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]
Medical uses
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.
Anabolic and androgenic activity
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 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).
Esters
Treatment of 4 with decanoic anhydride and
pyridine affords nandrolone decanoate.[52]
Acylation of 4 with phenylpropionyl chloride yields nandrolone phenpropionate.[53]
Detection in body fluids
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]
History
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.
Research
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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