Vaginal Estrogen Tablets Show No Increased Stroke Risk for Postmenopausal Women with Prior Stroke History

A nationwide Danish registry 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 among postmenopausal women with prior stroke history. The research analyzed data from more than 34,000 women aged 45 and older who had experienced a first ischemic stroke between 2008 and 2017, providing crucial safety evidence for a treatment option that could significantly improve quality of life for this vulnerable population.

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 common menopausal symptoms including vaginal dryness and discomfort during intercourse. While previous studies including the Women's Health Initiative and Nurses' Health Study 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 group considered more vulnerable to recurrent cerebrovascular events.

The study design excluded women who had used vaginal estrogen before their first stroke and compared recurrent stroke rates between users and non-users over a 10-year period. Researchers found no significant association between current, recent, or past use of vaginal estrogen tablets and second stroke risk, even when analyzing high-dose versus low-dose usage patterns. The findings remained consistent across different usage categories, with even women showing higher cumulative use demonstrating no elevated stroke risk compared to non-users.

Lead author Kimia Ghias Haddadan, M.D., from Copenhagen University Hospital, emphasized that while the findings suggest vaginal estrogen is likely safe for this high-risk population, they do not imply that the treatment prevents strokes. The research provides valuable reassurance for healthcare professionals treating postmenopausal women with stroke history, particularly those experiencing troubling menopausal symptoms that significantly impact quality of life. The study's large, nationwide design using Danish registries allowed for comprehensive tracking of stroke diagnoses, prescriptions, and relevant health information across the entire population.

Study limitations noted by researchers include the possibility that women using vaginal estrogen might have been healthier overall, though statistical adjustments were made for various health and demographic factors. Additionally, prescription records indicate medication dispensing but not necessarily adherence, and the findings apply specifically to vaginal tablets rather than other estrogen formulations like creams, patches, or rings. The research was conducted in Denmark's universal healthcare system where cost is not a barrier to treatment, which may affect generalizability to other healthcare environments. More information about the American Heart Association's research funding and policies is available at https://www.heart.org/en/about-us/statements-and-policies/financial-information.

This research addresses an important gap in clinical knowledge regarding hormone therapy safety in a population often excluded from clinical trials. For the millions of postmenopausal women worldwide who have experienced stroke and struggle with menopausal symptoms, these findings offer evidence-based guidance that could lead to improved symptom management without compromising cardiovascular safety.