BY280 - Lecture 32 - Women's Health Initiative (WHI)

Women's Health Initiative (WHI)

First large-scale clinical trial (e.g. experiment) investigating health consequences of HRT. • Announced 1991 by Bernadine Healy, 1st woman director of NIH • Funded directly by Congress ($625 million, 15 years) • 40 study sites • Enrolled women 50 - 79 years old (post-menopausal) • 4 arms: dietary (observational), hormones (experimental), calcium/vitamin D, observational

Results of WHI estr./prog. study

HR = 1, not different from control HR> 1 higher disease in hormone group HR < 1 lower in the hormone group

WHI Hormone replacement trial

Objectives: To investigate the health consequences of hormone replacement therapy (HRT). Participants: 16,000 participants (women with uteri) aged 50-79. Remember, women with uteri had an elevated risk of uterine cancer if taking estrogen alone. Taking?: Half taking estrogen/progesterone commercial product (this can benefit the sale of that product) the other half taking placebo. Study stopped early (after 5 years) because of excess of certain diseases in the hormone group. Instead of finding fewer diseases, there were more diseases.

Hormone Replacement Therapy (HRT)

Replacement of hormones, estrogen and/or progesterone, to treat symptoms associated with menopause.

Current medical practice

• It's complicated - Other, smaller trials had diverse results - HRT no longer "automatic" - Lots of options (synthetic hormones, routes of delivery, doses, timing) - Depends on severity of postmenopausal symptoms - Depends on family history of diseases - Perimenopausal HRT for few years more often prescribed now

How to interpret?

• Observational studies had some sort of consistent biases (systematic differences between women who did HRT vs women who didn't) • Something unusual about HRT in the women in the WHI? Who got recruited for study? • Women who were clearly menopausal • Women who were not previously on HRT Result: average participant didn't start HRT until ~10 years after menopause . • Younger participants (50's) had fewer disease problems

Benefits of hormone replacement seen in many "observational epidemiology" studies

• Women with later (earlier) menopause lived longer (shorter) on average. • Women taking "hormone replacement" (estrogen alone or estrogen + progesterone) had: - Longer life - Lower rate of cardiovascular disease - Fewer osteoporotic bone fractures - Less insomnia, hot flashes, reduced libido, etc. - Alzheimer's disease? Breast cancer?