The Women’s Health Initiative (WHI): Facts, Myths & Science
November 26, 2025
The Women’s Health Initiative (WHI): Facts, Myths & Science
Why This Addendum Matters
For more than 20 years, the WHI has shaped — and misshaped — the conversation around menopausal hormone therapy. Misinterpretations from this single study led to fear, confusion, and withdrawal of treatment from millions of women. With the FDA removing the boxed warning in 2025, it is time to set the record straight.
FACTS: What the WHI Actually Studied
1. The WHI Did Not Study Bioidentical Hormones
- Estrogen used: Conjugated equine estrogens (Premarin)
- Progestin used: Medroxyprogesterone acetate (MPA / Provera)
- No estradiol, no estriol, no micronized progesterone were studied.
2. Wrong Population
- Average age: 63
- Many >10 years past menopause onset
- Not representative of typical menopausal hormone therapy users.
3. Duration of the Study
- Combined arm (CEE + MPA / Prempro): ~5.2 years
- Estrogen-only (CEE): ~6.8 years
- Follow-up: 20 years of continued observational research.
4. Real Outcomes
Combined Arm (CEE + MPA / Provera):
- Slight ↑ breast cancer
- ↑ heart disease, ↑ stroke, ↑ blood clots
- BUT: ↓ colon cancer, ↓ osteoporotic fractures
- The risks stemmed from Provera, not estrogen.
Estrogen-Only Arm (CEE):
- ↓ breast cancer incidence
- ↓ breast cancer mortality
- ↓ all-cause mortality when started earlier
- No significant ↑ in heart disease in younger initiators
MYTHS: What the Headlines Got Wrong
MYTH #1 — “Hormones cause breast cancer.”
FACT: The increased breast cancer risk was linked to Provera, a synthetic progestin.
Bioidentical progesterone was never tested — and behaves very differently.
MYTH #2 — “Women of any age face the same risks.”
FACT: Risks were seen in women starting very late, long after menopause.
Early initiators often show improved cardiovascular and overall outcomes.
MYTH #3 — “Estrogen increases breast cancer.”
FACT: Estrogen alone reduced, not increased, breast cancer and mortality.
This has been reproduced in multiple follow-up studies through 2020.
MYTH #4 — “All hormone therapies are the same.”
FACT:
The WHI did not study estradiol, estriol, or real progesterone.
Different molecules = different receptors, effects, and safety profiles.
MYTH #5 — “Hormone therapy must stop by age 60.”
FACT:Physiologic, individualized, bioidentical hormone therapy can be safe and beneficial for women in their 60s, 70s, and 80s, when monitored correctly.
SCIENCE: Why the WHI Misled an Entire Generation
1. Prempro Was Never Tested Before WHI
The WHI was essentially Prempro’s first large trial, conducted after millions of women had already been prescribed it.
A drug trial conducted post-marketing is a recipe for disaster.
2. Women Were Historically Excluded From Research
From the 1940s–1990s, women — especially reproductive-age women — were excluded from most clinical trials.
The WHI reflected decades of missing data on female physiology.
3. Timing and Route Matter
The WHI studied:
- oral estrogens (which increase clotting)
- synthetic progestins (which affect breast and vascular tissue differently)
- older women starting late
Today we understand:
- transdermal estradiol
- micronized progesterone
- physiologic dosing
- appropriate timing
…produce entirely different risk profiles.
MODERN CONTEXT: What Happened After WHI
Dramatic decline in hormone therapy use
- From ~27% of postmenopausal women (1999–2000)
→ to under 5% by 2020
(over 75% drop)
Rise of compounded BHRT
- Estimated 1–2.5 million U.S. women using compounded hormones by 2015
- About one-third of all hormone therapy users now use compounded BHRT
- Market size exceeded $845 million by 2013
New FDA stance (2025)
Hormone therapy is safe when appropriately used — meaning:
- correct hormone
- correct dose
- correct route
- correct timing
- correct monitoring
- correct patient
The WHI did not disprove hormone therapy — it disproved Prempro!
It is time to replace fear with physiology, confusion with education, and outdated dogma with individualized, evidence-based women’s wellness care-a model I have had total faith in and one I have taught to practitioners and patients alike for over 25 years.
REFERENCES — WHI Evidence
- Writing Group for the Women’s Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: Principal results from the Women’s Health Initiative randomized controlled trial. JAMA. 2002;288:321–333.
- Anderson GL, et al. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: The Women’s Health Initiative randomized controlled trial. JAMA. 2004;291:1701–1712.
- Manson JE, Aragaki AK, et al. Menopausal hormone therapy and long-term all-cause and cause-specific mortality: The Women’s Health Initiative randomized trials. JAMA. 2017;318:927–938.
- North American Menopause Society. The 2022 Hormone Therapy Position Statement of The North American Menopause Society. Menopause. 2022;29:767–794.