comparison to progesterone, a 200 mg dose of oral progesterone is considered to be approximately equivalent in antimineralocorticoid effect to a 25 to 50 mg dose of spironolactone. Both drospirenone and progesterone are actually weak partial agonists of the MR in the absence of mineralocorticoids. Due to its antimineralocorticoid activity, drospirenone increases natriuresis, decreases water retention and blood pressure, and produces compensatory increases in plasma renin activity as well as circulating levels and urinary excretion of aldosterone. This has been shown to occur at doses of 2 to 4 mg/day. Similar effects occur during the luteal phase of the menstrual cycle due to increased progesterone levels and the resulting antagonism of the MR. Estrogens, particularly ethinylestradiol, activate liver production of angiotensinogen and increase levels of angiotensinogen and angiotensin II, thereby activating the renin–angiotensin–aldosterone system. As a result, they can produce undesirable side effects including increased sodium excretion, water retention, weight gain, and increased blood pressure. Progesterone and drospirenone counteract these undesirable effects via their antimineralocorticoid activity. Accumulating research indicates that antimineralocorticoids like drospirenone and spironolactone may also have positive effects on adipose tissue and metabolic health. Antiandrogenic activity Drospirenone is an antagonist of the AR, the biological target of androgens like testosterone and dihydrotestosterone (DHT). It has about 1 to 65% of the affinity of the synthetic anabolic steroid metribolone for the AR. The medication is more potent as an antiandrogen than spironolactone, but is less potent than cyproterone acetate, with about 30% of its antiandrogenic activity in animals. Progesterone displays antiandrogenic activity in some assays similarly to drospirenone, although this issue is controversial and many researchers regard progesterone as having no significant antiandrogenic activity. Drospirenone shows antiandrogenic effects on the serum lipid profile, including higher HDL cholesterol and triglyceride levels and lower LDL cholesterol levels, at a dose of 3 mg/day in women. The medication does not inhibit the effects of ethinylestradiol on sex hormone-binding globulin (SHBG) and serum lipids, in contrast to androgenic progestins like levonorgestrel but similarly to other antiandrogenic progestins like cyproterone acetate. SHBG levels are significantly higher with ethinylestradiol and cyproterone acetate than with ethinylestradiol and drospirenone, owing to the more potent antiandrogenic activity of cyproterone acetate relative to drospirenone. Androgenic progestins like levonorgestrel have been found to inhibit the procoagulatory effects of estrogens like ethinylestradiol on hepatic synthesis of coagulation factors, whereas this may occur less or not at all with weakly androgenic progestins