Additive effect of drospirenone/17-β-estradiol in hypertensive postmenopausal women receiving enalapril ☆

Abstract Background Aldosterone has been implicated in the pathogenesis of progressive cardiovascular disease. Drospirenone (DRSP) is a novel progestin with aldosterone receptor antagonist activity developed for hormone replacement therapy (HRT) as DRSP/17β-estradiol (DRSP/E2). We investigated the additive effect of DRSP/E2 versus placebo on 24-h ambulatory blood pressure (BP) in postmenopausal women with hypertension treated with enalapril maleate (ENA). Methods This was a double-blind, randomized, two-parallel group trial. Twenty-four nonsmoking postmenopausal women receiving 10 mg of ENA twice a day before study were randomized to DRSP/E2 + ENA ( n = 12) or placebo (P) + ENA ( n = 12) for 14 days. Twenty-four-hour ambulatory BP, plasma renin activity, and serum aldosterone were determined at baseline and on day 14. Results Compared to placebo, 24-h mean [SD] BP in the DRSP/E2 + ENA group decreased significantly from baseline (139/80 mm Hg), systolic (−9 [5] mm Hg, P = .014) and diastolic (−5 [4] mm Hg, P = .007). Essentially no change from baseline (139/83 mm Hg) in systolic or diastolic 24-h ambulatory BP were observed in the P + ENA group. Aldosterone (mean [SD]) increased from baseline by 2.6 [4.5] ng/dL in the DRSP/E2 + ENA group, and decreased by 0.3 [5.5] ng/dL in the P + ENA group ( P = .08) consistent with an antimineralocorticoid effect. Conclusions Our results suggest a significant additive BP-lowering effect of DRSP/E2 on both systolic and diastolic BP in hypertensive postmenopausal women receiving ENA, consistent with an antimineralocorticoid effect. DRSP/E2, a HRT with antimineralocorticoid effects, could offer a novel potential mechanism for reducing cardiovascular end points in postmenopausal women.