Chemical compound
Pharmaceutical compound
Trestolone Clinical data Other names MENT; MENTR; RU-27333; 7α-Methylnandrolone; 7α-Methyl-19-nortestosterone; 7α-Methylestr-4-en-17β-ol-3-one Routes of Subcutaneous implant ,intramuscular injection (astrestolone acetate )Drug class Androgen ;Anabolic steroid ;Progestogen ;Antigonadotropin ATC code Identifiers (7R ,8R ,9S ,10R ,13S ,14S ,17S )-17-hydroxy-7,13-dimethyl-2,6,7,8,9,10,11,12,14,15,16,17-dodecahydro-1H -cyclopenta[a ]phenanthren-3-one
CAS Number PubChem CID DrugBank ChemSpider UNII CompTox Dashboard (EPA) ECHA InfoCard 100.184.887 Chemical and physical data Formula C 19 H 28 O 2 Molar mass −1 3D model (JSmol ) InChI=1S/C19H28O2/c1-11-9-12-10-13(20)3-4-14(12)15-7-8-19(2)16(18(11)15)5-6-17(19)21/h10-11,14-18,21H,3-9H2,1-2H3/t11-,14+,15-,16+,17+,18-,19+/m1/s1
N Key:YSGQGNQWBLYHPE-CFUSNLFHSA-N
N (verify)
Trestolone , also known as7α-methyl-19-nortestosterone (MENT ), is anexperimental androgen /anabolic steroid (AAS) andprogestogen medication which has been under development for potential use as a form ofhormonal birth control for men and inandrogen replacement therapy forlow testosterone levels in men but has never been marketed for medical use.[ 1] [ 2] [ 3] [ 4] [ 5] implant that is placed into fat .[ 3] trestolone acetate , anandrogen ester andprodrug of trestolone, the medication can also be given byinjection into muscle .[ 1] [ 5]
Side effects Trestolone is an AAS, and hence is anagonist of theandrogen receptor , thebiological target of androgens liketestosterone .[ 3] [ 6] progestin , or asynthetic progestogen, and hence is an agonist of theprogesterone receptor , the biological target of progestogens likeprogesterone .[ 3] [ 6] antigonadotropic effects.[ 3] [ 6] sperm production and are responsible for thecontraceptive effects of trestolone in men.[ 3]
Trestolone was first described in 1963.[ 7] [ 8] [ 4] [ 9] [ 3] Population Council , anon-profit ,non-governmental organization dedicated toreproductive health .[ 3] [ 10]
Trestolone is an experimental medication and is not currently approved for medical use.[ 2] [ 3] male hormonal contraceptive and inandrogen replacement therapy forlow testosterone levels .[ 2] [ 3] [ 4] [ 9] [ 5] subcutaneous implant .[ 3] androgen ester andprodrug of trestolone,trestolone acetate , has also been developed, for use viaintramuscular injection .[ 1] [ 5]
Trestolone may causesexual dysfunction (e.g.,decreased sex drive ,reduced erectile function ) and decreasedbone mineral density due toestrogen deficiency .[ 5] [ 3] [ 11]
As an AAS, trestolone is anagonist of theandrogen receptor (AR), similarly toandrogens liketestosterone anddihydrotestosterone (DHT).[ 4] [ 3] substrate for5α-reductase and hence is not potentiated or inactivated in so-called "androgenic"tissues like theskin ,hair follicles , andprostate gland .[ 12] anabolic toandrogenic activity, similarly to other nandrolone derivatives.[ 4] [ 3] aromatase and hence produces theestrogen 7α-methylestradiol as ametabolite .[ 6] [ 13] estrogenic activity and an amount that would appear to be insufficient for replacement purposes, as evidenced by decreasedbone mineral density in men treated with it for hypogonadism.[ 5] [ 3] potent progestogenic activity.[ 6] [ 3] antigonadotropic activity.[ 6] [ 3]
Relative affinities (%) of trestolone and related steroids[ 14] [ 15] [ 16] [ 17] [ 18] Compound PR Tooltip Progesterone receptor AR Tooltip Androgen receptor ER Tooltip Estrogen receptor GR Tooltip Glucocorticoid receptor MR Tooltip Mineralocorticoid receptor SHBG Tooltip Sex hormone-binding globulin CBG Tooltip Corticosteroid binding globulin Nandrolone 20 154–155 <0.1 0.5 1.6 1 ? Trestolone 50–75 100–125 ? <1 ? ? ? 7α-Methylestradiol 1–3 15–25 101 <1 <1 ? ? Values are percentages (%). Referenceligands (100%) wereprogesterone for thePR Tooltip progesterone receptor ,testosterone for theAR Tooltip androgen receptor ,E2 for theER Tooltip estrogen receptor ,DEXA Tooltip dexamethasone for theGR Tooltip glucocorticoid receptor ,aldosterone for theMR Tooltip mineralocorticoid receptor ,DHT Tooltip dihydrotestosterone forSHBG Tooltip sex hormone-binding globulin , andcortisol forCBG Tooltip Corticosteroid-binding globulin .
Mechanism of action [ edit ] 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] [ 4] [ 3] [ 4] [ 3] oligozoospermia orazoospermia , and therefore infertility, in most men.[ 4] [ 3] [ 4] [ 3]
When LH release is inhibited, the amount of testosterone made in the testes declines dramatically.[ 4] [ 3] [ 4] [ 3] secondary 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]
Thepharmacokinetic properties of trestolone, such as poor oralbioavailability and shortelimination half-life , make it unsuitable fororal administration or long-termintramuscular injection .[ 19] [ 20] parenterally via a different and more practical route such assubcutaneous implant ,transdermal patch , ortopical gel .[ 19] Trestolone acetate , aprodrug of trestolone, can be administered viaintramuscular injection .[ 5]
Trestolone, also known as 7α-methyl-19-nortestosterone (MENT) or as 7α-methylestr-4-en-17β-ol-3-one, is asynthetic estrane steroid and aderivative ofnandrolone (19-nortestosterone).[ 1] methyl group at the C7α position.[ 1] 7α-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] progestin tibolone (7α-methyl-17α-ethynyl-δ5(10) -19-nortestosterone) is also closely related to trestolone.[ 1]
Trestolone was first described in 1963.[ 7] [ 8] [ 21] male hormonal contraception andandrogen replacement therapy was started by 1993, and continued thereafter.[ 4] [ 9] [ 3] [ 3] Population Council , anon-profit ,non-governmental organization dedicated toreproductive health ..[ 3] [ 10]
Society and culture [ edit ] Trestolone is thegeneric name of the drug and itsINN Tooltip International Nonproprietary Name .[ 1] 7α-methyl-19-nortestosterone (MENT ).[ 1] [ 2] [ 3]
^a b c d e f g h i J. Elks (14 November 2014).The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies ISBN 978-1-4757-2085-3 ^a b c d "7-alpha-methyl-19-nortestosterone - AdisInsight" .^a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab ac ad Nieschlag E, Kumar N, Sitruk-Ware R (2013). "7α-methyl-19-nortestosterone (MENTR): the population council's contribution to research on male contraception and treatment of hypogonadism".Contraception .87 (3):288– 95.doi :10.1016/j.contraception.2012.08.036 .PMID 23063338 . ^a b c d e f g h i j k l m n o Sundaram K, Kumar N, Bardin CW (April 1993). "7 alpha-methyl-nortestosterone (MENT): the optimal androgen for male contraception".Ann. Med .25 (2):199– 205.doi :10.3109/07853899309164168 .PMID 8489761 . ^a b c d e f g Corona G, Rastrelli G, Vignozzi L, Maggi M (2012). "Emerging medication for the treatment of male hypogonadism".Expert Opin Emerg Drugs .17 (2):239– 59.doi :10.1517/14728214.2012.683411 .PMID 22612692 .S2CID 22068249 . ^a b c d e f García-Becerra R, Ordaz-Rosado D, Noé G, Chávez B, Cooney AJ, Larrea F (2012)."Comparison of 7α-methyl-19-nortestosterone effectiveness alone or combined with progestins on androgen receptor mediated-transactivation" .Reproduction .143 (2):211– 9.doi :10.1530/REP-11-0171 PMID 22065861 . ^a b Lyster 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 .PMID 13931986 . ^a b Ma 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.PMID 2363352 . ^a b c Sundaram K, Kumar N, Bardin CW (1994). "7 alpha-Methyl-19-nortestosterone: an ideal androgen for replacement therapy".Recent Prog. Horm. Res .49 :373– 6.doi :10.1016/b978-0-12-571149-4.50027-1 .ISBN 9780125711494 PMID 8146434 . ^a b MENT – project information from the Population Council^ Anderson RA, Wallace AM, Sattar N, Kumar N, Sundaram K (June 2003)."Evidence for tissue selectivity of the synthetic androgen 7 alpha-methyl-19-nortestosterone in hypogonadal men" .J. Clin. Endocrinol. Metab .88 (6):2784– 93.doi :10.1210/jc.2002-021960 PMID 12788888 . ^ Attardi BJ, Hild SA, Koduri S, Pham T, Pessaint L, Engbring J, Till B, Gropp D, Semon A, Reel JR (October 2010)."The potent synthetic androgens, dimethandrolone (7α,11β-dimethyl-19-nortestosterone) and 11β-methyl-19-nortestosterone, do not require 5α-reduction to exert their maximal androgenic effects" .The Journal of Steroid Biochemistry and Molecular Biology .122 (4):212– 8.doi :10.1016/j.jsbmb.2010.06.009 .PMC 2949447 PMID 20599615 . ^ Attardi BJ, Pham TC, Radler LC, Burgenson J, Hild SA, Reel JR (June 2008)."Dimethandrolone (7,11β-dimethyl-19-nortestosterone) and 11β-methyl-19-nortestosterone are not converted to aromatic A-ring products in the presence of recombinant human aromatase" .The Journal of Steroid Biochemistry and Molecular Biology .110 (3– 5):214– 22.doi :10.1016/j.jsbmb.2007.11.009 .PMC 2575079 PMID 18555683 . ^ Ojasoo T, Delettré J, Mornon JP, Turpin-VanDycke C, Raynaud JP (1987). "Towards the mapping of the progesterone and androgen receptors".J. Steroid Biochem .27 (1– 3):255– 69.doi :10.1016/0022-4731(87)90317-7 .PMID 3695484 . ^ Delettré J, Mornon JP, Lepicard G, Ojasoo T, Raynaud JP (January 1980). "Steroid flexibility and receptor specificity".J. Steroid Biochem .13 (1):45– 59.doi :10.1016/0022-4731(80)90112-0 .PMID 7382482 . ^ Raynaud JP, Bouton MM, Moguilewsky M, Ojasoo T, Philibert D, Beck G, Labrie F, Mornon JP (January 1980). "Steroid hormone receptors and pharmacology".J. Steroid Biochem .12 :143– 57.doi :10.1016/0022-4731(80)90264-2 .PMID 7421203 . ^ Ojasoo T, Raynaud JP, Doé JC (January 1994). "Affiliations among steroid receptors as revealed by multivariate analysis of steroid binding data".J. Steroid Biochem. Mol. Biol .48 (1):31– 46.doi :10.1016/0960-0760(94)90248-8 .PMID 8136304 .S2CID 21336380 . ^ Raynaud J, Ojasoo T, Bouton M, Philibert D (1979)."Receptor Binding as a Tool in the Development of New Bioactive Steroids" .Drug Design: Medicinal Chemistry: A Series of Monographs 169–214 .doi :10.1016/B978-0-12-060308-4.50010-X .ISBN 9780120603084 ^a b Attardi 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 PMID 16497801 .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). ^ Suvisaari J, Sundaram K, Noé G, Kumar N, Aguillaume C, Tsong YY, Lähteenmäki P, Bardin CW (May 1997)."Pharmacokinetics and pharmacodynamics of 7alpha-methyl-19-nortestosterone after intramuscular administration in healthy men" .Hum. Reprod .12 (5):967– 73.doi :10.1093/humrep/12.5.967 PMID 9194649 . ^ 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 .PMID 2278844 .S2CID 37597215 .
ER Tooltip Estrogen receptor
Agonists Steroidal: 2-Hydroxyestradiol 2-Hydroxyestrone 3-Methyl-19-methyleneandrosta-3,5-dien-17β-ol 3α-Androstanediol 3α,5α-Dihydrolevonorgestrel 3β,5α-Dihydrolevonorgestrel 3α-Hydroxytibolone 3β-Hydroxytibolone 3β-Androstanediol 4-Androstenediol 4-Androstenedione 4-Fluoroestradiol 4-Hydroxyestradiol 4-Hydroxyestrone 4-Methoxyestradiol 4-Methoxyestrone 5-Androstenediol 7-Oxo-DHEA 7α-Hydroxy-DHEA 7α-Methylestradiol 7β-Hydroxyepiandrosterone 8,9-Dehydroestradiol 8,9-Dehydroestrone 8β-VE2 10β,17β-Dihydroxyestra-1,4-dien-3-one (DHED) 11β-Chloromethylestradiol 11β-Methoxyestradiol 15α-Hydroxyestradiol 16-Ketoestradiol 16-Ketoestrone 16α-Fluoroestradiol 16α-Hydroxy-DHEA 16α-Hydroxyestrone 16α-Iodoestradiol 16α-LE2 16β-Hydroxyestrone 16β,17α-Epiestriol (16β-hydroxy-17α-estradiol) 17α-Estradiol (alfatradiol )17α-Dihydroequilenin 17α-Dihydroequilin 17α-Epiestriol (16α-hydroxy-17α-estradiol) 17α-Ethynyl-3α-androstanediol 17α-Ethynyl-3β-androstanediol 17β-Dihydroequilenin 17β-Dihydroequilin 17β-Methyl-17α-dihydroequilenin Abiraterone Abiraterone acetate Alestramustine Almestrone Anabolic steroids (e.g.,testosterone andesters ,methyltestosterone ,metandienone (methandrostenolone) ,nandrolone andesters , many others; via estrogenic metabolites)Atrimustine Bolandiol Bolandiol dipropionate Butolame Clomestrone Cloxestradiol Conjugated estriol Conjugated estrogens Cyclodiol Cyclotriol DHEA DHEA-S ent -EstradiolEpiestriol (16β-epiestriol, 16β-hydroxy-17β-estradiol) Epimestrol Equilenin Equilin ERA-63 (ORG-37663) Esterified estrogens Estetrol Estradiol Estramustine Estramustine phosphate Estrapronicate Estrazinol Estriol Estrofurate Estrogenic substances Estromustine Estrone Etamestrol (eptamestrol) Ethinylandrostenediol Ethinylestradiol Ethinylestriol Ethylestradiol Etynodiol Etynodiol diacetate Hexolame Hippulin Hydroxyestrone diacetate Lynestrenol Lynestrenol phenylpropionate Mestranol Methylestradiol Moxestrol Mytatrienediol Nilestriol Norethisterone Noretynodrel Orestrate Pentolame Prodiame Prolame Promestriene RU-16117 Quinestradol Quinestrol Tibolone Xenoestrogens: Anise -related (e.g.,anethole ,anol ,dianethole ,dianol ,photoanethole )Chalconoids (e.g.,isoliquiritigenin ,phloretin ,phlorizin (phloridzin) ,wedelolactone )Coumestans (e.g.,coumestrol ,psoralidin )Flavonoids (incl.7,8-DHF ,8-prenylnaringenin ,apigenin ,baicalein ,baicalin ,biochanin A ,calycosin ,catechin ,daidzein ,daidzin ,ECG ,EGCG ,epicatechin ,equol ,formononetin ,glabrene ,glabridin ,genistein ,genistin ,glycitein ,kaempferol ,liquiritigenin ,mirificin ,myricetin ,naringenin ,penduletin ,pinocembrin ,prunetin ,puerarin ,quercetin ,tectoridin ,tectorigenin )Lavender oil Lignans (e.g.,enterodiol ,enterolactone ,nyasol (cis -hinokiresinol) )Metalloestrogens (e.g.,cadmium )Pesticides (e.g.,alternariol ,dieldrin ,endosulfan ,fenarimol ,HPTE ,methiocarb ,methoxychlor ,triclocarban ,triclosan )Phytosteroids (e.g.,digitoxin (digitalis ),diosgenin ,guggulsterone )Phytosterols (e.g.,β-sitosterol ,campesterol ,stigmasterol )Resorcylic acid lactones (e.g.,zearalanone ,α-zearalenol ,β-zearalenol ,zearalenone ,zeranol (α-zearalanol) ,taleranol (teranol, β-zearalanol) )Steroid -like (e.g.,deoxymiroestrol ,miroestrol )Stilbenoids (e.g.,resveratrol ,rhaponticin )Synthetic xenoestrogens (e.g.,alkylphenols ,bisphenols (e.g.,BPA ,BPF ,BPS ),DDT ,parabens ,PBBs ,PHBA ,phthalates ,PCBs )Others (e.g.,agnuside ,rotundifuran ) MixedSERMs Tooltip Selective estrogen receptor modulators ) Antagonists Coregulator-binding modulators: ERX-11
GPER Tooltip G protein-coupled estrogen receptor
Agonists Antagonists Unknown
PR Tooltip Progesterone receptor
Agonists Testosterone derivatives: Progestins:6,6-Difluoronorethisterone 6,6-Difluoronorethisterone acetate 17α-Allyl-19-nortestosterone Allylestrenol Altrenogest Chloroethynylnorgestrel Cingestol Danazol Desogestrel Dienogest Ethinylandrostenediol Ethisterone Ethynerone Etonogestrel Etynodiol Etynodiol diacetate Gestodene Gestrinone Levonorgestrel Levonorgestrel esters (e.g.,levonorgestrel butanoate )Lynestrenol Lynestrenol phenylpropionate Metynodiol Metynodiol diacetate Norelgestromin Norethisterone (norethindrone) Norethisterone esters (e.g.,norethisterone acetate ,norethisterone enanthate )Noretynodrel Norgesterone Norgestimate Norgestrel Norgestrienone Norvinisterone Oxendolone Quingestanol Quingestanol acetate Tibolone Tigestol Tosagestin ; Anabolic–androgenic steroids:11β-Methyl-19-nortestosterone 11β-Methyl-19-nortestosterone dodecylcarbonate 19-Nor-5-androstenediol 19-Nor-5-androstenedione 19-Nordehydroepiandrosterone Bolandiol Bolandiol dipropionate Bolandione Dimethisterone Dienedione Dienolone Dimethandrolone Dimethandrolone buciclate Dimethandrolone dodecylcarbonate Dimethandrolone undecanoate Dimethyldienolone Dimethyltrienolone Ethyldienolone Ethylestrenol (ethylnandrol) Methyldienolone Metribolone (R-1881) Methoxydienone (methoxygonadiene) Mibolerone Nandrolone Nandrolone esters (e.g.,nandrolone decanoate ,nandrolone phenylpropionate )Norethandrolone Normethandrone (methylestrenolone, normethandrolone, normethisterone) RU-2309 Tetrahydrogestrinone Trenbolone (trienolone) Trenbolone esters (e.g.,trenbolone acetate ,trenbolone enanthate )Trendione Trestolone Trestolone acetate MixedSPRMs Tooltip Selective progesterone receptor modulators ) Antagonists
mPR Tooltip Membrane progesterone receptor PAQR Tooltip Progestin and adipoQ receptor )
