The Hormone Therapy Fear That Killed Tens of Thousands of Women
In 2002, a study scared millions of women off hormone therapy. The study was right. The interpretation was catastrophically wrong.
In July 2002, the Women’s Health Initiative (WHI) made headlines worldwide. The estrogen-plus-progestin arm of the trial was stopped early. The message that reached patients: hormone therapy causes breast cancer and heart disease.
Millions of women stopped their prescriptions. Physicians stopped prescribing. Within two years, hormone therapy use dropped by more than half.
Here’s what the headlines didn’t say: the average participant was 63 years old, more than a decade past menopause. Two-thirds were over 60. The average BMI was 28.5. These were not the symptomatic 51-year-old women asking their doctors about hot flashes.
The study tested one specific formulation (Prempro) in one specific population. The results were generalized to all hormone therapy in all women.
The Number: Hormone therapy prescribing dropped from 27% of postmenopausal women in 1999-2000 to 4.7% by 2020. That’s a 22-percentage-point collapse in treatment for symptoms that affect 75% to 80% of menopausal women.
What the WHI Actually Found
The WHI tested two formulations in separate trials:
Estrogen-plus-progestin (for women with a uterus): The combination of conjugated equine estrogens (0.625 mg) plus medroxyprogesterone acetate (2.5 mg) showed increased breast cancer risk and cardiovascular events in older women. This arm was stopped early.
Estrogen-alone (for women after hysterectomy): This arm continued and found something remarkable: estrogen-only therapy reduced breast cancer by 23% and showed trends toward reduced heart disease and mortality in women ages 50-59.
The media reported one story. The data told two.
The Deaths We Don’t Count
In 2013, Yale researchers published an analysis that should have been front-page news. Philip Sarrel and colleagues calculated the mortality toll of estrogen avoidance among hysterectomized women aged 50-59.
Their estimate: between 18,000 and 91,000 excess deaths over ten years. Their best point estimate was approximately 50,000 women who died prematurely because they avoided estrogen therapy after the WHI publication.
Most died of heart disease. Before 2002, more than 90% of hysterectomized women in their 50s used estrogen therapy. After 2002, that dropped to roughly 10%. The mortality difference was 13 additional deaths per 10,000 women per year.
“Estrogen avoidance has resulted in a real cost in women’s lives every year for the last 10 years,” Sarrel said, “and the deaths continue.”
The Timing That Changes Everything
The WHI’s own reanalyses revealed what researchers now call the “timing hypothesis.” When you stratify the data by age at initiation, the story transforms:
Women ages 50-59:
Estrogen-alone: 35% reduction in coronary heart disease (HR 0.65)
18-year follow-up: 21% reduction in all-cause mortality (HR 0.79)
No significant increase in stroke or breast cancer
Women ages 70-79:
Increased cardiovascular events
Increased stroke risk
Different risk-benefit profile entirely
The WHI wasn’t wrong. It was misapplied.
Starting hormone therapy within 10 years of menopause, or before age 60, produces fundamentally different results than starting it at 65 in women with established cardiovascular disease.
What Professional Societies Now Say
The North American Menopause Society’s 2022 Position Statement is unequivocal:
“For women aged younger than 60 years or who are within 10 years of menopause onset and have no contraindications, the benefit-risk ratio is favorable for treatment of bothersome vasomotor symptoms and prevention of bone loss.”
The statement adds: “The benefits of hormone therapy outweigh the risks for most healthy symptomatic women who are aged younger than 60 years and within 10 years of menopause onset.”
This isn’t controversial among menopause specialists. It hasn’t been for years.
Yet prescribing rates remain at 4-5%. The fear persists.
The Breast Cancer Question
Let me be direct about breast cancer, because this drives most of the fear.
Estrogen-alone therapy: In the WHI, estrogen-only therapy reduced breast cancer incidence by 23% and reduced breast cancer mortality. This finding has held through 20 years of follow-up.
Estrogen-plus-progestin therapy: The absolute risk increase was 8 additional breast cancer cases per 10,000 women per year. After 5 years of use, that translates to about 4 additional cases per 1,000 women.
For context, that’s similar to or less than the breast cancer risk from:
Obesity (higher risk than combined HRT)
Alcohol consumption (2+ drinks daily)
Never having children
Sedentary lifestyle
Clinical Pearl: We don’t tell women to avoid these lifestyle factors with the same urgency we tell them to avoid hormone therapy. The risk communication has been wildly disproportionate to the actual risk.
The type of progestogen matters. Micronized progesterone appears to have a more favorable breast cancer profile than synthetic progestins like medroxyprogesterone acetate (which was used in the WHI). The route matters too: transdermal estrogen avoids first-pass liver effects and shows lower clotting risk.
What We Lost
Beyond the mortality statistics, consider what millions of women lost:
Quality of life: 75-80% of menopausal women experience vasomotor symptoms. For many, hot flashes are debilitating. Night sweats destroy sleep for years. The average duration of symptoms is 7-11 years.
Bone health: Estrogen prevents bone loss. The decade after menopause is when women lose bone most rapidly. Fractures in older women carry significant mortality.
Cardiovascular protection: The cardiovascular benefit of estrogen in younger menopausal women has been obscured by results in older women who already had atherosclerosis.
Sexual function: Genitourinary syndrome of menopause affects up to 50% of postmenopausal women. Vaginal estrogen is safe and effective, yet many women believe they can’t use even local treatment.
Mental health: Emerging evidence links estrogen deficiency to depression and cognitive changes during the menopause transition.
The tragedy isn’t just that women died. It’s that millions suffered unnecessarily for two decades, and many continue to suffer today.
Bottom Line for Free Readers:
The 2002 WHI findings were misinterpreted and over-generalized. For healthy women under 60 with bothersome menopausal symptoms, hormone therapy is the most effective treatment, and the benefits typically outweigh the risks. The fear that stopped millions of women from treatment was based on data from women in their 60s and 70s, not from symptomatic women at menopause. Professional societies have moved on. It’s time for the rest of medicine, and the public, to catch up.
The Evidence in Detail
