WHI fallout: How hormone fears stalled testosterone therapy for women

Bruce Dorr, MD, FACOG, URPS, IFMCP, describes the July 2002 release of the Women's Health Initiative (WHI) results as a defining moment in his career. He recalls his front office staff interrupting patient visits because callers were asking whether estrogen caused breast cancer, and knowing immediately that it would not go well. Although the WHI was not a testosterone trial, he says, testosterone became collateral damage, and the fallout changed clinicians' willingness to even have the conversation with patients.

Sharon J. Parish, MD, IF, NCMP, clarifies what the trial actually studied. The WHI evaluated oral estrogen with or without a progestin for prolongation of life and disease prevention rather than symptom relief. Participants entered without menopausal symptoms, anywhere from their 50s to early 70s, and outcomes were analyzed together across ages and comorbidities. A woman starting at 71 was analyzed the same way as a symptomatic woman in her early 50s.

Parish explains that small increases in events such as breast cancer, stroke, and heart attack were concerning enough that hormones came to be seen as harmful, even though benefits for bone were observed. Over the past 2 decades, however, reanalyses by age and risk factors, along with research on transdermal gels, patches, and vaginal rings, have prompted clinicians to look more carefully. Parish says menopausal hormone therapy is now clearly understood to help symptoms, whereas questions about disease prevention are still being navigated.

Asked whether the WHI was a step back for sexual medicine, Parish notes that vasomotor symptoms themselves undermine sexual health. Women deprived of systemic estrogen also faced vulvovaginal dryness and sexual pain, and vaginal estrogen products carried the same boxed warning. She welcomes the recent removal of that labeling, but she says the downstream effects on sexual health were substantial and also distracted attention from testosterone.

In the next episode, Parish walks through female testosterone physiology and the regulatory history of the transdermal products that sought approval for women.