Concerns about supplemental estrogen stem largely from the Women’s Health Initiative (WHI) study results that were released in 2002. Prior to the study, hormone therapy was considered the gold standard for menopausal symptom relief, but the WHI showed an increase in the risk of breast cancer, cardiovascular disease, and stroke. The 1998 HERS study also contributed to a wave of concern that has caused many to shy away from HRT in the years since.
Now, researchers have pointed out serious flaws in both studies. Specifically, WHI and HERS focused on older women — a mean age of 63 to 67. In the HERS study, all participants already had cardiovascular disease. About 70 percent of subjects in the WHI trial were overweight or obese, half were current or former smokers, and the majority were a decade or more past menopause.
“The risks and benefits of hormone therapy depend heavily on timing, formulation, and the individual patient’s health profile.”
These study participants were given oral conjugated equine estrogen, derived from the urine of pregnant horses, along with a synthetic progestin that differs markedly from the bioidentical progesterone that’s more widely used today.
“The real safety concern is around toxic, synthetic progesterone that we know increases risk for heart disease, cognitive decline, and breast cancer,” says Karen Kaufman, MD, a board-certified obstetrician and gynecologist, and the medical director of MIORA in Colorado. “I haven’t prescribed that in 25 years, and hopefully nobody is anymore.”
Timing matters, too. “Later reanalysis showed that starting hormones within 10 years of menopause produces very different outcomes than starting them decades later,” says Sara Szal, MD, author of Women, Food, and Hormones. “The risks and benefits of hormone therapy depend heavily on timing, formulation, and the individual patient’s health profile. The one-size-fits-all conclusion from 2002 doesn’t hold up today.”
In late 2025, when the FDA announced it would update the black-box warnings on menopause hormone therapies, it requested that companies remove references to increased risks of cardiovascular disease, breast cancer, and dementia.
A Balanced Approach to HRT
If you’re considering hormone replacement therapy (HRT), you probably have questions. We asked clinicians and hormone specialists for answers about how HRT works, what its real risks and benefits are, and how to decide whether it’s right for you at “A Balanced Approach to Hormone Replacement Therapy,” from which this article was excerpted.
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