Mestranol

Mestranol was employed as the estrogen component in many of the first oral contraceptives, such as mestranol/noretynodrel (brand name Enovid) and mestranol/norethisterone (brand names Ortho-Novum, Norinyl), and is still in use today. In addition to its use as an oral contraceptive, mestranol has been used as a component of menopausal hormone therapy for the treatment of menopausal symptoms. ==Side effects==

(EE), the active form of mestranol Mestranol is a biologically inactive prodrug of ethinylestradiol to which it is demethylated in the liver (via O-Dealkylation) with a conversion efficiency of 70% (50 μg of mestranol is pharmacokinetically bioequivalent to 35 μg of ethinylestradiol). The elimination half-life of mestranol has been reported to be 50 minutes. The elimination half-life of the active form of mestranol, ethinylestradiol, is 7 to 36 hours. The effective ovulation-inhibiting dosage of mestranol has been studied in women. It has been reported to be about 98% effective at inhibiting ovulation at a dosage of 75 or 80 μg/day. In another study, the ovulation rate was 15.4% at 50 μg/day, 5.7% at 80 μg/day, and 1.1% at 100 μg/day. ==Chemistry==

Mestranol, also known as ethinylestradiol 3-methyl ether (EEME) or as 17α-ethynyl-3-methoxyestra-1,3,5(10)-trien-17β-ol, is a synthetic estrane steroid and a derivative of estradiol. It is specifically a derivative of ethinylestradiol (17α-ethynylestradiol) with a methyl ether at the C3 position. ==History==

In April 1956, noretynodrel was investigated, in Puerto Rico, in the first large-scale clinical trial of a progestogen as an oral contraceptive. The trial was conducted in Puerto Rico due to the high birth rate in the country and concerns of moral censure in the United States. It was discovered early into the study that the initial chemical syntheses of noretynodrel had been contaminated with small amounts (1–2%) of the 3-methyl ether of ethinylestradiol (noretynodrel having been synthesized from ethinylestradiol). was developed and serendipitously identified as a very potent synthetic estrogen (and eventually as a prodrug of ethinylestradiol), given its name, and added back to the formulation. The rationale was that ethinylestradiol was approximately twice as potent by weight as mestranol and hence that the dose could be halved, which it was thought might result in a lower incidence of venous thromboembolism. Whether this actually did result in a lower incidence of venous thromboembolism has never been assessed. ==Society and culture==

Generic names Mestranol is the generic name of the drug and its , , , , , and , while mestranolo is its . Brand names Mestranol has been marketed under a variety of brand names, mostly or exclusively in combination with progestins, including Devocin, Enavid, Enovid, Femigen, Mestranol, Norbiogest, Ortho-Novin, Ortho-Novum, Ovastol, and Tranel among others. Today, it continues to be sold in combination with progestins under brand names including Lutedion, Necon, Norinyl, Ortho-Novum, and Sophia. Availability Mestranol remains available only in the United States, the United Kingdom, Japan, and Chile. It is only marketed in combination with progestins, such as norethisterone. ==Research==

Mestranol has been studied as a male contraceptive and was found to be highly effective. At a dosage of 0.45 mg/day, it suppressed gonadotropin levels, reduced sperm count to zero within 4 to 6 weeks, and decreased libido, erectile function, and testicular size. Gynecomastia occurred in all of the men. These findings contributed to the conclusion that estrogens would be unacceptable as contraceptives for men. ==Environmental presence==

In 2021, mestranol was one of the 12 compounds identified in sludge samples taken from 12 wastewater treatment plants in California that were collectively associated with estrogenic activity in in vitro. == References ==