Study debunks myth that vaginal estrogen therapy raises risk for CVD, cancer

Low-dose vaginal estrogen therapy—a treatment used to relieve genital and urinary discomfort in women during menopause—isn’t associated with an elevated risk of cardiovascular disease or cancer, researchers reported in Menopause Dec. 17.

That finding might come as a surprise to the general public, whose perception of vaginal estrogen therapy has, according to study author JoAnn E. Manson, MD, DrPH, and colleagues, been skewed by misinformation. Although multiple studies have found vaginal estrogen to be superior to oral and non-hormone therapies in relieving menopausal discomfort, the FDA issued a black-box warning in 2003 that alerts women to an increased risk of heart disease, MI, stroke and breast cancer with the therapy. That warning remains in place today on all Premarin, Prempro and Premphase packaging.

Manson and her coauthors said those warnings likely contribute to the low prescription rate for vaginal estrogen, since patients and physicians alike are put off by the possibility of death and chronic disease. But the researchers’ own work, an analysis of the 1982-2012 Nurses’ Health Study (NHS), supports the use of low-dose estrogen therapy to ease the symptoms of genitourinary syndrome of menopause (GSM)—an ongoing condition that, unlike hot flashes, doesn’t resolve without treatment.

The team included postmenopausal women from the NHS in their research, none of whom were using systemic hormone therapy at the study’s baseline or during follow-up. Patients self-reported use of vaginal estrogen in biennial questionnaires, and outcomes data were validated with medical records.

After adjusting for covariates including CVD risk factors, MI, stroke, pulmonary embolism and a host of cancers, Manson et al. reported no statistically significant increase in risk for CVD, cancer or hip fractures. Figures were similar between users and non-users of vaginal estrogen.

The authors said their findings lend support to the safety of vaginal estrogen therapy, which is the most effective treatment for GSM.

“Over-the-counter vaginal lubricants and moisturizers are often used as first-line treatments for women with symptoms of GSM,” JoAnn Pinkerton, executive director of the North American Menopause Society, said in a release. “Persistent symptoms often need therapies such as local vaginal estrogen, intravaginal dehydroepiandrosterone or oral ospemifene. This study adds to a growing body of data showing the long-term efficacy and safety of low-dose vaginal estrogen, which works primarily locally with minimal systemic absorption.”

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After graduating from Indiana University-Bloomington with a bachelor’s in journalism, Anicka joined TriMed’s Chicago team in 2017 covering cardiology. Close to her heart is long-form journalism, Pilot G-2 pens, dark chocolate and her dog Harper Lee.

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