Vaginal estrogen tablets not linked to recurrent stroke risk in postmenopausal women

Vaginal estrogen tablets not linked to recurrent stroke risk in postmenopausal women Image Credit: © peterschreiber.media - Getty Images/iStockphoto.

A nationwide study from Denmark found that the use of vaginal estrogen tablets was not associated with an increased risk of recurrent ischemic stroke among postmenopausal women with a prior stroke. The findings were published in Stroke, a journal of the American Stroke Association, a division of the American Heart Association.^1,2

Systemic estrogen replacement therapy, particularly oral formulations, is known to increase the risk of stroke and is contraindicated in women with a history of ischemic stroke. Vaginal estrogen tablets, however, are designed for local absorption to alleviate symptoms of genitourinary syndrome of menopause, such as vaginal dryness and dyspareunia. While previous studies in healthy women suggested that vaginal estrogen does not increase stroke risk, its safety in women with prior ischemic stroke had not been established.

“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,” said lead author Kimia Ghias Haddadan, MD, of Copenhagen University Hospital – Herlev and Gentofte.

Study design and population

The investigation utilized data from Danish national registries, which provide comprehensive information on health, prescriptions, and demographics. Researchers identified 56,642 women who experienced a first ischemic stroke between January 2008 and December 2017. After excluding women younger than 45 years, those with prior vaginal estrogen use, and those using systemic hormone therapy in the year before their stroke, 34,274 women remained eligible.

Among these, 3353 women developed a recurrent ischemic stroke. Each case was matched by birth year with a control who had not experienced recurrence, resulting in 3353 matched pairs. The median age was 75 years. Vaginal estrogen use was categorized as current (within 3 months), recent (3-24 months), or past (>24 months).

Key findings

The analysis demonstrated that use of vaginal estrogen tablets was not associated with increased recurrence of ischemic stroke. Adjusted HRs showed no significant difference in risk between users and nonusers: current use (0.79; 95% CI, 0.52-1.20), recent use (1.09; 95% CI, 0.73-1.63), and past use (1.48; 95% CI, 0.95-2.30).

No differences were observed between high-dose and low-dose users, nor was there an association with cumulative exposure. “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,” Haddadan said.

She added, “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.”

The investigators emphasized that the results should not be interpreted as evidence of a protective effect. “It is important to note that these findings suggest that vaginal estrogen is likely safe for this high-risk group of women who have already had a stroke; however, they do not imply that vaginal estrogen prevents strokes,” Haddadan said.

Implications and limitations

Samar R. El Khoudary, PhD, MPH, FAHA, professor of epidemiology at the University of Pittsburgh and chair of the American Heart Association’s 2020 statement on menopause transition and cardiovascular disease risk, commented on the study. “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: vaginal tablets,” she said. “While the study did not find a statistically significant association with stroke recurrence, the findings should be interpreted with caution. Real-world data can’t account for all clinical and behavioral factors, and prescription fill records don’t confirm whether the medication was actually used.”

The authors noted several limitations, including reliance on prescription data, lack of information on medication adherence, and restriction to vaginal tablets as the predominant mode of administration in Denmark. Data on stroke subtypes and patient lifestyle factors were also unavailable.

Despite these limitations, the study provides important evidence for clinical practice. “We hope our findings reassure health professionals caring for postmenopausal women with a history of stroke. 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,” Haddadan said.

References

1. Vaginal estrogen tablets may be safe for postmenopausal women who have had a stroke. 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?preview=22a2&preview_mode=True
2. 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. August 21, 2025. doi:10.1161/STROKEAHA.125.050986