIATING OR CONTINUING.
I THINK HELPING PROVIDE A SCRIPT
TO CLINICIANS WHO FEEL
UNCOMFORTABLE DISCUSSING SOME OF
THESE ISSUES CAN HELP IN SOME
CASES.
SO, IN A PATIENT WHO HAS
BOTHERSOME SYMPTOMS, CONSIDERING
INITIATING SYSTEMIC HT, I'LL SAY
SOMETHING LIKE HT IS HIGHLY
EFFECTIVE IN TREATING SYMPTOMS,
ALSO PREVENTING OSTEOPOROSIS AND
FRACTURES.
IF YOU CAN SEE THE SUGGESTED
SCRIPT, IF UTERUS IS ABSENT, IF
UTERUS IS PRESENT AND ESTROGEN
AND PROGESTERONE IS BEING
CONSIDERED OR REFILLED YOU CAN
SEE POTENTIAL SCRIPT, ALSO FOR
ORAL ESTROGEN RATHER THAN
TRANSDERMAL, WITH POINTING OUT
ORAL ESTROGEN AS WE HEARD TODAY
INCREASES RISK OF BLOOD CLOTS
SIMILAR TO YOUNGER WOMEN USING
ORAL CONTRACEPTIVES.
LET'S TALK ABOUT NUTS AND BOLTS
OF STARTING WOMEN ON SYSTEMIC
HORMONE THERAPY.
INCLUDING FORMULATIONS AND DOSE.
MANY CLINICIANS WILL START WITH
LOWER THAN STANDARD DOSES, MY
PREFER ENCE, THEY EVER BEEN
DEALING WITH SYMPTOMS AND MAJOR
SLEEP DISRUPTION FOR MONTHS OR
YEARS BEFORE THEY GET INTO MY
OFFICE.
SO I'LL START WITH THE STANDARD
DOSE, IT'S NOT UNUSUAL OR SIX
WEEKS, CONSIDER INCREASING THE
DOSE.
STANDARD IS 1 MILLIGRAM, .625,
FOR CONJUGATED EQUINE, USED IN
WOMEN'S HEALTH INITIATIVE.
EQUIVALENT STANDARD DOSES OF
PATCH, THERE'S TREMENDOUS
CONFUSION AMONG OUR COLLEAGUES
COMPARING DOSES OF TRANSDERMAL
ESTRADIOL OR PATCH WITH ORAL
ESTRADIOL.
1 MILLIGRAM TABLET REFERS TO
MILLIGRAM QUANTITY OF ESTROGEN
IN THAT TABLET, IN CONTRAST .05
PATCH RELEASES 24 -- RELEASES
.05 MILLIGRAMS OF ESTRADIOL PER
24 HOURS.
THE WATCH DOSE REFERS TO RELEASE
RATE, ORAL MILLIGRAM REFERS TO
QUANTITY OF STEROIDS IN THE
INDIVIDUAL TABLET.
IN WOMEN AT ELEVATED BASELINE
RISK FOR VTE, HIGH BMI PATIENTS,
OTHER WOMEN AT ELEVATED RISK FOR
ARTERIAL EVENTS I RECOMMEND
TRANSDERMAL VERSUS ORAL BECAUSE
OF SAFETY DIFFERENTIAL.
IN A PATIENT STARTED AFTER
SYMPTOMS REVOLVED ON THE INITIAL
DOSE, I'LL ENCOURAGE THE PATIENT
TO TRY LOWERING THE DOSE, AND IF
SYMPTOMS RETURN WITH A PHONE
CALL OR PATIENT PORTAL.
ONCE A PATIENT, NOW THE PATIENT
MIGHT BE IN HER LATE 50s OR
EARLY 60s, HAS BEEN USING
LOWER DOSE, MENTIONED HERE, FOR
SOME YEARS REPORTING NO
SYMPTOMS, IF HER UNDERLYING RISK
FOR OSTEOPOROSIS IS NOT
ELEVATED, I'LL ENCOURAGE HER TO
TRY DISCONTINUING SYSTEMIC
HORMONE THERAPY.
IF BOTHERSOME SYMPTOMS OR SENSE
OF WELL-BEING ARE LOST WITHOUT
USE OF SYSTEMIC THERAPY THE
PATIENT CAN RESTART.
ALSO KEEP IN MIND WHEN WOMEN
STOP SYSTEMIC HORMONE THERAPY OR
LOWER THEIR DOSE, VAGINAL
SYMPTOMS OF GSM MAY OCCUR, AND
USE OF VAGINAL ESTROGEN WOULD BE
APPROPRIATE IN THIS SETTING.
HOWEVER, IF THE WOMAN -- IF THE
PATIENT IS ON LOWER DOSE OF
SYSTEMIC HORMONE THERAPY FOR
SOME YEARS, IS AT ELEVATED
UNDERLYING RISK FOR OSTEOPOROSIS
AND FRACTURE, THAT MIGHT BE A
VERY SLENDER WOMAN, WITH A
POSITIVE FAMILY HISTORY,
CIGARETTE SMOKER, WHO USES
CORTICOSTEROIDS CONSIDER PROS
AND CONS OF LOW DOSE OR
ENDEFINITE USE.
WITH LOW DOSES OF ESTROGEN, THIS
IS WITHOUT ANY STRONG DATA TO
BACK IT UP, I WILL SOMETIMES USE
INTERMITTENT PRO GESTATIONAL
SUPPRESSION IN PATIENTS IS THAT
EXPERIENCE DYSPHORIA WITH
PROGESTINS, WHEN WE'RE USING
ESTROGEN LONG TERM, INDEFINITE
BASIS IN OLDER MENOPAUSAL
PATIENTS, I WOULD STRONGLY
PREFER TO USE TRANSDERMAL RATHER
THAN ORAL, AND I WOULD ALSO
BECAUSE OF THE BREAST HEALTH
SAFETY, I GUESS MENTION I WOULD
PREFER PROGESTERONE OVER
SYNTHETIC PROGESTINS.
IF WE ARE USING CYCLICAL OR
INTERMITTENT PROGESTATIONAL END
MEDIAL PROTECTION WITH
CONTINUOUS ESTROGEN USE, SINCE
WE DON'T HAVE DATA IN THIS
SETTING ABOUT END MEDIAL SAFETY
I WOULD MONITOR END MEDIAL
THICKNESS WITH VAGINAL
ULTRASOUND EVERY YEAR OR TWO.
OF COURSE, IN ANY WOMAN USING
HORMONE THERAPY REGARDLESS OF
DOSE, JUST AS TRUE FOR ANY
MENOPAUSAL PATIENT IN GENERAL,
WHETHER SHE'S USING HORMONES OR
NOT, IF THERE'S ANY REPORT OF
SPOTTING OR BLEEDING PROMPT END
MEDIAL ASSESSMENT IS
APPROPRIATE.
WHEN THINGS SEEM TO BE GOING
WELL WITH YOUR 72-YEAR-OLD
PATIENT AT ELEVATED BASELINE
RISK FOR OSTEOPOROSIS DOING
WELL, LOW DOSE, YOU GET A NOTE
FROM THE INSURANCE COMPANY,
REFERRING TO THE CRITERIA, THE
COMMITTEE RESPONSE FOR THE LIST
HAS NO MENOPAUSE EXPERTS ON THAT
COMMITTEE.
AND THE GOOD NEWS IS THAT BOTH
AMERICAN COLLEGE OF OB/GYNs
AND ALSO NORTH AMERICAN
MENOPAUSE SOCIETY, NEITHER
PROFESSIONAL GROUP ENDORSES
STOPPING SYSTEMIC HORMONE
THERAPY BASED ON ARBITRARY AGE
BUT RATHER INDIVIDUALIZING EACH
PATIENT'S CARE.
WE'VE TALKED ABOUT THE SAFETY OF
TRANSDERMAL ESTROGEN WITH
RESPECT TO BLOOD CLOT.
WE'VE TALKED ABOUT SAFETY OF
PROGESTERONE VERSUS SYNTHETIC IN
TERMS OF BREAST HEALTH.
I HOPE YOU CAN FEEL THAT THE
PENDULUM IS SWINGING BACK IN THE
DIRECTION AWAY FROM FEAR, MORE
TOWARD EVIDENCE BASED
DECISION-MAKING BETWEEN PATIENT
AND CLINICIAN REGARDING USE OR
NON-USE OF SYSTEMIC HORMONE
THERAPY.
DR. MANSON CLARIFIED FOR MOST
GENERALLY HEALTHY WOMEN WITHIN
TEN YEARS OR LESS OF THE ONSET
OF MENOPAUSE, WITH BOTHERSOME
SYMPTOMS, SYSTEMIC HORMONE
THERAPY IS SAFE.
I THINK THAT'S A MESSAGE WE
SHOULD TAKE TO HEART AND FOCUS
ON EVIDENCE BASE RATHER THAN
FEAR-BASED DECISION MAKING FOR
OUR PATIENTS AND SELVES IN TERMS
OF PRESCRIBING HORMONE THERAPY.
DR. TEMKIN ASKED ME FOR THE LAST
PART OF MY TALK TO COME UP WITH
A WISH LIST FOR THE OFFICE OF
RESEARCH ON WOMEN'S HEALTH, WHAT
CLINICAL TRIALS WOULD I LIKE TO
SEE THE OFFICE SPONSOR?
HERE GOES.
WE TALKED ABOUT THE LACK OF
RANDOMIZED DATA, IT WOULD BE
USEFUL TO SPONSOR SUCH A TRIAL.
LIKEWISE, WE TALKED ABOUT WHAT
SEEMS TO BE BASED ON
OBSERVATIONAL DATA, THE BETTER
BREAST HEALTH SAFETY WITH
RESPECT TO NATURAL , OUR PATIENS
COULD BENEFIT FROM RANDOMIZED
TRIAL DATA HERE.
I WOULD LOVE TO SEE THE OFFICE
OF RESEARCH ON WOMEN'S HEALTH
SPONSOR SUCH A TRIAL.
LET'S TALK ABOUT BREAST CANCER
CHEMOPROPHYLAXIS.
WE KNOW THAT DR. MANSON
MENTIONED IT THIS MORNING THAT
CONJUGATED EQUINE ESTROGEN WITH
20 YEARS OF FOLLOW-UP IN 10,000
WOMEN STUDY IN WHI, WOMEN POST
HYSTERECTOMY, CEE LOWERED BREAST
CANCER INCIDENCE AND MORTALITY
WITH 20 YEARS FOLLOW-UP, THERE
WAS A 40% REDUCTION IN BREAST
CANCER SPECIFIC MORTALITY.
THE TWO ARE AGENTS RECOMMENDED
IN HIGH RISK WOMEN, THESE HAVE
DEMONSTRATED REDUCING INCIDENCE,
NEITHER ONE HAVE BEEN DOCUMENTED
TO REDUCE BREAST CANCER
MORTALITY.
SO LEAVING THE OBSERVATION THAT
THE ONLY AGENT THAT HAS BEEN
DOCUMENTED TO REDUCE BREAST
CANCER MORTALITY IS CEE, AS
DEMONSTRATED IN THE 20-YEAR
FOLLOW-UP OF THE POST
HYSTERECTOMIZED.
>> THREE MINUTE WORK.
>> PROPHYLAXIS HASN'T CHANGED
IN TWO DECADES.
AND YOU CAN SEE OBSERVATIONS
MADE, THAT HE MAKES IN HIS 2021
REVIEW ARTICLE.
ESTROGEN RECEPTOR POSITIVE AND
PROGESTERONE RECEPTOR POSITIVE
CANSERS IS HAVE LOW MORTALITY,
ER PUSS/PR NEGATIVE HAVE HIGHER
MORTALITY.
THIS MAY BE WHY MORTALITY
REDUCTION HAS NOT BEEN OBSERVED
WITH SERMs OR AROMATASE
INHIBITORS.
MY HOPE IS THAT OFFICE OF
RESEARCH ON WOMEN'S HEALTH WOULD
CONSIDER A TRIAL OF CONJUGATED
ESTROGEN AS POSSIBLE BREAST
CANCER CHEMOPROPHYLAXIS IN HIGH
RISK WOMEN POST HYSTERECTOMY.
DO WE HAVE ONE MINUTE FOR
COGNITIVE DECLINE OR NOT?
>>YOU HAVE ONE MINUTE.
>> GREAT.
>> EXACTLY ONE MINUTE.
>> WE KNOW A.D. IS MORE
PREVALENT IN WOMEN.
AND WE KNOW THREE NIH-FUNDED
TRIALS, TWO OF WHICH YOU HEARD
ABOUT, THREE ALREADY TODAY,
FOUND WITH SHORTER TERM USE OF
HORMONE THERAPY NO IMPACT ON
COGNITIVE FUNCTION.
HOWEVER, LARGE WELL-CONDUCTED
NATIONAL INSTITUTES OF AGING
STUDY INITIALLY PUBLISHED SOME
YEARS AGO FOUND IN CONTRAST TO
OVERALL USE OF HORMONE THERAPY
WITH NO IMPACT, WOMEN WHO
STARTED HORMONE THERAPY AS
RECENTLY AS MENOPAUSAL WOMEN OR
CONTINUED HORMONE THERAPY FOR
MORE THAN A DECADE, THERE WAS
REDUCED INCIDENCE OF ALZHEIMER'S
DISEASE.
VERY SIMILAR FINDING IN A LARGE
NATIONWIDE FINNISH STUDY, NO
IMPACT OVERALL BUT WHEN USED FOR
MORE THAN A DECADE, A VERY
SUBSTANTIAL REDUCTION IN
ALZHEIMER'S DISEASE.
I WOULD LOVE TO SEE THE OFFICE
OF RESEARCH AND WOMEN'S HEALTH
SPONSOR A LONG-TERM TRIAL OF
HORMONE THERAPY, STARTING SOON
AFTER MENOPAUSE EXTENDING FOR A
DECADE.
I'D LIKE TO THANK THE NIH FOR
THIS OPPORTUNITY TO DISCUSS
SYSTEMIC HORMONE THERAPY.
>> I'M NOT SURE THAT
CONVERSATION WENT EXACTLY LIKE
THAT.
BUT I AM GLAD FOR YOU TO SHARE
YOUR THOUGHTS ABOUT FUTURE
RESEARCH.
THANK YOU.
>> THANKS VERY MUCH.
I WANT TO THANK THE SPEAKERS FOR
STAYING ON TIME.
WE'LL MOVE TO THE NEXT ONE
BECAUSE A LOT OF PEOPLE HAVE A
LOT TO SAY THAT'S IMPORTANT.
IT'S MY PLEASURE NEXT TO
INTRODUCE ANDREA LACROIX,
PROFESSOR OF EPIDEMIOLOGY,
UNIVERSITY OF CALIFORNIA SAN
DIEGO.
AND SHE WILL BE SPEAKING ABOUT
KEY INGREDIENTS FOR TRAVERSING A
HEALTHY MENOPAUSE.
>> I WANT TO MAKE SURE YOU CAN
HEAR ME.
>> WE CAN HEAR YOU.
>> NO SMALL MIRACLE TODAY.
THANK YOU FOR HAVING ME WITH
YOU.
I'M GRATEFUL TO TALK ABOUT KEY
INGREDIENTS FOR TRAVERSING
HEALTHY MENOPAUSE.
I JUST WANTED TO START WITH
QUARANTINE MENOPAUSE.
THIS IS A SLIDE THAT SHOWS NEWS
STORIES THAT CAME OUT OVER THE
COVID PANDEMIC FROM MARCH 2020
ON, AND I DON'T KNOW WHETHER IT
WAS CLOSE QUARTERS OR EXTRA TIME
TO THINK ABOUT OUR BODIES, ALL
THE EXTRA RESPONSIBILITIES THAT
WOMEN HAD DURING THIS PERIOD, OR
JUST GEN X AND YOUNGER WOMEN
COMING INTO PERIMENOPAUSE DURING
THIS EXPERIENCE, LESS ACCESS TO
THEIR HEALTH CARE SYSTEMS DURING
THE PANDEMIC, BUT IT GENERATED A
BUZZ ABOUT MENOPAUSE AND HOW
CONCERNS WERE RAISED ABOUT HOW
THEY DIDN'T KNOW WHAT WAS
HAPPENING IN THEIR BODIES,
RESEARCH HADN'T BEEN DONE IN
CERTAIN GROUPS OF WOMEN, THEY
HAD BEEN NOT PREPARED WELL BY
THEIR MOTHERS, NOT ADVISED WELL
BY THEIR CLINICIANS.
SO THESE WERE NEWS STORIES THAT
KEPT MOUNTING DURING THE
PANDEMIC, AND IF YOU FAST
FORWARD TO 2023, MAYBE THIS WAS
A CULMINATION OR MAYBE ANOTHER
STEP IN THE CURRENT EXPERIENCE
THAT WE'RE HAVING BUT THERE WAS
JUST A "NEW YORK TIMES"
EDITORIAL IN WHICH INVESTIGATORS
EXPRESSED DISMAY AT NOT BEING
COUNSELED WELL ABOUT HER
MENOPAUSE SYMPTOMS, NOT KNOWING
WHAT TO EXPECT IN THE
PERIMENOPAUSE, ARGUING
STRENUOUSLY I WOULD SAY AGAINST
IGNORANCE ABOUT THE SPACE OF
LIFE AND ALSO ASKING THE
QUESTION, WHAT IF YOU KNEW ABOUT
A PILL THAT COULD HELP YOU WITH
THESE SYMPTOMS?
AND WHY DON'T WE KNOW ABOUT
THAT?
AND SO WE'RE GOING TO ADDRESS
THIS BROADLY IN THIS TALK TODAY.
OPRAH WINFREY JUST HAD I THINK A
WEEK'S WORTH OF MENOPAUSE
SYMPOSIA FOR WOMEN WITH VARIOUS
GUEST SPEAKERS TALKING,
ACTRESSES, DOCTORS TALKING ABOUT
THEIR EXPERIENCE IN MENOPAUSE.
AS YOU'VE SEEN TODAY, MUCH OF
THE DIALOGUE ABOUT ESTROGEN
HORMONE THERAPY HAS SINCE 2002
BEEN THROUGH THE LENS OF THE
RESULTS OF THE WOMEN'S HEALTH
INITIATIVE, I'M A WHI
INVESTIGATORS FOR 30 YEARS, I
WANT TO ACKNOWLEDGE AS DR.
MANSON DID AND OTHER SPEAKERS
THIS TRIAL WAS MEANT ONLY TO
TEST WHETHER HORMONE THERAPY WAS
USEFUL FOR PREVENTION OF CHRONIC
DISEASES, THE RESULTS ESPECIALLY
OVER THE LONG TERM FOLLOW-UP ARE
NUANCED, ESTROGEN IF TAKEN MORE
A NUMBER OF YEARS HAS SERIOUS
RISKS AND BENEFITS.
COMPLETELY SEPARATE FROM THE
DISCUSSION ABOUT TREATMENT OF
VASOMOTOR SYMPTOMS.
SO PART OF WHAT WE'RE DOING
TODAY IS TRYING TO SEE HORMONE
THERAPY THROUGH VASOMOTOR RELIEF
AND I'D LIKE TO ADDRESS THE KEY
INGREDIENTS FOR MAKING DECISIONS
ABOUT TRAVERSING A HEALTHY
MENOPAUSE, AND DR. PINN HERSELF
SHORTLY AFTER THE MAIN WHI
RESULTS WERE PUBLISHED WROTE
THIS QUOTE.
GOOD DECISIONS INVOLVE GATHERING
AND EVALUATING INFORMATION,
WEIGHING WHAT IS IMPORTANT AT A
PERSONAL LEVEL, FINDING THE
NECESSARY RESOURCES FOR THE TYPE
AND QUALITY OF CARE REQUIRED,
AND MANAGING THE ASSOCIATED
COSTS.
ONE MIGHT ARGUE I THINK WISELY
THESE ARE THE KEY INGREDIENTS
FOR TRAVERSING A HEALTHY
MENOPAUSE.
I'M GOING TO FOCUS ON THIS FIRST
ONE INVOLVING GATHERING AND
EVALUATING INFORMATION.
NUMBER ONE INGREDIENT IN MY VIEW
IS HAVING KNOWLEDGE ABOUT WHAT'S
HAPPENING IN OUR BODIES, AND
KNOWLEDGE ABOUT WHAT IS
AVAILABLE TO US, TO TREAT
SYMPTOMS, AND WHAT OUR OWN
VALUES ARE RELATIVE TO THOSE
DIFFERENT KINDS OF THERAPIES.
SO, AFTER THE WOMEN'S HEALTH
INITIATIVE WAS DONE, THIS
COLLABORATION OF NIH INSTITUTES
INCLUDING THE ORWH CAME TOGETHER
TO HELP WOMEN GET MORE KNOWLEDGE
ABOUT ALTERNATIVE TREATMENTS FOR
RELIEVING MENOPAUSE SYMPTOMS
INCLUDING HORMONE THERAPY, BUT
INCLUSIVE OF A GREAT MANY OTHER
THERAPIES, AND MY COLLEAGUES AND
I WERE LUCKY ENOUGH TO COMPETE
FOR WHAT BECAME THE MS. FLASH
MET WORK BRINGING TOGETHER FOUR
CLINICAL CENTERS AND 20 TO 30
INVESTIGATORS SPECIALIZING IN
THIS AREA TO FIND NEW WAYS TO
ALLEVIATE THE MOST COMMON
BOTHERSOME SYMPTOMS OF THE
MENOPAUSE TRANSITION BY
DESIGNING AND CONDUCTING
MULTIPLE CONCURRENT CLINICAL
INTERVENTION STUDIES,
ACCOMMODATING A WIDE SCOPE OF
POPULATIONS AND INTERVENTION
STRATEGIES.
I READ THOSE BECAUSE WE REALLY
TRULY DEVOTED OURSELVES TO
INTERVENTION TRIALS THAT
EMBODIED THAT PURPOSE.
WE ESTABLISHED COMMON
ELIGIBILITY CRITERIA, AND MY
DEAR COLLEAGUE NOW DEPARTED,
KATHERINE NEWTON, WROTE A
METHODS PAPER ON COMMON
MS. FLASH CRITERIA TRANSLATING
WELL IN CURRENT NEW TRIALS FOR
VASOMOTOR SYMPTOMS.
WE SET THE AGE RANGE TO 40 TO
62, WOMEN HAD TO BE IN THE
MENOPAUSE TRANSITION OR
POSTMENOPAUSAL, AT LEAST 14
FLASHES PER WEEK, SOME
BOTHERSOME OR SEVERE.
THIS WE'LL COME BACK TO, BUT WE
DID NOT REQUIRE IN THE TRIALS
THAT WOMEN HAVE 7 OR MORE
MODERATE OR SEVERE HOT FLASHES
PER DAY.
THAT WAS BECAUSE WE WANTED TO
TARGET THIS BROADER POPULATION
OF WOMEN THAT ARE BOTHERED BY
HOT FLASHES BUT NOT AT THAT
LEVEL.
THEY HAD TO HAVE GOOD GENERAL
HEALTH AND SIGN INFORMED
CONSENT.
WHY IS IT IMPORTANT TO DO TRIALS
THAT ARE MORE INCLUSIVE OF THE
WOMEN WHO EXPERIENCED VASOMOTOR
SYMPTOMS?
THE REASON IS THAT IT'S
EXTREMELY RARE FOR WOMEN TO HAVE
7 OR MORE MODERATE OR SEVERE
VASOMOTOR SYMPTOMS A DAY.
U.S. REPRESENTATIVE DATA FROM A
WHILE AGO, BUT THE MOST CURRENT
I COULD FIND AT THE MOMENT WE
NEED TO DO MORE SURVEILLANCE OF
THIS REALLY.
BUT ANYWAYS, WHAT THIS SHOWS IS
AS A PERCENT OF THE WOMEN WHO
EXPERIENCE VMS, NOT EVEN
PREVALENCE IN THE WHOLE
POPULATION, JUST THE WOMEN IN
THIS AGE RANGE WHO EXPERIENCE
HOT FLASHES, NIGHT SWEATS, THE
PURPLE BARS ARE THE ONES HAVING
THE MOST HOT FLASHES, AND YOU
CAN SEE IT'S A SMALL PERCENTAGE
OF THE POPULATION, PROBABLY 2 TO
5% OF THE WHOLE POPULATION THAT
FIT INTO THIS CATEGORY OF 7 OR
MORE MODERATE OR SEVERE HOT
FLASHES A DAY.
WE TARGETED A BROADER AUDIENCE
OF WOMEN.
AND WE TESTED IN THE FIRST THREE
MSFLASH TRIALS SSRI VERSUS
PLACEBO, IN A 3 X 2 FACTORIAL
DESIGN TRIAL TESTED EXERCISE AND
YOGA VERSUS BEHAVIORAL CONTROL,
AND OMEGA 3 SUPPLEMENTATION
WHICH AT THE TIME WAS THOUGHT TO
HAVE SALUTARY EFFECTS ON HOT
FLASHES AND NIGHT SWEATS.
AND WE STUDIED LOW DOSES TRAY
DIOL AND VENLAFAXINE COMPARED TO
PLACEBO AND COMPARED SIDE BY
SIDE.
I WOULD NOT SAY HEAD TO HEAD BUT
WE HIDE BEHIND THE DESIRE FOR
HEAD TO HEAD TRIALS THAT ARE
ALMOST NEVER DONE, AS A WAY OF
NOT TELLING WOMEN HOW THESE
DIFFERENT THERAPIES COMPARE.
AND WE WANTED TO GET PAST THAT.
LET'S LOOK AT THE COMPARATIVE
EFFECTS ON VASOMOTOR SYMPTOM
FREQUENCY.
WE DO POOLED ANALYSIS, ALL
PUBLISHED, IT SAYS UNDER REVIEW,
THIS IS VERY MUCH PUBLISHED.
WE'RE COMPARING THE CHANGES FROM
BASELINE HERE, VMS FREQUENCY IN
INTERVENTION GROUP RELATIVE TO
COME BIBBED GROUP -- COMBINED
GROUP.
FOR FREQUENCY, LOW DOSE
ESTRADIOL RESULTED IN MOST
REDUCTION IN HOT FLASHES.
TWO OTHERS REDUCED HOT FLASHES.
THE DIFFERENCE BETWEEN THE THREE
MEDICINES IS HALF A HOT FLASH A
DAY COMPARED TO PLACEBO.
I WOULD ARGUE THAT MESSAGE IS
NOT GETTING ACROSS TO VIRTUALLY
ANYONE.
YOGA DIDN'T DO MUCH.
OMEGA 3 ACTUALLY DIDN'T DO MUCH.
THE OPPOSITE DIRECTION.
AND EXERCISE DIDN'T HELP WITH
FREQUENCY OF HOT FLASHES.
ALSO IMPORTANT INFORMATION.
WHEN WE LOOK AT VMS BOTHER, THIS
IS NOT SEVERITY BUT BOTHER, WE
SEE SIMILAR RESULTS, THREE-PILL
TRIALS REDUCED, MOST BY
ESCITALOPRAM AND ESTRADIOL
ALMOST EQUIVALENTLY.
GOING A RE-- YOGA REDUCED A
LITTLE BIT, NOT AS MUCH AS PILL
INTERVENTIONS.
IF WE LOOK AT CLINICAL
IMPROVEMENT, DEFINED AS AT LEAST
50% IMPROVEMENT FROM BASELINE
AND VMS FREQUENCY, YOU CAN SEE
THESE MEDICINES, THREE-PILL
INTERVENTIONS WERE VERY
COMPARABLE.
I THINK THAT THESE KIND OF
COMPARISONS ARE SUPER IMPORTANT
TO GET ACROSS IN CLINICAL
PRACTICE.
WOMEN HAVE CHOICE OF MEDICINES.
I DON'T THINK THEY REALIZE THAT.
SO, WE ALSO LOOKED AT INSOMNIA,
THE SECOND MOST BOTHERSOME
MID-LIFE SYMPTOM ACCORDING TO
WORK IN MSFLASH, VASOMOTOR
SYMPTOMS AND TROUBLE SLEEPING.
FOR THE NEXT COMPARISONS
RESTRICTING ARE THOSE WITH INDEX
OF 12, THE CUT POINT ON THE IS.
WE DID A FOURTH TRIAL TARGETING
SLEEP PROBLEMS THAT TESTED
COGNITIVE BEHAVIORAL THERAPY, AS
WELL AS MEASURING SLEEP OUTCOMES
IN ALL THE PREVIOUS TRIALS THAT
I SHOWED YOU.
THIS WAS PUBLISHED BY SUMMA
CURRY, CBT INTERVENTION INVOLVED
CBTI, TARGETING MENOPAUSAL AND
AGE-RELATED CHANGES IN SLEEP,
SOME KNOWLEDGE, SLEEP HYGIENE
EDUCATION, SLEEP RESTRICTION,
STIMULUS CONTROL PROCEDURES
REALLY IMPORTANT PART OF CBT-I,
AND I CAN ANSWER MORE QUESTIONS
ABOUT THAT LATER, IF PEOPLE HAVE
THEM.
COGNITIVE STRATEGIES TO DISRUPT
SLEEP-RELATED DYSFUNCTIONAL
BELIEFS AND ATTITUDES.
BOTH GROUPS GOT THE SAME AMOUNT
OF CONTACT WITH TELEPHONE
INTERVENTIONISTS, WE DID THIS ON
THE TELEPHONE SO IT WOULD BE
PRAGMATIC AND ABLE TO SCALE UP,
AND MENOPAUSE EDUCATION WAS THE
CONTROL.
AND SO NOW WE ADD THE CBT-I
INTERVENTION INTO THE MECHANICS,
IN WOMEN WITH INSOMNIA, AND WE
SEE THAT CBT-I FAR AND AWAY
SURPASSED ANY INTERVENTION FOR
IMPROVING SLEEP ON THE ISI IN
THESE WOMEN.
THE NEXT MOST EFFICACIOUS TWO
DRUGS, ESTROGEN LESS EFFECTIVE
THAN THOSE, YOU'LL SEE
CONFIDENCE INTERVALS
OVERLAPPING.
INTERESTINGLY EXERCISE AND YOGA
WERE AS EFFECTIVE AS SSRI AND
SNRI AT 12 WEEKS, A LONGER
TRIAL.
THESE HELP A LITTLE BIT WITH
SLEEP, CBT-I HELPS A LOT.
WHEN WE LOOK AT PITTSBURGH SLEEP
QUALITY INDEX WE GET THE VERY
SAME PICTURE.
DIFFERENT MEASURE OF SLEEP
OUTCOME AND SAME RESULTS.
A SUMMARY OF INTERVENTION
EFFECTS RELATED TO SLEEP WOULD
BE CBTI IS THE MOST EFFECTIVE
INTERVENTION FOR IMPROVING
INSOMNIA IN SLEEP QUALITY, WE
HEAR SO MUCH ABOUT THE
IMPORTANCE OF SLEEPING WELL IN
RELATION TO HEALTHY AGING, AND
THERE'S A TREMENDOUS AMOUNT OF
RESEARCH IN THIS AREA.
I THINK THAT HELPING WOMEN WITH
THEIR SLEEP PROBLEMS IN MID-LIFE
COULD SET US UP FOR HEALTHY
AGING IN A WAY WE'RE NOT
ATTENDING TO NOW.
I THINK IT'S IMPORTANT FOR IT TO
BE AVAILABLE, CBT-I, AND THIS
TELEPHONE INTERVENTION, IT'S
SOMETHING I REALLY HOPE COULD
MAKE HAPPEN TO ENCOURAGE
HAPPENING, BECAUSE IT'S SO MUCH
MORE EFFECTIVE THAN ANY PILL.
THE DRUGS WERE MODESTLY
EFFECTIVE AT IMPROVING SLEEP
QUALITY, YOGA AND EXERCISE WERE
ABOUT AS EFFECTIVE AS THE TWO
PILLS, AND ESTRADIOL WAS ABOUT
AS EFFECTIVE AS WELL.
LET'S TALK ABOUT
MENOPAUSE-RELATED QUALITY OF
LIFE.
A VERY SALUTORY OUTCOME BASED ON
AN INSTRUMENT DEVELOPED BY LUCE
IS, 29 QUESTIONS, THERE ARE FOUR
DOMAIN SCORES, VASOMOTOR,
PSYCHOSOCIAL, PHYSICAL, SEXUAL,
RANGING FROM 1 TO 8, HIGHER
SCORES INDICATE MORE OR MORE
BOTHERSOME SYMPTOMS.
HIGHER SCORES MEANS WORSE
QUALITY OF LIFE.
IN THAT DOMAIN.
YOU CAN SEE THERE ARE SOME --
THESE ARE THE QUESTION CONTENT
AREAS FOR EACH OF THE DOMAINS.
PHYSICAL DOMAIN IS, YOU KNOW,
BASKET OF IRRITATING SYMPTOMS OF
A PHYSICAL NATURE.
THE OTHERS ARE MUCH MORE
TARGETED.
PSYCHOSOCIAL DOMAIN INCLUDES
ANXIETY, DEPRESSION, VASOMOTOR
INCLUDES HOT FLASHES AND NIGHT
SWEATS, SEXUAL DOMAIN INCLUDES
DESIRE, VAGINAL DRYNESS,
INTIMACY.
SO WHEN WE LOOK AT TOTAL MENQOL
CHANGE FROM BASELINE WE SEE
IMPROVEMENTS IN QUALITY OF LIFE
--
>>THREE-MINUTE WARNING.
>> HOW MANY?
>> THREE MINUTES.
>> WE SEE THAT HALF A POINT
HERE IS WHAT YOU GET FOR
ESTRADIOL, ALMOST QUIFF LEAPT
FOR ECCITALOPRAM.
EFFECTS ON MANQOL ARE MODEST.
A NEW DRUG GOT APPROVED BY THE
FDA, AVAILABLE TO WOMEN IN THREE
WEEKS PURPORTEDLY.
THIS IS CALLED VESOLINITAN, THE
ICER PUT OUT A REPORT THAT MAKES
IT EASY TO COMPARE THE EFFICACY
OF THIS NEW MEDICINE TO OTHER
TRIALS THAT HAVE TESTED.
I PUT IN THIS SLIDE HERE LOW
DOSE ESTRADIOL AND ECCITALOPRAM.
HOW SEVERITY DOESN'T DIFFER THAT
MUCH BY TREATMENT OPTION AND
MENQOL SCORES ARE MODESTERLY
IMPROVED.
I WON'T SAY MUCH ABOUT
MYMENOPLN.
OUR GOAL WAS TO DISSEMINATE THIS
INFORMATION TO LEARN ABOUT
DIFFERENT TREATMENTS FOR
MENOPAUSE, WHAT'S HAPPENING IN
THEIR BODY, HOW OTHER WOMEN
EXPERIENCE THIS, HOW THEY MIGHT
TALK TO THEIR CLINICIANS.
THAT'S AVAILABLE TO EXPLORE.
WE DID A RANDOMIZED TRIAL
AGAINST REPUTABLE WEBSITES LIKE
THE NAMs WEBSITE AND OFFICE OF
WOMEN'S HEALTH WEBSITE ON
MENOPAUSE, AND MYMENOPLN WEBSITE
INCREASED KNOWLEDGE, WOMEN LIKED
IT MORE THAN OTHER REPUTABLE
WEBSITES, BUT, YOU KNOW, I THINK
THEY ARE ALL GOOD.
WE CERTAINLY WANT PEOPLE TO JUST
HAVE THE INFORMATION THAT THEY
NEED.
FINAL THOUGHTS, MID-LIFE WOMEN
ARE A MAJOR MARKET FOR PRODUCTS
AND SERVICES.
IT'S ESTIMATED THAT THAT MARKET
IS WORTH $24.4 BILLION BY 2030.
WOMEN ARE A TARGET FOR NEW
BUSINESS MODELS FOR BUSINESS
SERVICES BY FEM TECH AND
COMPANIES SUCH AS GWYNETH
PALTROW'S COMPANY.
WOMEN SHOULD NOT HAVE TO PAY
EXTRA TO MANAGE MENOPAUSE AND
ONCE TRIALS ARE IN THE PUBLIC
DOMAIN, PARTICULARLY THOSE PAID
FOR BY NIH, IT'S IMPORTANT THAT
A WOMAN NOT HAVE TO GIVE UP
NIAGARA HAVE THIS INFORMATION --
INFORMATION THAT OUR TAXPAYER
DOLLARS PAID FOR.
AND CURRENT TREATMENTS WITH
ADEQUATE EVIDENCE HAVE MODEST
AND SIMILAR EFFECTS ON VASOMOTOR
SYMPTOMS AND I ENCOURAGE ALL OF
YOU COUNSELING WOMEN TO MANGE
--
MAKE SURE THEY GET THE CHOICE
ABOUT WHICH MEDICINE AND NOT
ONLY THINK ONE WORKS, BECAUSE
THEY ALL WORK SIMILARLY WELL.
DR. PINN SAYS WOMEN AND HEALTH
CARE PROVIDERS NEED TRUSTWORTHY
INFORMATION TO MAKE RESPONSIBLE
INFORMED DECISIONS REGARDING
HEALTH AND WELL-BEING.
I COULD NOT AGREE MORE.
AND FOR THOSE TRYING TO IMPACT
POSITIVELY THE HEALTH OF WOMEN I
THINK WE ALL NEED TO JOIN
TOGETHER TO MAKE THIS HAPPEN.
I WILL STOP THERE.
>> THANK YOU VERY MUCH.
WE WILL MOVE TO THE FINAL
PRESENTATION OF THE SESSION.
AND WE'VE GOT NICE QUESTIONS
PILING UP IN THE Q&A.
LET ME INTRODUCE DR. ROBERT
WILD, PROFESSOR OF OB/GYN,
UNIVERSITY OF OKLAHOMA HEALTH
SCIENCES CENTER, HE IS GOING TO
ADDRESS THE ORWH RESEARCH
AGENDA.
>> GOOD AFTERNOON.
I BRING GREETINGS FROM OKLAHOMA,
IT'S MY PLEASURE TO PRESENT THE
LAST PRESENTATION OF A FABULOUS
SESSION.
I EXPRESS MY THANKS TO THE
ORGANIZERS FOR INCLUDING ME BUT
WHAT A GREAT SYMPOSIUM.
I THOUGHT IT WON IMPORTANT -- E
IMPORTANT TO CHANGE PACE.
WE'VE COME SO FAR BUT WE HAVE SO
FAR TO GO.
I'D LIKE TO BRING PERSPECTIVE.
NEXT SLIDE PLEASE.
I'LL TALK ABOUT WHERE WE WERE,
YOU'VE HEARD ABOUT WHERE WE ARE
ALL DAY.
I'M GOING TO SAY WORDS ABOUT
WHERE WE NEED TO BE.
NO CONFLICTS.
NEXT SLIDE PLEASE.
IN THE BEGINNING, IT'S IMPORTANT
TO RECOGNIZE THE ROLE OF DR. ED
BRANT, U.S. ASSISTANT SECRETARY
FOR U.S. HEALTH, LIVED ON NIH
CAMPUS WITH HIS WIFE PAT, HE WAS
NEVER AT THE NIH, AS THE NIH
DIRECTOR ACTUALLY NIH REPORTED
TO HIM AS DID ALL OF PUBLIC
HEALTH, AND HE APPOINTED C
EVERETT KOOP, HE PICKED A
WINNER, HE WAS IN THAT ROLE TWO
YEARS MYSELF.
HE WAS MY TEACHER AND MENTOR,
AND I WAS FUNDED BY THE NHLBI IN
PREVENTED CARD GEORGE.
CARDIOLOGY.
HIS RIGHT HAND WOMAN WAS VALERIE
WILLIAMS, SHE WAS THE STAFF
PERSON FOR NIH AND INDIAN HEALTH
SERVICE, IMPORTANT FOR OKLAHOMA
HEALTH.
SHE BECAME EXECUTIVE SECRETARY
FOR COORDINATING COMMITTEE ON
WOMEN'S HEALTH, IN A TIME LED BY
RUTH KIRSCHSTEIN AND DORIS
MERITT.
I WAS AN ADVISER BETWEEN 1999
AND 2003, VIVIAN ASKED ME TO BE
LIAISON TO THE WHI FOR THE ORWH.
I WAS NO STRANGER TO THE WHI, ON
THE REVIEW COMMITTEE FOR EASTERN
SEABOARD, HAD SOME OPPORTUNITY
TO HAVE INPUT IN TERMS OF WHO
GOT FUNDED.
I GOT TO PUT IN MY TWO CENTS
ABOUT DESIGN AT THE NCI, I
WARNED ABOUT ROUTE PREPARATION,
DOSAGE, MESSAGES TO CLINICIANS
AT THE TIME, I CAN TELL IT DID
COME TRUE, I'M HAPPY TO SEE THAT
HAPPENED IN THE PROCESS.
I CAME FROM THE PERSPECTIVE OF
REPRODUCTIVE ENDOCRINOLOGIST,
GYNECOLOGY'SI LATER
EPIDEMIOLOGY, A MENOPAUSE
PRACTITIONER NOW, I AM NOW.
I WOULD LIKE TO POINT OUT
SOMETIMES I WAS VIVIAN'S
MEMORIAL SIS.
NEMESIS, SHE TOLD ME DON'T TRY
SAVE MONEY GOING FROM CON
MEETING TO THE NEXT.
THERE ARE A LOT OF COURAGEOUS
PEOPLE WERE INVOLVED.
IT'S A MONUMENTAL TASK TO FOCUS
ON WOMEN.
A LOT OF COURAGEOUS PEOPLE
PUSHING UP AGAINST THE CURVE.
I TALKED ON THE FAR RIGHT RUTH
KIRSCHSTEIN MENTIONED WITH
BERNADINE HEALEY KNEW ABOUT
GENDER BIAS AND STUDIES, CAME AS
A CARDIOLOGIST FROM OHIO STATE
BEFORE SHE TOOK ON THAT TASK,
WHERE GENDER BIAS IS MORE ACUTE
THAN CARDIOLOGY, VIVIAN PINN, A
NICE PICTURE OF ED BRANT.
HIS TOLD ME HE ENJOYED THE ORWH
THE MOST.
HE TAUGHT IT'S MORE IMPORTANT TO
DEVELOP CAREERS OF OTHERS THAN
YOUR OWN.
HE ALSO TAUGHT ME THE BEST JOB
HE'S EVER ABOUT BY FAR WAS
BAGGING GROCERIES IN OKLAHOMA
CITY WHERE HE LEARNED A LOT.
IT TURNS OUT ED INVITED VIVIAN
TO OKLAHOMA TO SEE SITES, AND
BOUGHT HIMSELF A RED TRUCK FOR
THAT EVENT.
I GOT TO GO AROUND IN THE RED
TRUCK TO ENJOY THAT CAMERADERIE
AND INVOLVEMENT.
IT'S STILL AN ISSUE OF LACK OF
INCLUSION OF WOMEN, EVEN GREATER
ISSUE NOW UNDERSTANDING HOW TO
PROMOTE HEALTHY AGING FOR WHAT'S
A GENDER BIASED POPULATION
UNDERSTUDIED MAJORITY.
NEXT SLIDE PLEASE.
WELL, THAT GENDER GAP.
I THINK IT'S USEFUL TO POINT OUT
IN 2019 HEALTHY LIFE EXPECTANCY
FOR WOMEN 76, FOR MEN 71 YEARS.
NOTICE THE DIFFERENCE.
FOR WOMEN OVER 60, FROM 2015 TO
2050 THAT WILL GROW FROM 12% TO
22%.
THINK OF THE MAGNITUDE OF THAT
WORLDWIDE.
WE'VE HEARD ABOUT THE LACK OF
PEOPLE BEING ABLE TO ADDRESS IT,
ONE OF THE PROBLEMS WITH THE
ORGANIZATION WE DON'T HAVE
ENOUGH MENOPAUSE PRACTITIONERS
TO HANDLE THE CLINICAL
CHALLENGE.
MAJORITY OF STUDIES OF
SUCCESSFUL AGEERS, CONCEPT IS
OLDER ADULT WITH HEALTH STATUS
SIMILAR TO YOUNG PEOPLE, REFER
TO AS FUNCTIONAL IDEAL AGING, NO
DISABILITY OR PHYSICAL ILLNESS,
IS THAT REALLY OUR GOAL, OUR
BEST GOAL?
GREATER PHENOTYPE AND GREATER
NUMBER OF PEOPLE THAT HAVE A
DISABILITY OR CHRONIC ILLNESS,
THEY HAVE GOOD COGNITIVE
FUNCTION, CAN HAVE LIFE
SATISFACTION AND GOOD SOCIAL
ENGAGEMENT.
MY OPINION, THE GOAL SHOULD BE
TO HELP ALL.
NEXT SLIDE PLEASE.
THIS IS A FAMOUS CARDIOVASCULAR
CARTOON.
FOR ATHEROSCLEROSIS IT BEGINS IN
UTERO, INTO REPRODUCTIVE YEARS,
AND WE THINK ABOUT EVENTS AT THE
TIME OF MENOPAUSE.
RISK ESTIMATORS START AT 40.
THAT'S THE HORIZON.
TO BEGIN TO THINK ABOUT WHAT'S
HAPPENING, IT'S IMPORTANT TO
LOOK AS A CONTINUUM, THAT SHOULD
ENTER INTO DECISION MAKING, IN
MY OPINION.
FOR WOMEN THE MENOPAUSE
TRANSITION IS PARTICULARLY
IMPORTANT BECAUSE IT'S A CALL TO
ACTION.
IT'S BECAUSE OF ACCELERATION OF
CARDIOVASCULAR DISEASE, BONE
LOSS, PREVALENCE OF DIABETES,
OBESITY, PSYCHOLOGICAL DISTRESS,
YOU HEARD THAT TALKED ABOUT
TODAY.
FOCUS ON ROLE OF HORMONES IN
ORGAN SYSTEMS.
UNDERLYING CONDITIONS ARE
TREATED WITH VARIETY OF CLASSES
OF MEDICATIONS, I WOULD ARGUE WE
KNOW LITTLE ABOUT GENDER
DIFFERENCES, AND HEALTHY AGING
IN GENERAL.
VASCULAR INTEGRITY, BONE
DYNAMICS, BEYOND MENOPAUSE.
EFFECTS OF GENDER DIFFERENCE
GOING INTO MENOPAUSE AND BEYOND
ARE CHALLENGING, WE KNOW LESS
ABOUT PRIMARY, SECONDARY,
TERTIARY PREVENTION.
AND IN RELATIVE TERMS COMPARED
TO A LOT OF THINGS WE STUDY
THERE ARE FEWER LONGITUDINAL
STUDIES, NOT MINED WELL TO TAKE
INTO ACCOUNT NEWER RESEARCH
TECHNIQUES.
MANY ARE CROSS-SECTIONAL
HYPOTHESIS GENERATING WHICH CAN
ONLY SET UP HYPOTHESES.
NEXT SLIDE PLEASE.
BECAUSE OF THE RAPID CHANGES IN
DISEASE RISK, ASSOCIATED WITH
THIS DECLINE, THERE'S REASON TO
EXPECT MAINTAINING ESTROGEN
SHOULD ATTENUATE.
A FOCUS IS CLEARLY NEEDED.
I WON'T SPEND A LOT OF TIME ON
CURRENT INDICATIONS BUT AN
OVERFOCUS ON ESTROGEN PLUS
PROGESTERONE ALONE MISSES THE
BOAT AS JOANNE SAID SO OFTEN,
THE WHI GIVES, AND THAT'S TRUE.
NEXT SLIDE PLEASE.
LET'S LOOK AT DISEASE BURDEN.
LOOK AT RED, PERCENTAGES.
NOT THAT THE OTHER CONDITIONS
AREN'T IMPORTANT BECAUSE THE
VASCULAR INTEGRITY GOES TO ALL
THOSE ORGAN SYSTEMS.
THAT'S IMPORTANT.
IN TERMS OF BANG FOR THE BUCK,
HOW WE DESIGN OUR STUDIES, I
THINK UNDERSTANDING AND LOOKING
AT THAT WE NEED TO UNDERSTAND
THE PUBLIC HEALTH BURDEN.
NEXT SLIDE PLEASE.
PROMINENT MEDS ARE STATINS,
BISPHOSPHONATES, STATINS, SOME
HAVE ADVERSE EFFECTS ON OTHER
SYSTEMS COMMON TO POSTMENOPAUSAL
WOMEN NEEDS.
I WOULD SUGGEST POLYPHARMACY AT
ADVANCE AGED IS MOST OFTEN
IGNORED, A CHALLENGING PROBLEM
FOR PATIENTS AND FRAGMENTED
HEALTH SYSTEM.
ISCHEMIC HEART DISEASE ACCOUNTS
FOR MORE DEATHS THAN ALL CANCERS
COMBINED, NOT THAT EACH SYSTEM
IS NOT IMPORTANT ONE-THIRD OF
LIVING DISEASE IN WOMEN 50 OR
OLDER WORLDWIDE, MOST OF THE
STUDIES LEAVE OUT WOMEN WITH
THEIR UNIQUE RISKS.
WE'RE IMPROVING, BEGINNING TO
SEE WITH A LOT OF VOCIFEROUS
WORKS IMPORTANCE OF PREGNANCY
COMPLICATIONS TO VASCULAR RISK
LATER, BEGINNING TO SEE
POLYCYSTIC OVARY SYNDROME AND
THE WAY IT GOES INTO MENOPAUSE
MAY BE DIFFERENT, THAT'S
BEGINNING TO BE PUBLICIZED.
NEXT SLIDE PLEASE.
SO, THERE ARE GAPS, MEDICAL
INVASIVE TREATMENT,
UNDERUTILIZED IN WOMEN.
A LATER PRESENTATION, EVEN IF
TROPONIN IS ABNORMAL, GREATER
ODDS OF MORTALITY FROM
INFARCTION WITH MI LESS THAN 45,
MORE ANGINA, LESS OBSTRUCTIVE
DISEASE, WHY IS THAT?
THEY PRESENT WITH ATYPICAL
SYMPTOMS, WHY IS IT ATYPICAL?
THOSE ARE THE SYMPTOMS.
THEY ARE BROAD.
IT'S IMPORTANT.
SCIENTIFICALLY, EXCITING TO TRY
TO FIGURE OUT WHY THAT HAPPENS.
NEXT SLIDE PLEASE.
SO, A FEW WORDS ABOUT RISK
SCORING.
I WOULD SUGGEST MENOPAUSE IS A
PERFECT WINDOW TO SCREEN USING
RISK SCORE, I WILL WARN THERE'S
NO GOOD RISK SCORE THAT EXISTS
POST CARDIOVASCULAR EVENT.
I'VE STUDIED RISK SCORE SYSTEMS,
NONE ARE PERFECT BUT ACC/AHA
COHORT IS SURFACING BECAUSE IT'S
READILY AVAILABLE IN EMR
SYSTEMS.
NEXT SLIDE PLEASE.
I WANT TO POINT OUT THE
IMPORTANCE OF UNDERSTANDING WHAT
ARE PROPER RESIDUAL TARGETS,
WHEN WE MANAGE PREVENTION WE
HAVE TO UNDERSTAND TARGETS.
WE KNOW TARGETS BETTER FOR
CHOLESTEROL AND TRIGLYCERIDES,
BEGINNING TO SEE FOR BOTH LOWER
IS ALWAYS BETTER, EVEN LOWER
THAN WE'RE SHOWING HERE.
CERTAINLY FOR SECONDARY
PREVENTION.
THROMBOTIC ISSUE IS IMPORTANT TO
MEASURE ONCE AT LEAST.
YOU HEARD ABOUT HORMONES AND
THROMBOTIC RISKS, DIABETES,
PRESERVED EJECTION FRACTION, HOW
WE STUDY THAT EXCITING BUT I
DON'T WANT TO PUT SLIDES ON THE
IMPORTANCE OF BLOOD PRESSURE, SO
IMPORTANT TO CARDIOVASCULAR
OUTCOMES.
NEXT SLIDE PLEASE.
I WON'T SAY MUCH ABOUT ORAL
VERSUS TRANSDERMAL, BUT THE ROLE
OF INFLAMMATION, CRITICAL.
THIS IS REPETITIVE BUT SOME
BELIEVE INFLAMMATION IS THE ROOT
OF ALL EVIL.
MORE TO COME.
THAT ARROW SHOWS AVERAGE AGE OF
MENOPAUSE BUT YOU GOT TO
UNDERSTAND PRE AND POST,
LAUNCHED INTO LATER YEARS.
IT'S IMPORTANT TO POINT OUT M.I.
BEFORE 55 INCREASED OVERALL IN
THE PAST TWO DECADES, BUT FOR
WOMEN THEY HAVE GONE FROM A
FIFTH TO A THIRD, AND FOR WOMEN,
A LOT OF MORE COMORBIDITIES
ASSOCIATED WITH THAT.
NEXT SLIDE PLEASE.
THE THING TO REMEMBER,
SPONTANEOUS CORE ANOTHER
DISSECTION IS NON-TRAUMATIC,
NON-IATROGENIC.
LOOK GENDER BIAS FOR WOMEN, 24
TO 35% OF MI IN WOMEN LESS THAN
60.
HORMONE THERAPY IS
CONTRAINDICATED.
I PUT THIS CARTOON UP SHOWING
DIFFERENCE BETWEEN ATHEROGENESIS
OR PRECIPITATION EVENTS AND
PATHOPHYSIOLOGY, CONTRASTING
WOMEN VERSUS MEN AT EVERY LEVEL
IT'S DIFFERENT.
I WOULD LIKE TO DRAW YOUR
ATTENTION TO THE WORK OF DR.
HUCKSY, UNIVERSITY OF MISSOURI,
20 YEARS LOOKING AT PHYSIOLOGY
OF DIFFERENCE AT EVERY LEVEL,
ORGAN SYSTEMS, CELL SYSTEMS,
NEED TO ENCOURAGE BASIC
UNDERSTANDING TO FIGURE OUT
WHERE WE NEED TO GO.
NEXT SLIDE PLEASE.
AGAIN, HYPERTENSION, LET'S NOT
FORGET THE STATE OF THE ART IS
LIKE THAT ELEPHANT IN THE RIGHT
WITH HYPERTENSION.
WE ARE NOT PUTTING OUR ACT
TOGETHER.
SEX STEROIDS AFFECTING THE
SYMPATHETIC SYSTEM,
PARASYMPATHETIC SYSTEM WE NEED
IMPROVEMENT, NO DOUBT.
THERE ARE A LOT OF QUESTIONS
ABOUT DIET, PHYTOESTROGENS AS
HOW THEY INTERACT WHICH AFTER
ALL IS A CHALLENGING CLINICAL
ISSUE BECAUSE NOT ALL OFFICE PAY
ATTENTION AND MEASURE, RUN THE
ROOM QUICK, GO OUT, HAVE TO MOVE
THE PATIENT AHEAD, BUT IT'S OUR
RESPONSIBILITY TO KEEP PEOPLE ON
TARGET TO PREVENT EVENTS.
I DON'T WANT TO DIMINISH
IMPORTANCE OF NEUROGENERATIVE
DISEASE.
EFFECTS OF AGING ARE
UNDERSTUDIED AND UNCLEAR.
THE SAME FOR EXOGENOUS, THE
SECOND BULLET POINT.
THE REASON I BRING IT UP, WE
THINK ABOUT HORMONES AS
MENSTRUAL CYCLE, PREGNANCY, MEN
TAUS.
IT'S MORE.
IT'S A CONTINUUM THAT GOES INTO
THE OLDER YEARS.
WE KNOW IT PASSES THE
BLOOD-BRAIN BARRIER, IMPORTANT
TALK THIS MORNING ABOUT
CONNECTION TO AXIS LEARNING
ABOUT MENOPAUSE.
BE CAREFUL ABOUT ANIMAL VERSUS
HUMANS IN UNDERSTANDING OF
ESTROGEN AS MORE ADVANCED THAN
IN PROGESTERONE, LESS IS KNOWN,
WE'RE LEARNING MORE ABOUT
METABOLIC IMPLICATIONS OF
METABOLISM PROGESTERONE, HOW IT
AFFECTS THE BRAIN.
AREA UNDERSTUDIED WHAT AROMATASE
INHIBITORS DO TO BRAIN FUNCTION.
ESTRADIOL REGULATES GLYCOLYSIS,
PHOSPHORYLATION, IT'S
UNDERSTUDIED WITH AGING.
WE'VE GOT SEVERAL MANUSCRIPTING
ABOUT APOE 4, THOUGHTS WITH
HORMONES AND AGING, DEMENTIA,
MORE STUDY THERE.
ESTRADIOL AND PROGESTERONE HAVE
EFFECTS.
I PUT THIS CARTOON UP,
ILLUSTRATING ORGAN SYSTEMS.
LOOK AT THEM ALL.
I HIGHLIGHTED POLYCYSTIC OVARY
SYSTEM, PAYING ATTENTION TO
INFERTILITY AND THIS DISO.
CARDIOVASCULAR DISEASE AND
DIABETES ACCOUNT FOR HALF OF THE
MORTALITY, A THIRD IN WOMEN.
THEY SHARE RISK FACTORS THAT
COMPRISE METABOLIC SYSTEMS.
MEDICATIONS FOR DEMENTIA ARE
WANTING, A LOT OF LEADS ABOUT
HORMONE THERAPY AND MOOD.
HOW ARE THESE CONNECTED
METABOLICALLY TO THE ISSUE OF
OBSTRUCTIVE SLEEP APNEA OR
CONGESTIVE FAILURE IS EXCITING
TO LOOK AT.
NEXT SLIDE PLEASE.
WHERE WE NEED TO BE?
WE KNOW LITTLE ABOUT ENDOGENOUS
SYSTEMS AND ORGAN SYSTEMS IN
GENERAL BUT I WOULD SUGGEST
LEARNING ABOUT NORMAL TRANSITION
VERSUS ABNORMAL ONE, LONG-TERM
EFFECTS, DIFFERENCE IN GENE
MUTATION NEEDS TO COME TO THE
FOREFRONT.
YOU HEARD ABOUT GENETICS OF WHO,
WHEN, WHY SHOULD WE TEST.
NEXT SLIDE PLEASE.
PREVENTION OF DISEASE AND GENDER
DIFFERENCE IS IMPORTANT.
PHENOTYPES IN OLDER AGE,
IGNORANCE ABOUT WHAT MENOPAUSE
DOES TO ORGAN SYSTEMS LATER.
EFFECTS OF LIFESTYLE ARE
IMPORTANT, TARGET TISSUE EFFECTS
OF HORMONE OPTIONS WITH BREAST
CANCER RISK.
YOU'VE HEARD ABOUT OSTEOPOROSIS,
I'LL MOVE BEYOND THAT.
A PLUG WE NEED TO KNOW
DETERMINANTS OF MENTAL HEALTH
DISORDER, WE KNOW HORMONES ARE
PSYCHOACTIVE, SOME PEOPLE FEEL
WEEPY ON ESTROGEN, CONVERT AND
IT GOES AWAY.
COLORECTAL CANCER AND KIDNEY
DISEASE.
NEXT SLIDE PLEASE.
I WOULD PUT IN A PLUG AS WE
DESIGN MOVING AHEAD RANDOMIZED
TRIALS, OBSERVATIONAL STUDIES, A
LOT OF NEAT TECHNIQUES TO
OPTIMIZE THAT WEREN'T USED OVER
THE PAST TWO DECADES, NEED TO BE
INCLUDED.
I WANT TO PUT IN A PLUG WHILE WE
DO THAT WE WANT TO ADAPT SOME
BETTER METHODS OF ANALYSIS,
THERE'S A LOT OF
INDIVIDUALIZATION THAT'S NEEDED,
GAPS IN ASSESSMENT
POST-MENOPAUSE, DOESN'T APPLY TO
EVERY PERSON.
TRANSDERMAL DELIVERY, WE HAVE A
LONG WAY TO GO.
NEXT SLIDE PLEASE.
MY FORMULA TO FOCUS ON AGING,
LET'S PAY ATTENTION TO PHYSICAL
ACTIVITY, DIMINISHES OBESITY,
CUTS DOWN ON INFLAMMATION,
IMPROVES SLEEP.
POSITIVE ATTITUDE IS IMPORTANT,
HAPPINESS, LOVE, HOW DO WE TAKE
THAT INTO ACCOUNT IN PROPER
MENTAL HEALTH, RELATIONSHIPS ARE
CLEARLY IMPORTANT FOR SURVIVAL.
WE'RE SOCIAL BEINGS.
WE HEARD GREAT THINGS ABOUT
HISPANICS AND AFRICAN AMERICANEN
BUT A PLUG FOR AMERICAN INDIANS.
IF WE'RE GOING TO GET ANY
ATTRACTION IN THE AMERICAN
INDIAN COMMUNITY WE NEED TO
INVOLVE TRIBAL LEADERSHIP.
THERE ARE UNIQUE DIFFERENCES,
HIGHEST COUNTY FOR CANCER IN THE
UNITED STATES --
>>THAT'S TIME.
>> IS IN OKLAHOMA.
WE HAVE A LOT TO LEARN, BREAK
DOWN SILOS, CROSS-TALK AMONG
THEM AND I'LL FINISH MY QUOTE.
THE ONLY THROUGH WISDOM IS
KNOWING YOU KNOW NOTHING, TAUGHT
YEARS AGO, STILL TRUE.
THANK YOU VERY MUCH.
>> THANKS FOR THE FANTASTIC
PRESENTATIONS, SORRY FOR BEING
STRICT ON TIME BUT WE'VE GOT SO
MANY GOOD QUESTIONS.
THERE'S A GENERATION OF
CLINICIANS AFRAID OF MENOPAUSAL
HORMONE THERAPY, AND I THINK --
I DON'T THINK ANYONE DISAGREES
WITH THAT.
CAN YOU TELL US ABOUT ACCESSING
CBT-I FOR SLEEP, THAT WOULD BE
FOR DR. LACROIX.
>> I WOULD LOOK IN YOUR
COMMUNITY FOR CBT-I PROVIDERS,
AND WE NEED TO HAVE THIS BUILT
INTO HEALTH CARE SYSTEMS.
FOR EXAMPLE, I ASKED ABOUT THIS
AT UCSD, I WAS TOLD BY SLEEP
MEDICINE COLLEAGUE A WOMAN
SHOULD CALL UP UCSD AND GET
WORKED UP FOR SLEEP PROBLEM.
THAT'S NOT THE ANSWER I WANTED.
I WANT TO KNOW WHERE YOU CAN GO
GET CBT-I BY TELEPHONE.
I DON'T HAVE A PLACE TO SEND
YOU, BUT I THINK WE NEED TO
DEMAND THAT THESE SERVICES BE
MADE AVAILABLE TO WOMEN IN EACH
OF OUR COMMUNITIES.
>> I CAN SAY THERE IS AN APP,
CBT-I, IT'S BLUE WITH A CRESCENT
MOON.
IT'S MADE BY THE VETERANS
ADMINISTRATION, FREELY
AVAILABLE.
IT'S NOT A BAD PLACE TO START,
IF NEED INSOMNIA THERAPY.
>>THE PEOPLE WHO DEVELOPED
CBT-I, HAVING THE COACH INTERACT
IS SO IMPORTANT.
IF YOU TRY AN APP, IT DOESN'T
WORK, KNOW THAT A COACH CAN
REALLY HELP YOU DO THIS.
IT'S NOT EASY TO DO SLEEP
RESTRICTION WITHOUT THAT SUPPORT
OF A COACH.
SO, THAT'S ONE THING I WOULD SAY
ABOUT TRYING AN APP.
>> AND ONE OF THE OTHER
QUESTIONS THAT YOU'RE TALKING
ABOUT AS WELL, NEW TECHNOLOGY
USAGE, SOCIAL MEDIA STREAMING
TAKEN INTO ACCOUNT WHEN LOOKING
INTO INSOMNIA AND SLEEP QUALITY.
>> I THINK IT IS TAKEN INTO
ACCOUNT.
WITH RESPECT TO SLEEP HYGIENE,
TURNING OFF THE BLUE LIGHT,
STUFF LIKE THAT.
THAT'S PART OF THE COUNSELING.
BUT IT'S SOMETHING TO
INVESTIGATE WITH RESPECT TO THE
SLEEP DISTURBANCE TO BEGIN WITH.
>> ANOTHER QUESTION I'M GOING
TO FIELD TO YOU, DR. WILD, HOW
IS WEIGHT GAIN NOT CONSIDERED A
BOTHERSOME SYMPTOM BEING
ADDRESSED?
>> ARE YOU TALKING TO ME?
>>YES, SINCE THAT BEARS ON
CARDIOVASCULAR.
>> YEAH, GREAT TALK ABOUT
PHYSICAL ACTIVITY, WHAT CAN IT
DO, CAN'T DO.
CHRONIC EXERCISE VERSUS ACUTE.
HOW HORMONE THERAPY MODULATION
CAN BE AFFECTED.
IT'S AN IMPORTANT PART OF
EXACTLY WHAT WE DO, I THINK TO
OVERFOCUS ON BODY IMAGE CAN BE
CHALLENGING, AND I THINK AS WE
INCORPORATE OUR APPROPRIATE
MESSAGES INTO TOTAL HEALTHY
LIFESTYLE, UNDERSTANDING
NUTRITION IS PART OF THAT.
THAT'S THE MESSAGE AND THE WAY
TO GO.
AND AS WE GET BETTER WAYS TO
UNDERSTAND HEALTHY EXERCISE,
GREAT TALK TODAY ABOUT WEIGHT
BEARING VERSUS AEROBIC VERSUS
CHRONIC, AND ALL THOSE
COMPONENTS.
WE NEED ON WRAP OUR MESSAGES
AROUND THEM, A MULTI-SPECIALTY
APPROACH.
HAROLD TO DO ALONE FOR A GIVEN
INDIVIDUAL.
MANAGEMENT IS SUCCESSFUL IN MANY
CIRCUMSTANCES, IT HAS A LOT TO
DO WITH WHAT'S AVAILABLE TO A
GIVEN PERSON AND HOW THEY CAN
EFFECTIVELY AND COST EFFECTIVELY
TAKE ADVANTAGE OF WHAT RESOURCES
ARE AROUND.
>> I'LL ADD ONE OF THE AREAS
WE'RE INVESTIGATING IN WHI
ACTUALLY BUT OTHER COHORTS AS
WELL IS WHETHER OR NOT WEIGHT
LOSS IS GOOD FOR YOU WHEN YOU'RE
OLDER THAN A CERTAIN AGE.
AND IT REALLY LOOKS AS AN
EPIDEMIOLOGIST, I WOULD SAY ONE
OF THE PUBLIC HEALTH MYTHS, GOOD
EVIDENCE IT'S NOT GOOD FOR YOU,
WEIGHT STABILITY IS WHAT SHOULD
BE VALUING AS IN TERMS OF
HEALTHY AGING.
I HATE GAINING WEIGHT, AS MUCH
AS ANY OTHER WOMAN.
IT SUCKS.
AND I WANT TO BE AS SKINNY AS I
WAS AT THE SKINNIEST PART OF MY
LIFE, BUT I KNOW IT'S NOT GOOD
FOR ME.
>> ONE OF THE THINGS I DO IN MY
OFFICE, SHOW A PICTURE OF IDEAL
WEIGHT AND GET PEOPLE TO CIRCLE
IT.
WHAT'S HEALTHY AND WHAT ISN'T.
THE UNDERSTANDING IS ENORMOUS.
IT TAKES 10% OF YOUR WEIGHT
DOWN, IF YOU'RE WAY OVER, TO GET
METABOLICALLY NORMALLY, I USE
METABOLIC INDICATORS RATHER THAN
WEIGHT.
>> I SEE DR. PINN AND DR.
CLAYTON'S CAMERAS ON.
I'M GOING TO ALLOW FOR LAST
COMMENTS FROM THE SPEAKERS AND
DR. SANTORO.
>> I WANT TO SAY, ON THE WEIGHT
QUESTION, IN CLINICAL PRACTICE I
SEE MANY PATIENTS WHO ARE VERY
BENT OUT OF SHAPE WITH LARGE
AMOUNTS OF WEIGHT GAIN, YOU DO
NOT SEE THAT IN LARGER
POPULATION STUDIES.
YOU SEE MODEST AMOUNT OF WAIST
WEIGHT GAIN THAT DRIVES EVERYONE
NUTS, YOU CAN'T CLOSE THE
WAISTBAND, BUT THAT'S WHAT
HAPPENS ACROSS THE TRANSITION.
SO IF YOU LOOK AT THE WHOLE
POPULATION YOU'RE MISSING THIS
ONE GROUP.
BUT THIS MULTIPLE A GROUP WE
WANT TO BREAK OUT AND STUDY
SEPARATELY BECAUSE THEY PROBABLY
ARE AT SOME EXCESS RISK OR HAVE
SOME UNIQUE COMBINATION OF
FACTORS.
>> OR ALREADY ENTER WITH
COMORBIDITIES.
>> YES.
>> I WANT TO THANK EVERYBODY SO
MUCH FOR COMING HERE TODAY, FOR
SPEAKING, FOR ALL OF EVERYBODY'S
SHARING OF THOUGHTS.
IT'S BEEN A PLEASURE TO HOST
THIS SYMPOSIUM TODAY, FOCUS ON
MENOPAUSE.
TO CONCLUDE THIS I WOULD LIKE TO
WELCOME DR. VIVIAN PINN, THE
INAUGURAL FULL-TIME DIRECTOR OF
THE OFFICE OF RESEARCH ON
WOMEN'S HEALTH FROM 1991 UNTIL
HER RETIREMENT IN 2011.
AND NIH'S ASSOCIATE DIRECTOR
FROM 1994 UNTIL 2011 FOR WOMEN
HEALTH.
THE OFFICE LED IMPLEMENTATION OF
INCLUSION POLICIES FOR WOMEN AND
MINORITIES IN CLINICAL RESEARCH,
DEVELOPED THE FIRST AND SEVERAL
SUBSEQUENT NATIONAL STRATEGIC
PLANS FOR WOMEN'S HEALTH
RESEARCH, AND ESTABLISHED MANY
NEW FUNDING INITIATIVES.
WE'RE SO DELIGHTED TO HAVE YOU
HERE TODAY.
WELCOME, DR. PINN.
>> THANK YOU.
AGAIN, I'M REALLY HONORED THAT
THE OFFICE HAS THIS SYMPOSIUM IN
MY NAME.
THANK YOU, JANINE.
THANK YOU TO THE STAFF AND
COORDINATING COMMITTEE FOR DOING
THIS.
IT'S QUITE AN HONOR FOR ME
ESPECIALLY SINCE I CAN SIT BACK
AND LEARN.
I DON'T HAVE TO TRY TO PRESENT
BUT REALLY TO LEARN FROM THE
PRESENTATIONS EACH YEAR.
I MUST SAY THIS YEAR WAS
ESPECIALLY OF INTEREST TO ME
BECAUSE OF DEALING WITH YOUR
PRIORITIES, DEAL WITH LOOKING AT
THE MENOPAUSE AND MID-LIFE
CHANGES FOR WOMEN, VERY
IMPORTANT.
I'M PLEASED YOU STARTED WITH THE
WOMEN'S HEALTH INITIATIVE.
I WAS THE CO-DIRECTOR OF THAT
STUDY IN THE EARLY YEARS, ALONG
WITH BILL HARLAN, AND I STILL
THINK I HAVE A LOT OF SCARS ON
MY BACK FROM REACTIONS TO THE
FINDINGS OF THE WOMEN'S HEALTH
INITIATIVE WHEN THEY WERE NOT
WHAT WE EXPECTED.
AND RECENTLY I'VE BEEN DISTURBED
SEEING SO MUCH REACTION, OP-ED,
PEOPLE ON TV TALKING ABOUT USE
OF HORMONES AS THOUGH HORMONAL
THERAPY, AS THOUGH WE NEVER HAD
THE WOMEN'S HEALTH INITIATIVE
AND ADVOCATING FOR ITS USE
WITHOUT RECOGNIZING THAT THERE
ARE SOME RISKS INVOLVED, AT
LEAST FOR SOME WOMEN.
AND OPPOSED TO WHAT I HEARD
REITERATED AGAIN THAT MANY
PHYSICIANS ARE AFRAID OF HORMONE
THERAPY.
I THINK BACK TO THE NON-USE WHEN
RESULTS OF THE WOMEN'S HEALTH
INITIATIVE, THE FIRST STUDY WAS
STOPPED, WE PRESENTED THAT RISKS
SEEMED TO OUTWEIGH THE BENEFITS,
THAT OUR CHARGE WAS REALLY TO
GET PHYSICIANS TO MOVE AWAY
THINKING ALWAYS ABOUT HORMONE
THERAPY AS THE FIRST THING AND
THAT EVERY WOMAN REACHING
MENOPAUSE SHOULD BE GOING ON
HORMONE THERAPY.
AND IT'S SORT OF COME FULL
CIRCLE BECAUSE WHAT I WAS
HEARING IN A LOT OF
PRESENTATIONS TODAY WERE
JUSTIFICATION FOR WHY WE NEED TO
GO BACK TO ADVOCATE FOR USE OF
HORMONES.
I HOPE WE DON'T FORGET LESSONS
OF THE WOMEN'S HEALTH INITIATIVE
BUT THAT A SET DOSE USING
DOSAGES THAT WERE THE USUAL
DOSAGES, AND WAS A BIG STUDY BUT
LEFT A LOT OF QUESTIONS.
AND I'M JUST PLEASED WITH ALL OF
THE PRESENTATIONS THAT DEALT
WITH SO MANY OTHER ISSUES GOING
BEYOND JUST HORMONE THERAPY BUT
OTHER ISSUES THAT ARE IMPORTANT
TO WOMEN IN MID-LIFE.
I THOUGHT DEALING WITH THE
QUESTIONS ABOUT BRCA1 AND BRCA2
AND DECISIONS TO BE MADE ABOUT
POSSIBILITY OF DEVELOPING
OVARIAN CANCER AND LOOKING AT
THE FALLOPIAN TUBES, THESE ARE
THINGS THAT WE THOUGHT ABOUT
YEARS AGO BUT OBVIOUSLY HAVEN'T
BEEN PURSUED, STILL ARE
IMPORTANT FOR WOMEN AS THEY
APPROACH MID-LIFE, LOOKING
PARTICULARLY IMPRESSED WITH THE
PATIENT ADVOCACY PERSPECTIVES,
DR. FRIEDMAN AND HEARING ABOUT
WOMEN WITH HIV AND THEN THE
MENOPAUSAL SYMPTOMS INTERACTING
WITH SYMPTOMS OF HIV AND DILEMMA
WOMEN AND PHYSICIANS HAVE TRYING
TO DIED -- DECIDE WHERE TO GO.
DR. WILD, I NEVER THOUGHT OF YOU
AS MY NEMESIS.
I THOUGHT OF YOU AS MY SUPPORT,
AS MY ADVISER.
ESPECIALLY WHEN YOU WERE ON THE
ADVISORY COMMITTEE AND WORKING
WITH THE WOMEN'S HEALTH
INITIATIVE.
BUT I DO REMEMBER THAT TRIP TO
OKLAHOMA, AND ACTUALLY WE
LABELED DR. ED BRANT THE
GODFATHER OF WOMEN'S HEALTH
BECAUSE HE REALLY WAS THE ONE
WHO GOT THE WHOLE IDEA OF
WOMEN'S HEALTH IN THE DEPARTMENT
OF HHS, AND REALLY STARTED THAT
COORDINATING COMMITTEE AND
CERTAINLY ADVISED AND WORKED
WITH US AT ORWH ON JUST ABOUT
EVERYTHING WE DID, LOSING HIM
WAS A BIG LOSS FOR US BUT HE WAS
SUCH A GREAT SUPPORT FOR US AND
DEALING WITH NOT JUST SCIENCE
BUT THE POLITICS AND DIPLOMACY
AND HOW TO MOVE FORWARD.
HE WAS REALLY A GENIUS, TO MY
MIND, SUCH A WONDERFUL SUPPORT.
BUT I DIDN'T REALIZE YOU WERE A
NEMESIS.
I'M GOING TO REMEMBER THIS.
I WANT TO JUST EXPRESS MY
APPRECIATION TO THE OFFICE FOR
ALL THE NEW INITIATIVES YOU HAVE
BECAUSE WE CAN'T FORGET YOU
MOVED ON FAR FROM WHEN I
RETIRED, WHICH IS NOW IN AUGUST
OF 2011.
AND SEEING THE NEW INITIATIVES
AND NEW PROGRAMS, AND THE NEW
INVESTIGATORS YOU BROUGHT
FORWARD AND HAVE IDENTIFIED, AND
NEW OPPORTUNITIES FOR FUNDING,
IT'S VERY EXCITING TO ME.
AGAIN, I DO WHATEVER I CAN TO
SUPPORT YOUR EFFORTS, AND OF
COURSE SINCE I'M NO LONGER
EMPLOYED BY THE GOVERNMENT I CAN
MAKE A PLEA FOR INCREASED
FUNDING FOR THE ORWH WHICH I
COULDN'T DO WHEN I WAS REALLY
WORKING THERE BUT I CAN DO.
AND I HOPE THAT THOSE WHO ARE
YOUR SUPPORTERS AND ADVISORS
WILL DO THAT.
THERE WERE SUGGESTIONS ABOUT
RESEARCH, NEW RESEARCH
INITIATIVES.
SOME OF THOSE WE THOUGHT ABOUT
WHEN THE WOMEN'S HEALTH
INITIATIVE WAS FIRST -- RESULTS
WERE FIRST COMING OUT, KNOWING
WE NEEDED TO DO MANY OTHER
STUDIES TO GO BEYOND ESPECIALLY
LOOKING AT DIFFERENT
PREPARATIONS AND DIFFERENT
MANNERS OF ADMINISTERING
THERAPIES.
I REMEMBER WHEN THERE WERE NO
STUDIES ON MENOPAUSE.
DR. HEALEY CAME UP WITH THE IDEA
FOR THE WOMEN'S HEALTH
INITIATIVE AND GOT IT GOING.
450 STUDIES ON MENOPAUSE, THIS
WAS BACK IN THE EARLY '90s,
I'M SURE KNOLL THERE ARE MANY
MORE BUT WE CAN'T GET AWAY FROM
THAT AND WE SHOULD NOT GET AWAY
FROM THE FINDINGS, MONUMENTAL
FINDINGS OF THE WOMEN'S HEALTH
INITIATIVE BUT LOOKING BEYOND
THAT AS WE EXPAND, AS YOU EXPAND
RESEARCH.
I JUST AM VERY IMPRESSED AND
THRILLED WITH WHAT I HEARD
TOGETHER.
THE DIFFERENT VIEWPOINTS WERE
INFORMATIVE.
REALLY STIMULATING.
AND IF YOU'RE GOING TO CARRY OUT
THOSE NEW INITIATIVES AND THOSE
NEW RESEARCH AREAS THAT WERE
IDENTIFIED, THE OFFICE IS GOING
TO NEED ADDITIONAL FUNDING, WE
NEED TO DO WHAT WE CAN TO HELP
BRING ADDITIONAL SUPPORT TO THE
OFFICE.
SO THAT YOU CAN BE THE LEAD ON
THESE ISSUES AND LOOK AT SEX AND
GENDER FACTORS AFFECTING
MID-LIFE AREAS OF WOMEN AS WE
KNOW THAT HELPS PROJECT WHAT THE
LATER YEARS WILL BE.
I WAS DISAPPOINTED RECENTLY AS
I'M SURE MANY OF YOU HEARD WHEN
A NEWS ANCHOR SAID WOMEN WERE
ONLY IN THEIR PRIME IN THEIR
20s, 30s, 40s.
I'M THINKING, OH MY GOSH, THIS
GUY NEEDS TO BE ASSOCIATED WITH
ORWH SO WE CAN EXPLAIN TO HIM
THAT THAT WAS THE WHOLE PURPOSE
OF THE OFFICE TO LOOK BEYOND THE
REPRODUCTIVE YEARS AND
REPRODUCTIVE LIVES OF WOMEN AND
TO THINK HOW WOMEN IN THEIR
POST-MENOPAUSAL YEARS ARE
ACTIVE, LEADERS, CEOS, NOT
SITTING IN A ROCKING CHAIR ON
THE PORCH SO SOMETIMES I WISH
THAT'S WHAT I WAS DOING.
IT'S IMPORTANT TO IDENTIFY
HEALTH ISSUES AND WELLNESS FOR
WOMEN ACROSS THE LIFESPAN
ESPECIALLY POSTMENOPAUSAL YEARS.
JANINE, WE'LL DO WHAT WE CAN TO
BRING SUPPORT.
I CONGRATULATE YOU ON PUTTING
TOGETHER ANOTHER WONDERFUL
SYMPOSIUM AND I KNOW MEMBERS OF
THE OFFICE HAVE TO WORK TO PULL
IT TOGETHER.
I'M JUST THRILLED WITH IT.
THANK YOU FOR ATTACHING MY NAME
TO SUCH A WONDERFUL EVENT.
THANK YOU.
>> OF COURSE, IT IS OUR
PLEASURE TO RECOGNIZE ALL OF
YOUR AMAZING EFFORTS.
NONE OF US WOULD BE HERE WITHOUT
THE EFFORTS THAT YOU PUT IN
PLACE.
AND MANY OTHERS WHO WERE -- I
SAW ONE SLIDE, I THINK IT WAS
DR. WILD, THERE WERE MANY BRAVE
FOLKS OUT FRONT MAKING CHANGE
WHEN THIS WAS VERY DIFFICULT AND
WE'RE IN SOME SIMILAR CHALLENGES
THESE DAYS, THAT WE MIGHT NOT
HAVE ANTICIPATED, BUT WE DO ALL
BELIEVE PUTTING SCIENCE TO WORK
FOR THE HEALTH OF WOMEN IS WHERE
WE NEED TO PUT OUR EFFORTS.
AND THAT INCLUDES THE HELP OF
ALL WOMEN, AND OUR INTENTION
TODAY WAS BRING FOCUS ON
MENOPAUSE RESEARCH, MID-LIFE
WOMEN, OPTIMIZING HEALTH, HOW
HOW
MANY QUESTIONS AWAY HAVE.
NO ONE CAN DISAGREE THE WOMEN'S
HEALTH INITIATIVE REPRESENTED
AMAZING EXAMPLE OF ADDRESSING
NEEDS OF WOMEN THROUGH SCIENCE
AND RESEARCH AND INVESTMENTS.
THAT LANDMARK INVESTMENT
CONTINUES TO PAY OFF.
WE HAVE MORE QUESTIONS WE STILL
NEED TO ASK AND ANSWER.
WHY WOMEN EXPERIENCE DIFFERENT
SEVERITIES OF HOT FLASHES, HOW
THE MENOPAUSAL TRANSITION AND
CHRONOLOGICAL AGING SEPARATELY
AND TOGETHER INFLUENCE MID-LIFE
HEALTH.
SO MANY QUESTIONS WE HAVE, WE
WANT TO SEE THOSE ADDRESSED.
THE TAG LINE PUTTING SCIENCE TO
WORK FOR THE HEALTH OF WOMEN,
THAT'S WHAT WE NEED TO DO ACROSS
THE BOARD.
I THANK DR. SARAH TEMKIN AT ORWH
FOR LEADING THE PLANNING OF THIS
SESSION.
WITH THE CLINICAL RESEARCH
SECTION AT ORWH AND PLANNING
COMMITTEE WHICH REPRESENTED
INDIVIDUALS FROM VARIOUS
INSTITUTES AND CENTERS AND
OFFICES.
I ACKNOWLEDGE ALL OF THE
SPEAKERS FOR SHARING YOUR
PERSPECTIVES, DR. WILD AND DR.
MANSON, INCREDIBLE BOOK ENDS,
WITH THE KEYNOTE AND BRINGING IT
ALL TOGETHER AT THE END.
I WANT TO ACKNOWLEDGE OUR
COMMUNICATIONS CONTRACTORS AND
COLLEAGUES FOR MANAGING AND
LOGISTICAL SUPPORT, FOLKS BEHIND
THE SCENES WHO DON'T GET
ACKNOWLEDGED.
EVERYONE ATTENDING, THANK YOU
FOR JOINING AND STAYING ON ALL
DAY.
THERE'S SO MUCH YET TO LEARN BUT
THERE'S INCREDIBLE ADVANCES MADE
BECAUSE WE HAVE INVESTED IN
HEALTH OF WOMEN AND RESEARCH ON
THE HEALTH OF WOMEN.
I WILL END BY THANKING YOU,
VIVIAN, FOR BEING THE GODMOTHER
OF WOMEN'S HEALTH RESEARCH AND
MAKING IT POSSIBLE FOR ALL OF US
TO BE HERE.
WE NEED TO CONTINUE THIS FIGHT.
SCIENCE, WE BELIEVE SCIENCE WILL
SOLVE SOCIETY'S PROBLEMS, WE
HAVE TO HAVE SCIENCE IN PLACE TO
DO THAT.
THANK YOU ALL, SPEAKERS.
THANK YOU, DR. PINN, FOR PAVING
THE WAY FOR THE ROAD.
FIRST IS HARD.
AND WE APPRECIATE IT GREATLY.
THANKS, EVERYONE, FOR JOINING
US.
DR.
DR. TEMKIN, ANY LAST WORDS?
>> I WANT TO REITERATE THANKS,
AND THANKS ALL THE SPEAKERS AND
THE AUDIENCE FOR JOINING US.
>> THANK YOU, EVERYONE.