Pharmacodynamics The affinity of<unk> -DHET for the androgen receptor (AR) is relatively high, in the range of 38 to 100% of that of dihydrotestosterone (DHT). A study found that, similarly to norethisterone and its<unk> -reduced metabolite<unk> -dihydronorethisterone,<unk> -DHET showed increased affinity for the AR but decreased androgenic potency relative to ethisterone (Ki = 16.1 nM for<unk> -DHET and 101.1 nM for ethisterone, a 6-fold difference in affinity). The decreased androgenic activity of<unk> -DHET in spite of increased affinity for the AR relative to ethisterone suggests that it has comparatively reduced efficacy as an agonist of the receptor, analogously to selective androgen receptor modulators (AR partial agonists) and antiandrogens (AR antagonists).<unk> -DHET has relatively low affinity for the progesterone receptor, only about 12% of that of the progestogen progesterone. This is significantly less than that of ethisterone, which has been found to bind to the receptor with an affinity of 35% of that of progesterone. Conversely, it has relatively high affinity for the glucocorticoid receptor, about 120% of that of the corticosteroid dexamethasone. In regards to the estrogen receptors,<unk> -DHET has weak affinity for the ERα of about 3.5% of that of estradiol, and does not bind to the ERβ (Ki > 10 μM). In addition to steroid hormone receptors,<unk> -DHET has very high affinity for sex hormone-binding globulin (Kd = 0.18 nM), an androgen and estrogen binding and transport protein that has the effect of intermittently inactivating steroid hormones (but also prolonging their half-life in the body). Its affinity for this protein is among the highest of any known compound and has been found to be roughly equal to that of DHT and mesterolone (1α-methyl-DHT). This property may contribute to the androgenic activity of<unk> -DHET's parent drug ethisterone by displacing endogenous androgens like testosterone and DHT from SHBG. Pharmacokinetics Metabolism studies of ethynylandrostanediol revealed that<unk> -DHET can be metabolized via C7β and C16α hydroxylation.
5α-Dihydroethisterone
3α-Androstanediol
3β-Androstanediol
8,9-Dehydroestradiol
17β-Dihydroequilin
8,9-Dehydroestrone
17α-Dihydroequilin
17β-Dihydroequilenin