Vaginal Estrogen Tablets Do Not Increase Risk of Stroke Recurrence in Women With Prior Stroke: Study

A new nationwide study published in the journal of Stroke found that the use of vaginal estradiol tablets is not associated with an increased risk of recurrent ischemic stroke, a finding that contrasts with the well-documented risks tied to systemic estrogen therapy.

Estrogen replacement therapy delivered systemically (oral or transdermal routes) is contraindicated for women with prior ischemic stroke, owing to its link with stroke recurrence. However, little was previously known about the safety of local, vaginally administered estrogen in this high-risk group.

To address this gap, investigators conducted a large nested case-control study using comprehensive nationwide health registers. The study tracked all women aged 45 years and older in Denmark who suffered a first ischemic stroke between 2008 and 2017, excluding anyone with prior vaginal estrogen use. This research compared 3,353 women who experienced a recurrent stroke with 3,353 age-matched controls who did not.

Prescription records were used to classify exposure to vaginal estradiol tablets into three groups: current use (within 3 months before the recurrent stroke or index date), recent use (between three and 24 months), and past use (more than 24 months earlier).

The average age of women in the study was 75 years, reflecting the typical stroke demographic. After adjusting for comorbidities, medications, education, and income, the results revealed no statistically significant association between vaginal estradiol use and recurrent stroke.

Specifically, women who were current users of vaginal estradiol tablets had a hazard ratio (HR) of 0.79, indicating a slightly lower risk when compared with non-users. Recent users had an HR of 1.09, reflecting no meaningful difference, while past users showed a non-significant HR of 1.48, suggesting a possible but unconfirmed higher risk. Also, none of these results reached statistical significance, as the confidence intervals overlapped with 1 and the p-values exceeded 0.05.

Overall, these findings suggest that vaginal estradiol tablets, unlike systemic hormone therapy, are unlikely to elevate the risk of recurrent ischemic stroke in women who have already experienced one. The results provide critical insight for physicians and patients weighing options for managing genitourinary symptoms of menopause, such as vaginal dryness, burning, and discomfort, which are particularly common after midlife.

Source:

Haddadan, K. G., Eckert-Lind, C., Meaidi, A., Johansen, N. D., Højbjerg Lassen, M. C., Skaarup, K. G., Jensen, J. U. S., Torp-Pedersen, C., Gislason, G., Biering-Sørensen, T., & Modin, D. (2025). Recurrent ischemic stroke and vaginal estradiol in women with prior ischemic stroke: A nationwide nested case-control study. Stroke; a Journal of Cerebral Circulation, STROKEAHA.125.050986. https://doi.org/10.1161/strokeaha.125.050986