The Not So Risky Business of HRT

May 21, 2024

By: Rachel Noonan, PharmD

Over 68,000 women have spoken. It only took us 20 years to hear them.  

Let’s travel back in time to the infamous clinical trials designed by the Women’s Health Initiative (WHI). The one that stopped mainstream hormone replacement therapy in its tracks.  

Misleading data from the WHI studies drastically changed the landscape for menopausal hormone therapy across the world. Hormones became taboo overnight. Once considered a trusted source of relief to address frustrating menopausal symptoms, hormone prescribing rapidly diminished. Fear took its place and millions of women were left adrift. 

But a breaking review is changing all that.  

Analyzing data spanning over two decades, the Journal of the American Medical Association (JAMA) concludes hormone replacement therapy is appropriate and beneficial for women under 60 struggling with problematic issues, like vasomotor symptoms. This is an important step toward recognizing the impact of estrogen and progesterone support during unpredictable hormonal shifts in menopause.  

Specifically citing the ‘significant quality of life benefits from symptom relief’ in younger menopausal women, the information presented in JAMA’s The Women’s Health Initiative Randomized Trials and Clinical Practice: A Review, is a long time coming – literally.  

Results over the last 20 years highlight that the chronic diseases investigated by the original WHI studies are definitively less likely for younger women who are interested in starting hormone replacement in early menopause. On average, hormone therapy appears to result in less than one additional adverse event per 1,000 women, per year. Certainly not the risky business patients and providers were historically led to believe.    

And it keeps getting better. Study investigators point out that many of the risks may have had a lot to do with the type of hormone replacement regularly prescribed in the late 90s (looking at you, medroxyprogesterone). In fact, women who’d had a hysterectomy (therefore eligible for estrogen therapy alone), experienced a reduced rate of breast cancer both 10 and 20 years later when compared to placebo. Estrogen replacement therapy in these populations didn’t just play nice; all-cause mortality rates in women aged 50-59 went down. Synthetic progestin (brand name Provera) appears to paint a different picture, but we’ll let the evidence speak for itself.  

While this review is certainly a breath of fresh air for women everywhere, many would argue there’s more conventional medicine could do to strip the stigma of HRT. What if the hormones evaluated by the WHI had been bioidentical? Would millions have avoided waking up mid-REM drenched in sweat?  

One thing is for certain: when the time comes, women can leave fear behind.  


  1. Manson JE, Crandall CJ, Rossouw JE, Chlebowski RT, Anderson GL, Stefanick ML, Aragaki AK, Cauley JA, Wells GL, LaCroix AZ, Thomson CA, Neuhouser ML, Van Horn L, Kooperberg C, Howard BV, Tinker LF, Wactawski-Wende J, Shumaker SA, Prentice RL. The Women’s Health Initiative Randomized Trials and Clinical Practice: A Review. JAMA. 2024 May 1. doi: 10.1001/jama.2024.6542. Epub ahead of print. PMID: 38691368.