Vaginal Estrogen Tablets Found Safe for Postmenopausal Stroke Survivors in Danish Study

Vaginal estrogen tablets were not associated with an increased risk of recurrent ischemic stroke among postmenopausal women in a registry in Denmark, according to research published in Stroke, the peer-reviewed scientific journal of the American Stroke Association, a division of the American Heart Association. Unlike oral estrogen or transdermal formulations such as creams and patches, the women in this registry-based study had prescriptions for estrogen tablets designed for vaginal use. These tablets dissolve locally, and the estrogen is absorbed through the vaginal mucosa to help manage common menopausal symptoms, such as vaginal dryness and discomfort during intercourse.

This study examined prescription data for more than 34,000 postmenopausal women, aged 45 and older, who had experienced a first ischemic stroke in a national registry in Denmark. Women who used vaginal estrogen before their first stroke were excluded. During the 10-year study, researchers compared the rates of recurrent stroke in women who used vaginal estrogen tablets with the rates of women who did not use the vaginal treatment. The analysis found that the use of vaginal estrogen tablets was not associated with an increased risk of having a second stroke in postmenopausal women with a previous stroke.

When compared to not using vaginal estrogen tablets, there was no significant association among current use, recent use or past use of the vaginal estrogen tablets with a second stroke. Similarly, no increased risk of a second stroke was found between high-dose current use or low-dose current use. Even women with higher cumulative use of vaginal estrogen tablets did not have a higher risk of a second stroke compared to non-users. The study's lead author Kimia Ghias Haddadan, M.D., affiliated with the department of cardiology at Copenhagen University Hospital, stated that these findings suggest vaginal estrogen is likely safe for this high-risk group of women who have already had a stroke.

Samar R. El Khoudary, Ph.D., M.P.H., FAHA, chair of the American Heart Association's 2020 Statement on Menopause Transition and Cardiovascular Disease Risk, noted that this study focuses on a population often excluded from hormone therapy research and examines an increasingly used route of administration. While the study did not find a statistically significant association with stroke recurrence, the findings should be interpreted with caution as real-world data cannot account for all clinical and behavioral factors. The study has several limitations, including that women who used vaginal estrogen might have been healthier overall, which could affect the results.

The findings should be applicable to postmenopausal women in the U.S. and other countries, especially where similar vaginal estrogen products are used. The study's strengths include its large, nationwide design, which provided a comprehensive view of real-world clinical outcomes in a high-risk population. By using Danish registries, researchers could accurately track stroke diagnoses, prescriptions and relevant health and demographic information across the entire population. Additional information about the American Heart Association's research and policies can be found at https://www.heart.org.