Vaginal Estradiol Not Linked to Recurrent Ischemic Stroke in Women With Prior Stroke

Kimia Ghias Haddadan, MD

Courtesy of Reza Farsangi

Use of vaginal estradiol tablets was not associated with an increased risk of recurrent ischemic stroke among women with a prior ischemic stroke, according to findings from a nationwide nested case-control study published in Stroke.1

“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,” lead author Kimia Ghias Haddadan, MD, affiliated with the department of cardiology at Copenhagen University Hospital – Herlev and Gentofte in Copenhagen, Denmark, said in a press release.2

Researchers from Copenhagen University Hospital analyzed data from 34 274 women aged 45 years and older who experienced a first ischemic stroke in Denmark between 2008 and 2017. Among these, 3353 cases of recurrent stroke were identified and matched by birth year to 3353 controls. The median age was 75 years.1

When adjusted for comorbidities, medications, income, and education, vaginal estradiol exposure was not associated with an increased rate of recurrent ischemic stroke. The adjusted hazard ratio (aHR) for current use (within 0–3 months before the index date) was 0.79 (95% CI, 0.52–1.20; P = .27). For recent use (3–24 months before the index date), the aHR was 1.09 (95% CI, 0.73–1.63; P = .67), and for past use (>24 months before the index date), the aHR was 1.48 (95% CI, 0.95–2.30; P = .08). Results did not differ by dose or cumulative exposure.1

The investigators noted that systemic hormone replacement therapy has been linked to an increased risk of ischemic stroke in postmenopausal women, and guidelines generally contraindicate its use in women with prior stroke. Vaginal estrogen, however, is often prescribed as first-line therapy for genitourinary syndrome of menopause, a condition affecting up to 70% of postmenopausal women. Because vaginal estrogen products are absorbed systemically and can mildly raise plasma estradiol levels, the study sought to clarify whether these changes influence stroke recurrence risk.1

The study found no evidence of increased risk associated with vaginal estradiol use, providing reassurance for clinicians treating genitourinary syndrome of menopause in women with a history of stroke. “Based on our findings, vaginal estradiol tablets are not likely to increase the risk of recurrent ischemic stroke in women with prior stroke,” authors concluded.1

Limitations included the observational design, potential residual confounding, and reliance on prescription records rather than confirmed medication use. Data were limited to vaginal estradiol tablets, the most common formulation in Denmark, and findings may not generalize to other forms of vaginal estrogen therapy.1

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. Published online August 21, 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 21, 2025. https://newsroom.heart.org/news/vaginal-estrogen-tablets-may-be-safe-for-postmenopausal-women-who-have-had-a-stroke