The History of Hormone Therapy: How We Got Here and Why It Matters for Your Care

Apr 20

If you've ever asked a doctor about hormone therapy and gotten a hesitant, inconsistent, or flat-out dismissive response — the history of this treatment is a big part of why.

Menopausal hormone therapy (MHT), also called hormone replacement therapy (HRT) or hormone therapy (HT), has one of the most turbulent scientific and cultural histories in modern medicine. It has been celebrated, catastrophized, abandoned, and rehabilitated — sometimes within the same decade. Understanding that history isn't just academic. It explains the confusion patients encounter, why recommendations have shifted so dramatically, and why individualized care matters more than a blanket policy.

The Beginning: Estrogen as a Cure-All (1940s–1960s)

The story of MHT in the United States begins in 1942, when the FDA approved Premarin — conjugated equine estrogen derived from pregnant mare urine — for the treatment of menopausal symptoms. Hot flashes, night sweats, vaginal dryness, mood changes: estrogen worked, and it worked well.

By the 1960s, enthusiasm had reached a fever pitch. In 1966, gynecologist Robert Wilson published Feminine Forever, a bestselling book arguing that menopause was an estrogen-deficiency disease and that hormone therapy could — and should — keep women youthful, vital, and sexually available into old age. The framing was deeply paternalistic, and Wilson had undisclosed financial ties to pharmaceutical manufacturers. But the book sold millions of copies and drove an enormous surge in estrogen prescribing.

By the mid-1970s, Premarin was one of the most prescribed drugs in the United States.

The First Crisis: Endometrial Cancer (1970s)

The celebration was short-lived. In 1975, two landmark studies published in the New England Journal of Medicine found that women taking unopposed estrogen — estrogen without progesterone — had a significantly elevated risk of endometrial cancer. Prescriptions plummeted almost overnight.

The medical response was to add progestogen to estrogen regimens for women with a uterus, creating what became known as combined hormone therapy. This largely addressed the endometrial cancer risk. But the damage to public confidence had been done, and hormone therapy carried a new cloud of uncertainty into the 1980s.

The Rehabilitation: Cardiovascular Promise (1980s–1990s)

Through the 1980s and into the 1990s, observational data began suggesting that hormone therapy might do more than treat symptoms — it might actively protect the heart. Multiple large observational studies, including the influential Nurses' Health Study, found that women using estrogen had lower rates of coronary heart disease compared to non-users.

This was a striking finding. Cardiovascular disease was — and remains — the leading cause of death in women, and the prospect of a treatment that could simultaneously relieve menopause symptoms and protect the heart drove a major resurgence in prescribing. By the late 1990s, hormone therapy was once again one of the most commonly used medications in the country, and major medical organizations were cautiously endorsing it for long-term use.

The Second Crisis: The WHI Study (2002)

Then came July 2002 and the publication that changed everything.

The Women's Health Initiative (WHI), a large NIH-funded randomized controlled trial, published results from its combined estrogen-progestin arm. The trial was stopped early because data showed increased risks of breast cancer, stroke, blood clots, and — contrary to what the observational data had suggested — coronary heart disease.

The reaction was immediate and severe. Hormone therapy prescriptions dropped by more than 50% within a year. Medical societies revised their guidelines. A generation of physicians learned to discourage or refuse MHT requests. Many women who were managing menopause well on hormone therapy were abruptly taken off it.

The problem, which took years to fully unpack, was that the WHI findings had critical limitations that were not clearly communicated in the initial media coverage or clinical response.

Re-Reading the WHI: What the Data Actually Showed

In the years following the 2002 publication, researchers went back to the WHI data and found a more nuanced picture.

The average age of women enrolled in the WHI was 63, more than a decade past the typical onset of menopause. Many already had subclinical cardiovascular disease. The formulation used was oral conjugated equine estrogen plus medroxyprogesterone acetate (a synthetic progestogen, not the estrogen formulations or the bioidentical progesterone increasingly used in clinical practice today.

When researchers analyzed outcomes by age and time since menopause, the results shifted significantly. Women who started hormone therapy before age 60 or within 10 years of menopause onset showed no increase in cardiovascular risk, and in some analyses, showed a reduction. This became known as the timing hypothesis or the window of opportunity.

The estrogen-alone arm of the WHI (for women without a uterus) told a different story still: no significant increase in breast cancer risk, and a possible reduction.

The 2002 headlines had flattened a complicated dataset into a simple warning, and millions of women paid the price in undertreated symptoms and unnecessarily withheld care.

The Modern Era: Individualized, Nuanced, Evidence-Based (2010s–Present)

The rehabilitation of MHT has been gradual but significant. Over the past decade, major medical organizations including the Menopause Society (formerly NAMS), the British Menopause Society, and the Endocrine Society have moved toward individualized risk-benefit frameworks rather than blanket restrictions.

The current consensus, supported by a growing body of evidence, recognizes several key points:

The timing matters. Hormone therapy initiated within 10 years of menopause onset or before age 60 carries a different risk profile than therapy started later. The window of opportunity is real.

The formulation matters. Transdermal estrogen (patch, gel, spray) carries a lower clotting risk than oral estrogen. Bioidentical micronized progesterone (Prometrium) appears to carry a lower breast cancer signal than synthetic progestogens like medroxyprogesterone acetate.

The indication matters. For women with significant vasomotor symptoms — hot flashes, night sweats — that affect sleep, mood, and quality of life, MHT remains the most effective treatment available. It also addresses genitourinary syndrome of menopause (GSM), which is underdiagnosed and undertreated.

The individual matters. A woman's personal and family history, cardiovascular risk factors, breast cancer history, bone density, mood symptoms, and preferences all shape whether and how MHT is appropriate for her.

Why This History Matters for Psychiatric Care

The overlap between menopause and mental health is significant and still underappreciated. Perimenopause is one of the highest-risk windows for new-onset depression, anxiety, and mood instability — driven in part by fluctuating and declining estrogen's effects on serotonin, dopamine, and GABA systems. Sleep disruption from hot flashes compounds everything.

For many perimenopausal women, what looks like a primary mood disorder is substantially driven by hormonal transition. Treating mood symptoms without addressing the hormonal context often produces incomplete results.

This is exactly the intersection that reproductive psychiatry is designed to navigate. At Estela, we evaluate the full picture: where you are in your hormonal transition, how your symptoms interact, and what combination of approaches — which may include MHT, antidepressants, or both — makes the most sense for you.

The history of hormone therapy is a story about what happens when medicine overcorrects. Women were overprescribed in the 1960s, then undertreated after 2002, and the pendulum is only now finding a more careful center. You deserve care that reflects where the evidence actually stands — not where it stood twenty years ago.

Ready to take the next step? Estela Mental Health is located in Austin and accepts several major insurance plans including Aetna, Blue Cross Blue Shield, Cigna/Evernorth, Optum, and United Healthcare. Book an appointment today — and let's figure this out together.

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References

The following are primary peer-reviewed sources cited in this post. Only references verified with high confidence for accuracy of authorship, publication, and year are included.

Ziel HK, Finkle WD. Increased risk of endometrial carcinoma among users of conjugated estrogens. N Engl J Med. 1975;293(23):1167–1170.
Smith DC, Prentice R, Thompson DJ, Herrmann WL. Association of exogenous estrogen and endometrial carcinoma. N Engl J Med. 1975;293(23):1164–1167.
Stampfer MJ, Colditz GA, Willett WC, et al. Postmenopausal estrogen therapy and cardiovascular disease: ten-year follow-up from the Nurses' Health Study. N Engl J Med. 1991;325(11):756–762.
Rossouw JE, Anderson GL, Prentice RL, et al.; 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(3):321–333.
Anderson GL, Limacher M, Assaf AR, et al.; Women's Health Initiative Steering Committee. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial. JAMA. 2004;291(14):1701–1712.
Manson JE, Chlebowski RT, Stefanick ML, et al. Menopausal hormone therapy and health outcomes during the intervention and extended poststopping phases of the Women's Health Initiative randomized trials. JAMA. 2013;310(13):1353–1368.
Canonico M, Oger E, Plu-Bureau G, et al.; Estrogen and Thromboembolism Risk (ESTHER) Study Group. Hormone therapy and venous thromboembolism among postmenopausal women: impact of the route of estrogen administration and progestogens. Circulation. 2007;115(7):840–845.
Fournier A, Berrino F, Clavel-Chapelon F. Unequal risks for breast cancer associated with different hormone replacement therapies: results from the E3N cohort study. Breast Cancer Res Treat. 2008;107(1):103–111.
The Menopause Society. The 2022 Hormone Therapy Position Statement of The Menopause Society. Menopause. 2022;29(7):767–794.
Cohen LS, Soares CN, Vitonis AF, Otto MW, Harlow BL. Risk for new onset of depression during the menopausal transition: the Harvard Study of Moods and Cycles. Arch Gen Psychiatry. 2006;63(4):385–390.
Freeman EW, Sammel MD, Liu L, Gracia CR, Nelson DB, Hollander L. Hormones and menopausal status as predictors of depression in women in transition to menopause. Arch Gen Psychiatry. 2004;61(1):62–70.

This post is intended for general educational purposes and does not constitute medical advice. Please consult a qualified clinician to discuss your individual risk profile and treatment options.