What's the backstory on hormone replacement therapy?
When it comes to menopause and hormones, few topics have been as misunderstood—or as hotly debated—as hormone therapy. So how did we get from “everyone’s on it” to “hormones are dangerous” to where we are today? Let’s take a quick trip through history.
1940s–1950s: The Beginning
- 1942: Premarin (made from pregnant mare’s urine → PREgnant MARe urINe) hit the market as the first widely used synthetic estrogen.
- Estrogen was promoted as the cure-all for “menopausal disorders.”
- By 1975, it was one of the top 5 prescribed drugs in the U.S.
1970s: Trouble in Paradise
- Doctors started noticing a rise in uterine cancer in women taking estrogen.
- Prescriptions nosedived.
- The missing piece? Progesterone. It is needed in the presence of estrogen to protect the uterus.
1980s–1990s: Back in Favor
- Studies confirmed: pairing progesterone with estrogen solved the problem.
- Prescriptions soared again. By 2001, 42% of women ages 50–75 were on hormone therapy, with 90 million prescriptions written that year.
2002: Enter the Women’s Health Initiative (WHI)
- The WHI study set out to see if hormones could prevent heart disease and other chronic illnesses.
- Over 27,000 women enrolled in the study that started in 1991. At that time, the most common hormone formulations taken were Conjugated equine estrogen (Premarin) and synthetic progestin—neither very similar to the body’s natural hormones.
- In 2002, the trial was stopped early after reports of higher risks of breast cancer, heart disease, stroke, and blood clots.
2002 Fallout: Fear and Confusion
- Headlines sparked panic. Overnight, women were pulled off their prescriptions.
- Hormone use plummeted—from 42% of women over ages 50-75 to less than 5% a decade later.
- The message that stuck: “Hormones are dangerous.” For two generations, menopause treatment virtually disappeared, and women were even shamed for wanting relief.
The Rise of “Bioidenticals”
- In the search for safer options, bioidentical hormones were marketed as “natural” and lower risk.
New FDA-Approved Options
- Around the same time, new hormone formulations—closer to the body’s natural versions—were approved.
- Estradiol patches (late 90s)
- Estradiol gel (2004)
- Estradiol spray (2007)
- Micronized progesterone (1998)
- These were approved after that start of the WHI, so they were not the formulations used in the study.
The Truth Comes Out: 20 Years of Data
The good news is that researchers continued to follow women who were enrolled in the WHI, and we now have an additional 20 years of data (Can confirm - I spent a summer in med school calling women enrolled in the study to complete their follow up surveys). With long-term follow-up of the WHI and newer studies, here’s what we now know:
- Age matters. Hormone therapy is safest and most effective if started before 60 or within 10 years of menopause.
- Formulation matters. Lower doses, patches/gels, and oral micronized progesterone are generally safer than the older synthetic versions (although there is a time and a place for those, too).
- The original WHI conclusions were oversimplified. The media headlines overstated risks, ignored age differences, and left lasting fear.
Where We Are Today
- Hormone therapy is considered safe and effective for healthy women in early menopause who are struggling with hot flashes, night sweats, and more.
- It may also protect bone and heart health when started at the right time.
- But thanks to the WHI fallout, many doctors are still hesitant to prescribe—and many women still suffer in silence.