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

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Understanding the Perimenopause: Setting the Stage

Cynthia A. Stuenkel, MD Clinical Professor of Medicine, Department of Medicine Division of Endocrinology and Metabolism University of California, San Diego, School of Medicine

The Menopausal Transition

20s 30s 40s 50s 60s 70s 80s+

Reproductive Menopause transition Postmenopause

Perimenopause

Final menstrual period

Stuenkel CA

‘The Menopause Megatrend’ 1992

“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 their daughters about menopause.” “Neither does anyone else. But the demographics behind the menopause megatrend are about to change how the medical community deals with this rite of passage and the myriad health problems that can follow.”

Megatrends for Women by Patricia Aburdene and John Naisbitt; 1992, published by Megatrends, Ltd.

Stuenkel CA November 20, 2018 Lisa Selin Davis

“If only, on your 45th birthday, a doctor would sit you down, look you squarely in the eyes and say, Here’s what’s going to happen…” “We put a lot of time and effort into preparing teenagers for what changes puberty will wreak, but for women, midlife brings another kind of puberty—perimenopause…”

Stuenkel CA

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NAMS 2000 Consensus on Perimenopause

• “Perimenopause (menopause transition) is a largely

unstudied and ill‐defined period in the lifespan of women

• “Data are lacking regarding
• Diagnosis
• Screening
• Treatment options
• Effect of physiologic, racial, cultural,

and socioeconomic factors

Menopause 2000:7:5‐13

2019 Perimenopause

• “Our knowledge of how reproductive aging and

menopause affects women has grown tremendously in recent decades.

• “Menopause transects aging, and somatic aging

is an essential confounding factor that must be addressed in studies of the menopausal transition.

Santoro N, Kravitz HM, eds. Obstet Gynecol Clin N Am 2018;45:xv‐xvii

2019 Perimenopause

• “The critical need for serial study of the same

woman over time to fully capture the impact of menopausal milestones on health was appreciated and embraced by a number of worldwide, longitudinal cohort studies, some of which collected data for over 20 years.

Santoro N, Kravitz HM, eds. Obstet Gynecol Clin N Am 2018;45:xv‐xvii

Longitudinal Studies of the Menopause Transition

STUDY N Duration (y)

• The Melbourne Women’s Midlife Health Project

438 9

• The Massachusetts Women’s Health Study 2,572

5

• The Seattle Midlife Women’s Health Study

508 23

• University of Pittsburgh Healthy Woman Study

532 24

• Penn Ovarian Aging Study

436 18

• The Rotterdam Study

14,926 28

• Study of Women’s Health Across the Nation 3,302 24

Allshouse A, et al. Obstet Gynecol Clin N Am 2018; 45:613‐628.

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https://www.swanstudy.org/about/swan‐history

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
• f aging from the process of menopause.”

Santoro N, Kravitz HM, eds. Obstet Gynecol Clin N Am 2018;45:xv‐xvii

“The basis of reproductive senescence in women is oocyte depletion of the ovary.”

Stages of Reproductive Aging Workshop Report

Model of Reproductive Aging

NGF: nongrowing follicles; Hansen KR, et al. Human Reproduction 2008;23:699‐708.

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Ovarian Follicles at Various Stages of Development

Santoro N and Johnson JH. JAMA 2019;322:775‐776; FSH, Follicle Stimulating Hormone; AMH, antimullerian hormone

Antimüllerian Hormone (AMH) from Neonatal to Postmenopause

Cui L, et al. Fertil Steril 2016;105:481–485.

90th percentile 50th percentile 10th percentile

Oocyte endowment and rates of atresia are highly variable

Hormones in Relation to FMP:

Melbourne Women’s Midlife Health Project

FMP = final menstrual period Burger H. et al. J Clin Endocrinol Metab 1999;84:4025–4030.

Mean Daily Urinary Gonadotropin and Sex Steroid Excretion Patterns

Santoro N, et al. J Clin Endocrinol Metab 1996;81:1495‐1501; n=11 perimenopausal women age 43‐52.

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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.

2 years (1+1) 3-6 years Remaining lifespan +1a

POSTMENOPAUSE

Early Late +1b

 Variable* Low Low Very Low Vasomotor symptoms Most Likely Stabilizes Very Low Very Low Very Low

+1c +2

Increasing symptoms of urogenital atrophy

The Stages of Reproductive Aging +10 Staging System for Reproductive Aging in Women

Harlow et al. STRAW+10 Staging Reproductive Aging . Climacteric, Fertil Steril, JCEM, Menopause 2012

Stages:

Terminology: Duration: Menstrual cycle: Endocrine: FSH AMH Inhibin B

Principal Criteria: Supportive Criteria:

Antral Follicle Count: Symptoms

Descriptive Characteristics:

Harlow SD, et al. Menopause 2012;19: Feb 15. [Epub ahead of print]

• 5
• 3b
• 3a

REPRODUCTIVE

Early Peak Late

Variable

• 4

Variable to regular Regular Regular Subtle Changes In flow/ length

Low Low Low Variable* Low Low Low

Variable 1-3 years

• 2

MENOPAUSAL TRANSITION Early Late PERIMENOPAUSE

• 1

Variable Length Persistent ≥7 day difference in length

• f consecutive

cycles

Interval

• f

amenorrhea

• f ≥60 days

 Variable* Low Low Low Vasomotor symptoms Likely  >25 IU/L** Low Low Low

*Blood draw on cycle days 2-5  = elevated ** Approximate expected level based on assays using current international pituitary standard67-69

Final Menstrual Period Menarche

How do you know if a woman is perimenopausal?

• No one symptom or test is accurate enough by itself to

rule in or rule out the perimenopause

• Clinicians should diagnose perimenopause based on

menstrual history, age, and symptoms such as hot flashes without relying on laboratory test results

Bastian et al. JAMA 2003;289:895–902; Stuenkel CA, et al. J Clin Endocrinol Metab 2015; 100:3975‐4011.

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Intersection of Multiple Risk Factors for Depression during the Menopause Transition

Bromberger JT and Epperson CN. Obstet Gynecol Clin N Am 2018;45:663‐678.

Symptoms and Signs during Perimenopause

Vasomotor symptoms Vaginal dryness Urogenital changes Sexual complaints Sleep disturbances Altered mood including depression and anxiety Menstrual cycle alterations Cognitive complaints Metabolic disturbances Fertility issues

Stuenkel CA

Menopause Transition: Hot Flashes

Tepper PG, et al. Menopause 2016; 23:1067‐1074.

Early onset VMS associated with subclinical CVD

The Perimenopause

• Understanding Perimenopause: Setting the Stage
• Physiology of the Menopause Transition: The Hormone

Milieu

• Recognizing and Managing Irregular Menstrual Bleeding

in the Menopause Transition

• Contraception During the Menopause Transition
• 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