Trestolone was first described in 1963.[7] Subsequently, it was not studied again until 1990.[8] Development of trestolone for potential clinical use started by 1993 and continued thereafter.[4][9] No additional development appears to have been conducted since 2013.[3] The medication was developed by thePopulation Council, anon-profit,non-governmental organization dedicated toreproductive health.[3][10]
Spermatozoa are produced in thetestes of males in a process calledspermatogenesis. In order to render a man infertile, a hormone-based male contraceptive method must stop spermatogenesis by interrupting the release ofgonadotropins from thepituitary gland. Even in low concentrations, trestolone is a potent inhibitor of the release of the gonadotropins,luteinizing hormone (LH) andfollicle stimulating hormone (FSH).[4][3] In order for spermatogenesis to occur in the testes, both FSH and testosterone must be present. By inhibiting release of FSH, trestolone creates an endocrine environment in which conditions for spermatogenesis are not ideal.[4][3] Manufacture of sperm is further impaired by the suppression of LH, which in turn drastically curtails the production of testosterone.[4][3] Sufficient regular doses of trestolone cause severeoligozoospermia orazoospermia, and therefore infertility, in most men.[4][3] Trestolone-induced infertility has been found to be quickly reversible upon discontinuation.[4][3]
When LH release is inhibited, the amount of testosterone made in the testes declines dramatically.[4][3] As a result of trestolone's gonadotropin-suppressing qualities, levels of serum testosterone fall sharply in men treated with sufficient amounts of the medication.[4][3] Testosterone is the main hormone responsible for maintenance of malesecondary sex characteristics. Normally, an inadequate testosterone level causes undesirable effects such asfatigue, loss ofskeletal muscle mass, reducedlibido, and weight gain. However, the androgenic and anabolic properties of trestolone largely ameliorate thisproblem[4][3] —essentially, trestolone replaces testosterone's role as the primary male hormone in the body.[4][3]
Trestolone, also known as 7α-methyl-19-nortestosterone (MENT) or as 7α-methylestr-4-en-17β-ol-3-one, is asyntheticestranesteroid and aderivative ofnandrolone (19-nortestosterone).[1] It is a modification of nandrolone with amethyl group at the C7α position.[1] Closely related AAS include7α-methyl-19-norandrostenedione (MENT dione, trestione) (anandrogen prohormone of trestolone) anddimethandrolone (7α,11β-dimethyl-19-nortestosterone) (the C11β methylated derivative of trestolone), as well asmibolerone (7α,17α-dimethyl-19-nortestosterone) anddimethyltrienolone (7α,17α-dimethyl-δ9,11-19-nortestosterone).[1] Theprogestintibolone (7α-methyl-17α-ethynyl-δ5(10)-19-nortestosterone) is also closely related to trestolone.[1]
The chemical synthesis of trestolone is reported:[21][22][23]
Trestolone is an intermediate used in the synthesis of mibolerone, tibolone & isotibolone. If it is oxidized tomentabolan, this in-turn can be used to synthesizealmestrone, a compound with manifold steroid synthesis applications.
Trestolone is thegeneric name of the drug and itsINNTooltip International Nonproprietary Name.[1] It is also commonly known as7α-methyl-19-nortestosterone (MENT).[1][2][3]
^abLyster SC, Duncan GW (July 1963). "Anabolic, androgenic and myotropic activities of derivatives of 7alpha-methyl-19-nortestosterone".Acta Endocrinol.43 (3):399–411.doi:10.1530/acta.0.0430399.PMID13931986.
^abMa JB, Li ZS (1990). "[Synthesis of 4-substituted 17 beta-hydroxy-7 alpha-methyl-4-estren-3-one and their 17-acetates as antifertility compounds]".Yao Xue Xue Bao (in Chinese).25 (1):18–23.PMID2363352.
^abAttardi BJ, Hild SA, Reel JR (June 2006)."Dimethandrolone undecanoate: a new potent orally active androgen with progestational activity".Endocrinology.147 (6):3016–26.doi:10.1210/en.2005-1524.PMID16497801.The pharmacokinetic properties of MENT make it unsuitable for once-daily oral treatment or long-term injection; thus, administration by sc implant or by patch or gel is required (27). MENT showed a more rapid metabolic clearance rate than T in men and monkeys, probably due in part to its failure to bind SHBG (28). In monkeys, MENT acetate in subdermal implants was 10 times as potent as T in suppression of gonadotropin secretion and anabolic effects, but was only twice as potent in stimulating prostate growth (29).
^J. Stoelwinder, M. Ostendorf, & Van P.A.M. Buggenum, WO2003059931 (to Akzo Nobel NV).
^Marc Willuhn, et al. US20040010138 (to Bayer Pharma AG).
^Joyce F. Grunwell & Harvey D. Benson, US4000273 (1976 to Richardson Vicks Inc).
^Kumar N, Didolkar AK, Ladd A, Thau R, Monder C, Bardin CW, Sundaram K (November 1990). "Radioimmunoassay of 7 alpha-methyl-19-nortestosterone and investigation of its pharmacokinetics in animals".J. Steroid Biochem. Mol. Biol.37 (4):587–91.doi:10.1016/0960-0760(90)90405-a.PMID2278844.S2CID37597215.
