In early November, Dr. Marty Makary, the new head of the FDA, made a headline-grabbing announcement: the agency would remove the black-box warning from all menopause hormone-therapy labels in the United States. Those warnings—added in 2003 after the Women's Health Initiative (WHI) sparked widespread alarm about elevated risks of breast cancer and blood clots—have shaped two decades of clinical practice and public perception.

"After 23 years of dogma," Makary declared, "the FDA today is announcing that we are going to stop the fear machine steering women away from this life-changing, even life-saving treatment."

The reaction was swift, and split. Many physicians and menopause specialists cheered the move as long overdue. But even among the supporters, something felt off: Several leading experts took issue with Makary's sweeping language, arguing he'd overstated the science and risked swapping one dogma for another.

The problem wasn’t the decision—it was the overselling. One stark example: Makary said in press interviews that hormone therapy lowers the risk of cognitive decline or Alzheimer’s disease, a claim that has no support from randomized trials. The only chronic disease HRT has ever been definitively proven to prevent is osteoporosis.

For women trying to make informed decisions about their bodies, it feels like déjà vu: yet another whiplash moment in an eighty-year cycle that swings menopause hormone therapy from "miracle cure" to "toxic menace," depending on the decade.

Here's how we got here, and why it matters.

Act I: Made in Montreal — From Emmenin to Premarin

Before Premarin became the world's best-selling menopause drug, it started in a McGill lab in 1930: part insulin breakthrough, part entrepreneurial hustle.

Biochemist James Collip, fresh off his insulin fame, partnered with Montreal drugmaker Ayerst, McKenna & Harrison on their next big swing: cracking the menopause problem.

Their first breakthrough was Emmenin, a pill made from the urine of pregnant Canadian women. It was the world's first orally active estrogen, a big step up from the steroid injections available at the time. It worked brilliantly, but there was an obvious bottleneck: there are only so many pregnant women willing to donate their pee to pharmaceutical science.

Meanwhile in Germany, researchers at the Berlin Zoo had been testing urine from female mammals and finally struck gold: the urine of pregnant equines (horses and zebras) was especially rich in potent conjugated estrogens. When word reached Montreal, the Ayerst team sprang into action. By 1939, they had perfected a way to extract these estrogens from mares on rural Quebec farms, and two years later Premarin (PREgnant MARes' urINe) was on Canadian pharmacy shelves. As demand skyrocketed in the 1960s and beyond, ranching operations expanded west to the Prairies and south into the U.S. Midwest.

Through a combination of scientific ingenuity, barnyard logistics, and bold marketing, Premarin would become one of the most prescribed (and controversial) drugs in pharma history.

Having perfected the chemistry, Ayerst's next task was perfecting the sell.

Act II: The Pitch — Happy Husband, Wealthy Doctor

"It makes no difference whether castration is brought about by removing the ovaries with a knife—as in their surgical removal—or whether the ovaries shrivel up and die as the result of menopause. In either case, the effect is the same: the woman becomes the equivalent of a eunuch."

-Dr. Robert Wilson, Feminine Forever, Chapter 2: "Must Women Tolerate Castration?"

In 1966, 24 years after the FDA approved hormone therapy to treat menopause symptoms, an unlikely blockbuster hit bookstore shelves. Written by celebrity gynaecologist Robert Wilson, *Feminine Forever* was a breathless ode to estrogen therapy as a magical, youth-preserving elixir.

Among other colorful anecdotes, Wilson told of a visit to his office from a prominent Brooklyn mobster, who threatened to kill his wife if the doctor couldn’t fix her foul temper. (Spoiler: Wilson restored the couple to marital bliss with his prescription pad…). Sales of Premarin quadrupled in the years following its release. After Dr Wilson’s death, reporters were shocked, shocked to discover that Ayerst had bankrolled the whole thing.

MHT's mid-century advertising targeted men as much as women. The message was unmistakable: medicate her so everyone else feels better.

Husbands would come home to a charming smile and hopefully a little heat in the bedroom. Teenagers would get a break from mom's wrath. Doctors would grow their practices and enjoy the perks offered by pharma back then.

The ads painted a picture of domestic bliss, all thanks to a pill. Milprem combined Premarin with blockbuster tranquilizer Miltown to create a menopausal mother’s little helper. Calm for her, peace for everyone else. The subtext was always the same: her menopause is everyone's problem. The solution? Medication.

By the mid-1970s, millions of women were taking Premarin, blissfully ignorant of the dark discovery about to be made.

Act III: Reality Bites — Cancer Concerns in the 1970s

In 1975, two papers landed in the New England Journal of Medicine with devastating news: the estrogen therapy millions of women had been prescribed for relief was fueling an unexpected epidemic of endometrial cancer. The studies showed that women taking estrogen alone were at least 5–10 times more likely to develop endometrial carcinoma. One later analysis estimated more than 15,000 U.S. cases (1971–1975) were attributable to estrogen therapy. It was called "one of the largest epidemics of serious iatrogenic disease [i.e a disease caused by medical treatment]" in U.S. history.

This was a massive problem for Premarin, then prescribed to millions. Researchers quickly figured out that the cancer risk stemmed from estrogen's effect on the uterine lining: it stimulated continuous cell growth without the natural checks provided by progesterone during a pre-menopausal cycle.

The solution turned out to be another win for pharma: add a progestin. Progestins (synthetic progesterone) counteract estrogen's effect on the uterus and keep the lining from growing out of control. They were already prescribed for endometriosis and uterine fibroids. Clinical trials in the late 1970s showed that combining estrogen with a progestin almost entirely eliminated the excess risk of endometrial cancer.

By the early 1980s, "estrogen + progestin" therapy became the new standard for women with a uterus, while estrogen alone remained acceptable only for women who had undergone hysterectomy. That shift saved Premarin's market dominance, re-launched as Prempro (estrogen + progestin), and laid the foundation for the next big marketing push in the 1990s.

Act IV: The 1990s — Premarin’s Second Act

With observational studies hinting at benefits for brain and heart health, the 1990s saw hormones rebranded as preventive medicine—not just for hot flashes, but as protection against the ravages of aging itself.

Pharma turned up the volume: celebrity spokespeople fronted ads. “Believe me,” supermodel Lauren Hutton said in a famous 2000 TV spot warning of the dangers of estrogen loss. “The time to protect your future is now.”

But the real persuasion happened behind the scenes. Wyeth's communications agencies paid medical writers to draft flattering journal articles, then recruited respected doctors to sign their names. They poured millions into glossy CME courses and educational initiatives, painting hormones as protection against everything from heart disease to Alzheimer's.

The pitch worked. By 2001, Premarin and Prempro were among the most prescribed drugs in America, taken by over 40% of postmenopausal women, not just to manage symptoms, but to "stay young."

Act V: 2002 — The WHI Plot Twist

On July 9, 2002, the NIH dropped a bombshell. At a packed press conference, Dr. Jacques Rossouw announced that the Women's Health Initiative trial of combined estrogen + progestin therapy was being stopped early. The verdict: women on hormones were experiencing more breast cancers, more heart attacks, more strokes, more blood clots.

The headlines detonated:

"Hormone Therapy Raises Cancer, Heart Risks—Landmark Trial Halted" (New York Times)
"Hormones Linked to Breast Cancer, Stroke" (Washington Post)
"Millions of Women May Be at Risk" (Associated Press)

Women quit therapy mid-pack. Doctors' offices were deluged with calls. Prescriptions collapsed—down nearly 40% in a single year.

Then came what looked like confirmation: U.S. breast-cancer rates fell sharply. Between 2002 and 2003, incidence dropped roughly 7%—the steepest one-year decline ever recorded—driven largely by decreases in estrogen-progestin–related cancers. By 2004, rates were down 8–9% overall, with the steepest declines in women aged 50 to 69, the very group most likely to have been on hormones. To many observers, it looked like an unmistakable cause-and-effect moment: women quit HRT, and breast-cancer diagnoses plummeted.

What the Headlines Missed: The Absolute Risk

But here's what got lost in the panic: the risks weren't cataclysmic in absolute terms.

In the WHI, combined therapy caused 8 additional breast cancers per 10,000 women per year. That's 0.08% annually. Over five years, a 50-year-old woman's lifetime risk might rise from 6.1% to 6.7%—an absolute increase of 0.6%. Over 10 years, maybe 6.1% to 7.7%— a 1.6% increase.

In the Million Women Study, five years of combined HRT raised breast cancer incidence from 19 per 1,000 women to 31 per 1,000—about a 1.2% absolute risk increase.

Important? Yes. Apocalypse? No.

The apparent contradiction—small risk per woman, big impact on national statistics—is resolved by scale: millions of women were taking hormones, so modest individual risks multiplied into thousands of cases.

And the story was more complicated than it first appeared. A 2007 study found that mammography use, which had risen steadily through the 1980s and '90s, slipped from about 70% in 2000 to 66% in 2005 among U.S. women over 40. That small drop in screening almost certainly contributed to the fall in diagnoses. And breast cancer incidence had already been flattening in the late 1990s, so the WHI didn't single-handedly reverse an upward curve—it accelerated an existing slowdown.

The WHI had significant limitations. The most important was timing: the average participant was 63—more than a decade past the age when most women start therapy. By then, many women have already undergone the metabolic and vascular changes that accumulate in the years after menopause. Their cardiovascular risks are simply not the same as those of women who initiate therapy in their 40s and 50s. Later analyses confirmed this “timing effect.”

In the years that followed, more than 13,000 patients sued Wyeth, and the litigation forced thousands of internal documents into public view. Those records didn’t just raise questions about risk—they revealed how deeply the “preventive medicine” narrative had been embedded into medical culture. Ads, educational materials, and physician-targeted campaigns all reinforced the idea of hormones as protection against heart disease, Alzheimer’s, and even blindness. The lawsuits didn’t introduce a new story; they confirmed the one women had been living inside for a decade.

So the WHI was both true and misleading: it revealed real risks, but the way it was announced—stark, sweeping, front-page—erased nuance about age, timing, and regimen. The panic was understandable, but the pendulum swing left millions of women untreated while the medical community slowly sorted out what the study really showed.

Act VI: The "Debunking" and the Slow Rebound

Later analyses refined the picture:

Timing matters. Starting under 60 or within 10 years of menopause is safer (the "timing hypothesis").
Regimen matters. Estrogen-only therapy (in women without a uterus) was associated with lower breast cancer risk compared with placebo.
Route and dose matter. Lower-dose, transdermal regimens carry different risk profiles than oral pills.

The WHI wasn't "wrong." It was over-interpreted. But for too many doctors, the black mark on hormones was indelible. They practiced as if it were 2003, leaving millions of women to white-knuckle their way through the perimenopause transition and beyond.

While mainstream medicine was still nursing its WHI hangover, a new generation of marketers spotted an opening.

Act VII: "Bioidentical HRT" as the Fountain of Youth

Into the vacuum stepped a new narrative: hormones as nature’s anti-aging elixir.

**Wellness celebrities extolled "bioidentical hormones" as natural and safe.**

Suzanne Somers (the blonde from *Three’s Company*-turned-wellness guru) dubbed hormones "the juice of youth" and promised relief from the "Seven Dwarves of Menopause: Itchy, Bitchy, Sweaty, Sleepy, Bloated, Forgetful, All Dried Up."

Yes, estradiol and micronized progesterone are molecularly identical to what your ovaries used to make. But here's the sleight of hand: the marketing term "bioidentical" was co-opted in the late 1990s to sell custom-compounded hormone mixes as if they were safer, more "natural," and tailor-made for your body.

The problem? These compounded versions are not FDA- or Health Canada-approved, not standardized, and not batch-tested (not to mention expensive and rarely covered by health insurance). One pharmacy's mixture can differ from the next, and the "personalized" saliva or blood tests often used to justify them have little scientific validity. In fact, every hormone therapy—whether made from soy, yams, or horse urine—is synthesized in a lab. Ironically, the only truly "natural" product was Premarin, extracted straight from horse urine.

So while the term "bioidentical" makes compounded hormones sound superior, the reality is the opposite:

FDA/Health Canada-approved estradiol patches and micronized progesterone capsules are also bioidentical—but with rigorous quality control.
The biggest safety factor isn't whether a hormone is "bioidentical" or "synthetic," but how it's delivered. A transdermal patch, for instance, is safer for blood clot risk than an oral pill, regardless of marketing label.
Claims that compounded hormones are automatically safer or more effective are not backed by evidence.

In short: "bioidentical" is more branding than science. Natural ≠ risk-free—and in this case, it often means less regulated and less studied.

The Pendulum's Still Swinging

For eight decades, women have been caught in medicine's pendulum:

1940s–60s: Miracle. Hormones marketed as the cure for "living decay."
1970s: Menace. Endometrial cancer link sparks retreat.
1990s: Miracle again. Sold as protection for heart, brain, and bones.
2002: Menace again. WHI panic, lawsuits, black-box warnings.
2010s–20s: The swing back. Nuanced science trickles in while wellness influencers market bioidentical panaceas.

The truth? Hormones are neither poison nor panacea. They’re a tool — powerful, imperfect, sometimes genuinely life-changing. But after 80 years of hype, panic, and spin, women are still left sorting through the wreckage of every swing.

Part of the problem is structural: for most of modern medical history, women have been left out of clinical trials. Until the 1990s, the majority of drug studies — including some that shaped hormone-therapy warnings — were conducted primarily on men. The Coronary Drug Project, for example, tested high-dose estrogen in men and found increased cardiovascular risk — findings that helped solidify early assumptions about estrogen’s danger and influenced how later warnings for women were framed. When the evidence base itself is skewed, the conclusions are bound to be distorted.

The real question isn’t whether hormones are “good” or “bad.” It’s whether medicine has finally learned anything from the last eight decades.

Women deserve:

Doctors who know the science of 2025, not the panic of 2002
Access to regulated options, not wellness markups
Trusted sources of information that are science-based and easy to understand
The freedom to decide based on their bodies and priorities, not the latest headlines.

Maybe the real miracle would be science without the spin.

Menopause, Marketed: How We Got Here (and Why It's Infuriating)