Finding Our Reasons to Choose Estrogen PRE- HRT. Learning Objectives. Disclosure. Learning Objectives. Replacement Therapy. For Previvors 6/1/17

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1 Hormone Replacement Therapy Mefile:///Reimagined: How to Look Hot and Feel Healthy For Previvors Without Fear and Confusion Mache Seibel, MD HRT PRE- FOR VIVORS Mache Seibel, MD DrMache.com Disclosure Finding Our Reasons to Choose Estrogen Learning Objectives Mache Seibel, MD does not receive funding from the pharmaceu>cal industry Learning Objectives 1.Describe the impact of early surgical menopause 2.Describe the benefits of treatment 3.Clarify the risks of HT on early menopause Half of women < 50 without cancer NOT using HT 1

2 How I got interested in BRCA and Hormone Therapy Mighty Might: Fattest Kid in The County I believed this was an opportunity! People magazine One of the early IVF successes! Women s Health Ini>a>ve (WHI) 2002: The Headlines 1. Rossouw JE et al. JAMA. 2002;288(3): ; 2. Health guide: menopause. New York Times Web site. health/guides/disease/menopause/news-and-features.html?page=4. Accessed January 21, 2010; 3. Anstett P. Knight-Ridder Newspapers (KRT). July 8,

3 2003 a new test widely available the BReast CAncer or BRCA gene Sharon was diagnosed with pancreahc cancer Dr. Sharon Seibel MenopauseQuiz.com Find out how much your menopause symptoms impact your health, happiness and your life. 3

4 How HT Timing Influences Risks and Benefits Mache Seibel, MD Professor, University of Mass Medical School What is The Estrogen Window? The optimum window of time to begin estrogen for most women Usually a decade long time frame between ages yrs from beginning menopause For early menopause, sooner is better EstrogenWindowBook.com Until you know the facts, you couldn't possibly know what your choices are or BRCA 1 what might be the best choice for you. Cancer Risk by Age 70 Breast Cancer Ovarian Cancer 60 75% 39 59% BRCA 2 Cancer Risk by Age 70 Breast Cancer Ovarian Cancer 45 55% 11 17% 4

5 Premenopausal RRSO Ovarian, Tubes and Peritoneum Cancer 90% Breast Cancer 50% Timing MaIers For BRCA 1 Risk of Ovarian Cancer 4% 40 years 14.2% at 50 years Hartmann LC, Noralane ML. The role of risk- reducing surgery in hereditary breast and ovarian cancer. NEJM 2016;374:454-68; Hsieh G, Chen L- M. Inden>fying and counseling women with BRCA muta>ons. Contemporary Ob/Gyn 2016;61: Timing MaIers Rule of Thumb: Surgery 10 years before the age of earliest family cancer Premarin +Provera Mean age is % < Age 45 Some before 40 Some before 30 Hysterectomy Impacts Rx WHI Uterus 16,608 AGE OF Menopause No Uterus 10,739 Premarin Only Uterus In: E + P Uterus Out: E only 5

6 6/1/17 WHI WHI Uterus 16,608 No Uterus 10,739 Uterus 16,608 No Uterus 10,739 Premarin +Provera Premarin Only Premarin +Provera Premarin Only There was a major flaw in the study. Premarin + Provera Placebo yrs Medica>on yrs 3 Confusing Variables 3 Important Variables: The results were mind blowing! Estrogen or E+P ±Uterus Timing It showed an increased risk of breast cancer and coronary heart disease. 6

7 Millions of women threw away their estrogen Many doctors feared estrogen too! Previvor s Challenge HT! up to 80% since 2002 Decision surrounded by anxiety & confusion Estrogen void filled by unregulated alternatives Most menopausal women are untreated New generation of graduates and PCPs lack competency in ET and in treating menopause Professional societies support using HT Manson JE, Kaunitz AM. Menopause Management Gemng Clinical Care Back on Track. March 3, Don t Tough it out; Figure it out! So many women are confuse and anxious! 7

8 AGE OF Menopause Mean age is 51 Surgical Menopause < 45 Without Estrogen Shows Risks For: All cause mortality 28% Heart Disease 33% Depression 50% Stroke 62% Cogni>ve Impairment 60% Parkinsonism 68% Sexual Problems % 5-10% < Age 45 Some before 40 Some before 30 Faubion SS, Kuhle CL, Shuster LT, Rocca WA. Long- term health consequences of premature or early menopause and considerahons for management. Climacteric. 2015;18(4): No Estrogen & Fatal MI BSO < 45 years old1 No ET "67%; ET! 41% Women < 60 or < 10 yrs post menopause2 ET!39%!47% sooner started the better3 BSO < 45 years old4 No ET " 23% Chest Pressure Doubles with RRSO Menopause; From 12% To 22% 1. Rivera CM et al. Increased cardiovascular mortality aner bilateral oophorectomy. Menopause 2009;16: HT- Cochrane Database Syst Rev. 2015: reduc>on = 39% 3. Savolainen- Peltonen. Cardiac death risk in rela>on to age at ini>a>on or the proges>n JCEM 2016;101: Taulant M, et al. Time since onset of menopause with Cardiovascular outcomes, intermediate vascular traits, and all- cause mortality. JAMA Cardiol Published online September 14, doi: /jamacardio Kronenberg F. Ann N Y Acad Sci. 1990;592: Estrogen Window and Brain Natural Menopause Estrogen Window and Mental Health Early/ Premature Menopause 8

9 6/1/17 Early BSO, No E Depression Anxiety Suicidal Thoughts CogniHve Impairment Alzheimer s disease Kronenberg F. Ann N Y Acad Sci. 1990;592: Rosenberg G et al. Early menopause and the risk of myocardial infarc>on. AJOG 1981;139:47-51 Rocca WA, Henderson VW. Is there a link between gynecologic surgeries and Alzheimer s disease. Neurology 2014; 82: Rocca WA, et al. Long term risks of depressive and anxiety sx aner early BSO. Menopause 2008;15(6): > <38 Bove R et al. Age at surgical menopause influences cogni>ve decline and Alzheimer pathology in older women. Neurology 2014;82: Estrogen Window and Bones Bone loss 1 st 5 years a`er menopause is 2-3%/year By age 80, women lose on average ~53% of peak bone mass Estrogen Window and The Vagina Estrogen Window and Bladder Lip Gloss Half of women have a sensihve bladder 9

10 The 800 Pound Gorilla Hormones & Breast Cancer Manson JE, Kaunitz AM. Menopause Management Gemng Clinical Care Back on Track. March 3, A 2013 publication reanalyzed the 2002 WHI Premarin + Provera study Manson JE, Kaunitz AM. Menopause Management Gemng Clinical Care Back on Track. March 3, HRT & Breast CA Risk < 50 For Women < 50 All forms of HRT lower Breast Cancer risk more than NOT using HRT Ewertz M, et al. Hormone use for menopausal symptoms and risk of breast cancer. A Danish cohort study. Br J Cancer 2005;92:

11 Estrogen Breast Cancer Risk Induces cancer cell death1,2 BRCA 1/2 Trials3 Two Sisters Study4 WHI findings2 DOPS Study5 Below Age 45 RRSO:! Cancer Risk " Chronic Diseases HRT is safe and beneficial 1. Carrol JS, Meyer CA, Song J, et al. Genome- wide analysis of estrogen receptor binding sites. Nature 2006;38:11: Chlebowski RT, Anderson GL. Changing Concepts: Menopausal hormone therapy and breast cancer. J Natl Cancer Inst 2012;104: Rebbeck TR, Knoff ND, Domcheck SM. Meta- analysis of risk reduc>on es>mates associated with risk reducing salpingo oophorectomy in BRCA1 or BRCA2 muta>on Carriers. JNCI 2009;191: O Brien KM, et al. Hormone therapy in young- onset breast cancer. Am J Epidemiol 2015;181:10: Schierbeck LL et al. Effect of HRT on CVD on recently menopausal women. BMJ 2012;345:e6409 How HT Timing Influences Risks and Benefits Mache Seibel, MD Professor, University of Mass Medical School EstrogenWindowBook.com Hormone Replacement Therapy Mefile:///Reimagined: How to Look Hot and Feel Healthy For Previvors Without Fear and Confusion Mache Seibel, MD HRT PRE- FOR VIVORS Mache Seibel, MD DrMache.com 11