Ethisterone/[email protected]

Ethisterone (pregneninolone, 17α-ethynyltestosterone or 19-norandrostane) is a progestin. It was the first orally-active progestin.

Ethisterone (brand names Pranone, Progestoral, Lutocylol, Proluton C, many others), also known as 17α-ethinyltestosterone, pregneninolone, or anhydrohydroxyprogesterone, is a steroidal progestin with androgenic activity which is derived from testosterone. It was the second progestogen to be marketed and was both the first orally active progestogen and the first progestin (or synthetic progestogen) to be introduced.Although ethisterone has largely been superseded by newer drugs and is now little used, it continues to be available in some countries.Moreover, the 19-nortestosterone progestins, such as norethisterone, are derived from ethisterone and are widely used as hormonal contraceptives and for other indications.

Ethisterone is described as a relatively weak progestogen, similarly to its analogue dimethisterone.

Androgenic activity

Based on in vitro research, ethisterone and norethisterone are about equipotent in their EC50 values for the androgen receptor (AR), whereas, conversely, norethisterone shows markedly increased potency relative to ethisterone in terms of its EC50 for the progesterone receptor (PR).[8] 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 strong androgenic effects relative to norethisterone and other 19-nortestosterone progestins, and this has limited its clinical use.

Due to its androgenic activity, ethisterone has been associated with the masculinization of female fetuses in women who have taken it during pregnancy.

Estrogenic activity

High dosages of norethisterone and noretynodrel, which are 19-nortestosterone derivatives of ethisterone, were 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 are either not estrogenic or are only weak so.As such, ethisterone does not appear to share the estrogenic activity of norethisterone and noretynodrel.