Pharmacodynamics<unk>  has weak progestogenic activity and weak androgenic activity, but does not seem to have estrogenic activity.<unk>  is a major active metabolite of danazol (2,3-isoxazolethisterone), and is thought to contribute importantly to its effects. Progestogenic activity<unk>  is a progestogen, or an agonist of the progesterone receptors. It has about 44% of the affinity of progesterone for the progesterone receptor. The medication is described as a relatively weak progestogen, similarly to its analogue dimethisterone. Its total endometrial transformation dosage per 10 to 14 days in women is 200 to 700 mg.<unk>  has about 20-fold lower potency as a progestogen relative to norethisterone. It is said to have minimal antigonadotropic effect and to not suppress ovulation, which has precluded its use in hormonal contraception. Androgenic activity Based on in vitro research,<unk>  and norethisterone are about equipotent in their values for activation of the androgen receptor (AR), whereas, conversely, norethisterone shows markedly increased potency relative to<unk>  in terms of its EC50 for the progesterone receptor. As such, there is a considerable separation in the ratios of androgenic and progestogenic activity for<unk>  and norethisterone. Moreover, at the larger dosages in which it is used to achieve equivalent progestogenic effect,<unk>  has more androgenic effect relative to norethisterone and other 19-nortestosterone progestins. However, the androgenic activity of<unk>  has in any case been described as weak. Due to its androgenic activity,<unk>  has been associated with the masculinization of female fetuses in women who have taken it during pregnancy. The 5α-reduced metabolite of<unk> , 5α-dihydroethisterone, has been found to show reduced androgenic activity relative to<unk> . Interestingly,<unk>  showed antiandrogenic activity when co-administered with dihydrotestosterone (DHT) in animals, whereas 5α-dihydroethisterone did not. Estrogenic activity Testosterone is aromatized into estradiol, and norethisterone, the 19-nortestosterone analogue of<unk> , has similarly been shown to be aromatized into ethinylestradiol. In accordance, high doses of norethisterone have been found to be associated with marked increases in urinary estrogen excretion (due to metabolism into ethinylestradiol), as well as with high rates of estrogenic side effects such as breast enlargement in women and gynecomastia in men and improvement of menopausal symptoms in postmenopausal women. In contrast,<unk>  and other progestogens such as progesterone and hydroxyprogesterone caproate do not increase estrogen excretion and are not associated with estrogenic effects, indicating that they have little or no estrogenic activity. Similarly, although<unk>  showed estrogenic effects in the uterus and vagina in rats, few or no such effects were observed in women treated with the medication, even at very high doses. As such,<unk>  does not appear to share the estrogenic activity of norethisterone, at least in humans. Aside from ethinylestradiol, 17α-ethynyl-3α-androstanediol and 17α-ethynyl-3β-androstanediol may be estrogenic metabolites of<unk> . Pharmacokinetics Absorption<unk>  is active both orally and sublingually in humans. Good oral bioavailability of<unk>  has been observed in rats. The medication was the first orally active progestin to be discovered and introduced for clinical use. Distribution<unk>  has relatively high affinity for sex hormone-binding globulin, about 14% of that of dihydrotestosterone and 49% of that of testosterone in one study. Metabolism In terms of metabolism,<unk>  is not converted into pregnanediol in humans. This indicates that it is not metabolized into progesterone. No aromatization of<unk>  has been detected in vivo, and no estrogenic metabolites were observed in vitro upon incubation of<unk>  in placental homogenates. This suggests that<unk>  may not be transformed into ethinylestradiol (17α-ethynylestradiol). 5α-Dihydroethisterone (5α-dihydro-17α-ethynyltestosterone), formed by 5α-reductase, is an active metabolite of<unk> . 17α-Ethynyl-3α-androstanediol and 17α-ethynyl-3β-androstanediol, also formed via 5α-reductase, as well as other enzymes, are also potential metabolites of<unk> .
Ethisterone
Metenolone acetate
Vinyltestosterone
Ethinylestradiol
Ethinylestradiol sulfonate
Fluoxymesterone
Formestane
Estradiol enantate