|Trade names||Proluton C, Pranone, others|
|Synonyms||Ethinyltestosterone; Ethynyltestosterone; Pregneninolone; Anhydrohydroxyprogesterone; Etisteron; Pregnin; Ethindrone|
|By mouth, sublingual|
|Drug class||Progestin; Progestogen; Androgen; Anabolic steroid|
|Chemical and physical data|
|Molar mass||312.446 g/mol|
|3D model (JSmol)|
Ethisterone, also known as ethinyltestosterone, pregneninolone, and anhydrohydroxyprogesterone and formerly sold under the brand names Proluton C and Pranone among others, is a progestin medication which was used in the treatment of gynecological disorders but is now no longer available. It was used alone and was not formulated in combination with an estrogen. The medication is taken by mouth.
Side effects of ethisterone include masculinization among others. Ethisterone is a progestin, or a synthetic progestogen, and hence is an agonist of the progesterone receptor, the biological target of progestogens like progesterone. It has some androgenic and anabolic activity and no other important hormonal activity.
Ethisterone was discovered in 1938 and was introduced for medical use in Germany in 1939 and in the United States in 1945. It was the second progestogen to be marketed, following injected progesterone in 1934, and was both the first orally active progestogen and the first progestin to be introduced. Ethisterone was followed by the improved and much more widely used and known progestin norethisterone in 1957.
|Values are percentages (%). Reference ligands (100%) were progesterone for the PR, testosterone (a = DHT) for the AR, E2 for the ER, DEXA for the GR, aldosterone for the MR, DHT for SHBG, and cortisol for CBG. Sources:|
Ethisterone is a progestogen, or an agonist of the progesterone receptors (PRs). It is described as a relatively weak progestogen, similarly to its analogue dimethisterone. Ethisterone has about 20-fold lower potency as a progestogen relative to norethisterone. It is said to have minimal antigonadotropic effect and to not suppress ovulation, which has precluded its use in hormonal contraception.
Based on in vitro research, ethisterone and norethisterone are about equipotent in their EC50 values for activation of the androgen receptor (AR), whereas, conversely, norethisterone shows markedly increased potency relative to ethisterone in terms of its EC50 for the progesterone receptor (PR). As such, there is a considerable separation in the ratios of androgenic and progestogenic activity for ethisterone and norethisterone. Moreover, at the larger dosages in which it is used to achieve equivalent progestogenic effect, ethisterone has more androgenic effect relative to norethisterone and other 19-nortestosterone progestins. However, the androgenic activity of ethisterone has in any case been described as weak. Due to its androgenic activity, ethisterone has been associated with the masculinization of female fetuses in women who have taken it during pregnancy. The 5α-reduced metabolite of ethisterone, 5α-dihydroethisterone, has been found to show reduced androgenic activity relative to ethisterone.
Testosterone is aromatized into estradiol, and norethisterone, the 19-nortestosterone analogue of ethisterone, has similarly been shown to be aromatized into ethinylestradiol. In accordance, high dosages of norethisterone have been found to be associated with high rates of estrogenic side effects such as breast enlargement in women and gynecomastia in men, as well as with improvement of menopausal symptoms in postmenopausal women. In contrast, ethisterone and other progestogens such as progesterone and hydroxyprogesterone caproate were not associated with such effects, suggesting that they have little or no estrogenic activity. Similarly, although ethisterone showed estrogenic effects in the uterus and vagina in rats, few or no such effects were observed in women treated with the medication, even at very high doses. As such, ethisterone does not appear to share the estrogenic activity of norethisterone, at least in humans.
- 17α-Ethynyltestosterone (or simply ethinyltestosterone or ethynyltestosterone)
- 17α-Pregn-4-en-20-yn-17β-ol-3-one (or simply pregneninolone or pregnenynolone)
- 20,21-Anhydro-17β-hydroxyprogesterone (or simply anhydrohydroxyprogesterone)
Closely related analogues of ethisterone include dimethisterone (6α,21-dimethylethisterone), norethisterone (19-norethisterone), and danazol (the 2,3-d-isoxazole ring-fused derivative of ethisterone), as well as vinyltestosterone, allyltestosterone, methyltestosterone, ethyltestosterone, and propyltestosterone.
Ethisterone was synthesized in 1938 by Hans Herloff Inhoffen, Willy Logemann, Walter Hohlweg, and Arthur Serini at Schering AG in Berlin. It was derived from testosterone via ethynylation at the C17α position, and it was hoped, that, analogously to estradiol and ethinylestradiol, ethisterone would be an orally active form of testosterone. However, the androgenic activity of ethisterone was attenuated and it showed considerable progestogenic activity. As such, it was developed as a progestogen instead and was introduced for medical use in Germany in 1939 as Proluton C and by Schering in the United States in 1945 as Pranone.
Society and culture
Ethisterone is the generic name of the drug and its INN, USAN, and BAN, while ethistérone is its DCF. It has also been referred to as ethinyltestosterone, pregneninolone, and anhydrohydroxyprogesterone.
Ethisterone has been marketed under a variety of brand names including Amenoren, Cycloestrol-AH Progestérone, Duosterone, Estormon, Etherone, Ethisteron, Luteosterone, Lutocyclin, Lutocylol, Lutogynestryl, Menstrogen, Nugestoral, Oophormin Luteum, Ora-Lutin, Orasecron, Pranone, Pre Ciclo, Prodroxan, Produxan, Progestab, Progesteron lingvalete, Progestoral, Proluton C, Syngestrotabs, and Trosinone among others.
Ethisterone was previously available in France, Germany, Italy, Japan, the United Kingdom, and the United States, among other countries. It is no longer marketed and hence is no longer available in any country.
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