<unk> s are agonists of the<unk>  receptors (ERs), the biological target of endogenous<unk> s such as estradiol. When used in<unk> <unk> s,<unk> s are powerful antigonadotropins, strongly inhibiting secretion of the gonadotropins luteinizing hormone and follicle-stimulating hormone from the pituitary gland, and in men are able to completely suppress gonadal androgen production and reduce testosterone levels into the castrate range. This is most of the basis of their use in prostate cancer and benign prostatic hyperplasia. When estradiol or an estradiol ester is used for HDE in men, levels of estradiol of at least approximately 200 pg/mL are necessary to suppress testosterone levels into the castrate range. Synthetic and nonsteroidal<unk> s like ethinylestradiol and diethylstilbestrol are resistant to hepatic metabolism and for this reason have dramatically increased local potency in the liver. As a result, they have disproportionate effects on hepatic protein production and a greatly increased risk of blood clots relative to endogenous and bioidentical forms of<unk>  like estradiol and estradiol esters. Unlike synthetic<unk> s, bioidentical<unk> s are efficiently inactivated in the liver even at<unk>  dosages or<unk>  circulating levels, as in pregnancy, although changes in hepatic protein production can still occur. A study that used<unk> - to very-high-dose oral estradiol to treat postmenopausal women with<unk>  receptor-positive breast cancer found that mean steady-state estradiol levels in the 6 mg/day group were about 300 pg/mL and in the 30 mg/day group were about 2,400 pg/mL. An example pseudopregnancy regimen in women which has been used in clinical studies is intramuscular injections of 40 mg/week estradiol valerate and 250 mg/week hydroxyprogesterone caproate. It has been found to result in estradiol levels of about 3,100 pg/mL at 3 months of therapy and 2,500 pg/mL at 6 months of therapy. Levels of<unk>  and progesterone in normal human pregnancy are very<unk> . Estradiol levels are 1,000 to 5,000 pg/mL during the first trimester, 5,000 to 15,000 pg/mL during the second trimester, and 10,000 to 40,000 pg/mL during the third trimester, with a mean of 25,000 pg/mL at term and levels as<unk>  as 75,000 pg/mL measurable in some women. Levels of progesterone are 10 to 50 ng/mL in the first trimester and rise to 50 to 280 ng/mL in the third trimester, with a mean of around 150 ng/mL at term. Although only a small fraction of estradiol and progesterone are unbound in circulation, the amounts of free and thus biologically active estradiol and progesterone increase to similarly large extents as total levels during pregnancy. As such, pregnancy is a markedly hyperestrogenic and hyperprogestogenic state. Levels of estradiol and progesterone are both up to 100-fold<unk> er during pregnancy than during normal menstrual cycling. Pseudopregnancy simulates the hormonal profile of the first trimester of pregnancy.
High-dose estrogen
Nonsteroidal estrogen
Phytoprogestogen
Antiprogestogen
Male contraceptive
Phytoestrogen
Gestodene
Algestone