Vaginal Estrogen Not Tied to Added Heart, Cancer Risks

Use of vaginal estrogen wasn’t tied to increased cardiovascular or cancer risks, according to a new study.

Looking at postmenopausal women who participated in the Nurses’ Health Study, vaginal estrogen use in women with or without an intact uterus was not associated with any increased risks of several cancers or cardiovascular outcomes over an 18-year follow-up period, reported JoAnn E. Manson, MD, DrPH, of Brigham and Women’s Hospital in Boston, and colleagues.

The study, published in Menopause, found that the risk for several health outcomes was not statistically higher compared with the risk in women who did not use vaginal estrogen in a fully adjusted model:

• Myocardial infarction: HR 0.73 (95% CI 0.47-1.13)
• Stroke: HR 0.85 (95% CI 0.56-1.29)
• Pulmonary embolism/Deep vein thrombosis: HR 1.06 (95% CI 0.58-1.93)
• Hip fracture: HR 0.91 (95% CI 0.60-1.38)
• All cancers: HR 1.05 (95% CI 0.89-1.25)

Included in the assessment of all cancers was the risk for invasive breast cancer, ovarian cancer, endometrial cancer, and colorectal cancer, although the risk for endometrial cancer included only women with an intact uterus:

• Invasive breast cancer: HR 1.07 (95% CI 0.78-1.47)
• Ovarian cancer: HR 1.17 (95% CI 0.52-2.65)
• Endometrial cancer: HR 1.62 (95% CI 0.88-2.97)
• Colorectal cancer: HR 0.77 (95% CI 0.45-1.34)

“Over-the-counter vaginal lubricants and moisturizers are often used as first-line treatments for women with symptoms of [genitourinary syndrome of menopause, GSM],” said JoAnn Pinkerton, MD, executive director of the North American Menopause Society (NAMS), in a statement. “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,” she added.

Currently, all estrogens — including vaginal estrogen — carry a black-box warning issued by the FDA for a potentially increased risk for heart attacks, strokes, blood clots, GSM, and breast cancer. “Despite lack of any observational or clinical trial evidence for chronic disease risks related to vaginal estrogen use, the FDA has issued a boxed warning on the package label for low-dose vaginal estrogen,” noted the study authors.

Despite this warning, low-dose vaginal estrogen is recommended for treatment of GSM by several organizations, including NAMS, the American College of Obstetricians and Gynecologists, and the Endocrine Society. Furthermore, the American Association of Clinical Endocrinologists’ 2017 update to their menopause clinical practice guidelines recommended the use of transdermal estrogen compared with oral forms, stating that these preparations “may be considered less likely to produce thrombotic risk and perhaps the risk of stroke and coronary artery disease.”

The prospective analysis included nearly 900 postmenopausal women currently using vaginal estrogen who were compared with approximately 53,000 non-users. Current users of systemic hormone therapy were excluded from the analysis. During the follow-up period, in which the participants completed a questionnaire every 2 years during 1982 and 2012, the average length of vaginal estrogen use was around 36 months. Neither information on the type of vaginal estrogen — whether it be a tablet, cream, ring, or suppository — nor the dosage of estrogen were collected, a limitation to the findings, the researchers said.

Other limitations included the observational design of the study and, in addition, at the early years of follow-up, some women potentially used higher doses of vaginal estrogen rather than low-doses that are commonly prescribed now, the team noted.