Randomized, placebo-controlled trial of the effects of drospirenone-estradiol on blood pressure and potassium balance in hypertensive postmenopausal women receiving hydrochlorothiazide

Objective: Drospirenone (DRSP), a spironolactone analog with aldosterone antagonist activity, is a novel progestogen developed for use as hormone therapy in postmenopausal women in combination with 17A-estradiol (E2). DRSP/E2 lowers blood pressure when used alone in hypertensive postmenopausal women or when administered concomitantly with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. DRSP/E2 has not been studied in combination with the widely prescribed hydrochlorothiazide (HCTZ). We investigated the effects of 3 mg DRSP/1 mg E2 versus placebo on blood pressure and potassium balance when added to existing therapy with 25 mg HCTZ in postmenopausal women with established stage I hypertension. Design: This was a single-center, double-blind, randomized, placebo-controlled, two-treatment, two 4-week treatment period crossover study in 36 postmenopausal women with stage I hypertension maintained on 25 mg HCTZ. The endpoint was a change from baseline in systolic and diastolic blood pressures by 24-hour ambulatory blood pressure monitoring. Safety monitoring included serum potassium (mEq/L) and adverse events. Results: Mean systolic and diastolic blood pressures by 24-hour ambulatory blood pressure monitoring were reduced significantly, by j7.2 and j4.5 mm Hg, respectively, with DRSP/E2 as compared with placebo. The decrease in potassium with HCTZ was 0.2 mEq/L less with DRSP/E2 than placebo, suggesting a potassiumsparing effect. The most frequently observed adverse events with DRSP/E2 were vaginal bleeding and breast tenderness, which were attributable to the hormone therapy. Conclusions: DRSP/E2 substantially lowers systolic and diastolic blood pressure when added to existing antihypertensive therapy with HCTZ in hypertensive postmenopausal women. In addition, DRSP/E2 has a potassium-sparing effect that counteracts HCTZ-induced potassium loss.