Hormone Therapy and the WHI Fallout: A Wake-Up Call for Women and Doctors: Part 1

In the next several blog posts, I want to summarize a very important discussion that was presented to the FDA by a table of experts.  These experts were physicians from a variety of specialties and were speaking on behalf of the more than 50 million women in the United States between the ages of 40-60, who are either menopausal or perimenopausal.  This roundtable discussion can be found on YouTube, but for those who do not wish to watch two hours of data presentation, I will summarize. For those science and data nerds, I highly recommend taking the time to educate yourselves and watch this powerful discussion on the truth about menopausal hormones and the misconceptions that have plagued two decades of women and healthcare providers alike since the 2002 Women’s Health Initiative (WHI) study that changed the landscape of hormone therapy in the United States and the world. Because of the extent of data that was presented, this will be spread out over three blog posts. 

FDA commissioner, Dr. Marty Makary, opened the discussion with some data dating back to the 1950s, where Mayo Clinic researchers discovered that women who had their ovaries removed developed early heart disease. This highlighted the powerful cardiovascular protection that intrinsic estrogen provides. Since then, studies have shown that starting menopausal hormone therapy (MHT) within 10 years of menopause can reduce the risk of fatal heart attacks and cardiovascular disease (CVD) by 25–50%, a benefit comparable to or even greater than that of statins. Given that CVD is the number one cause of death in women, this is a crucial finding. A 2015 Finnish study found that when women stopped MHT, their risk of fatal heart attacks rose by 26% in just the first year. The 2002 Women’s Health Initiative (WHI) study (which was widely cited at the time) had an average participant age of 63, well past the ideal window to start MHT. A 2017 reanalysis of the WHI data (Manson et al., JAMA) revealed that women under 60 who took MHT had reduced all-cause mortality. Despite fears raised about breast cancer in the original WHI publication, there was no statistically significant increase in breast cancer mortality. Many women, including the author’s own mother, were taken off or denied MHT due to this misconception, leading in her case to preventable bone fractures, even though estrogen reduces fracture risk by up to 50% (per a New England Journal of Medicine RCT). Additionally, research shows estrogen therapy may reduce the risk of cognitive decline by 64% and Alzheimer’s disease by 35%.

The next presenter, Dr. Heather Hirsch, puts it bluntly. She states “history got it wrong” when it comes to hormone therapy for women. A major misconception lies in the failure to distinguish between topical (vaginal) estrogen and systemic menopausal hormone therapy (MHT). Vaginal estrogen (VE), which is FDA-approved for treating genitourinary syndrome of menopause (GSM), does not enter the bloodstream in meaningful amounts and is considered safe for all women. Yet, the FDA still mandates a black box warning on these products claiming risks of cancer, stroke, and blood clots, despite no evidence supporting such outcomes with VE. The same black box warning applies to systemic estrogen, even though no study has ever shown a link between estrogen and increased breast cancer mortality. Adding to the confusion, many don't understand that each formulation and route of administration carries different safety profiles, making individualized care essential. With over 50 million women between ages 40–60, a lack of proper medical training and lingering fears from the misinterpreted WHI study has left too many women without access to potentially life-changing hormone therapy.

Next, Dr. Barbara Levy emphasizes a critical but often overlooked truth: “Not all hormones are the same.” The hormone therapy used in the WHI study, specifically conjugated equine estrogens (CEE) and medroxyprogesterone acetate, is chemically different from the 17-beta estradiol and bioidentical progesterone commonly used in modern MHT. These differences matter because each compound interacts with the body’s hormone receptors in distinct ways. The WHI was designed to answer whether all women should be placed on hormones to prevent cardiovascular disease, so it included a broad population of women, many with comorbidities, including smokers and those with preexisting CVD, with an average age of 63. The data from that study applies only to those specific hormone types and demographics, yet it continues to influence perceptions of all MHT today. As Dr. Levy points out, we urgently need studies that account for age, dose, and hormone formulation to reflect current practices. Unfortunately, the outdated conclusions from WHI have even contributed to MHT being placed on the Beers List (a list of medications considered potentially inappropriate for older adults) despite significant advances and differences in today’s hormone therapies.

Please see “Hormone Therapy and the WHI Fallout: A Wake-Up Call for Women and Doctors: Part 2” for continuation of this discussion. Please keep in mind that this information is for educational purposes only and is not considered to be individual medical advice.