A nationwide Danish study published in Stroke, the journal of the American Stroke Association, found that vaginal estrogen tablet use was not associated with increased risk of recurrent ischemic stroke in postmenopausal women who had previously experienced a stroke. The research analyzed prescription data for more than 34,000 women aged 45 and older from Denmark's national health registry between 2008 and 2017.
Unlike systemic hormone replacement therapies such as oral estrogen or transdermal formulations, vaginal estrogen tablets dissolve locally and are absorbed through the vaginal mucosa to manage menopausal symptoms including vaginal dryness and discomfort during intercourse. While previous studies had shown no increased stroke risk with vaginal estrogen in healthy postmenopausal women, this was the first major investigation focusing specifically on women with prior stroke history, a population considered more vulnerable to recurrent strokes.
Lead author Kimia Ghias Haddadan, M.D., from Copenhagen University Hospital, explained the significance: "It is well known that taking systemic hormone replacement therapy, such as oral estrogen tablets, may increase the risk of stroke after menopause. While other studies have not detected an increased risk of stroke associated with the use of vaginal estrogen in healthy postmenopausal women, there is no data on whether vaginal estrogen tablets pose an increased risk for women who have already had a stroke."
The analysis revealed no significant association between vaginal estrogen use and recurrent stroke risk across all usage categories—current use (within 3 months), recent use (3-24 months), or past use (more than 24 months). Additionally, no increased risk was found between high-dose or low-dose current use, and even women with higher cumulative use showed no elevated stroke risk compared to non-users. The study's comprehensive design utilized Danish registries to accurately track stroke diagnoses, prescriptions, and relevant health information across the entire population.
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 the study's importance despite limitations: "As an epidemiologist, I see this study as a valuable contribution because it focuses on a population often excluded from hormone therapy research, midlife women with a prior stroke, and examines an increasingly used route of administration." The findings are expected to be applicable to postmenopausal women in the U.S. and other countries where similar vaginal estrogen products are used.
Researchers emphasized that while the findings suggest vaginal estrogen is likely safe for this high-risk group, they do not imply that the treatment prevents strokes. The study provides crucial reassurance for healthcare professionals treating postmenopausal women with stroke history who experience troubling menopause symptoms, potentially improving quality of life without increasing stroke risk.
