Physiology of Menopause and the Women’s Health Initiative

Michelle Berlin, M.D., M.P.H.Co-Director, OHSU Center for Women’s HealthVice Chair, OHSU Dept of OBGYN

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Key Objectives and Goals

1) Review the changes in hormones that happen at menopause

2) Discuss the major effects of these changes

3) Briefly review the Women's Health Initiative

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Overview

• What is menopause?(Hint: it’s not just that your periods stop)

• What do all the terms mean?• That major study released in 2002..

Menopause Basics• Definition: cessation of periods for 1

year– Average age: 51– Most common age range: 45-55

• What causes menopause?– Ovaries stop producing estrogen and

progesterone – Estrogen levels decrease as you reach

the menopause, which causes the ovaries to stop producing an egg each month (ovulation).

www.nhs.uk/Conditions/Menopause/Pages/Causes.aspx

https://medlineplus.gov/menopause.html

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Menopause Basics

• Perimenopause (“menopausal transition”)– when periods can become irregular– have some symptoms intermittently– not truly in menopause until no menses x 12

months

• Postmenopausal: after the menopause

www.nhs.uk/Conditions/Menopause/Pages/Causes.aspx

https://medlineplus.gov/menopause.html

What organs are affected?

Many if not all..

Terminology

• HRT: hormone replacement therapy– HT: hormone therapy– MHT: menopausal hormone therapy

• What hormones?– E: estrogen– P: progesterone– E+P: estrogen + progesterone

• also called PERT: progesterone & estrogen replacement therapy

Terminology (cont)

• Genitourinary Syndrome of Menopause (GSM)– Aka “atrophic vaginitis”

• Women’s Health Initiative (WHI)

Women’s Health Initiative (WHI)

• WHI = 6 studies• 160,000+ women

– 50-79 years of age– enrolled 1993-1998

• 40 clinical centers

Women’s Health Initiative (WHI)

• Estrogen + Progesterone

• Estrogen only

Had hysterectomy: Estrogen only

“intact uterus”:Estrogen + Progesterone

WHI: Estrogen + Progestin Study

• Designed to evaluate if using HRT– decreases the risk of heart disease– increases the risk of breast cancer

WHI: Estrogen + Progestin Study• 16,600+ women• post-menopausal

– 50-79 years of age– “intact uterus” (had not undergone

hysterectomy)• Assignment:

– half of group: estrogen + progestin– half of group: placebo (“sugar pill”)

Are the people studied appropriate?

• 16,600+ women• post-menopausal

– 50-79 years of age– “intact uterus” (had not undergone

hysterectomy)

WHI: Estrogen + Progestin Study Results

Heart disease 29%

Stroke 41%

Blood clot 13%

Breast cancer 26%

Colon cancer 37%

Hip fracture 33%

Study Results

Additional lives lost/saved

for each 10,000 women

Heart disease 29% 7

Stroke 41% 8

Blood clot 13% 18

Breast cancer 26% 8

Colon cancer 37% 6

Hip fracture 33% 5

Another way to look at the results..

Placebo HRT (Estrogen +

Progesterone)

Additional/Fewer

Cases

Heart disease 30 37 7 more Stroke 20 29 8- 9 more Blood clot 16 34 18 more Breast cancer 30 38 8 more Colon cancer 16 10 6 fewer Hip fracture 15 10 5 fewer

AMA July 8, 2002

Comparing 10,000 women in one year taking a placebo to 10,000

women taking HRT:

WHI: Estrogen Only Study

• Designed to evaluate if using Estrogen only– decreases the risk of heart disease– increases the risk of breast cancer

WHI: Estrogen Only Study

• 10,739 women• post-menopausal

– 50-79 years of age– had undergone hysterectomy

• Assignment:– half of group: estrogen only– half of group: placebo (“sugar pill”)

Are the people studied appropriate?

• 16,600+ women• post-menopausal

– 50-79 years of age– had undergone hysterectomy

Another way to look at the results..

Placebo Estrogen

only

Additional/Fewer Cases

Heart

disease - 54 49 5 fewer

Stroke 32 44 12 more Blood clot 15 21 6 more Breast

cancer - 33 27 7 fewer

Colon

cancer - 16 17 6 fewer

Hip fracture 17 11 6 fewer

JAMA April 14,2004

Comparing 10,000 women in one year taking a placebo to 10,000

women taking Estrogen only:

Timing Hypothesis

“The current study suggest that younger women who use (estrogen) may be at reduced risk of (heart disease) but this possible association may be due to chance.”

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AUGUST 29, 2016 6:45 AM August 29, 2016 6:45 am 150

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