mesterolone

Mesterolone is used in the treatment of androgen deficiency in male hypogonadism, anemia, and to support male fertility among other indications.{{cite book| vauthors = Allahbadia GN, Das RB |title=The Art and Science of Assisted Reproductive Techniques|url=https://books.google.com/books?id=_ldpcClfnrgC&pg=PA824|date=12 November 2004|publisher=CRC Press|isbn=978-0-203-64051-7|pages=824–}}{{cite book| vauthors = Becker KL |title=Principles and Practice of Endocrinology and Metabolism|url=https://books.google.com/books?id=FVfzRvaucq8C&pg=PA1186|year=2001|publisher=Lippincott Williams & Wilkins|isbn=978-0-7817-1750-2|pages=1186–}} It has also been used to treat delayed puberty in boys.{{cite book | vauthors = Hart I, Newton RW |title=Endocrinology|url=https://books.google.com/books?id=QbjUBgAAQBAJ&pg=PA119|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-94-010-9298-2|pages=119–}} Because it lacks estrogenic effects, mesterolone may be indicated for treating cases of androgen deficiency in which breast tenderness or gynecomastia is also present.{{cite journal | vauthors = Corona G, Rastrelli G, Vignozzi L, Maggi M | title = Emerging medication for the treatment of male hypogonadism | journal = Expert Opinion on Emerging Drugs | volume = 17 | issue = 2 | pages = 239–259 | date = June 2012 | pmid = 22612692 | doi = 10.1517/14728214.2012.683411 | s2cid = 22068249 }} The drug is described as a relatively weak androgen with partial activity and is rarely used for the purpose of androgen replacement therapy, but is still widely used in medicine.{{cite journal | vauthors = Nieschlag E, Behre HM, Bouchard P, Corrales JJ, Jones TH, Stalla GK, Webb SM, Wu FC | display-authors = 6 | title = Testosterone replacement therapy: current trends and future directions | journal = Human Reproduction Update | volume = 10 | issue = 5 | pages = 409–419 | year = 2004 | pmid = 15297434 | doi = 10.1093/humupd/dmh035 | doi-access = free }}

Mesterolone is used in androgen replacement therapy at a dosage of 50 to 100 mg 2 to 3 times per day.{{cite book| vauthors = Rastrelli G, Reisman Y, Ferri S, Prontera O, Sforza A, Maggi M, Corona G |title=Sexual Medicine|chapter=Testosterone Replacement Therapy|year=2019|pages=79–93|publisher=Springer |doi=10.1007/978-981-13-1226-7_8|isbn=978-981-13-1225-0|doi-access=free}}

{{Androgen replacement therapy formulations and dosages used in men}}

Mesterolone has been used for physique- and performance-enhancing purposes by competitive athletes, bodybuilders, and powerlifters.

{{See also|Anabolic steroid#Adverse effects}}

Side effects of mesterolone include virilization among others.

Like other AAS, mesterolone is an agonist of the androgen receptor (AR). Mesterolone is described as a very poor anabolic agent due to inactivation by 3α-hydroxysteroid dehydrogenase (3α-HSD) in skeletal muscle tissue, similarly to DHT and mestanolone (17α-methyl-DHT). In contrast, testosterone is a very poor substrate for 3α-HSD, and so is not similarly inactivated in skeletal muscle. 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 androgenic potency and its anabolic potency. However, it does still show a greater ratio of anabolic activity to androgenic activity relative to testosterone.

Mesterolone is not a substrate for 5α-reductase, as it is already 5α-reduced, and hence is not potentiated in so-called "androgenic" tissues such as the skin, hair follicles, and prostate gland.

Mesterolone is not a substrate for aromatase, and so cannot be converted into an estrogen. As such, it has no propensity for producing estrogenic side effects such as gynecomastia and fluid retention. It also has no progestogenic activity.

Because mesterolone is not 17α-alkylated, it has little or no potential for hepatotoxicity. However, its risk of deleterious effects on the cardiovascular system is comparable to that of several other oral AAS.

The C1α methyl group of mesterolone inhibits its hepatic metabolism and thereby confers significant oral activity, although its oral bioavailability is still much lower than that of 17α-alkylated AAS. In any case, mesterolone is one of the few non-17α-alkylated AAS that is active with oral ingestion. 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.{{cite journal | vauthors = Saartok T, Dahlberg E, Gustafsson JA | title = 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 | journal = Endocrinology | volume = 114 | issue = 6 | pages = 2100–2106 | date = June 1984 | pmid = 6539197 | doi = 10.1210/endo-114-6-2100 }}{{cite journal | vauthors = Pugeat MM, Dunn JF, Nisula BC | title = Transport of steroid hormones: interaction of 70 drugs with testosterone-binding globulin and corticosteroid-binding globulin in human plasma | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 53 | issue = 1 | pages = 69–75 | date = July 1981 | pmid = 7195405 | doi = 10.1210/jcem-53-1-69 }} 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.

{{See also|List of androgens/anabolic steroids}}

Mesterolone, also known as 1α-methyl-4,5α-dihydrotestosterone (1α-methyl-DHT) or as 1α-methyl-5α-androstan-17β-ol-3-one, is a synthetic androstane steroid and derivative of DHT.{{cite book| vauthors = Elks J |title=The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies|url=https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA775|date=14 November 2014|publisher=Springer|isbn=978-1-4757-2085-3|pages=775–}}{{cite book|title=Index Nominum 2000: International Drug Directory|url=https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA656|year=2000|publisher=Taylor & Francis|isbn=978-3-88763-075-1|pages=656–}} It is specifically DHT with a methyl group at the C1α position. Closely related AAS include metenolone and its esters metenolone acetate and metenolone enanthate. The antiandrogen rosterolone (17α-propylmesterolone) is also closely related to mesterolone.{{cite journal | vauthors = Brooks JR, Primka RL, Berman C, Krupa DA, Reynolds GF, Rasmusson GH | title = Topical anti-androgenicity of a new 4-azasteroid in the hamster | journal = Steroids | volume = 56 | issue = 8 | pages = 428–433 | date = August 1991 | pmid = 1788861 | doi = 10.1016/0039-128x(91)90031-p | s2cid = 21500107 }}

Mesterolone was developed in the 1960s{{cite book| vauthors = Carruthers M |title=Androgen Deficiency in the Adult Male: Causes, Diagnosis and Treatment|url=https://books.google.com/books?id=YFYgyAEACAAJ|year=2006|publisher=CRC Press|isbn=978-0-367-80018-5|pages=137–178}} and was first described by 1966.{{cite book| vauthors = Behre HM, Wang C, Handelsman DJ, Nieschlag E |title=Testosterone|chapter=Pharmacology of testosterone preparations|year=2004|pages=405–444|publisher=Cambridge University Press |doi=10.1017/CBO9780511545221.015|isbn=9780521833806}}{{cite journal | vauthors = Neumann F, Wiechert R, Kramer M, Raspé G | title = [Experimental animal studies with a new androgen--mesterolone (1-alpha-methyl-5-alpha-androstan-17-beta-ol-one)] | language = de | journal = Arzneimittel-Forschung | volume = 16 | issue = 4 | pages = 455–458 | date = April 1966 | pmid = 6014248 }}{{cite journal| vauthors = Laschet U, Niermann H, Laschet L, Paarmann HF |title=Mesterolone, a potent oral active androgen without gonadotropin inhibition|journal=Acta Endocrinologica|volume=56|issue=1_Suppl|year=1967|pages=S55|issn=0804-4643|doi=10.1530/acta.0.056S055}}{{cite book | vauthors = Tausk M | chapter = Practically Applicable Results of Twenty Years of Research in Endocrinology | title = Progress in Drug Research / Fortschritte der Arzneimittelforschung / Progrès des recherches pharmaceutiques | journal = Progress in Drug Research. Fortschritte der Arzneimittelforschung. Progres des Recherches Pharmaceutiques | volume = 12 | pages = 137–164 | date = 1968 | pmid = 4307936 | doi = 10.1007/978-3-0348-7065-8_3 | isbn = 978-3-0348-7067-2 }} It was introduced for medical use by Schering under the brand name Proviron by 1967. The well-established brand name Proviron had previously been used by Schering for testosterone propionate starting in 1936.{{cite book| vauthors = Nieschlag E, Nieschlag S |title=Testosterone|chapter=The History of Testosterone and The Testes: From Antiquity to Modern Times|year=2017|pages=1–19|publisher=Springer |doi=10.1007/978-3-319-46086-4_1|isbn=978-3-319-46084-0|doi-access=free}} Following the introduction of mesterolone as Proviron, Schering continued to market testosterone propionate under the brand name Testoviron. A number of sources incorrectly state that mesterolone was synthesized or introduced for medical use in 1934.{{cite book| vauthors = Hohl A |title=Testosterone: From Basic to Clinical Aspects|url=https://books.google.com/books?id=Et6TDgAAQBAJ&pg=PA204|date=6 April 2017|publisher=Springer|isbn=978-3-319-46086-4|pages=204–}}{{cite book| vauthors = Kalinchenko S, Tyuzikov I, Mskhalaya G, Tishova Y |title=Testosterone|chapter=Testosterone Therapy: Oral Androgens|year=2017|pages=203–224|publisher=Springer |doi=10.1007/978-3-319-46086-4_10|isbn=978-3-319-46084-0|doi-access=free}}

Mesterolone is the generic name of the drug and its {{abbrlink|INN|International Nonproprietary Name}}, {{abbrlink|USAN|United States Adopted Name}}, {{abbrlink|BAN|British Approved Name}}, and {{abbrlink|DCIT|Denominazione Comune Italiana}}, while mestérolone is its {{abbrlink|DCF|Dénomination Commune Française}}.{{cite book| vauthors = Morton IK, Hall JM |title=Concise Dictionary of Pharmacological Agents: Properties and Synonyms|url=https://books.google.com/books?id=tsjrCAAAQBAJ&pg=PA177|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-94-011-4439-1|pages=176–177}}{{Cite web|url=https://www.drugs.com/international/mesterolone.html|title = Mesterolone}}

Mesterolone is marketed mainly under the brand name Proviron.

Mesterolone is available widely throughout the world, including in the United Kingdom, Australia, and South Africa, as well as many non-English-speaking countries. It is not available in the United States, Canada, or New Zealand. The drug has never been marketed in the United States.

Mesterolone, along with other AAS, is a schedule III controlled substance in the United States under the Controlled Substances Act and a schedule IV controlled substance in Canada under the Controlled Drugs and Substances Act.{{cite book|vauthors = Karch SB|title=Drug Abuse Handbook, Second Edition|url=https://books.google.com/books?id=ZjrMBQAAQBAJ&pg=PA30|date=21 December 2006|publisher=CRC Press|isbn=978-1-4200-0346-8|pages=30–}}{{cite book| vauthors = Lilley LL, Snyder JS, Collins SR |title=Pharmacology for Canadian Health Care Practice|url=https://books.google.com/books?id=dNgoDwAAQBAJ&pg=PA50|date=5 August 2016|publisher=Elsevier Health Sciences|isbn=978-1-77172-066-3|pages=50–}}

In one small scale clinical trial of depressed patients, an improvement of symptoms which included anxiety, lack of drive and desire was observed.{{cite journal | vauthors = Itil TM, Michael ST, Shapiro DM, Itil KZ | title = The effects of mesterolone, a male sex hormone in depressed patients (a double blind controlled study) | journal = Methods and Findings in Experimental and Clinical Pharmacology | volume = 6 | issue = 6 | pages = 331–337 | date = June 1984 | pmid = 6431212 }} In patients with dysthymia, unipolar, and bipolar depression significant improvement was observed. In this series of studies, mesterolone lead to a significant decrease in luteinizing hormone and testosterone levels. In another study, 100 mg mesterolone cipionate was administered twice monthly.{{cite journal | vauthors = Kövary PM, Lenau H, Niermann H, Zierden E, Wagner H | title = Testosterone levels and gonadotrophins in Klinefelter's patients treated with injections of mesterolone cipionate | journal = Archives for Dermatological Research | volume = 258 | issue = 3 | pages = 289–294 | date = May 1977 | pmid = 883846 | doi = 10.1007/bf00561132 | s2cid = 1222130 }} With regards to plasma testosterone levels, there was no difference between the treated versus untreated group, and baseline luteinizing hormone levels were minimally affected.

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• {{cite book | vauthors = Morrison MC |title=Hormones, Gender and the Aging Brain: The Endocrine Basis of Geriatric Psychiatry |publisher=Cambridge University Press |location=Cambridge, UK |year=2000 |page=134 |isbn=0-521-65304-5 |url=https://books.google.com/books?id=I7QsN6hx8IQC}}

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• [https://anabolic.org/proviron-mesterolone/ Proviron (mesterolone) - William Llewellyn's Anabolic.org] {{Webarchive|url=https://web.archive.org/web/20160923141415/http://anabolic.org/proviron-mesterolone/ |date=2016-09-23 }}.

{{Androgens and antiandrogens}}

{{Androgen receptor modulators}}

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Category:Anabolic–androgenic steroids

Category:Androstanes

Category:Ketones