Nandrolone decanoate

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Nandrolone decanoate
Nandrolone decanoate.svg
Clinical data
Trade names Deca-Durabolin, others
Synonyms • Nandrolone decylate
• 19-Nortestosterone 17β-decanoate
Pregnancy
category
  • AU: D
  • US: X (Contraindicated)
Routes of
administration
Intramuscular injection
Drug class Androgen; Anabolic steroid; Androgen ester; Progestogen
Legal status
Legal status
Pharmacokinetic data
Bioavailability Intramuscular: 53–73%[3]
Metabolism Blood (hydrolysis), liver (reduction)[1][2]
Metabolites Nandrolone[1][4]
5α-Dihydronandrolone[1][4]
19-Norandrosterone[1]
19-Noretiocholanolone[1]
Conjugates[2]
Elimination half-life • Intramuscular: 6–12 days[1][5]
• Nandrolone: <4.3 hours[1]
Duration of action • Intramuscular: 2–3 weeks[4][6]
Excretion Urine[1]
Identifiers
CAS Number
PubChem CID
ChemSpider
UNII
ECHA InfoCard 100.006.037 Edit this at Wikidata
Chemical and physical data
Formula C28H44O3
Molar mass 428.66 g·mol−1
3D model (JSmol)

Nandrolone decanoate, sold under the brand name Deca-Durabolin among others, is an androgen and anabolic steroid (AAS) medication which is used primarily in the treatment of anemias and wasting syndromes, as well as osteoporosis in menopausal women.[7][8][9][10][4] It is given by injection into muscle once every one to four weeks.[4]

Side effects of nandrolone decanoate include symptoms of masculinization like acne, increased hair growth, voice changes, and increased sexual desire.[4] The drug is a synthetic androgen and anabolic steroid and hence is an agonist of the androgen receptor (AR), the biological target of androgens like testosterone and dihydrotestosterone (DHT).[4][11] It has strong anabolic effects and weak androgenic effects, which give it a mild side effect profile and make it especially suitable for use in women.[4][11] Nandrolone decanoate is a nandrolone ester and a long-lasting prodrug of nandrolone in the body.[4][12]

Nandrolone decanoate was first described in 1960 and was introduced for medical use in 1962,[4] it was the second nandrolone ester to be introduced, following nandrolone phenylpropionate (NPP) in 1959, and is one of the most widely used nandrolone esters.[4][13] It is also one of the most widely used AAS worldwide;[4] in addition to its medical use, nandrolone decanoate is used to improve physique and performance, and is said to be the most widely used AAS for such purposes.[4][14] The drug is a controlled substance in many countries and so non-medical use is generally illicit.[4]

Medical uses[edit]

Nandrolone decanoate is approved in the United States specifically for the treatment of anemia of renal insufficiency and in the United Kingdom specifically for the treatment of osteoporosis in postmenopausal women.[15][16][4] In Australia, it is approved specifically for the treatment of acute renal failure, chronic renal insufficiency, anemia of renal failure, aplastic anemia, osteoporosis (in women in whom estrogens are contraindicated), inoperable breast cancer, and for patients on long-term corticosteroid therapy.[6] In New Zealand, it is approved for osteoporosis, inoperable breast cancer, and as an adjunct to therapy for conditions characterized by a negative nitrogen balance,[1] the drug is often used off-label to preserve lean mass in HIV/AIDS patients and in other wasting syndromes.[4]

In the past, nandrolone decanoate has also been indicated and used for a variety of other conditions and situations including pre- and postoperative use for increasing lean mass, weight loss due to convalescence or disease, geriatric states (e.g., general weakness, fatigue), burns, severe trauma, ulcers, and selected cases of growth failure in children.[4] Starting in the 1970s, the indications of nandrolone decanoate were refined and use of the drug became more selective and restricted,[4] its use in medicine continues to decline and has become limited, with its sale having been discontinued in many countries.[4]

Because of their reduced androgenic effects, nandrolone esters have not generally been used as a form of androgen replacement therapy for treatment of androgen deficiency in men and have instead been used solely as anabolic agents.[17][18] However, nandrolone decanoate has been and can be used at low doses as a means of androgen replacement in postmenopausal women, for instance to maintain or increase bone mineral density and decrease the risk of osteoporosis.[19][20][21][22] It is one of only three androgens approved for androgen replacement in postmenopausal women, the others being testosterone (and esters) and methyltestosterone.[22] Nandrolone esters have also more recently been proposed for the treatment of androgen deficiency in men due to favorable properties including their high ratio of anabolic to androgenic effect and consequent much lower risk of prostate enlargement, prostate cancer, and scalp hair loss relative to testosterone.[23][24]

Available forms[edit]

Nandrolone decanoate is or has been available in 25 mg/mL, 50 mg/mL, 100 mg/mL, and 200 mg/mL formulations in oil for intramuscular injection.[4] In the United States, only the 200 mg/mL formulation remains available.[15][25] The 50 mg/mL formulation is used for administering very low dosages (usually 50–100 mg every 3–4 weeks) and is considered to be appropriate for women.[4] The 100 mg/mL formulation is used to treat women with inoperable breast cancer, which requires a higher dosage.[4]

Non-medical uses[edit]

Nandrolone decanoate is used for physique- and performance-enhancing purposes by competitive athletes, bodybuilders, and powerlifters.[4] It is one of the most popular injectable AAS worldwide and nandrolone esters have been said to be the most popular AAS used by bodybuilders and in sports,[4][14] this is in part due to the high ratio of anabolic to androgenic effect of nandrolone and its weak propensity for androgenic and estrogenic side effects.[4]

Contraindications[edit]

Contraindications for nandrolone decanoate include pregnancy, breastfeeding, prostate cancer, male breast cancer, breast cancer in women with hypercalcemia, hypersensitivity (to nandrolone decanoate or excipients such as arachis (peanut) oil; includes those with peanut and soy allergies), nephrosis or nephritis, liver disease with impaired bilirubin excretion, and cardiac failure.[6][15] High dosages may also be considered contraindicated in women due to their high potential for virilization.[4][6]

Side effects[edit]

The side effects of nandrolone decanoate are dependent on dosage, duration of treatment, and individual sensitivity.[6][16] A number of common, uncommon, and rare side effects have been observed with the medication at recommended dosages.[6][16] While less common or severe than with many other AAS, the most common side effect of nandrolone decanoate is virilization (masculinization) in women.[6][16] Uncommon side effects of nandrolone decanoate at recommended dosages include fluid retention, inhibition of spermatogenesis, testicular atrophy, erectile dysfunction, gynecomastia, increased frequency of penile erections, increased penis size in pre-pubertal boys, clitoral hypertrophy, increased pubic hair growth, oligomenorrhea, amenorrhea, hyperlipidemia, decreased HDL cholesterol, increased hemoglobin (to abnormal high levels), hypertension, nausea, epididymitis, bladder irritability, reduced urine flow, benign prostatic hyperplasia, priapism, premature epiphyseal closure (in children), and acne.[6] Rare side effects include abnormal liver function, jaundice, peliosis hepatis, liver tumors, oily skin, greasy hair, rash, pruritus, exanthema, urticaria at the injection site, and furunculosis.[6] Local injection site reactions may also occur.[16]

Virilization[edit]

Nandrolone decanoate can cause virilization as a common side effect in women, including acne, hoarseness of the voice, hirsutism (excessive facial/body hair growth), and libido changes among others.[6] Clitoral enlargement is an uncommon symptom of virilization that can occur.[6] Virilization is especially prevalent and marked at high dosages and/or with long-term treatment, and some aspects of virilization like voice deepening can be irreversible.[6][16][4] Hoarseness is often the first sign of voice changes,[6] although said to be only slightly androgenic, nandrolone decanoate at recommended dosages may still occasionally cause virilization in women, especially with long-term treatment.[4] A minor though statistically insignificant incidence of virilization has been observed in women treated with nandrolone decanoate short-term at a dosage of 100 mg every two weeks for 12 weeks.[4] Conversely, long-term (>1 year) studies have shown significant virilization in women even at a dosage as low as 50 mg every two or three weeks (considered to be a very low dosage).[4]

Overdose[edit]

The acute toxicity of nandrolone esters in animals is very low and there are no reports of acute overdosage with nandrolone decanoate in humans.[6][1] There are no specific recommendations for the management of nandrolone decanoate.[6]

Interactions[edit]

Antiestrogens like aromatase inhibitors (e.g., anastrozole) and selective estrogen receptor modulators (e.g., tamoxifen, raloxifene) can interfere with and prevent the estrogenic effects of nandrolone decanoate.[4] 5α-Reductase inhibitors like finasteride and dutasteride can prevent the inactivation of nandrolone in so-called "androgenic" tissues like the skin, hair follicles, and prostate gland and may therefore considerably increase its androgenic side effects.[4] This is opposite to the case of most other AAS, which are either potentiated by 5α-reductase in such tissues or are not substrates of 5α-reductase.[4] Antiandrogens like cyproterone acetate, spironolactone, and bicalutamide can block both the anabolic and androgenic effects of AAS like nandrolone decanoate.[26]

Pharmacology[edit]

Pharmacodynamics[edit]

Nandrolone decanoate is a nandrolone ester, or a prodrug of nandrolone.[6][27][4][11] As such, it is an androgen and anabolic steroid, or an agonist of the AR, the biological target of androgens like testosterone and DHT.[6][4][11][27] Relative to testosterone, nandrolone decanoate has enhanced anabolic effects and reduced androgenic effects.[6][27][11] It is considered to have strong anabolic effects but weak androgenic effects, with respective potency ratios of 3.29–4.92 and 0.31–0.41 (index value 10.6–12.1 or about an 11:1 ratio of myotrophic to androgenic effect) relative to testosterone propionate.[4][11][24] Along with oxandrolone (which has a ratio of about 10:1), nandrolone esters are thought to have the highest ratio of anabolic to androgenic effect of any other AAS,[4][23] for this reason, they are considered to be among the most appropriate AAS for use in women.[4]

Androgenic effects like virilization are relatively uncommon with nandrolone decanoate at recommended dosages, though may still occur especially at higher dosages or with extended use,[6][4] the low androgenicity of nandrolone decanoate is thought to be due to the fact that whereas many other AAS like testosterone are potentiated via transformation by 5α-reductase in specific tissues including the skin, hair follicles, prostate gland, liver, and certain areas in the brain, nandrolone is instead inactivated by 5α-reductase via conversion into the low-affinity AR ligand 5α-dihydronandrolone in such tissues.[4][2][11] This is thought to result in a much lower risk and/or severity of increased facial/body hair growth, scalp hair loss, prostate enlargement, and prostate cancer with nandrolone esters relative to testosterone.[4][23][24]

In addition to its anabolic and androgenic activity, nandrolone decanoate has low estrogenic activity (via its metabolite estradiol) and moderate progestogenic activity.[4] This may result in side effects such as fluid retention and gynecomastia.[4] Like other AAS, nandrolone decanoate has antigonadotropic effects,[4] it has been found to suppress testosterone levels by 57% at a dosage of 100 mg/week and by 70% at a dosage of 300 mg/week in men following 6 weeks of treatment.[4] Both the androgenic activity and the progestogenic activity of nandrolone decanoate are thought to contribute to its antigonadotropic potency.[4] Relative to testosterone, due to its lower estrogenic potency, much less of the antigonadotropic potency of nandrolone decanoate is derived from its estrogenic activity.[4]

Pharmacokinetics[edit]

Nandrolone levels over 32 days after a single 50, 100, or 150 mg intramuscular injection of nandrolone decanoate.[3]
Nandrolone levels over 32 days after a single 100 mg intramuscular injection of nandrolone decanoate or nandrolone phenylpropionate in 4 mL or 1 mL arachis oil into gluteal or deltoid muscle.[5]

Upon intramuscular injection in oil, which results in the formation of a long-lasting depot in the muscle, nandrolone decanoate is slowly absorbed unchanged into the body.[2] It is converted into nandrolone in the body, which is the active form of the drug.[1] There is a sharp spike in nandrolone levels 24 to 48 hours after an intramuscular injection of nandrolone decanoate followed by a steady decline to baseline levels within approximately two or three weeks.[4][6] The bioavailability of nandrolone decanoate is 53 to 73% with intramuscular injection and varies with the site of injection, with the highest bioavailability seen when injected into the gluteal muscle.[3] Like testosterone, nandrolone is highly protein-bound and is present in the blood in both bound and free fractions.[2] However, it has very low affinity for human serum sex hormone-binding globulin (SHBG), about 5% of that of testosterone and 1% of that of DHT.[2][28]

Nandrolone decanoate is rapidly hydrolyzed in the blood by esterases into nandrolone with a terminal half-life of one hour or less.[2][1] The metabolism of nandrolone occurs in the liver and is very similar to that of testosterone, including reduction by 5α-reductase and 5β-reductase, dehydrogenation by 3α-hydroxysteroid dehydrogenase, 3β-hydroxysteroid dehydrogenase, and 17β-hydroxysteroid dehydrogenase, and conjugation.[2] The metabolites of nandrolone include 5α-dihydronandrolone, 19-norandrosterone, and 19-noretiocholanolone, with 19-norandrosterone being the major metabolite.[2] Other metabolites include 19-norandrostenedione, 19-norandrostanediols, 19-norepiandrosterone, and conjugates.[2] Nandrolone also undergoes aromatization into estradiol similarly to testosterone, though at a rate of only about 20% of that of testosterone or possibly even less; one study found virtually no aromatization of nandrolone in men.[4][14][2][29]

The elimination half-life of nandrolone decanoate administered via intramuscular injection is approximately 6 to 12 days.[1][4] The blood half-life for the combined process of hydrolysis into nandrolone and elimination of nandrolone is 4.3 hours.[1] Nandrolone and its metabolites are excreted in the urine, mainly in the form of conjugates.[2]

Although nandrolone decanoate is usually administered by intramuscular injection, it has been found to be similarly effective when administered by subcutaneous injection,[30] the pharmacokinetics of nandrolone decanoate via subcutaneous injection closely resemble those of intramuscular injection.[30] However, subcutaneous injection is considered to be easier, more convenient, and less painful relative to intramuscular injection;[30] in addition, research suggests that most intramuscular injections in general are in fact subcutaneous injections.[30]

Chemistry[edit]

Nandrolone decanoate, or nandrolone 17β-decanoate, is a synthetic estrane steroid and a derivative of testosterone.[7][8] It is an androgen ester; specifically, it is the C17β decylate (decanoate) ester of nandrolone (19-nortestosterone), which itself is the 19-demethylated analogue of testosterone.[7][8]

History[edit]

Nandrolone decanoate was first described in the literature in 1960,[4] it was developed by Organon and was introduced for medical use under the brand name Deca-Durabolin in 1962.[4][31] Shortly thereafter it became one of the most widely used AAS in the world.[4] Nandrolone decanoate was the second form of nandrolone to be introduced, and was preceded by nandrolone phenylpropionate in 1959.[31]

Society and culture[edit]

Generic names[edit]

Nandrolone decanoate is the generic name of the drug and its USAN and BAN.[7][8][9][10] It has also been referred to as nandrolone decylate.[7][8][9][10]

Brand names[edit]

Nandrolone decanoate is or has been marketed under the brand names Deca-Durabolin, Deca-Durabol, Decaneurabol, Metadec, and Retabolil among others.[7][8][9][10]

Availability[edit]

Nandrolone decanoate is available widely throughout the world, including in the United States, the United Kingdom, elsewhere in Europe, Australia, New Zealand, Latin America, Asia, and elsewhere in the world.[8][10][4][13] It has been discontinued in Canada,[32] its availability is becoming increasingly more limited with time.[4]

United States[edit]

Nandrolone decanoate is one of the few AAS that remains available for medical use in the United States,[25] the others (as of November 2017) are testosterone, testosterone cypionate, testosterone enanthate, testosterone undecanoate, methyltestosterone, fluoxymesterone, oxandrolone, and oxymetholone.[25] Nandrolone phenylpropionate was marketed in the United States previously but is no longer available in this country.[25]

Legal status[edit]

Nandrolone decanoate, along with other AAS, is a schedule III controlled substance in the United States under the Controlled Substances Act.[33]

References[edit]

  1. ^ a b c d e f g h i j k l m n http://www.medsafe.govt.nz/profs/Datasheet/d/Decadurabolininj.pdf
  2. ^ a b c d e f g h i j k l John A. Thomas (6 December 2012). Drugs, Athletes, and Physical Performance. Springer Science & Business Media. pp. 27–29. ISBN 978-1-4684-5499-4. 
  3. ^ a b c 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. PMID 15713722. 
  4. ^ 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 ae af ag ah ai aj ak al am an ao ap aq ar as at au av aw ax ay az ba bb bc William Llewellyn (2011). Anabolics. Molecular Nutrition Llc. pp. 402–412,193–194. ISBN 978-0-9828280-1-4. 
  5. ^ a b 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. PMID 9103484. 
  6. ^ a b c d e f g h i j k l m n o p q r s t https://gp2u.com.au/static/pdf/D/DECA-DURABOLIN-PI.pdf
  7. ^ a b c d e f J. Elks (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 660–. ISBN 978-1-4757-2085-3. 
  8. ^ a b c d e f g Index Nominum 2000: International Drug Directory. Taylor & Francis. January 2000. pp. 716–717. ISBN 978-3-88763-075-1. 
  9. ^ a b c d I.K. Morton; Judith M. Hall (6 December 2012). Concise Dictionary of Pharmacological Agents: Properties and Synonyms. Springer Science & Business Media. ISBN 978-94-011-4439-1. 
  10. ^ a b c d e https://www.drugs.com/international/nandrolone.html
  11. ^ a b c d e f g Kicman AT (2008). "Pharmacology of anabolic steroids". Br. J. Pharmacol. 154 (3): 502–21. doi:10.1038/bjp.2008.165. PMC 2439524Freely accessible. PMID 18500378. 
  12. ^ Wijnand HP, Bosch AM, Donker CW (1985). "Pharmacokinetic parameters of nandrolone (19-nortestosterone) after intramuscular administration of nandrolone decanoate (Deca-Durabolin) to healthy volunteers". Acta Endocrinol Suppl (Copenh). 271: 19–30. PMID 3865478. 
  13. ^ a b Walter Sneader (23 June 2005). Drug Discovery: A History. John Wiley & Sons. pp. 206–. ISBN 978-0-471-89979-2. 
  14. ^ a b c J. Larry Jameson; Leslie J. De Groot (25 February 2015). Endocrinology: Adult and Pediatric E-Book. Elsevier Health Sciences. pp. 2388–. ISBN 978-0-323-32195-2. 
  15. ^ a b c https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3f059e04-1ebc-40bb-a49c-f9d90d41b1cb
  16. ^ a b c d e f https://www.medicines.org.uk/emc/files/pil.5374.pdf?filename=PIL.5374.pdf
  17. ^ Kenneth L. Becker (2001). Principles and Practice of Endocrinology and Metabolism. Lippincott Williams & Wilkins. pp. 1185–. ISBN 978-0-7817-1750-2. 
  18. ^ A. Wayne Meikle (1 June 1999). Hormone Replacement Therapy. Springer Science & Business Media. pp. 271–. ISBN 978-1-59259-700-0. 
  19. ^ Davis S (1999). "Androgen replacement in women: a commentary". J. Clin. Endocrinol. Metab. 84 (6): 1886–91. doi:10.1210/jcem.84.6.5802. PMID 10372681. 
  20. ^ Abraham D, Carpenter PC (1997). "Issues concerning androgen replacement therapy in postmenopausal women". Mayo Clin. Proc. 72 (11): 1051–5. doi:10.4065/72.11.1051. PMID 9374980. 
  21. ^ A. Wayne Meikle (24 April 2003). Endocrine Replacement Therapy in Clinical Practice. Springer Science & Business Media. pp. 519–. ISBN 978-1-59259-375-0. 
  22. ^ a b Davis SR (1999). "The therapeutic use of androgens in women". J. Steroid Biochem. Mol. Biol. 69 (1-6): 177–84. doi:10.1016/s0960-0760(99)00054-0. PMID 10418991. 
  23. ^ a b c Wu C, Kovac JR (2016). "Novel Uses for the Anabolic Androgenic Steroids Nandrolone and Oxandrolone in the Management of Male Health". Curr Urol Rep. 17 (10): 72. doi:10.1007/s11934-016-0629-8. PMID 27535042. 
  24. ^ a b c Pan MM, Kovac JR (2016). "Beyond testosterone cypionate: evidence behind the use of nandrolone in male health and wellness". Transl Androl Urol. 5 (2): 213–9. doi:10.21037/tau.2016.03.03. PMC 4837307Freely accessible. PMID 27141449. 
  25. ^ a b c d "Drugs@FDA: FDA Approved Drug Products". United States Food and Drug Administration. Retrieved 17 December 2016. 
  26. ^ Carrie Bagatell; William J. Bremner (27 May 2003). Androgens in Health and Disease. Springer Science & Business Media. pp. 25–. ISBN 978-1-59259-388-0. 
  27. ^ a b c Gao W, Bohl CE, Dalton JT (2005). "Chemistry and structural biology of androgen receptor". Chem. Rev. 105 (9): 3352–70. doi:10.1021/cr020456u. PMC 2096617Freely accessible. PMID 16159155. 
  28. ^ Saartok T, Dahlberg E, Gustafsson JA (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. PMID 6539197. 
  29. ^ Behre HM, Kliesch S, Lemcke B, von Eckardstein S, Nieschlag E (December 2001). "Suppression of spermatogenesis to azoospermia by combined administration of GnRH antagonist and 19-nortestosterone cannot be maintained by this non-aromatizable androgen alone" (PDF). Hum. Reprod. 16 (12): 2570–7. doi:10.1093/humrep/16.12.2570. PMID 11726576. 
  30. ^ a b c d Singh GK, Turner L, Desai R, Jimenez M, Handelsman DJ (2014). "Pharmacokinetic-pharmacodynamic study of subcutaneous injection of depot nandrolone decanoate using dried blood spots sampling coupled with ultrapressure liquid chromatography tandem mass spectrometry assays". J. Clin. Endocrinol. Metab. 99 (7): 2592–8. doi:10.1210/jc.2014-1243. PMID 24684468. 
  31. ^ a b Consolidated List of Products Whose Consumption And/or Sale Have Been Banned, Withdrawn, Severely Restricted Or Not Approved by Governments. United Nations Publications. 1983. pp. 153–154. ISBN 978-92-1-130230-1. 
  32. ^ "Drug Product Database - Health Canada". Health Canada. Retrieved 13 December 2017. 
  33. ^ Steven B. Karch, MD, FFFLM (21 December 2006). Drug Abuse Handbook, Second Edition. CRC Press. pp. 30–. ISBN 978-1-4200-0346-8. 

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External links[edit]