Mesterolone was first described by 1966[7] and introduced for medical use by 1967.[8][9] In addition to its medical use, mesterolone has been used to improve physique and performance, although it is not commonly used for such purposes due to its weak anabolic effects.[2] The drug is a controlled substance in many countries and so non-medical use is generally illicit.[2][10]
Notes: Men produce about 3 to 11 mg testosterone per day (mean 7 mg/day in young men). Footnotes:a = Never marketed. b = No longer used and/or no longer marketed. Sources: See template.
Like other AAS, mesterolone is an agonist of the androgen receptor (AR).[2] Mesterolone is described as a very poor anabolic agent due to inactivation by 3α-hydroxysteroid dehydrogenase (3α-HSD) in skeletal muscletissue, similarly to DHT and mestanolone (17α-methyl-DHT).[2] In contrast, testosterone is a very poor substrate for 3α-HSD, and so is not similarly inactivated in skeletal muscle.[2] Because of its lack of potentiation by 5α-reductase in "androgenic" tissues and its inactivation by 3α-HSD in skeletal muscle, mesterolone is relatively low in both its androgenicpotency and its anabolic potency.[2] However, it does still show a greater ratio of anabolic activity to androgenic activity relative to testosterone.[2]
Because mesterolone is not 17α-alkylated, it has little or no potential for hepatotoxicity.[2] However, its risk of deleterious effects on the cardiovascular system is comparable to that of several other oral AAS.[2]
Pharmacokinetics
The C1α methyl group of mesterolone inhibits its hepaticmetabolism and thereby confers significant oral activity, although its oral bioavailability is still much lower than that of 17α-alkylated AAS.[2] In any case, mesterolone is one of the few non-17α-alkylated AAS that is active with oral ingestion.[2] Uniquely among AAS, mesterolone has very high affinity for human serum sex hormone-binding globulin (SHBG), about 440% that of DHT in one study and 82% of that of DHT in another study.[17][2][18] As a result, it may displace endogenous testosterone from SHBG and thereby increase free testosterone concentrations, which may in part be involved in its effects.[2]
Mesterolone was developed in the 1960s[22] and was first described by 1966.[7][23][24][25] It was introduced for medical use by Schering under the brand name Proviron by 1967.[8][9] The well-established brand name Proviron had previously been used by Schering for testosterone propionate starting in 1936.[26] Following the introduction of mesterolone as Proviron, Schering continued to market testosterone propionate under the brand name Testoviron.[26] A number of sources incorrectly state that mesterolone was synthesized or introduced for medical use in 1934.[22][2][27][28]
Society and culture
Generic names
Mesterolone is the generic name of the drug and its INNTooltip International Nonproprietary Name, USANTooltip United States Adopted Name, BANTooltip British Approved Name, and DCITTooltip Denominazione Comune Italiana, while mestérolone is its DCFTooltip Dénomination Commune Française.[19][20][29][30]
Brand names
Mesterolone is marketed mainly under the brand name Proviron.[19][20][30][2]
In one small scale clinical trial of depressed patients, an improvement of symptoms which included anxiety, lack of drive and desire was observed.[32] In patients with dysthymia, unipolar, and bipolar depression significant improvement was observed.[32] In this series of studies, mesterolone lead to a significant decrease in luteinizing hormone and testosterone levels.[32] In another study, 100 mg mesterolone cipionate was administered twice monthly.[33] With regards to plasma testosterone levels, there was no difference between the treated versus untreated group, and baseline luteinizing hormone levels were minimally affected.[33]
^ abBehre HM, Wang C, Handelsman DJ, Nieschlag E (2004). "Pharmacology of testosterone preparations". Testosterone. Cambridge University Press. pp. 405–444. doi:10.1017/CBO9780511545221.015. ISBN9780521833806.
^ abTausk M (1968). "Practically Applicable Results of Twenty Years of Research in Endocrinology". Progress in Drug Research / Fortschritte der Arzneimittelforschung / Progrès des recherches pharmaceutiques. Vol. 12. pp. 137–164. doi:10.1007/978-3-0348-7065-8_3. ISBN978-3-0348-7067-2. PMID4307936. {{cite book}}: |journal= ignored (help)
^Corona G, Rastrelli G, Vignozzi L, Maggi M (June 2012). "Emerging medication for the treatment of male hypogonadism". Expert Opinion on Emerging Drugs. 17 (2): 239–259. doi:10.1517/14728214.2012.683411. PMID22612692. S2CID22068249.
^Rastrelli G, Reisman Y, Ferri S, Prontera O, Sforza A, Maggi M, Corona G (2019). "Testosterone Replacement Therapy". Sexual Medicine. Springer. pp. 79–93. doi:10.1007/978-981-13-1226-7_8. ISBN978-981-13-1225-0.
^Saartok T, Dahlberg E, Gustafsson JA (June 1984). "Relative binding affinity of anabolic-androgenic steroids: comparison of the binding to the androgen receptors in skeletal muscle and in prostate, as well as to sex hormone-binding globulin". Endocrinology. 114 (6): 2100–2106. doi:10.1210/endo-114-6-2100. PMID6539197.
^Pugeat MM, Dunn JF, Nisula BC (July 1981). "Transport of steroid hormones: interaction of 70 drugs with testosterone-binding globulin and corticosteroid-binding globulin in human plasma". The Journal of Clinical Endocrinology and Metabolism. 53 (1): 69–75. doi:10.1210/jcem-53-1-69. PMID7195405.
^Brooks JR, Primka RL, Berman C, Krupa DA, Reynolds GF, Rasmusson GH (August 1991). "Topical anti-androgenicity of a new 4-azasteroid in the hamster". Steroids. 56 (8): 428–433. doi:10.1016/0039-128x(91)90031-p. PMID1788861. S2CID21500107.
^Neumann F, Wiechert R, Kramer M, Raspé G (April 1966). "[Experimental animal studies with a new androgen--mesterolone (1-alpha-methyl-5-alpha-androstan-17-beta-ol-one)]". Arzneimittel-Forschung (in German). 16 (4): 455–458. PMID6014248.
^Laschet U, Niermann H, Laschet L, Paarmann HF (1967). "Mesterolone, a potent oral active androgen without gonadotropin inhibition". Acta Endocrinologica. 56 (1_Suppl): S55. doi:10.1530/acta.0.056S055. ISSN0804-4643.
^Tausk M (1968). "Practically Applicable Results of Twenty Years of Research in Endocrinology". Progress in Drug Research / Fortschritte der Arzneimittelforschung / Progrès des recherches pharmaceutiques. Vol. 12. pp. 137–164. doi:10.1007/978-3-0348-7065-8_3. ISBN978-3-0348-7067-2. PMID4307936. {{cite book}}: |journal= ignored (help)
^ abcItil TM, Michael ST, Shapiro DM, Itil KZ (June 1984). "The effects of mesterolone, a male sex hormone in depressed patients (a double blind controlled study)". Methods and Findings in Experimental and Clinical Pharmacology. 6 (6): 331–337. PMID6431212.
^ abKövary PM, Lenau H, Niermann H, Zierden E, Wagner H (May 1977). "Testosterone levels and gonadotrophins in Klinefelter's patients treated with injections of mesterolone cipionate". Archives for Dermatological Research. 258 (3): 289–294. doi:10.1007/bf00561132. PMID883846. S2CID1222130.