Data published in the journal Stroke show that use of vaginal estradiol tablets was not associated with an increased risk of recurrent ischemic stroke in post-menopausal women with a prior history of ischemic stroke.1
The study also found no association between high-dose current use or low-dose current use and recurrent ischemic stroke.
“We were cautiously hopeful about the findings, and it was reassuring to discover that the use of vaginal estrogen did not raise the risk of recurrent stroke in this high-risk population,” said lead author Kimia Ghias Haddadan, MD, of the department of cardiology at Copenhagen University Hospital – Herlev and Gentofte in Copenhagen, Denmark, in a news release on the findings.2 “US-based studies, such as the Women’s Health Initiative and the Nurses’ Health Study, have shown no increased stroke risk with vaginal estrogen in healthy women. Our study extends this reassurance to women with a history of stroke.”
In total, the nested case-control study included data from 34,274 postmenopausal women using a national registry in Denmark. All patients were aged 45 or older, had a prior history of a stroke from 2008 to 2017, and had no history of vaginal estrogen use prior to their stroke diagnosis. The median age of participants was 75 years (SD, 12).
Using incidence density sampling, the investigators matched 3353 cases of women who developed recurrent ischemic stroke during the follow-up period with 3353 controls (women who did not experience a second stroke) based on birth year. Use of vaginal estrogen tablets was characterized as current (within 3 months), recent (3 to 24 months), or past (more than 24 months prior to the study).
Overall, the study found no association between current use of vaginal estradiol tablets and recurrent ischemic stroke compared with no use (aHR, 0.79; 95% CI, 0.52 to 1.20; P = .27). Patients with recent use (aHR, 1.09; 95% CI, 0.73 to 1.63; P = .67) or past use (aHR, 1.48; 95% CI, 0.95 to 2.30; P = .08) of vaginal estradiol tablets also showed no increased risk of recurrent ischemic stroke compared with patients who had no use.
Additionally, the study found no association between high-dose current use (aHR, 0.70; 95% CI, 0.41 to 1.21; P = .20) or low-dose current use (aHR, 1.14; 95% CI, 0.68 to 1.91; P = .62) and recurrent ischemic stroke.
The authors also added, “There was no significant association between quintiles of total cumulative dose and recurrent ischemic stroke compared with no use.”
Based on these findings, the authors suggest that vaginal estradiol tablets are unlikely to increase the risk of recurrent ischemic stroke in women with a prior history of stroke.
However, they note several limitations of the current analysis. Data for the study were collected from prescription records, which prohibited confirmation of actual use or adherence. Additionally, the study only assessed vaginal estradiol tablets, since they are the most common mode of administration in Denmark. The findings, therefore, cannot necessarily be generalized to all forms of vaginal estradiol therapy.
Despite these limitations, the authors suggest that these findings are valuable for clinicians prescribing vaginal estrogen tablets.
“We hope our findings reassure health professionals caring for postmenopausal women with a history of stroke,” Haddadan concluded in the news release.2 “For these women, especially those with troubling menopause symptoms, the study shows that this type of therapy may be a safe choice. It could improve their quality of life without raising the risk of another stroke.”
REFERENCES
1. Haddadan KG, Eckert-Lind C, Meaidi A, et al. Recurrent ischemic stroke and vaginal estradiol in women with prior ischemic stroke: A nationwide nested case-control study. Stroke. 2025. doi:10.1161/STROKEAHA.125.050986
2. Vaginal estrogen tablets may be safe for postmenopausal women who have had a stroke. News release. American Heart Association. August 21, 2025. Accessed August 22, 2025. https://newsroom.heart.org/news/vaginal-estrogen-tablets-may-be-safe-for-postmenopausal-women-who-have-had-a-stroke