Drospirenone, a new progestogen, for postmenopausal women with hypertension.
The prevalence of hypertension increases in women after the menopause. Associated with the rise in postmenopausal blood pressure (BP) are increased salt sensitivity and imbalance between the renin-angiotensin-aldosterone system and nitric oxide pathways that lead to sodium and water retention. Drospirenone is the first synthetic progestogen with antialdosterone activity similar to natural progesterone. Drospirenone counteracts the salt- and water-retaining effects of estrogen and causes natriuresis, which leads to a reduction in BP. In preclinical studies as well as early efficacy studies (for menopausal symptoms), drospirenone exhibited antihypertensive and natriuretic effects. Subsequent clinical trials in postmenopausal women proved that drospirenone with 17beta-estradiol has a significant BP-lowering effect in untreated hypertension and has additive effects when coadministered with ACE inhibitors, angiotensin II type 1 receptor antagonists and thiazide diuretics. The lowest effective dose of drospirenone for reduction in BP is 2mg, a dose that is also protective of the uterus in women treated with estrogen therapy. Additionally, clinical trials have shown that drospirenone up to 3 mg/day has an acceptable safety profile with no clinically significant elevations in plasma potassium in patients with concomitant NSAID use, diabetes mellitus or mild to moderate renal insufficiency. In addition to effectively relieving menopausal symptoms and lowering BP, drospirenone reduces bodyweight and lipoprotein concentrations. Thus, drospirenone is a unique progestogen that confers the additional benefit of BP reduction, an effect that could lead to potential benefit with respect to some cardiovascular risk concerns in women taking hormone therapy.