Hormone replacement therapy use and the risk of stroke

Randomised trials reported an increase risk of stroke with an estrogen plus progestogen formulation of hormone replacement therapy (HRT). A recent trial also reported an increased risk with tibolone, a selective tissue estrogenic activity regulator.

We used the General Practice Research Database to conduct a case-control study within a cohort of women aged 50-79 between January 1987 and October 2006, without history of stroke prior to cohort entry. We identified all cases of stroke occurring during the study period and selected up to four controls matched to each case on age, general practice and year of start in the practice. Information on HRT use during the year preceding the index date was obtained. Conditional logistic regression was used to estimate the rate ratios of stroke associated with current use of the different HRTs.

The cohort included 870,286 women, of whom 15,710 experienced a stroke during follow-up and were matched to 59,958 controls. The adjusted rate ratio of stroke associated with current use of tibolone relative to non-use of HRT was 1.08 (95% CI: 0.82-1.44). The rate ratios with current use of estrogens alone and estrogen plus progestogen were 1.26 (95% CI: 1.10-1.45) and 1.19 (95% CI: 1.05-1.36) respectively.

We found no evidence of an elevated risk of stroke associated with the use of tibolone, although the low number of subjects using tibolone does not permit to rule out a small risk. The small elevated risk of stroke with estrogens or estrogens plus progestogen is consistent with that reported in randomised trials.