Conjugated equine estrogen plus estradiol tied to increased risk of haemorrhagic stroke

Menopausal hormone therapy with conjugated equine estrogen (CEE) appears to confer a heightened risk of developing haemorrhagic stroke among postmenopausal women as compared with the use of estradiol (E2), as reported in a retrospective cohort study.

The study drew data from Taiwan's National Health Insurance Research Database and included menopausal women aged 40–65 years who received menopausal hormone therapy with oral CEE or E2.

Researchers performed propensity score matching with menopausal age and comorbidities and included 14,586 women each in the CEE and E2 groups. The mean menopausal ages of the respective groups were 50.45 and 50.31 years.

The incidence of haemorrhagic stroke was 1.23-fold higher among women treated with CEE than among those who received E2 (8.04 vs 6.49 per 10,000 person-years). Multivariable Cox proportional hazard regression models confirmed that menopausal hormone treatment with CEE was associated with an elevated risk of haemorrhagic stroke (hazard ratio [HR], 1.50, 95 percent confidence interval [CI], 1.04–2.17).

On further analysis, the risk increase was pronounced among patients who initiated CEE vs E2 hormone therapy within 5 years of menopause (HR, 1.47, 95 percent CI, 1.01–2.14).

While menopausal hormone therapy has been reported to have a protective effect on the risk of haemorrhagic stroke, the risk depends on the type of hormones used, with CEE contributing to a risk increase. This finding highlights the importance of discussing the increased risk of haemorrhagic stroke with patients using CEE.

Larger studies are needed to validate the data.