Nandrolone esters were first described and introduced for medical use in the late 1950s.[8] They are among the most widely used anabolic steroid worldwide.[8] In addition to their medical use, nandrolone esters are used toimprove physique and performance, and are said to be the most widely used anabolic steroid for such purposes.[8][17] The drugs arecontrolled substances in many countries and so non-medical use is generally illicit.[8]
Nandrolone esters are used clinically, although increasingly rarely, for people in catabolic states with major burns, cancer, and AIDS, and an ophthalmological formulation was available to support cornea healing.[18]: 134
In addition to its AR agonistic activity, unlike many other anabolic steroids, nandrolone is also a potentprogestogen.[24] It binds to theprogesterone receptor with approximately 22% of the affinity ofprogesterone.[24] The progestogenic activity of nandrolone serves to augment itsantigonadotropic effects,[25][8] as antigonadotropic action is a known property of progestogens.[26][27]
Notes: Values are percentages (%). Referenceligands (100%) wereprogesterone for thePRTooltip progesterone receptor,testosterone for theARTooltip androgen receptor,estradiol for theERTooltip estrogen receptor,dexamethasone for theGRTooltip glucocorticoid receptor,aldosterone for theMRTooltip mineralocorticoid receptor,dihydrotestosterone forSHBGTooltip sex hormone-binding globulin, andcortisol forCBGTooltip corticosteroid-binding globulin.Sources: See template.
Nandrolone has a very high ratio of anabolic to androgenic activity.[15] In fact, many nandrolone-like anabolic steroids and even nandrolone itself are said to have among the highest ratio of anabolic to androgenic effects of all anabolic steroids.[25] This is attributed to the fact that whereas testosterone is potentiated via conversion intodihydrotestosterone (DHT) in androgenic tissues, the opposite is true with nandrolone and similar anabolic steroids (i.e., other 19-nortestosterone derivatives).[15] As such, nandrolone-like anabolic steroids, namely nandrolone esters, are the most frequently used anabolic steroids in clinical settings in which anabolic effects are desired; for instance, in the treatment ofAIDS-associatedcachexia, severeburns, andchronic obstructive pulmonary disease.[25] However, anabolic steroids with a very high ratio of anabolic to androgenic action like nandrolone still have significant androgenic effects and can produce symptoms ofmasculinization likehirsutism andvoice deepening in women and children with extended use.[15]
Dose-normalized nandrolone exposure (serum level divided by dose administered) withnandrolone decanoate in oil solution by intramuscular or subcutaneous injection in men.[41][42]
Nandrolone, with the differences from testosterone highlighted in red. Themethyl group in testosterone at the C19 position has been removed, and the C17β position is where esters are attached to nandrolone.
Nandrolone is the parent compound of a large group of anabolic steroids. Notable examples include the non-17α-alkylatedtrenbolone and the17α-alkylatedethylestrenol (ethylnandrol) andmetribolone (R-1881), as well as the 17α-alkylateddesigner steroidsnorboletone andtetrahydrogestrinone (THG). The following is list of derivatives of nandrolone that have been developed as anabolic steroids:[8]
The elaboration of a method for the reduction of aromatic rings to the corresponding dihydrobenzenes under controlled conditions by A. J. Birch opened a convenient route to compounds related to the putative19-norprogesterone.
This reaction, now known as theBirch reduction,[51] is typified by the treatment of the monomethyl ether ofestradiol (1) with a solution of lithium metal in liquid ammonia in the presence of alcohol as a proton source. Initial reaction constituents of 1,4-dimetalation of the most electron deficient positions of the aromatic ring–in the case of an estrogen, the 1 and 4-positions. Rxn of the intermediate with the proton source leads to a dihydrobenzene; a special virtue of this sequence in steroids is the fact that the double bind at 2 is in effect becomes an enol ether moiety. Treatment of this product (2) with weak acid,oxalic acid for e.g., leads to the hydrolysis of the enol ether, producing β,γ-unconjugated ketone3. Hydrolysis under more strenuous conditions (mineral acids) results in migration/conjugation of the olefin to yield nandrolone (4).
Nandrolone use is directly detectable in hair or indirectly detectable in urine by testing for the presence of19-norandrosterone, ametabolite. TheInternational Olympic Committee has set a limit of 2.0 μg/L of 19-norandrosterone in urine as the upper limit,[54] beyond which anathlete is suspected ofdoping. In the largest nandrolone study performed on 621 athletes at the1998 Nagano Olympic Games, no athlete tested over 0.4 μg/L. 19-Norandrosterone was identified as a trace contaminant in commercial preparations ofandrostenedione, which until 2004 was available without a prescription as a dietary supplement in the U.S.[55][56][57][58]
A number of nandrolone cases inathletics occurred in 1999, which included high-profile athletes such asMerlene Ottey,Dieter Baumann, andLinford Christie.[59] However, the following year the detection method for nandrolone at the time was proved to be faulty.Mark Richardson, a British Olympic relay runner who tested positive for the substance, gave a significant amount of urine samples in a controlled environment and delivered a positive test for the drug, demonstrating that false positives could occur, which led to an overhaul of his competitive ban.[60]
Heavy consumption of the essential amino acidlysine (as indicated in the treatment of cold sores) has allegedly shown false positives in some and was cited by AmericanshotputterC. J. Hunter as the reason for his positive test, though in 2004 he admitted to a federalgrand jury that he had injected nandrolone.[61] A possible cause of incorrect urine test results is the presence of metabolites from other anabolic steroids, though modernurinalysis can usually determine the exact anabolic steroid used by analyzing the ratio of the two remaining nandrolone metabolites. As a result of the numerous overturned verdicts, the testing procedure was reviewed byUK Sport. In October 2007, three-time Olympic gold medalist for track and fieldMarion Jones admitted to use of the drug, and was sentenced to six months in jail for lying to a federal grand jury in 2000.[62]
Mass spectrometry is also used to detect small amounts of nandrolone in urine samples.[63]
QV Nandrolone Deca, a form of nandrolone used by athletes.
Nandrolone was firstsynthesized in 1950.[2][43][18]: 130 [64] It was first introduced, as nandrolone phenylpropionate, in 1959, and then as nandrolone decanoate in 1962, followed by additional esters.[65]
Nandrolone was probably among the first anabolic steroids to be used as a doping agent in sports in the 1960s.[citation needed] It has been banned at the Olympics since 1974.[18]: 128 There are many known cases ofdoping in sports with nandrolone esters byprofessionalathletes.
Nandrolone esters have been studied in several indications. They were intensively studied forosteoporosis, and increased calcium uptake and decreased bone loss, but caused virilization in about half of the women who took them and were mostly abandoned for this use when better drugs like thebisphosphonates became available.[21] They have also been studied inclinical trials forchronic kidney failure,aplastic anemia, and asmale contraceptives.[18]: 134
^abcdefghijklmnoElks J, Ganellin CR, eds. (2014).The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. New York City: Springer. pp. 660–.ISBN978-1-4757-2085-3.OCLC1079003025.
^abcMinto CF, Howe C, Wishart S, Conway AJ, Handelsman DJ (April 1997). "Pharmacokinetics and pharmacodynamics of nandrolone esters in oil vehicle: effects of ester, injection site and injection volume".The Journal of Pharmacology and Experimental Therapeutics.281 (1):93–102.doi:10.1016/S0022-3565(24)36598-X.PMID9103484.
^abcdHemmersbach P, Große J (2009). "Nandrolone: A Multi-Faceted Doping Agent". In Thieme D, Hemmersbach P (eds.).Doping in sports. Berlin: Springer. pp. 127–154.ISBN978-3-540-79088-4.
^Handelsman DJ (2013)."Androgen Physiology, Pharmacology and Abuse". In De Groot LJ (ed.).Endotext. MDText.com. 4.1.2 Pharmacologic Androgen Therapy.PMID25905160 – via NCBI Bookshelf.Both testosterone and its non-aromatizable derivative nandrolone, produce increased bone density in men with glucocorticoid-induced osteoporosis with minimal short-term side-effects....
^abBergink EW, Janssen PS, Turpijn EW, van der Vies J (June 1985). "Comparison of the receptor binding properties of nandrolone and testosterone under in vitro and in vivo conditions".Journal of Steroid Biochemistry.22 (6):831–6.doi:10.1016/0022-4731(85)90293-6.PMID4021486.
^Furman RH, Howard RP, Norcia LN, Keaty EC (January 1958). "The influence of androgens, estrogens and related steroids on serum lipids and lipoproteins".The American Journal of Medicine.24 (1):80–97.doi:10.1016/0002-9343(58)90364-4.PMID13498038.
^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):2100–6.doi:10.1210/endo-114-6-2100.PMID6539197.
^abcBergink EW, Geelen JA, Turpijn EW (1985). "Metabolism and receptor binding of nandrolone and testosterone under in vitro and in vivo conditions".Acta Endocrinologica. Supplementum.271 (3_Suppla):31–7.doi:10.1530/acta.0.109S0031.PMID3865479.
^Bagchus WM, Smeets JM, Verheul HA, De Jager-Van Der Veen SM, Port A, Geurts TB (2005). "Pharmacokinetic evaluation of three different intramuscular doses of nandrolone decanoate: analysis of serum and urine samples in healthy men".J. Clin. Endocrinol. Metab.90 (5):2624–30.doi:10.1210/jc.2004-1526.PMID15713722.
^Minto CF, Howe C, Wishart S, Conway AJ, Handelsman DJ (1997). "Pharmacokinetics and pharmacodynamics of nandrolone esters in oil vehicle: effects of ester, injection site and injection volume".J. Pharmacol. Exp. Ther.281 (1):93–102.PMID9103484.
^Belkien L, Schürmeyer T, Hano R, Gunnarsson PO, Nieschlag E (May 1985). "Pharmacokinetics of 19-nortestosterone esters in normal men".J. Steroid Biochem.22 (5):623–9.doi:10.1016/0022-4731(85)90215-8.PMID4010287.
^Kalicharan RW, Schot P, Vromans H (February 2016). "Fundamental understanding of drug absorption from a parenteral oil depot".Eur J Pharm Sci.83:19–27.doi:10.1016/j.ejps.2015.12.011.PMID26690043.
^Bricout V, Wright F (June 2004). "Update on nandrolone and norsteroids: how endogenous or xenobiotic are these substances?".European Journal of Applied Physiology.92 (1–2):1–12.doi:10.1007/s00421-004-1051-3.PMID15042372.S2CID6472015.
^Lippi G, Franchini M, Banfi G (May 2011). "Biochemistry and physiology of anabolic androgenic steroids doping".Mini Reviews in Medicinal Chemistry.11 (5):362–73.doi:10.2174/138955711795445952.PMID21443514.S2CID3862299.
^Meikle AW (24 April 2003).Endocrine Replacement Therapy in Clinical Practice. Springer Science & Business Media. pp. 489–.ISBN978-1-59259-375-0.Estranes. Estrane and gonane progestogens are derived from 19-nortestosterone, the progestogenic parent compound used in oral contraceptives in the United States. Estranes are characterized by the presence of an ethinyl group at position 17 and by the absence of a methyl group between the A and B rings (see Fig. 10). The estrane progestogens that are related structurally to norethindrone (norethynodrel, lynestrenol, norethindrone acetate, ethynodiol diacetate) are converted to this parent compound. Norethindrone is the second most commonly used progestogen in the United States for HRT. Gonanes. The gonanes share the structural modifications found in the estranes and also possess an ethinyl group at position 13 and a keto group at position 3 (see Fig. 11). Norgestrel was synthesized in 1963 and is a racemic mixture of dextro and levorotatory forms. The levorotatory form, levonorgestrel, provides the biologic activity. Third-generation gonanes (desogestrel, gestodene, and norgestimate) have been developed to reduce unwanted side effects of progestogens, [...]
^Wilds AL, Nelson NA (1953). "The Facile Synthesis of 19-Nortestosterone and 19-Norandrostenedione from Estrone".Journal of the American Chemical Society.75 (21):5366–5369.Bibcode:1953JAChS..75.5366W.doi:10.1021/ja01117a065.
^Ueberwasser H, Heusler K, Kalvoda J, Meystre CH, Wieland P, Anner G, Wettstein A (1963). "19-Norsteroide II. Ein einfaches Herstellungsverfahren für 19-Norandrostan-Derivate. Über Steroide, 193. Mitteilung".Helvetica Chimica Acta.46:344–352.doi:10.1002/hlca.19630460135.
^Shimizu I, Naito Y, Tsuji J (1980). "Synthesis of optically active (+)-19-nortestosterone by asymmetric bis-annulation reaction".Tetrahedron Letters.21 (5):487–490.doi:10.1016/S0040-4039(00)71440-7.
^Birch AJ (1950). "The reduction of organic compounds by metal-ammonia solutions".Quarterly Reviews, Chemical Society.4: 69.doi:10.1039/QR9500400069.
^Bresson M, Cirimele V, Villain M, Kintz P (May 2006). "Doping control for metandienone using hair analyzed by gas chromatography-tandem mass spectrometry".Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences.836 (1–2):124–8.doi:10.1016/j.jchromb.2006.03.040.PMID16597518.
^Ueki M, Ikekita A, Takao Y (2000). "[Nandrolone metabolite in urine of Nagano Olympic athlete]".Jap. J. For. Tox. (in Japanese).18:198–199.
^Birch AJ (1950). "80. Hydroaromatic steroid hormones. Part I. 10-Nortestosterone".Journal of the Chemical Society (Resumed): 367.doi:10.1039/jr9500000367.ISSN0368-1769.
Geusens P (September 1995). "Nandrolone decanoate: pharmacological properties and therapeutic use in osteoporosis".Clinical Rheumatology.14 (Suppl 3):32–9.doi:10.1007/bf02210686.PMID8846659.S2CID24365057.
Velema MS, Kwa BH, de Ronde W (March 2012). "Should androgenic anabolic steroids be considered in the treatment regime of selected chronic obstructive pulmonary disease patients?".Current Opinion in Pulmonary Medicine.18 (2):118–24.doi:10.1097/MCP.0b013e32834e9001.PMID22189453.S2CID6155275.
Wu C, Kovac JR (October 2016). "Novel Uses for the Anabolic Androgenic Steroids Nandrolone and Oxandrolone in the Management of Male Health".Current Urology Reports.17 (10): 72.doi:10.1007/s11934-016-0629-8.PMID27535042.S2CID43199715.
