Estradiol, the active form of<unk> . Pharmacodynamics Esters of estradiol like<unk>  are readily hydrolyzed prodrugs of estradiol, but have an extended duration when administered in oil via intramuscular injection due to a depot effect afforded by their fatty acid ester moiety. As prodrugs of estradiol,<unk>  and other estradiol esters are estrogens.<unk>  is of about 62% higher molecular weight than estradiol due to the presence of its C17β<unk>  ester. Because<unk>  is a prodrug of estradiol, it is considered to be a natural and bioidentical form of estrogen. The effects of<unk>  on cortisol, dehydroepiandrosterone sulfate, testosterone, and prolactin levels as well as on the hypothalamic–pituitary–adrenal axis have been studied in men with prostate cancer and compared with those of high-dose cyproterone acetate therapy. The effects of<unk>  on serum lipids and ceruloplasmin levels have been studied as well. Antigonadotropic activity Testosterone levels with 300 mg/week cyproterone acetate or 100 mg/month<unk>  both by intramuscular injection. The solid lines are the average levels and the dashed lines are the highest and lowest observed levels. Estradiol, testosterone, and prolactin levels with 100 mg/month<unk>  by intramuscular injection in men with prostate cancer. A phase III clinical trial comparing high-dose intramuscular cyproterone acetate (300 mg/week) and high-dose intramuscular<unk>  (100 mg/month) in the treatment of prostate cancer found that<unk>  suppressed testosterone levels into the castrate range (< 50 ng/dL) within at least 3 months whereas testosterone levels with cyproterone acetate were significantly higher and above the castrate range even after 6 months of treatment. With<unk> , testosterone levels fell from 416 ng/dL to 38 ng/mL (-91%) after 3 months and to 29.6 ng/dL (-93%) after 6 months, whereas with cyproterone acetate, testosterone levels fell from 434 ng/dL to 107 ng/mL (-75%) at 3 months and to 102 ng/mL (-76%) at 6 months. In another study using the same dosages,<unk>  suppressed testosterone levels by 97% while CPA suppressed them by 70%. In accordance, whereas estrogens are well-established as able to suppress testosterone levels into the castrate range at sufficiently high dosages, progestogens like cyproterone acetate on their own are able to decrease testosterone levels only up to an apparent maximum of around 70 to 80%. The long-term effects of<unk>  on testicular morphology in transgender women have been studied. Pharmacokinetics The pharmacokinetics of<unk>  have been assessed in a few studies. Following a single intramuscular injection of 100 mg<unk>  in oil, mean levels of estradiol were about 500 pg/mL a day after injection and about 340 pg/mL 14 days after injection. Levels of estradiol with intramuscular<unk>  were reported to be very irregular and to vary by as much as 10-fold between individuals. In another study, following a single intramuscular injection of 32.2 mg<unk> , levels of estradiol peaked at around 400 pg/mL after 3 days and decreased from this peak to around 200 pg/mL after 6 days. In a continuous administration study of 100 mg/month<unk> , estradiol levels were about 560 pg/mL at 3 months and about 540 pg/mL at 6 months of therapy. Due to its more protracted duration, doses of<unk>  that are typical of other estradiol esters produce only "subthreshold" estradiol levels, and for this reason, higher single doses of<unk>  are necessary for similar effects. However, the relatively low levels of estradiol produced by lower doses of<unk>  are favorable for menopausal replacement therapy. The duration of<unk>  is markedly prolonged relative to that of estradiol benzoate, estradiol valerate, and many other estradiol esters. A single intramuscular injection of 10 to 12.5 mg<unk>  has a duration of 40 to 60 days (~1–2 months) and of 25 to 50 mg<unk>  has an estimated duration of effect of 2 to 4 months in postmenopausal women. A single intramuscular injection of 20 to 30 mg<unk>  has been found to inhibit ovulation when used as an estrogen-only injectable contraceptive in premenopausal women for 1 to 3 months (mean 1.7 months) as well. When used at a higher dose of 100 mg per injection in men with prostate cancer,<unk>  has been given usually once a month. After a single subcutaneous injection of<unk>  in rats, its duration of effect was 80 days (about 2.5 months). Due to its very prolonged duration,<unk>  has been described in general as a favorable alternative to estradiol implants. The excretion of<unk>  has been studied as well.<unk>  has not been used via oral administration. However, a closely related estradiol ester, estradiol decanoate (estradiol decylate), has been studied via the oral route, and has been found to possess significant oral bioavailability, to produce relatively high estradiol levels of about 100 pg/mL after a single 0.5 mg oral dose and about 100 to 150 pg/mL with continuous 0.25 mg/day oral therapy, and to have a much higher estradiol-to-estrone ratio than oral estradiol of about 2:1. It is thought that this is due to absorption of estradiol decanoate by the lymphatic system and a consequent partial bypass of first-pass metabolism in the liver and intestines, which is similarly known to occur with oral testosterone undecanoate.
Estradiol undecylate
Estradiol dienantate
Estradiol enantate
Estradiol furoate
Estradiol valerate
Estradiol hemisuccinate
Estradiol diundecylenate
Estradiol dipropionate