Pharmacodynamics<unk>  is an estrogen similarly to natural estrogens like estradiol and conjugated estrogens (Premarin) and synthetic estrogens like diethylstilbestrol. It binds to and activates both isoforms of the estrogen receptor, ERα and ERβ. In one study,<unk>  was found to have 233% and 38% of the affinity of estradiol for the ERα and ERβ, respectively. In another study, it was found to possess 194% and 151% of the affinity of estradiol for the ERα and ERβ, respectively.<unk>  also appears to act as a potent agonist of the G protein-coupled estrogen receptor (GPER) (affinity unknown), a membrane estrogen receptor, similarly to estradiol. Estrogens have antigonadotropic effects through activation of the ERα. As a contraceptive,<unk>  acts in concert with a progestin to inhibit the mid-cycle surge in luteinizing hormone (LH) and follicle-stimulating hormone (FSH) via its antigonadotropic effects, thereby inhibiting folliculogenesis and preventing ovulation and hence the possibility of pregnancy.<unk>  is a long-acting estrogen, with a nuclear retention of about 24 hours. Orally,<unk>  is on the order of 100 times as potent by weight as natural estrogens like micronized estradiol and conjugated estrogens, which is largely due to substantially greater resistance to first-pass metabolism. It is specifically in the range of 80 to 200 times as potent as estropipate (piperazine estrone sulfate), which has similar potency to micronized estradiol, in terms of systemic estrogenic potency. In contrast, the potencies of<unk>  and natural estrogens are similar when they are administered intravenously, due to the bypassing of first-pass metabolism. Relative to its prodrug mestranol,<unk>  is about 1.7 times as potent by weight orally. Antiandrogenic and antigonadotropic effects Testosterone levels with no treatment and with various estrogens in men with prostate cancer. Determinations were made with an early radioimmunoassay (RIA). Source was Shearer et al. (1973).<unk>  is a potent functional antiandrogen in both women and men. It mediates its antiandrogenic effects by 1) stimulating the production of sex hormone-binding globulin (SHBG) in the liver, which decreases free and thus bioactive concentrations of testosterone in the blood; and by 2) suppressing luteinizing hormone (LH) secretion from the pituitary gland, which decreases production of testosterone by the gonads. Birth control pills that contain<unk>  are useful in the treatment of androgen-dependent conditions like acne and hirsutism by virtue of their antiandrogenic effects. Birth control pills containing<unk>  have been found to increase circulating SHBG levels by 2- to 4-fold in women and to reduce free testosterone concentrations by 40 to 80%. Birth control pills containing high doses of<unk>  can increase SHBG levels in women by as much as 5- to 10-fold. This is similar to the 5- to 10-fold increase in SHBG levels that occurs during pregnancy. Due to the marked increase in SHBG levels, free testosterone levels become very low during treatment with<unk> -containing birth control pills. In men, a study found that treatment with a relatively low dosage of 20 μg/day<unk>  for five weeks increased circulating SHBG levels by 150% and, due to the accompanying decrease in free testosterone levels, increased total circulating levels of testosterone by 50% (via upregulation of gonadal testosterone production due to reduced negative feedback by androgens on the hypothalamic–pituitary–gonadal axis). The stimulation of hepatic SHBG production by<unk>  is far stronger than with other estrogens like estradiol, owing to the high resistance of<unk>  to inactivation in the liver and hence its disproportionate effects in this part of the body. Estrogens are antigonadotropins and are able to suppress the secretion of LH and FSH from the pituitary gland and by extension gonadal testosterone production. High-dose estrogen therapy, including with<unk> , is able to suppress testosterone levels in men by around 95%, or into the castrate/female range. The dosage of<unk>  required for use as a component of hormone therapy for preoperative transgender women is 50 to 100 µg/day. This high dosage is associated with a high incidence of VTE, particularly in those over the age of 40 years, and it has been said that it should not be used. The dosage of<unk>  used in the treatment of prostate cancer in men is 150 to 1,000 µg/day (0.15–1.0 mg/day). A dosage of<unk>  of 50 μg twice daily (100 μg/day total) has been found to suppress testosterone levels in men to an equivalent extent as 3 mg/day oral diethylstilbestrol, which is the minimum dosage of diethylstilbestrol required to consistently suppress testosterone levels into the castrate range. The ovulation-inhibiting dose of<unk>  by itself and not in combination with a progestin in women is 100 μg/day. However, it has been found to be about 75 to 90% effective at inhibiting ovulation at a dosage of 20 μg/day and about 97 or 98% effective at a dosage of 50 μg/day. In another study, ovulation occurred in 25.2% with an<unk>  dose of 50 μg/day. Lower dosages of<unk>  also have significant antigonadotropic effects. A "very low" dosage of 15 µg/day<unk>  has been described as the "borderline" amount required for suppression of LH and testosterone levels in men, and a study found that LH and testosterone levels were "reliably" suppressed in men by a dosage of 30 µg/day<unk> . However, other clinical studies have found that 20 µg/day<unk>  increased testosterone levels by 50% in men (as described above) and that dosages of 32 µg/day and 42 µg/day<unk>  suppressed FSH levels in men but did not significantly affect LH levels. A stronger suppression of testosterone levels was observed in men following daily treatment with a combined oral contraceptive containing 50 µg<unk>  and 0.5 mg norgestrel for 9 days. However, investigation revealed that the progestin was the more important component responsible for the suppression in testosterone levels. In accordance, the progestin component of COCs is primarily responsible for inhibition of ovulation in women. A combination of 20 µg/day<unk>  and 10 mg/day methyltestosterone was found to suppress FSH secretion in men to an extent sufficient to stop spermatogenesis. Studies in women have found that 50 µg/day<unk>  suppresses LH and FSH levels both by about 70% in postmenopausal women. In addition to its antigonadotropic effects,<unk>  can significantly suppress androgen production by the adrenal glands at high concentrations. One study found that treatment with a high dosage of 100 µg/day<unk>  suppressed circulating adrenal androgen levels by 27 to 48% in transgender women. This may additionally contribute to suppression of androgen levels by estrogens. Effects on liver protein synthesis<unk>  has marked effects on liver protein synthesis, even at low dosages and regardless of route of administration. These effects are mediated by its estrogenic activity. The medication dose-dependently increases circulating levels of SHBG, corticosteroid-binding globulin (CBG), and thyroxine-binding globulin (TBG), and also affects a broad range of other liver proteins.<unk>  affects triglyceride levels at a dose as low as 1 μg/day and LDL and HDL cholesterol levels at a dose as low as 2.5 μg/day.<unk>  affects several hepatic proteins at a dosage as low as 5 µg/day. At doses above 20 µg/day, the incremental effects of<unk>  on liver protein synthesis become continuously smaller.<unk>  at 5 μg/day has been found to increase SHBG levels by 100% in postmenopausal women, while a dosage of 20 µg/day<unk>  increased them by 200%. Androgens decrease hepatic SHBG production, and have been found to oppose the effects of<unk>  on SHBG levels. This is of particular relevance when it is considered that many progestins used in COCs have varying degrees of weak androgenic activity. A combination of 20 µg/day<unk>  and 0.25 mg/day levonorgestrel, a progestin with relatively high androgenicity, decreases SHBG levels by 50%; 30 µg/day<unk>  and 0.25 mg/day levonorgestrel has no effect on SHBG levels; 30 µg/day<unk>  and 0.15 mg/day levonorgestrel increases SHBG levels by 30%; and triphasic COCs containing<unk>  and levonorgestrel increase SHBG levels by 100 to 150%. The combination of 30 µg/day<unk>  and 150 µg/day desogestrel, a progestin with relatively weak androgenicity than levonorgestrel, increases SHBG levels by 200%, while the combination of 35 µg/day<unk>  and 2 mg/day cyproterone acetate, a progestin with potent antiandrogenic activity, increases SHBG levels by 400%. As such, the type and dosage of progestin contained in COCs potently moderates the effects of<unk>  on SHBG levels. A dosage of 10 µg/day<unk>  has been found to increase CBG levels by 50%, while a dosage of 20 µg/day<unk>  increased them by 100%. Progestins that are progesterone derivatives have no effect on CBG levels, while androgenic progestins like the 19-nortestosterone derivatives have only a weak effect on CBG levels. COCs may increase CBG levels by 100 to 150%. A dosage of 5 µg/day<unk>  has been found to increase TBG levels by 40%, while a dosage of 20 µg/day<unk>  increased them by 60%. Progestins that are progesterone derivatives do not affect TBG levels, while progestins with androgenic activity may decrease TBG levels. A combination of 30 µg/day<unk>  and 1 mg/day norethisterone, a moderately androgenic progestin, have been found to increase TBG levels by 50 to 70%, while
Ethinylestradiol
Vinyltestosterone
Haloprogesterone
Ethyltestosterone
Progestogen
Progestogen 
Methylestradiol
Cloxestradiol acetate