Incidence of endometrial spotting or bleeding during continuous-combined estrogen-progestin therapy in postmenopausal women with and without hypertension

Objective: Endometrial spotting or bleeding is a common adverse effect among women taking continuouscombined estrogen-progestin therapy. The renin- angiotensin-aldosterone system plays a major role in hypertension and is present in the endometrium. We hypothesized that postmenopausal women with hypertension would have a higher incidence of bleeding compared with postmenopausal women without hypertension. Methods: A multivariate mixed-effects logistic model estimated the odds ratios for the relationship of hypertension status or use of antihypertensive drugs with endometrial bleeding using the Women's Health Initiative database. Results: The incidence of spotting or bleeding in the first 12 months of estrogen-progestin use was 42% in women aged 50 to 79 years.Women with hypertension were more likely to experience bleeding than women without hypertension (odds ratio, 1.07; 95% CI, 1.02- 1.13). Overall antihypertensive medication use increased bleeding with an odds ratio of 1.24, whereas angiotensin II receptor antagonists had a reduced odds ratio (0.53). Conclusions: Postmenopausal women with hypertension are more likely to bleed than postmenopausal women without hypertension when taking continuous estrogen-progestin, with less bleeding in women using angiotensin II receptor antagonists. This finding is novel and supports our hypothesis that the endometrial renin-angiotensinaldosterone system may contribute to endometrial bleeding.