Pharmacodynamics<unk>  is a highly potent progestogen, and also possesses weak androgenic, antimineralocorticoid, and glucocorticoid activity. Due to its progestogenic activity, it has antigonadotropic and functional antiestrogenic effects. The medication has little or no estrogenic and no antiandrogenic activity. Relative affinities (%) of<unk>  Compound<unk>  90–432 85 0 27–38 97–290 40 0 Notes: Values are percentages (%). Reference ligands (100%) were promegestone for the , metribolone for the , for the , for the , aldosterone for the , for , and cortisol for . Sources: Progestogenic activity<unk>  is a progestogen, and hence is an agonist of the progesterone receptor. Based on the dosage necessary to inhibit ovulation in women,<unk>  is the most potent of all of the currently used oral contraceptive progestogens. The oral dosage of<unk>  required for ovulation inhibition is 30 or 40 μg per day. This is about 10,000 times lower than the oral dosage of progesterone required to inhibit ovulation (300 mg/day). A dosage of<unk>  of 75 μg/day is used in contraceptives. Androgenic activity<unk>  has relatively high affinity for the androgen receptor (AR), with twice that of levonorgestrel (which is known to be one of the more androgenic 19-nortestosterone derivatives). However, the ratio of progestogenic to androgenic effects of<unk>  is distinctly higher than that of levonorgestrel, and the increase in sex hormone-binding globulin (SHBG) levels (a marker of androgenicity) produced by oral contraceptives containing<unk>  is slightly less than that produced by oral contraceptives containing desogestrel (which is known to be one of the more weakly androgenic 19-nortestosterone derivatives). In addition, no difference in acne incidence has been observed with oral contraceptives containing<unk>  and oral contraceptives containing desogestrel.<unk>  may also act to some extent as a 5α-reductase inhibitor. Taken together, like desogestrel,<unk>  appears to have a low potential for androgenic effects. Glucocorticoid activity<unk>  has relatively high affinity for the glucocorticoid receptor, about 27% of that of the corticosteroid dexamethasone. It has weak glucocorticoid activity. Antimineralocorticoid activity<unk>  has very high affinity for the mineralocorticoid receptor (MR), but has only a relatively weak antimineralocorticoid effect that is comparable to that of progesterone. Other activities Although<unk>  does not bind to the estrogen receptor itself, the drug may have some estrogenic activity, and this would appear to be mediated by its weakly estrogenic metabolites 3β,5α-tetrahydrogestodene and to a lesser extent 3α,5α-tetrahydrogestodene.<unk>  binds to SHBG with relatively high affinity; it is 75% bound to the protein in circulation.<unk>  shows some inhibition of cytochrome P450 enzymes in vitro, and has greater potency in this action compared to other progestins ( = 5.0 μM). The medication also shows some inhibition of 5α-reductase in vitro (14.5% at 0.1 μM, 45.9% at 1.0 μM). Like with cytochrome P450 inhibition,<unk>  was more potent in this action compared to other progestins, including desogestrel and levonorgestrel. Pharmacokinetics The oral bioavailability of<unk>  has been found to range from 87 to 111%, with a mean of 96%. Unlike other third-generation progestins like desogestrel and norgestimate,<unk>  is not a prodrug. Peak levels of<unk>  occur within 1 to 4 hours after an oral dose, but usually within 1 to 2 hours. The plasma protein binding of<unk>  is 98%. It is bound 64% to sex hormone-binding globulin and 34% to albumin, with 2% circulating freely.<unk>  is metabolized in the liver via reduction of the δ4-3-keto group to form 3,5-tetrahydrogenated metabolites (major pathway) and via hydroxylation at the C1, C6, and C11 positions (substantial). In spite of differing from it only by the presence of an additional double bond between the C15 and C16 positions,<unk>  is not metabolized into levonorgestrel in the body. The biological half-life of<unk>  is 12 to 15 hours.<unk>  is eliminated 50% in urine and 33% in feces. Of<unk>  excreted in urine, 25% is in the form of glucuronide conjugates, 35% is as sulfate conjugates, and 25% is unconjugated.
Gestodene
Hexestrol
Mestanolone
Formestane
Fosfestrol
Dimestrol
Gestrinone
Dienestrol