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 to improve physique and performance, and are said to be the most widely used anabolic steroid for such purposes.[8][17] The drugs are controlled 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 potent progestogen.[24] It binds to the progesterone receptor with approximately 22% of the affinity of progesterone.[24] The progestogenic activity of nandrolone serves to augment its antigonadotropic effects,[25][8] as antigonadotropic action is a known property of progestogens.[26][27]
Notes: Values are percentages (%). Reference ligands (100%) were progesterone for the PRTooltip progesterone receptor, testosterone for the ARTooltip androgen receptor, estradiol for the ERTooltip estrogen receptor, dexamethasone for the GRTooltip glucocorticoid receptor, aldosterone for the MRTooltip mineralocorticoid receptor, dihydrotestosterone for SHBGTooltip sex hormone-binding globulin, and cortisol for CBGTooltip 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 effect of all anabolic steroids.[25] This is attributed to the fact that whereas testosterone is potentiated via conversion into dihydrotestosterone (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 of AIDS-associated cachexia, severe burns, and chronic 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 of masculinization like hirsutism and voice deepening in women and children with extended use.[15]
Dose-normalized nandrolone exposure (serum level divided by dose administered) with nandrolone decanoate in oil solution by intramuscular or subcutaneous injection in men.[41][42]
Nandrolone, with the differences from testosterone highlighted in red. The methyl 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-alkylated trenbolone and the 17α-alkylatedethylestrenol (ethylnandrol) and metribolone (R-1881), as well as the 17α-alkylated designer steroidsnorboletone and tetrahydrogestrinone (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 putative 19-norprogesterone.
This reaction, now known as the Birch reduction,[51] is typified by the treatment of the monomethyl ether of estradiol (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 ketone 3. 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 of 19-norandrosterone, a metabolite. The International Olympic Committee has set a limit of 2.0 μg/L of 19-norandrosterone in urine as the upper limit,[54] beyond which an athlete is suspected of doping. In the largest nandrolone study performed on 621 athletes at the 1998 Nagano Olympic Games, no athlete tested over 0.4 μg/L. 19-Norandrosterone was identified as a trace contaminant in commercial preparations of androstenedione, 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 in athletics occurred in 1999, which included high-profile athletes such as Merlene Ottey, Dieter Baumann, and Linford 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 acid lysine (as indicated in the treatment of cold sores) has allegedly shown false positives in some and was cited by American shotputterC. J. Hunter as the reason for his positive test, though in 2004 he admitted to a federal grand 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 modern urinalysis 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 by UK Sport. In October 2007, three-time Olympic gold medalist for track and field Marion 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 first synthesized 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 of doping in sports with nandrolone esters by professionalathletes.
Nandrolone esters have been studied in several indications. They were intensively studied for osteoporosis, 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 the bisphosphonates became available.[21] They have also been studied in clinical trials for chronic kidney failure, aplastic anemia, and as male contraceptives.[18]: 134
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^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....
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^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.
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^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, [...]
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![Nandrolone levels after a single 50, 100, or 150 mg intramuscular injection of nandrolone decanoate in oil solution in men.[38]](http://en.wikipedia.org/wiki/File:Nandrolone_levels_after_a_single_intramuscular_injection_of_different_doses_of_nandrolone_decanoate.png)
![Nandrolone levels after a single 100 mg intramuscular injection of nandrolone decanoate or nandrolone phenylpropionate in 4 mL or 1 mL arachis oil solution into gluteal or deltoid muscle in men.[39]](http://en.wikipedia.org/wiki/File:Nandrolone_levels_after_a_single_100_mg_intramuscular_injection_of_nandrolone_esters.png)
![Nandrolone levels with a single 50 mg intramuscular injection of nandrolone decanoate or nandrolone hexyloxyphenylpropionate in oil solution in men.[40]](http://en.wikipedia.org/wiki/File:Nandrolone_levels_with_a_single_dose_of_nandrolone_decanoate_or_nandrolone_hexyloxyphenylpropionate_by_intramuscular_injection_in_men.png)
![Dose-normalized nandrolone exposure (serum level divided by dose administered) with nandrolone decanoate in oil solution by intramuscular or subcutaneous injection in men.[41][42]](http://en.wikipedia.org/wiki/File:Dose-normalized_nandrolone_exposure_with_nandrolone_decanoate_by_intramuscular_or_subcutaneous_injection_in_men.png)
