Hormone Therapy and the WHI Fallout: A Wake-Up Call for Women and Doctors: Part 2
This is the second 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; Part 1. Please keep in mind that this information is for educational purposes only and is not considered to be individual medical advice.
The next expert, Dr. JoAnn Manson, presented compelling data from the 2002 Women’s Health Initiative (WHI) study showing that estrogen alone, particularly in women aged 50–59, was associated with a reduced risk of coronary heart disease, stroke, breast and colorectal cancer, all fractures, diabetes, and even all-cause mortality. In contrast, estrogen combined with progestin (E/P) showed a slight increase in risk for coronary disease, stroke, blood clots, and breast cancer, but notably no increase in breast cancer mortality. Dr. JoAnn Pinkerton highlighted another major concern: genitourinary syndrome of menopause (GSM) and the increased incidence of urinary tract infections (UTIs) that comes with it. Despite the effectiveness of vaginal estrogen (VE) in treating GSM, the FDA’s boxed warning, citing risks like cancer, cardiovascular disease, and even dementia, continues to scare women away. However, there are no randomized controlled trials or consistent observational evidence linking VE to these serious adverse effects, underscoring the disconnect between data and current regulatory warnings.
Dr. James Simon raised concerns about inconsistent and misleading class labeling of hormone therapies, emphasizing that labels should align with both FDA-submitted product data and the broader scientific literature. He pointed out discrepancies, such as DHEA (Intrarosa) and vaginal estradiol (Imvexxy) receiving different boxed warnings, despite DHEA converting into estrogen and testosterone in the body. He also clarified a critical scientific fact: vaginal estrogen doesn't enter the bloodstream in measurable amounts, and for it to cause the risks listed in the boxed warning (like cancer or stroke), it would need to circulate systemically, yet large studies involving over 600,000 women from the U.S. and Denmark showed no effect on the endometrium, further supporting why progesterone is not required when using VE alone. Dr. Philip Sarrel highlighted the economic and health impact of untreated vasomotor symptoms (VMS) like hot flashes. A large insurance claims study of over 500,000 working women found that those with untreated hot flashes had 1.5 million more medical visits and generated $400 million more in healthcare and productivity losses in just one year. Even more alarming, Dr. Sarrel’s research estimated that nearly 50,000 women died between 2002 and 2012 due to unnecessary avoidance of estrogen after the WHI study, and another 100,000 have died since, particularly women in their 50s and 60s who had hysterectomies. He stressed that estradiol is a master regulator of the brain, and more recent WHI data show that estrogen use in women aged 50–59 leads to a 32% reduction in all-cause mortality, a powerful argument for revisiting outdated fears and offering more women the benefits of hormone therapy.
Dr. Roberta Diaz Brinton highlighted the alarming reality that two-thirds of Americans with Alzheimer’s disease are women, largely because the neurological decline begins during the menopause transition. Advanced imaging studies have shown that during this time, women experience a drop in glucose metabolism in the brain, along with increased beta-amyloid buildup and loss of white matter, which is essential for communication between neural circuits, explaining symptoms like brain fog and word-finding difficulties. As mitochondria become less efficient, the brain shifts into a kind of starvation mode, drawing energy from white matter and contributing to both cognitive decline and hot flashes. Dr. Brinton emphasized that early initiation of MHT can reduce the risk of Alzheimer’s, Parkinson’s, Multiple Sclerosis, Amyotrophic Lateral Sclerosis (ALS), and other dementias, by supporting the brain before these changes become irreversible. On a related front, orthopedic surgeon Dr. Vonda Wright addressed the critical issue of bone health, noting that 40% of women will develop osteoporosis, with a 20% loss in bone density at menopause. Half of these women will suffer a fracture, most commonly hip fractures, which carry a 30% one-year mortality risk and a 50% chance of never regaining full function. Estrogen has been shown to reduce the risk of osteoporotic fractures by 35–50%, yet only 4% of eligible women are currently receiving its benefits. Dr. Wright stressed that estrogen is FDA-approved for the prevention of osteoporosis, but it must be taken for at least 10 years, and within 6 years of stopping, bone loss resumes as if therapy had never occurred. Together, these insights reinforce that estrogen isn’t just about symptom relief, it’s about protecting the brain and bones for the long term.
Please see “Hormone Therapy and the WHI Fallout: A Wake-Up Call for Women and Doctors: Part 3” for continuation of this discussion.