The Menopausal Transition 20s 30s 40s 50s 60s 70s 80s+ Understanding - PDF document

10/17/2019 The Menopausal Transition 20s 30s 40s 50s 60s 70s 80s+ Understanding the Perimenopause: Reproductive Menopause transition Postmenopause Setting the Stage Perimenopause Cynthia A. Stuenkel, MD Clinical Professor of Medicine, Department of Medicine Final menstrual period Division of Endocrinology and Metabolism University of California, San Diego, School of Medicine Stuenkel CA November 20, 2018 ‘ The Menopause Megatrend’ 1992 Lisa Selin Davis “Mothers do a good job teaching little girls about menstruation,” says Dr. Cynthia Stuenkel, medical director of San Diego’s menopause program, “but they don’t talk to “If only, on your 45 th birthday, a doctor would their daughters about menopause.” sit you down, look you squarely in the eyes “Neither does anyone else. But the demographics and say, Here’s what’s going to happen…” behind the menopause megatrend are about to change “We put a lot of time and effort into preparing how the medical community deals with this rite of teenagers for what changes puberty will wreak, passage and the myriad health problems that can follow.” but for women, midlife brings another kind of puberty—perimenopause…” Stuenkel CA Megatrends for Women by Patricia Aburdene and John Naisbitt; 1992, published by Megatrends, Ltd. Stuenkel CA 1

10/17/2019 2019 Perimenopause NAMS 2000 Consensus on Perimenopause  “Perimenopause (menopause transition) is a largely  “Our knowledge of how reproductive aging and unstudied and ill ‐ defined period in the lifespan of menopause affects women has grown women tremendously in recent decades.  “Data are lacking regarding  “Menopause transects aging, and somatic aging  Diagnosis  Screening is an essential confounding factor that must be  Treatment options addressed in studies of the menopausal  Effect of physiologic, racial, cultural, transition. and socioeconomic factors Santoro N, Kravitz HM, eds. Obstet Gynecol Clin N Am 2018;45:xv ‐ xvii Menopause 2000:7:5 ‐ 13 Longitudinal Studies of the 2019 Perimenopause Menopause Transition  “The critical need for serial study of the same STUDY N Duration (y) woman over time to fully capture the impact of  The Melbourne Women’s Midlife Health Project 438 9  The Massachusetts Women’s Health Study 2,572 menopausal milestones on health was 5  The Seattle Midlife Women’s Health Study 508 23 appreciated and embraced by a number of  University of Pittsburgh Healthy Woman Study 532 24 worldwide, longitudinal cohort studies, some of  Penn Ovarian Aging Study 436 18 which collected data for over 20 years.  The Rotterdam Study 14,926 28  Study of Women’s Health Across the Nation 3,302 24 Santoro N, Kravitz HM, eds. Obstet Gynecol Clin N Am 2018;45:xv ‐ xvii Allshouse A, et al. Obstet Gynecol Clin N Am 2018; 45:613 ‐ 628. 2

10/17/2019 2019 Perimenopause  “Now, we can provide a more complete picture of how the menopausal transition in its entirety is related to women’s health  Because we are able to center findings on the final menstrual period  And can thereby begin to separate the process of aging from the process of menopause.” https://www.swanstudy.org/about/swan ‐ history Santoro N, Kravitz HM, eds. Obstet Gynecol Clin N Am 2018;45:xv ‐ xvii Model of Reproductive Aging “The basis of reproductive senescence in women is oocyte depletion of the ovary.” Stages of Reproductive Aging Workshop Report NGF: nongrowing follicles; Hansen KR, et al. Human Reproduction 2008;23:699 ‐ 708. 3

10/17/2019 Ovarian Follicles at Various Antimüllerian Hormone (AMH) from Neonatal to Postmenopause Stages of Development 90 th percentile Oocyte endowment and rates of atresia are highly variable 50th percentile 10 th percentile Santoro N and Johnson JH. JAMA 2019;322:775 ‐ 776; FSH, Follicle Stimulating Hormone; AMH, antimullerian hormone Cui L, et al. Fertil Steril 2016;105:481–485. Mean Daily Urinary Gonadotropin Hormones in Relation to FMP: and Sex Steroid Excretion Patterns Melbourne Women’s Midlife Health Project FMP = final menstrual period Santoro N, et al. J Clin Endocrinol Metab 1996;81:1495 ‐ 1501; n=11 perimenopausal women age 43 ‐ 52. Burger H. et al. J Clin Endocrinol Metab 1999;84:4025–4030. 4

10/17/2019 Pattern of Hormone Excretion in a Perimenopausal Woman Santoro N, et al. J Clin Endocrinol Metab 1996;81:1495 ‐ 1501 Harlow SD, et al. Menopause 2012; 19:387 ‐ 95. The Stages of Reproductive Aging +10 Staging System How do you know if a woman is for Reproductive Aging in Women Menarche Final Menstrual Period perimenopausal? 0 Stages: -5 -4 -3b -3a -2 -1 +1a +1b +1c +2 REPRODUCTIVE POSTMENOPAUSE MENOPAUSAL TRANSITION Terminology: Early Peak Late Early Late Early Late PERIMENOPAUSE Duration: Variable Variable 1-3 years 2 years (1+1) 3-6 years Remaining lifespan Principal Criteria :  No one symptom or test is accurate enough by itself to Variable Length Interval Subtle Variable Changes Persistent ≥ 7 day of Menstrual cycle : to Regular Regular difference in length In flow/ amenorrhea of consecutive regular length of ≥ 60 days cycles rule in or rule out the perimenopause Supportive Criteria: Endocrine:  Variable*  >25 IU/L**  Variable*  Clinicians should diagnose perimenopause based on Low Variable* Stabilizes FSH Low Low Low Low Low Very Low AMH Inhibin B Low Low Low Low Very Low menstrual history, age, and symptoms such as hot Antral Follicle Count : Low Low Low Low Very Low Very Low Descriptive Characteristics: flashes without relying on laboratory test results Vasomotor Vasomotor Increasing Symptoms symptoms symptoms symptoms of Likely Most Likel y urogenital atrophy *Blood draw on cycle days 2-5  = elevated ** Approximate expected level based on assays using current international pituitary standard 67-69 Harlow SD, et al. Menopause 2012;19: Feb 15. [Epub ahead of print] Bastian et al. JAMA 2003;289:895–902; Stuenkel CA, et al. J Clin Endocrinol Metab 2015; 100:3975 ‐ 4011. Harlow et al. STRAW+10 Staging Reproductive Aging . Climacteric, Fertil Steril, JCEM, Menopause 2012 5

10/17/2019 Intersection of Multiple Risk Factors for Symptoms and Signs during Perimenopause Depression during the Menopause Transition Sleep disturbances Vasomotor symptoms Altered mood including depression and anxiety Vaginal dryness Cognitive complaints Urogenital changes Sexual complaints Metabolic disturbances Menstrual cycle alterations Fertility issues Stuenkel CA Bromberger JT and Epperson CN. Obstet Gynecol Clin N Am 2018;45:663 ‐ 678. Menopause Transition: Hot Flashes The Perimenopause  Understanding Perimenopause: Setting the Stage  Physiology of the Menopause Transition: The Hormone Milieu  Recognizing and Managing Irregular Menstrual Bleeding Early onset VMS associated in the Menopause Transition  Contraception During the Menopause Transition with subclinical CVD  The Complex Web of Hot Flashes, Sleep Disruption, Depression, and Well ‐ being  Metabolic Changes During the Menopause Transition  Reproductive Challenges in Perimenopause  Managing a Healthy Menopause Transition Tepper PG, et al. Menopause 2016; 23:1067 ‐ 1074. 6