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| Other names | SKF-7690; FC-612; 17α-Methyl-B-nortestosterone; 17α-Methyl-B-norandrost-4-en-17β-ol-3-one |
| Routes of administration | By mouth,topical[1] |
| Drug class | Steroidal antiandrogen |
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| Chemical and physical data | |
| Formula | C19H28O2 |
| Molar mass | 288.431 g·mol−1 |
| 3D model (JSmol) | |
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Benorterone, also known by its developmental code nameSKF-7690 and as17α-methyl-B-nortestosterone, is asteroidal antiandrogen which was studied for potential medical use but was never marketed.[2][3] It was the first known antiandrogen to be studied in humans.[1] It is takenby mouth or byapplication to skin.[1]
Benorterone is anantiandrogen, or anantagonist of theandrogen receptor (AR), thebiological target of theandrogensex hormonestestosterone anddihydrotestosterone.[3] In one study, theaffinity of benorterone for the AR was found to be about 5-fold greater than that ofcyproterone acetate in ratprostatecytosol; the Ki values were 0.7 nM for benorterone and 3.7 nM for cyproterone acetate, which were 243% and 46% of those of testosterone (Ki = 1.7 nM), respectively.[4][5] However, another study found that benorterone had only 11% of the affinity of dihydrotestosterone for the androgen receptor.[4] Although an antiandrogen, benorterone actually is a very weakpartial agonist of the AR and has been reported to possess weakandrogenic activity.[6] The same is true for cyproterone acetate and other steroidal antiandrogens.[7][8]
Unlike certain other steroidal antiandrogens such as cyproterone acetate, benorterone is not also aprogestogen, instead being described as aselective and pure AR antagonist similarly tononsteroidal antiandrogens such asflutamide andbicalutamide.[9][3] However, although it is described as not being a progestogen, benorterone was found to produce "a highly variable decrease in plasma testosterone levels," indicating that it has weakantigonadotropic effects.[3][10] The reasons for this are unclear, as other pure antiandrogens such ascyproterone (not cyproterone acetate) and flutamide do not do this and instead produce consistent increases in testosterone levels.[11] However, it is notable that theanabolic steroidmethyltestosterone, which benorterone differs from inchemical structure only by the removal of acarbonatom in the B ring, isaromatized into theestrogenmethylestradiol and haspotentestrogenic activity.[12] Estrogens are antigonadotropic similarly to androgens and progestogens and are likewise able to suppress testosterone levels.[13] In accordance, the compound corresponding to what would be the aromatized form of benorterone, 17α-methyl-B-norestradiol, has been described and has been reported to possess estrogenic activity, although the aromatization of benorterone has not been assessed.[14]
A couple of studies found thatprothrombin levels decreased by 50% in some patients treated with benorterone, although a causal relationship between this change and benorterone could not be shown.[3]
Benorterone is activeorally andtopically and has been studied by both of theseroutes of administration.[1]
Benorterone, also known as 17α-methyl-B-nortestosterone or as 17α-methyl-B-norandrost-4-en-17β-ol-3-one, is asyntheticandrostanesteroid and aderivative oftestosterone.[2] Specifically, it is the C17αmethyl andB-noranalogue of testosterone and theB-nor analogue ofmethyltestosterone.[2] Other testosterone-derived steroidal antiandrogens includeabiraterone acetate,BOMT,delanterone,dienogest,galeterone,metogest,mifepristone,oxendolone,rosterolone,topterone,trimethyltrienolone, andzanoterone, whileprogesterone-derived steroidal antiandrogens include examples likecyproterone andcyproterone acetate.[2]
Benorterone was developed in the late 1950s, was first reported to possess antiandrogenic activity in 1964, and was investigated inclinical trials in the mid-to-late 1960s.[2][1][6] It was the first known antiandrogen to be studied in humans.[1] The drug was found to be effective in the treatment ofacne,seborrhea, andhirsutism in women.[3][15][16] In addition, unlike progestogenic antiandrogens such as cyproterone acetate, it seldom producedside effects in women and did not affectmenstruation.[3] However, in males, benorterone was not effective for acne, and produced high rates ofgynecomastia (in 12 out of 13 or 92% of young men treated with 75 to 300 mg/day benorterone).[17][18][19] Shortly following the observance of this side effect, it was withdrawn from clinical studies.[3][1] Subsequently, cyproterone acetate, which has a greatly reduced risk of gynecomastia by virtue of its concomitant progestogenic and antigonadotropic actions (which results in suppression of estrogen levels), was developed instead and was introduced for medical use in 1973.[20] In addition, spironolactone, a steroidalantimineralocorticoid that was introduced for medical use in 1959, was discovered to possess potent antiandrogenic activity in 1969, and became widely used clinically as an antiandrogen after its first use in an androgen-dependent condition in 1978.[21][22][23]
Benorterone is thegeneric name of the drug and itsINNTooltip International Nonproprietary Name andUSANTooltip United States Adopted Name.[2] It is also known by its developmental code namesSKF-7690 andFC-612.[2]
Limited clinical experience also exists with benorterone, the first anti-androgen tried in man, and with free cyproterone. In the late sixties benorterone was reported to give promising results in 93 androgenized women but was soon withdrawn from clinical trial, mainly because of the development of gynaecomastia in the male. As a big advantage compared with CPA, it was found to be effective not only orally but also topically. Free cyproterone, on the other hand, proved to be without clinical value for reasons that cannot be discussed here. Thus we are left with CPA as the only anti-androgen that is already on the market in several countries.
