Antimineralocorticoid activity of a novel oral contraceptive containing drospirenone, a unique progestogen resembling natural progesterone

Sex hormones are known to interfere with the renin-angiotensin-aldosterone system (RAAS) in two ways. First, estrogens strongly stimulate the production of renin substrate (angiotensinogen), leading to increased levels of angiotensin and aldosterone, and sodium retention. Second, progesterone is a potent aldosterone antagonist, which acts on the mineralocorticoid receptor to prevent sodium retention. In combined oral contraceptives, progestogens devoid of antimineralocorticoid and antiandrogenic activity are unable to counteract the sodium-retaining effect of the ethinylestradiol component. As a consequence, these preparations may increase fluid retention, and promote related symptoms such as edema and body weight. Drospirenone is a new progestogen with antimineralocorticoid and antiandrogenic activity. The relationship between the progestogenic and antimineralocorticoid potency of drospirenone is similar to that of endogenous progesterone. At a dosage that suppresses ovulation, drospirenone induces mild natriuresis, which is followed by compensatory stimulation of the RAAS (comparable to a low sodium diet). An oral contraceptive containing 3 mg drospirenone and 30 mug ethinylestradiol (Yasmin(R), Schering AG, Berlin, Germany) provides reliable contraception and, due to a lack of sodium retention, may counteract cyclical weight gain and other symptoms related to estrogen-induced fluid retention.