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

A nationwide Danish 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 in postmenopausal women who had previously experienced a stroke. The research, which analyzed health registry data from over 34,000 women aged 45 and older, provides crucial safety information for a population previously excluded from hormone therapy research due to stroke vulnerability concerns.

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 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 women, this is among the first investigations focusing specifically on women with prior stroke history.

Lead author Kimia Ghias Haddadan, M.D., from Copenhagen University Hospital, explained the significance: "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."

The study examined prescription data from the Danish national registry covering women who experienced their first ischemic stroke between 2008 and 2017. Researchers compared recurrent stroke rates between vaginal estrogen users and non-users over a 10-year period, finding no significant association between current, recent, or past use of vaginal estrogen tablets and second stroke risk. Even high-dose users and those with higher cumulative use showed no increased risk compared to non-users.

Samar R. El Khoudary, Ph.D., M.P.H., FAHA, chair of the American Heart Association's 2020 Statement on Menopause Transition and Cardiovascular Disease Risk, noted the study's importance despite limitations: "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." The research was published in Stroke, available at https://www.ahajournals.org/journal/str after the embargo period.

Study limitations include potential healthier user bias among estrogen users and reliance on prescription records rather than confirmed medication adherence. The findings apply specifically to vaginal tablets, the most common treatment form in Denmark, and may not extend to other estrogen formulations like creams, patches, or rings. The research also lacked racial diversity data since Denmark doesn't collect patient race information.

Haddadan concluded that the findings should reassure healthcare professionals: "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." The research provides critical evidence supporting treatment options for postmenopausal stroke survivors seeking relief from menopausal symptoms without compromising cardiovascular safety.