Hormone Therapy and the WHI Fallout: A Wake-Up Call for Women and Doctors: Part 3

This is the third in a three-part series of blog posts covering the data presented by a panel of physician experts to the FDA regarding menopausal hormone therapy (MHT).  For context, please first read Hormone Therapy and the WHI Fallout: A Wake-Up Call for Women and Doctors; Parts 1 and 2.

Dr. Kelly Casperson, a urologist, shed light on the often-overlooked role of testosterone in women’s health, noting that a 2025 study found women who received female-dose testosterone were 50% less likely to require a cane or walker after a hip fracture. Although testosterone was first developed in 1935 and widely prescribed to men diagnosed with hypogonadism (which affects 1 in 5 men), virtually all women will eventually experience testosterone deficiency if they live long enough, yet the treatment landscape remains unequal. Testosterone is a neurohormone that supports not just libido, but nerve health, muscle strength, bone density, and brain function, including increased dopamine and cerebral blood flow. Despite its longstanding use in women since the 1940s (with as many U.S. women as men currently on testosterone) the FDA has twice rejected a female-dose formulation, citing lack of safety data, even though male formulations were approved with only 6 months of safety data. Women are left to microdose and pay out-of-pocket, while countries like New Zealand, Australia, South Africa, and the UK have approved female-dose testosterone, but only for low sexual desire, further stigmatizing its broader health benefits. Dr. Casperson highlighted that higher brain testosterone levels are linked with reduced dementia risk, urging the FDA to fast-track approval, expand indications beyond libido, and ease regulatory barriers. Meanwhile, Dr. Mary Jane Minkin, an OB/GYN, addressed another critical gap: education. Since July 9, 2002, the day after the Women's Health Initiative (WHI) study results were released, menopause education in medical training dropped off dramatically. A 2013 study showed only 20% of medical residents received training in menopause management; by 2023, that number had barely increased to 30%. Dr. Minkin stressed the urgent need for comprehensive, evidence-based training for all healthcare providers, including MDs, PAs, and NPs, to close the care gap for midlife women.

Dr. Rachel Rubin delivered a passionate and deeply personal message about genitourinary syndrome of menopause (GSM), a condition that affects millions of women yet remains underrecognized and undertreated. In 2014, a roundtable of experts, including Dr. Irwin Goldstein, a key founding member and first president of ISSWSH (International Society for the Study of Women's Sexual Health), redefined what was once called “vulvovaginal atrophy” to GSM, a broader term that acknowledges the urinary symptoms many women face in menopause, including recurrent urinary tract infections (UTIs), urinary urgency, urinary frequency, painful urination, incontinence, and painful sex. In April 2025, after seven years of work, the American Urological Association released new GSM guidelines, naming vaginal estrogen (VE) as the first-line treatment. Urinary tract infections cause seven million hospital visits annually, and 25% of adult infections, with rising mortality and risks from chronic antibiotic use, yet VE can prevent over 50% of UTIs. A 2024 study led by Dr. Rubin estimated that if all Medicare women used VE, it could save billions in healthcare costs. Still, due to the FDA’s 2003 boxed warning, which falsely links all estrogen products, including local VE, to stroke, heart attack, blood clots, breast cancer, and dementia, many women and even healthcare providers avoid or deny its use. Dr. Rubin shared a harrowing personal story: her mother, hospitalized and comatose in the ICU, was denied her regular VE despite being at high risk for urosepsis. ICU doctors, pharmacists, and nurses, misled by the black box warning, either refused to prescribe, dispense, or administer the cream until Dr. Rubin, armed with evidence, fought to get her mother the care she needed. Her story underscores how this warning continues to harm patients and obstruct care, and she closed by urging the FDA to remove the boxed label on VE, declaring, “Everyone deserves better.”

Dr. Howard Hodis offered a much-needed reality check on the misinterpreted data from the WHI, highlighting how the original 2002 publication misled the public and medical community. He pointed out that the reported increase in breast cancer in the estrogen plus progestin (E+P) arm of the study never reached statistical significance yet was included in the manuscript and sparked widespread fear. Dr. Hodis broke down the data specifically for women who started hormone therapy (HT) before age 60. In that group, the only statistically significant adverse event in the E+P arm was DVT, occurring at a rate of just 1 per 1,000 women per year. Other feared outcomes, including breast cancer, all-cause mortality, and cancer deaths, were either reduced or statistically insignificant compared to placebo. In fact, colorectal cancer, all fractures, and diabetes were reduced in both the E-only and E+P arms. Importantly, ovarian cancer was not increased, and lung cancer was not affected by hormone use. Long-term follow-up revealed that Alzheimer’s diagnoses and dementia mortality were significantly reduced in the E-only group, and breast cancer risk remained lower even after 20 years. A Cochrane meta-analysis confirmed that for women who begin HT before age 60 or within 10 years of menopause, there is a 50% reduction in coronary heart disease (CHD) and a 30% reduction in all-cause mortality, with no increased risk of stroke. Dr. Hodis’ analysis makes it clear: when used appropriately, hormone therapy offers substantial benefits with minimal risk, a message that continues to be drowned out by lingering fear from outdated data.

This concludes this three-part series that summarizes the information and data that was presented to the FDA, urging for the removal of black box warnings that cite unsubstantiated and misleading information on potential side effects of menopausal hormone therapy.  I hope you have gained some insight and are inspired to continue educating yourself and others on the options for management of menopausal and perimenopausal symptoms.  This information is for educational purposes only and is not considered to be individual medical advice.