Mestranol, sold under the brand names Enovid, Norinyl, and Ortho-Novum among others, is an estrogen medication which has been used in birth control pills, menopausal hormone therapy, and the treatment of menstrual disorders. It is formulated in combination with a progestin and is not available alone. It is taken by mouth.
Benorterone, also known by its developmental code name SKF-7690 and as 17α-methyl-B-nortestosterone, is a steroidal antiandrogen which was studied for potential medical use but was never marketed. It was the first known antiandrogen to be studied in humans. It is taken by mouth or by application to skin.
Anordrin, also known as 2α,17α-diethynyl-A-nor-5α-androstane-2β,17β-diol dipropionate, is a synthetic, steroidal selective estrogen receptor modulator (SERM) which is used in China as an emergency contraceptive. It is the most commonly used emergency contraceptive in China. The drug is marketed in a combination formulation with mifepristone under the brand name Zi Yun. Anordrin has not been studied for use or marketed outside of China. It has been used in China since the 1970s.
Estriol glucuronide (E3G), or oestriol glucuronide, also known as estriol monoglucuronide, as well as estriol 16α-β-D-glucosiduronic acid, is a natural, steroidal estrogen and the glucuronic acid conjugate of estriol. It occurs in high concentrations in the urine of pregnant women as a reversibly formed metabolite of estriol. Estriol glucuronide is a prodrug of estriol, and was the major component of Progynon and Emmenin, estrogenic products manufactured from the urine of pregnant women that were introduced in the 1920s and 1930s and were the first orally active estrogens. Emmenin was succeeded by Premarin, which is sourced from the urine of pregnant mares and was introduced in 1941. Premarin replaced Emmenin because it was easier and less expensive to produce.
Estrone glucuronide, or estrone-3-D-glucuronide, is a conjugated metabolite of estrone. It is formed from estrone in the liver by UDP-glucuronyltransferase via attachment of glucuronic acid and is eventually excreted in the urine by the kidneys. It has much higher water solubility than does estrone. Glucuronides are the most abundant estrogen conjugates and estrone glucuronide is the dominant metabolite of estradiol.
Droloxifene, also known as 3-hydroxytamoxifen, is a nonsteroidal selective estrogen receptor modulator (SERM) of the triphenylethylene group that was developed originally in Germany and later in Japan for the treatment of breast cancer, osteoporosis in men and postmenopausal women, and cardiovascular disorders but was abandoned and never marketed. It reached phase II and phase III clinical trials for these indications before development was discontinued in 2000. The drug was found to be significantly less effective than tamoxifen in the treatment of breast cancer in two phase III clinical trials.
Miproxifene (INN) is a nonsteroidal selective estrogen receptor modulator (SERM) of the triphenylethylene group that was never marketed. It is a derivative of afimoxifene (4-hydroxytamoxifen) in which an additional 4-isopropyl group is present in the β-phenyl ring. The drug has been found to be 3- to 10-fold more potent than tamoxifen in inhibiting breast cancer cell growth in in vitro models. Miproxifene is the active metabolite of miproxifene phosphate (TAT-59), a phosphate ester and prodrug of miproxifene that was developed to improve its water solubility. Miproxifene phosphate was under development for the treatment of breast cancer and reached phase III clinical trials for this indication but development was discontinued.
Miproxifene phosphate is a nonsteroidal selective estrogen receptor modulator (SERM) of the triphenylethylene group that was under development in Japan for the treatment of breast cancer but was abandoned and never marketed. It reached phase III clinical trials for this indication before development was discontinued. The drug is a phosphate ester and prodrug of miproxifene (DP-TAT-59) with improved water solubility that was better suited for clinical development. Miproxifene has been found to be 3- to 10-fold as potent as tamoxifen in inhibiting breast cancer cell growth in in vitro models. It is a derivative of afimoxifene (4-hydroxytamoxifen) in which an additional 4-isopropyl group is present in the β-phenyl ring.
Anordiol, or anordriol, also known as 2α,17α-diethynyl-A-nor-5α-androstane-2β,17β-diol, is a synthetic steroid-like mixed estrogen and antiestrogen and an active metabolite of anordrin, a postcoital contraceptive that is marketed and used in China. Relative to anordrin, anordiol has similar but more potent actions.
Zindoxifene is a nonsteroidal selective estrogen receptor modulator (SERM) that was under development in the 1980s and early 1990s for the treatment of breast cancer but was not marketed. It showed estrogenic-like activity in preclinical studies and failed to demonstrate effectiveness as a treatment for breast cancer in clinical trials. Zindoxifene was the lead compound of the distinct 2-phenylindole class of SERMs, and the marketed SERM bazedoxifene was derived from the major active metabolite of zindoxifene, D-15414. Zindoxifene was first described in 1984.
Estrone sulfate (E1S) is an estrogen medication and naturally occurring steroid hormone. It is used in menopausal hormone therapy among other indications. As the sodium salt, it is the major estrogen component of conjugated estrogens (Premarin) and esterified estrogens. In addition, E1S is used on its own as the piperazine salt estropipate. The compound also occurs as a major and important metabolite of estradiol and estrone. E1S is most commonly taken by mouth, but in the form of Premarin can also be taken by parenteral routes such as transdermal, vaginal, and injection.
Estriol dipropionate, or estriol 3,17β-dipropionate, is a synthetic estrogen and estrogen ester – specifically, the C3 and C17β dipropionate ester of estriol – which was first described in 1963 and was never marketed. Following a single intramuscular injection of 6.94 mg estriol dipropionate in an oil solution, peak levels of estriol occurred after 0.83 days, an elimination half-life of 12.7 hours was observed, and estriol levels remained elevated for up to 4 days. For comparison, the duration of estriol was much shorter, while that of estriol dihexanoate was much longer.
Estriol dihexanoate, or estriol 3,17β-dihexanoate, is a synthetic estrogen and estrogen ester – specifically, the C3 and C17β dihexanoate ester of estriol – which was first described in 1963 and was never marketed. Following a single intramuscular injection of 8.90 mg estriol dihexanoate in an oil solution, peak levels of estriol occurred after 2.1 to 3.4 days, an elimination half-life of 187 to 221 hours was observed, and estriol levels remained elevated for up to 20 to 50 days. For comparison, the durations of estriol and estriol dipropionate were far shorter.
Estrone benzoate, or estrone 3-benzoate, is a synthetic estrogen and estrogen ester – specifically, the C3 benzoate ester of estrone – which was first reported in 1932 and was never marketed. It led to the development in 1933 of the more active estradiol benzoate, the first estradiol ester to be introduced for medical use.
Estradiol 3-saccharinylmethyl ether (E2SME), also known as 3-O-(saccharinylmethyl)-17β-estradiol, is a synthetic estrogen and estrogen ether – specifically, the C3 saccharinylmethyl ether of estradiol – which was described in the mid-1990s and was never marketed. It is a prodrug of estradiol and appears to be partially protected from first-pass metabolism in the liver and intestines with oral administration, showing greatly improved oral potency compared to estradiol.
Estradiol acetylsalicylate, or estradiol 3-acetylsalicylate, is a synthetic estrogen and estrogen ester – specifically, the C3 acetylsalicylic acid (aspirin) ester of estradiol – which was described in the late 1980s and was never marketed. In dogs, the oral bioavailability of estradiol acetylsalicylate was found to be 17-fold higher than that of unmodified estradiol. However, a subsequent study found that the oral bioavailability of estradiol and estradiol acetylsalicylate did not differ significantly in rats, suggestive of a major species difference.
Estradiol anthranilate, or estradiol 3-anthranilate, is a synthetic estrogen and estrogen ester – specifically, the C3 anthranilic acid ester of estradiol – which was described in the late 1980s and was never marketed. In dogs, the oral bioavailability of estradiol anthranilate was found to be 5-fold higher than that of unmodified estradiol. However, a subsequent study found that the oral bioavailability of estradiol and estradiol anthranilate did not differ considerably in rats, suggestive of a major species difference.
Cyclodiol is a synthetic estrogen which was studied in the 1990s and was never marketed. It is a derivative of estradiol with a bridge between the C14α and C17α positions. Cyclodiol has 100% of the relative binding affinity of estradiol for the human ERα and similar transactivational capacity as estradiol at the receptor. It has comparable potency to estradiol when administered by subcutaneous injection. The drug shows genotoxicity similarly to estradiol. Cyclodiol showed an absolute bioavailability of 33 ± 19% and an elimination half-life of 28.7 hours in pharmacokinetic studies in women.
Cyclotriol is a synthetic estrogen which was studied in the 1990s and was never marketed. It is a derivative of estriol with a bridge between the C14α and C17α positions. The drug has 40% of the relative binding affinity of estradiol for the human ERα. It showed an absolute bioavailability of 40% with high interindividual variability and an elimination half-life of 12.3 hours in pharmacokinetic studies in women.
Ethinylestradiol sulfate, also known as 17α-ethynylestradiol 3-sulfate, is an estrogen ester – specifically, the C3 sulfuric acid (sulfate) ester of the synthetic estrogen ethinylestradiol (EE) – and is the major metabolite of EE. Circulating levels of EE sulfate range from 6 to 22 times those of EE when EE is taken orally. EE sulfate can be transformed back into EE (14–21%) via steroid sulfatase, and it has been suggested that EE sulfate may serve as a circulating reservoir for EE, similarly to the case of estrone sulfate with estradiol. However, the EE sulfate pool with EE is far smaller than the pool of estrone sulfate that occurs with estradiol. In addition, in contrast to the case of estrone sulfate and estrone, the conversion rate of EE sulfate back into EE is relatively low, and has been said probably isn't of clinical significance. However, other studies have suggested that EE sulfate may nonetheless contribute up to 20% of total EE levels.
