Dihydrotestosterone and Androstanolone: Difference between pages

{{Short description|Androgenic and anabolic steroid medication}}

{{cs1 config|name-list-style=vanc}}

{{Use dmy dates|date=December 2023}}

{{About|dihydrotestosterone as a medication|the natural hormone|Dihydrotestosterone}}

{{Infobox drug

| Verifiedfields = verified

| Watchedfields = verified

| verifiedrevid = 459443200

| IUPAC_name = (5''S'',8''R'',9''S'',10''S'',13''S'',14''S'',17''S'')-17-hydroxy-10,13-dimethyl-1,2,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydrocyclopenta[''a'']phenanthren-3-one

| image = Androstanolone.svg

| width = 225px

| image2 = Dihydrotestosterone molecule ball.png

| width2 = 225px

| tradename = Andractim, others

| pregnancy_category = X

| routes_of_administration = [[Transdermal]] ([[gel]]), [[buccal administration|in the cheek]], [[sublingual administration|under the tongue]], [[intramuscular injection]] (as [[Androgen ester#Dihydrotestosterone esters|ester]]s)

| class = [[Androgen]]; [[Anabolic steroid]]

<!-- Legal status -->

| legal_BR = C5

| legal_BR_comment = <ref>{{cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=31 March 2023 |title=RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial |trans-title=Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control|url=https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |url-status=live |archive-url=https://web.archive.org/web/20230803143925/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |archive-date=3 August 2023 |access-date=15 August 2023 |publisher=[[Diário Oficial da União]] |language=pt-BR |publication-date=4 April 2023}}</ref>

| bioavailability = [[Oral administration|Oral]]: Very low<ref name="Llewellyn2011" /><br />[[Transdermal administration|Transdermal]]: 10%<ref name="Llewellyn2011" /><ref name="pmid9365393" /><br />[[Intramuscular injection|{{Abbr|IM|Intramuscular injection}} injection]]: 100%<ref name="pmid9365393">{{cite journal | vauthors = Coutts SB, Kicman AT, Hurst DT, Cowan DA | title = Intramuscular administration of 5 alpha-dihydrotestosterone heptanoate: changes in urinary hormone profile | journal = Clinical Chemistry | volume = 43 | issue = 11 | pages = 2091–2098 | date = November 1997 | pmid = 9365393 | doi = 10.1093/clinchem/43.11.2091 | doi-access = free }}</ref>

| metabolism = [[Liver]]

| elimination_half-life = [[Transdermal administration|Transdermal]]: 2.8 hours<ref name="MozayaniRaymon2003" />

| excretion = [[Urine]]

| CAS_number_Ref = {{cascite|correct|CAS}}

| ATC_prefix = A14

| ATC_suffix = AA01

| PubChem = 10635

| IUPHAR_ligand = 2856

| DrugBank_Ref = {{drugbankcite|correct|drugbank}}

| DrugBank = DB02901

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = 08J2K08A3Y

| ChEBI_Ref = {{ebicite|correct|EBI}}

| ChEBI = 16330

| ChEMBL_Ref = {{ebicite|correct|EBI}}

| ChEMBL = 27769

| synonyms = Stanolone; Dihydrotestosterone; DHT; 5α-Dihydrotestosterone; 5α-DHT

<!--Chemical data-->

| C=19 | H=30 | O=2

| SMILES = O=C4C[C@@H]3CC[C@@H]2[C@H](CC[C@]1(C)[C@@H](O)CC[C@H]12)[C@@]3(C)CC4

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChI = 1S/C19H30O2/c1-18-9-7-13(20)11-12(18)3-4-14-15-5-6-17(21)19(15,2)10-8-16(14)18/h12,14-17,21H,3-11H2,1-2H3/t12-,14-,15-,16-,17-,18-,19-/m0/s1

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey = NVKAWKQGWWIWPM-ABEVXSGRSA-N

<!-- Definition and medical uses -->

'''Androstanolone''', or '''stanolone''', also known as '''dihydrotestosterone''' ('''DHT''') and sold under the brand name '''Andractim''' among others, is an [[androgen]] and [[anabolic steroid]] (AAS) medication and [[sex hormone|hormone]] which is used mainly in the treatment of [[hypogonadism|low testosterone levels]] in men.<ref name="Llewellyn2011">{{cite book| vauthors = Llewellyn W |title=Anabolics|url=https://books.google.com/books?id=afKLA-6wW0oC&pg=PT353|year=2011|publisher=Molecular Nutrition Llc|isbn=978-0-9828280-1-4|pages=8,23–25,353–359}}</ref> It is also used to treat [[gynecomastia|breast development]] and [[micropenis|small penis]] in males.<ref name="Llewellyn2011" />

Compared to [[testosterone]], androstanolone (DHT) is less likely to [[aromatase|aromatize]] into [[estrogen]], and therefore it shows less pronounced [[estrogen (medication)|estrogen]]ic side effects, such as [[gynecomastia]] and [[Water retention (medicine)|water retention]]. On the other hand, androstanolone (DHT) show more significant [[androgenic]] side effects, such as [[acne]], [[hair loss]] and [[prostate enlargement]].

It has strong [[androgen]]ic effects and [[myotrophy|muscle-building]] effects, as well as relatively weak [[estrogen (medication)|estrogen]]ic effects.<ref name="Llewellyn2011" />

It is typically given as a [[gel]] for [[topical medication|application to the skin]], but can also be used as an [[dihydrotestosterone ester|ester]] by [[intramuscular injection|injection into muscle]].<ref name="Llewellyn2011" /><ref name="HydeGengenbach2007" />

<!-- Side effects and mechanism of action -->

[[Side effect]]s of androstanolone include [[symptom]]s of [[virilization|masculinization]] like [[acne]], [[hirsutism|increased hair growth]], [[voice deepening|voice changes]], and increased [[libido|sexual desire]].<ref name="Llewellyn2011" /> The medication is a [[natural product|naturally occurring]] androgen and anabolic steroid and hence is an [[agonist]] of the [[androgen receptor]] (AR), the [[biological target]] of androgens like [[testosterone]] and DHT.<ref name="Llewellyn2011" /><ref name="pmid18500378">{{cite journal | vauthors = Kicman AT | title = Pharmacology of anabolic steroids | journal = British Journal of Pharmacology | volume = 154 | issue = 3 | pages = 502–521 | date = June 2008 | pmid = 18500378 | pmc = 2439524 | doi = 10.1038/bjp.2008.165 }}</ref>

<!-- History, society, and culture -->

Androstanolone was discovered in 1935 and was introduced for medical use in 1953.<ref name="Llewellyn2011" /><ref name="Schnitzer1967" /><ref name="Krüskemper2013" /><ref name="Publishing2007" /> It is used mostly in [[France]] and [[Belgium]].<ref name="Llewellyn2011" /><ref name="Drugs.com" /><ref name="GoorenBunck2004" /> The drug has been used by weightlifters to increase performance due to its powerful androgenic properties.<ref>{{cite web | url=https://www.iwf.net/2018/05/30/public-disclosure-104/ |title = Public Disclosure|date = 30 May 2018}}</ref><ref>{{cite web | url=http://www.chicagotribune.com/news/ct-xpm-1994-12-10-9412100116-story.html |title = Steroid Use by Chinese Hints at Systematic Doping| website=[[Chicago Tribune]] | date=10 December 1994 }}</ref> The medication is a [[controlled substance]] in many countries and so non-medical use is generally illicit.<ref name="Llewellyn2011" />

{{TOC limit|3}}

==Medical uses==

Androstanolone is available in [[pharmaceutical drug|pharmaceutical]] [[drug form|formulation]]s for [[medicine|medical use]] as an androgen.<ref name="HydeGengenbach2007">{{cite book | vauthors = Hyde TE, Gengenbach MS | title = Conservative Management of Sports Injuries|url=https://books.google.com/books?id=uzPwfNYyjjUC&pg=PA1100|year=2007|publisher=Jones & Bartlett Learning|isbn=978-0-7637-3252-3|pages=1100–}}</ref> It is used mainly as a form of [[androgen replacement therapy]] in the treatment of male [[hypogonadism]] and is specifically approved for this indication in certain countries.<ref name="AdisInsight-HPG-CHX" /><ref name="WangSwerdloff2009">{{cite journal | vauthors = Wang C, Swerdloff RS | title = Androgen replacement therapy | journal = Annals of Medicine | volume = 29 | issue = 5 | pages = 365–370 | date = October 1997 | pmid = 9453281 | doi = 10.3109/07853899708999363 | doi-access = free }}</ref><ref name="SwerdloffDudley2017">{{cite journal | vauthors = Swerdloff RS, Dudley RE, Page ST, Wang C, Salameh WA | title = Dihydrotestosterone: Biochemistry, Physiology, and Clinical Implications of Elevated Blood Levels | journal = Endocrine Reviews | volume = 38 | issue = 3 | pages = 220–254 | date = June 2017 | pmid = 28472278 | pmc = 6459338 | doi = 10.1210/er.2016-1067 }}</ref><ref name="SwerdloffWang1998">{{cite journal | vauthors = Swerdloff RS, Wang C | title = Dihydrotestosterone: a rationale for its use as a non-aromatizable androgen replacement therapeutic agent | journal = Baillière's Clinical Endocrinology and Metabolism | volume = 12 | issue = 3 | pages = 501–506 | date = October 1998 | pmid = 10332569 | doi = 10.1016/S0950-351X(98)80267-X }}</ref><ref name="WangSwerdloff2002">{{cite journal | vauthors = Wang C, Swerdloff RS | title = Should the nonaromatizable androgen dihydrotestosterone be considered as an alternative to testosterone in the treatment of the andropause? | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 87 | issue = 4 | pages = 1462–1466 | date = April 2002 | pmid = 11932265 | doi = 10.1210/jcem.87.4.8488 | doi-access = free }}</ref><ref name="ByrneNieschlag2014">{{cite journal | vauthors = Byrne M, Nieschlag E | title = Testosterone replacement therapy in male hypogonadism | journal = Journal of Endocrinological Investigation | volume = 26 | issue = 5 | pages = 481–489 | date = May 2003 | pmid = 12906378 | doi = 10.1007/BF03345206 | s2cid = 19557568 }}</ref><ref name="GoorenBunck2004">{{cite journal | vauthors = Gooren LJ, Bunck MC | title = Androgen replacement therapy: present and future | journal = Drugs | volume = 64 | issue = 17 | pages = 1861–1891 | year = 2004 | pmid = 15329035 | doi = 10.2165/00003495-200464170-00002 | s2cid = 46959273 }}</ref> However, it is no longer recommended for this purpose due to biological differences from testosterone such as lack of estrogenic effects and partial androgenic effects.<ref name="RastrelliReisman2019">{{cite book | vauthors = Rastrelli G, Guaraldi F, Reismann Y, Sforza A, Isidori AM, Maggi M, Corona G | chapter = Testosterone Replacement Therapy | title = Sexual Medicine | journal = Sexual Medicine Reviews | volume = 7 | issue = 3 | pages = 464–475 | date = July 2019 | publisher = Springer | pmid = 30803919 | doi = 10.1007/978-981-13-1226-7_8 | isbn = 978-981-13-1225-0 | doi-access = free }}</ref> [[Topical medication|Topical]] androstanolone is useful in the treatment of [[gynecomastia]].<ref name="AgrawalGanie2017">{{cite book | vauthors = Agrawal S, Ganie MA, Nisar S | chapter = Gynaecomastia | title = Basics of Human Andrology | date = 2017 | pages = 451–458 | publisher = Springer | location = Singapore | doi = 10.1007/978-981-10-3695-8_26 | isbn=978-981-10-3694-1 }}</ref> Similarly, [[androstanolone enanthate]] via [[intramuscular injection]] has been found to be effective in the treatment persistent [[puberty|pubertal]] [[gynecomastia]].<ref name="pmid3088241">{{cite journal | vauthors = Eberle AJ, Sparrow JT, Keenan BS | title = Treatment of persistent pubertal gynecomastia with dihydrotestosterone heptanoate | journal = The Journal of Pediatrics | volume = 109 | issue = 1 | pages = 144–149 | date = July 1986 | pmid = 3088241 | doi = 10.1016/S0022-3476(86)80596-0 }}</ref> The medication has also been used as a topical gel to treat [[micropenis|small penis]] in pre- and peripubertal boys with [[mild androgen insensitivity syndrome|mild]] or [[partial androgen insensitivity syndrome]].<ref name="Hohl2017">{{cite book | vauthors = Hohl A |title=Testosterone: From Basic to Clinical Aspects|url=https://books.google.com/books?id=Et6TDgAAQBAJ&pg=PA91|date=30 March 2017|publisher=Springer|isbn=978-3-319-46086-4|pages=91–}}</ref><ref name="Llewellyn2011" /><ref name="pmid26352087">{{cite journal | vauthors = Becker D, Wain LM, Chong YH, Gosai SJ, Henderson NK, Milburn J, Stott V, Wheeler BJ | display-authors = 6 | title = Topical dihydrotestosterone to treat micropenis secondary to partial androgen insensitivity syndrome (PAIS) before, during, and after puberty - a case series | journal = Journal of Pediatric Endocrinology & Metabolism | volume = 29 | issue = 2 | pages = 173–177 | date = February 2016 | pmid = 26352087 | doi = 10.1515/jpem-2015-0175 | s2cid = 30671775 }}</ref>

Androstanolone was found to be effective in the treatment of advanced [[breast cancer]] in women in the 1950s, although it was used in very high doses and caused severe [[virilization]].<ref name="pmid13151839">{{cite journal | vauthors = Gelhorn A, Holland J, Herrmann JB, Moss J, Smelin A | title = An evaluation of stanolone in treatment of advanced mammary cancer | journal = Journal of the American Medical Association | volume = 154 | issue = 15 | pages = 1274–1277 | date = April 1954 | pmid = 13151839 | doi = 10.1001/jama.1954.02940490038010 }}</ref><ref name="pmid14379136">{{cite journal | vauthors = Kennedy BJ | title = The effect of stanolone in the treatment of advanced breast cancer | journal = Cancer | volume = 8 | issue = 3 | pages = 488–497 | year = 1955 | pmid = 14379136 | doi = 10.1002/1097-0142(1955)8:3<488::AID-CNCR2820080309>3.0.CO;2-Y | s2cid = 5330089 | doi-access = free }}</ref><ref name="pmid13231036">{{cite journal | vauthors = Segaloff A, Horwitt BN, Carabasi RA, Murison PJ, Schlosser JV | title = Hormonal therapy in cancer of the breast. VIII. The effect of dihydrotestosterone (androstanolone) on clinical course and hormonal excretion | journal = Cancer | volume = 8 | issue = 1 | pages = 82–86 | year = 1955 | pmid = 13231036 | doi = 10.1002/1097-0142(1955)8:1<82::AID-CNCR2820080110>3.0.CO;2-R | doi-access = free }}</ref> It was used as a [[microcrystalline]] [[aqueous suspension]] by [[intramuscular injection]].<ref name="Dao1975">{{cite book | vauthors = Dao TL | chapter = Pharmacology and Clinical Utility of Hormones in Hormone Related Neoplasms | year = 1975 | pages = 170–192 | doi = 10.1007/978-3-642-65806-8_11 | veditors = Sartorelli AC, Johns DJ | title = Antineoplastic and Immunosuppressive Agents | series = Handbuch der experimentellen Pharmakologie / Handbook of Experimental Pharmacology | publisher = Springer | chapter-url = https://books.google.com/books?id=aU_oCAAAQBAJ&pg=PA170 | isbn = 978-3-642-65806-8}}</ref><ref name="AMA1960">{{cite journal | vauthors = ((Council on Drugs)) | year = 1960 | title = Androgens and estrogens in the treatment of disseminated mammary carcinoma: retrospective study of nine hundred forty-four patients | journal = JAMA | volume = 172 | issue = 12 | pages = 1271–83 | doi = 10.1001/jama.1960.03020120049010}}</ref><ref name="SegaloffHorwitt1955">{{cite journal | vauthors = Segaloff A, Horwitt BN, Carabasi RA, Murison PJ, Schlosser JV | title = Hormonal therapy in cancer of the breast. VIII. The effect of dihydrotestosterone (androstanolone) on clinical course and hormonal excretion | journal = Cancer | volume = 8 | issue = 1 | pages = 82–86 | year = 1955 | pmid = 13231036 | doi = 10.1002/1097-0142(1955)8:1<82::AID-CNCR2820080110>3.0.CO;2-R | doi-access = free }}</ref> Shortly thereafter, [[drostanolone propionate]] (2α-methylandrostanolone propionate) was developed for this use instead of androstanolone due to its superior [[pharmacokinetics]] and was introduced for this indication in the [[United States]] and [[Europe]] in the early 1960s.<ref name="pmid13658242">{{cite journal | vauthors = Blackburn CM, Childs DS | title = Use of 2 alpha-methyl androstan-17 beta-ol, 3-one (2-methyl dihydrotestosterone) in the treatment of advanced cancer of the breast | journal = Proceedings of the Staff Meetings of the Mayo Clinic | volume = 34 | issue = 5 | pages = 113–126 | date = March 1959 | pmid = 13658242 }}</ref><ref name="pmid13706491">{{cite journal | vauthors = Goldenberg IS, Hayes MA | title = Hormonal therapy of metastatic female breast carcinoma. II. 2alpha-Methyl dihydrotestosterone propionate | journal = Cancer | volume = 14 | issue = 4 | pages = 705–706 | year = 1961 | pmid = 13706491 | doi = 10.1002/1097-0142(199007/08)14:4<705::AID-CNCR2820140405>3.0.CO;2-I | s2cid = 20924879 | doi-access = free }}</ref><ref name="pmid13920749">{{cite journal | vauthors = Thomas AN, Gordan GS, Lowe R | title = Antitumor efficacy of 2alpha-methyl dihydrotestosterone propionate in advanced breast cancer | journal = Cancer | volume = 15 | pages = 176–178 | year = 1962 | pmid = 13920749 | doi = 10.1002/1097-0142(196201/02)15:1<176::AID-CNCR2820150124>3.0.CO;2-N | s2cid = 71255788 | doi-access = free }}</ref><ref name="Publishing2013">{{cite book | vauthors = Sittig M | publisher = William Andrew Publishing|title=Pharmaceutical Manufacturing Encyclopedia | edition = 3rd |url=https://books.google.com/books?id=_J2ti4EkYpkC&pg=PA1402|date=22 October 2013|isbn=978-0-8155-1856-3|pages=1402–}}</ref>

Androstanolone was used at a dose of 25&nbsp;mg sublingually two to three times per day in androgen replacement therapy for men.<ref name="Brotherton1976" /> This is also the [[anabolic]] dosage of androstanolone in men.<ref name="Brotherton1976" />

{{Androgen replacement therapy formulations and dosages used in men}}

{{Androgen/anabolic steroid dosages for breast cancer}}

===Available forms===

Androstanolone is available as a 2.5% [[hydroalcoholic]] [[gel]] given [[transdermal administration|transdermally]] in doses of 5 or 10&nbsp;g/day (brand name Andractim).<ref name="RastrelliReisman2019" /> The medication was previously available as a 10&nbsp;mg [[oral administration|oral]] [[tablet (pharmacy)|tablet]] with 300&nbsp;mg [[lysine|<small>L</small>-lysine]] (brand name Lysinex) and as a 25&nbsp;mg [[sublingual administration|sublingual]] tablet (brand names Anabolex, Anaprotin, Anabolene, Anaboleen, Proteina).<ref name="Brotherton1976">{{cite book| vauthors = Brotherton J |title=Sex Hormone Pharmacology|url=https://books.google.com/books?id=zt5sAAAAMAAJ|year=1976|publisher=Academic Press|isbn=978-0-12-137250-7|pages=19,43,336,355}}</ref><ref>{{cite book| vauthors = Krüskemper HL |title=Anabolic Steroids|url=https://books.google.com/books?id=4xIlBQAAQBAJ&pg=PA196|date=22 October 2013|publisher=Elsevier|isbn=978-1-4832-6504-9|pages=196–}}</ref> The medication has also been marketed in the form of several [[androstanolone ester]]s, including [[androstanolone benzoate]] (brand names Ermalone-Amp, Hermalone, Sarcosan), [[androstanolone enanthate]] (brand name Anaboleen Depot), [[androstanolone propionate]] (brand name Pesomax), and [[androstanolone valerate]] (brand name Apeton), which are provided as [[oil solution]]s for [[intramuscular injection]] at regular intervals.<ref name="Elks2014" />

==Side effects==

{{See also|Anabolic steroid#Adverse effects}}

[[Adverse effect]]s of androstanolone are similar to those of other AAS and include [[androgen]]ic side effects like [[oily skin]], [[acne]], [[seborrhea]], increased [[facial hair|facial]]/[[body hair]] [[hair growth|growth]], [[pattern hair loss|scalp hair loss]], and increased [[aggressiveness]] and [[sex drive]].<ref name="Llewellyn2009" /><ref name="pmid18500378"/> In women, androstanolone can cause partially irreversible [[virilization]], for instance [[voice deepening]], [[hirsutism]], [[clitoromegaly]], [[breast atrophy]], and [[muscle hypertrophy]], as well as [[menstrual irregularity|menstrual disturbance]]s and reversible [[infertility]].<ref name="Llewellyn2009" /><ref name="pmid18500378"/> In men, the medication may also cause [[hypogonadism]], [[testicular atrophy]], and reversible infertility at sufficiently high dosages.<ref name="Llewellyn2009" /><ref name="pmid18500378"/>

Androstanolone can have adverse effects on the [[cardiovascular system]], especially with long-term administration of high dosages.<ref name="Llewellyn2009" /> AAS like androstanolone stimulate [[erythropoiesis]] ([[red blood cell]] production) and increase [[hematocrit]] levels and at high dosages can cause [[polycythemia]] (overproduction of red blood cells), which can greatly increase the risk of [[thrombosis|thrombic]] events such as [[embolism]] and [[stroke]].<ref name="Llewellyn2009" /> Unlike many other AAS, androstanolone is not [[aromatase|aromatized]] into estrogens and hence has no risk of [[estrogen (medication)|estrogen]]ic side effects like [[gynecomastia]], [[water retention (medicine)|fluid retention]], or [[edema]].<ref name="Llewellyn2009" /><ref name="pmid18500378"/><ref name="BagatellBremner2003">{{cite book| vauthors = Bagatell C, Bremner WJ|title=Androgens in Health and Disease|url=https://books.google.com/books?id=vDcBCAAAQBAJ&pg=PA149|date=27 May 2003|publisher=Springer Science & Business Media|isbn=978-1-59259-388-0|pages=149, 325}}</ref><ref name="Jones2009">{{cite book| vauthors = Jones TH |title=Advances in the Management of Testosterone Deficiency|url=https://books.google.com/books?id=-wOeOf-oR4oC&pg=PA40|year=2009|publisher=Karger Medical and Scientific Publishers|isbn=978-3-8055-8622-1|pages=40–}}</ref> In addition, as it is not a [[17α-alkylated anabolic steroid|17α-alkylated]] AAS and is administered parenterally, androstanolone has no risk of [[hepatotoxicity]].<ref name="Llewellyn2009" /><ref name="pmid18500378"/>

It has been theorized that androstanolone may have less risk of [[benign prostatic hyperplasia]] and [[prostate cancer]] than testosterone because it is not aromatized into estrogens.<ref name="BagatellBremner2003" /><ref name="Jones2009" /> This is relevant because estrogens are thought to possibly be necessary for the manifestation of these diseases.<ref name="BagatellBremner2003" /> In accordance, androstanolone has been found to not increase [[prostate gland]] size in men.<ref name="Jones2009" /> Conversely, due to lack of aromatization into estrogens, androstanolone therapy for androgen replacement may result in decreased [[bone mineral density]], incomplete effects in the [[brain]], and undesirable changes in [[cholesterol]] levels.<ref name="BagatellBremner2003" />

==Pharmacology==

===Pharmacodynamics===

{{Relative androgenic to anabolic activity in animals}}

Androstanolone is a [[potency (pharmacology)|potent]] [[agonist]] of the AR. It has an [[affinity (pharmacology)|affinity]] (K_d) of 0.25 to 0.5&nbsp;nM for the human AR, which is about 2- to 3-fold higher than that of [[testosterone]] (K_d = 0.4 to 1.0&nbsp;nM)<ref name="MozayaniRaymon2011">{{cite book | vauthors = Mozayani A, Raymon L | title = Handbook of Drug Interactions: A Clinical and Forensic Guide | url = https://books.google.com/books?id=NhBJ6kg_uP0C&pg=PA656 | date = 18 September 2011 | publisher = Springer Science & Business Media|isbn=978-1-61779-222-9|pages=656–}}</ref> and the [[dissociation rate]] of androstanolone from the AR is also about 5-fold slower than that of testosterone.<ref>{{cite journal | vauthors = Grino PB, Griffin JE, Wilson JD | title = Testosterone at high concentrations interacts with the human androgen receptor similarly to dihydrotestosterone | journal = Endocrinology | volume = 126 | issue = 2 | pages = 1165–1172 | date = February 1990 | pmid = 2298157 | doi = 10.1210/endo-126-2-1165 }}</ref> The [[EC50|EC₅₀]] of androstanolone for activation of the AR is 0.13&nbsp;nM, which is about 5-fold stronger than that of testosterone (EC₅₀ = 0.66&nbsp;nM).<ref>{{cite book | vauthors = Wilderer PA | title = Treatise on Water Science, Four-Volume Set | chapter = Bioassays for Estrogenic and Androgenic Effects of Water Constituents | chapter-url = https://books.google.com/books?id=HSPtBDpRSXMC&pg=PT1805 | date = 1 September 2010 | publisher = Newnes | isbn = 978-0-444-53199-5 | pages = 1805– }}</ref> In [[bioassay]]s, androstanolone has been found to be 2.5- to 10-fold more potent than testosterone.<ref name="MozayaniRaymon2011" /> Upon intramuscular injection in rats, androstanolone is about 1.5- to 2.5-fold the potency of testosterone.<ref name="Brotherton1976" />

Unlike testosterone and various other AAS, androstanolone cannot be [[aromatase|aromatized]], and for this reason, poses no risk of [[estrogen (medication)|estrogen]]ic [[side effect]]s like [[gynecomastia]] at any dosage.<ref name="Malven1993">{{cite book | vauthors = Malven PV | title = Mammalian Neuroendocrinology|url=https://books.google.com/books?id=nZoRPQa_qTkC&pg=PA228|date=12 January 1993|publisher=CRC Press|isbn=978-0-8493-8757-9|pages=228–}}</ref> In addition, androstanolone cannot be [[metabolism|metabolized]] by [[5α-reductase]] (as it is already 5α-reduced), and for this reason, is not potentiated in so-called "androgenic" tissues like the [[skin]], [[hair follicle]]s, and [[prostate gland]], thereby improving its ratio of [[anabolic]] to [[androgen]]ic effects. However, androstanolone is nonetheless described as a very poor anabolic agent.<ref name="Llewellyn2009">{{cite book | vauthors = Llewellyn W |title=Anabolics|url=https://books.google.com/books?id=afKLA-6wW0oC|year=2009|publisher=Molecular Nutrition Llc|isbn=978-0967930473|pages=19,163}}</ref> This is attributed to its high affinity as a [[substrate (biochemistry)|substrate]] for [[3α-hydroxysteroid dehydrogenase]] (3α-HSD), which is highly expressed in [[skeletal muscle]] and inactivates androstanolone into [[3α-androstanediol]], a metabolite with very weak AR activity.<ref name="Llewellyn2009" /> Unlike androstanolone, testosterone is very resistant to metabolism by 3α-HSD, and so is not similarly inactivated in skeletal muscle.<ref name="Llewellyn2009" /> For the preceding reasons, androstanolone has been described as a "partial androgen".<ref name="RastrelliReisman2019" />

===Pharmacokinetics===

====Absorption====

The [[bioavailability]] of androstanolone differs considerably depending on its [[route of administration]].<ref name="Llewellyn2011" /><ref name="pmid9365393" /> Its [[oral administration|oral]] bioavailability is very low, and androstanolone has been considered to be ineffective by the oral route.<ref name="Llewellyn2011" /> However, it has been used orally, and is described as a weak AAS by this route.<ref name="Brotherton1976" /> The [[transdermal administration|transdermal]] bioavailability of androstanolone is approximately 10%.<ref name="Llewellyn2011" /><ref name="pmid9365393" /> Its bioavailability with [[intramuscular injection]], on the other hand, is complete (100%).<ref name="pmid9365393" />

Doses of topical androstanolone gel of 16, 32, and 64&nbsp;mg have been found to produce total testosterone and DHT levels in the low, mid, and high normal adult male range, respectively.<ref name="BagatellBremner2003" />

====Distribution====

The [[plasma protein binding]] of androstanolone is about 98.5 to 99.0%.<ref name="NieschlagBehre2012">{{cite book | vauthors = Nieschlag E, Behre HM, Nieschlag S | title = Testosterone: Action, Deficiency, Substitution | url = https://books.google.com/books?id=MkrAPaQ4wJkC&pg=PA61|date=26 July 2012|publisher=Cambridge University Press|isbn=978-1-107-01290-5|pages=61–}}</ref> It is bound 50 to 80% to [[sex hormone-binding globulin]], 20 to 40% to [[human serum albumin|albumin]], and less than 0.5% to [[corticosteroid-binding globulin]], with about 1.0 to 1.5% circulating freely or unbound.<ref name="NieschlagBehre2012" />

====Metabolism====

The [[terminal half-life]] of androstanolone in the circulation (53&nbsp;minutes) is longer than that of testosterone (34&nbsp;minutes), and this may account for some of the difference in their potency.<ref name="Publishers1999">{{cite journal | vauthors = Diamanti-Kandarakis E | title = Current aspects of antiandrogen therapy in women | journal = Current Pharmaceutical Design | volume = 5 | issue = 9 | pages = 707–723 | date = September 1999 | pmid = 10495361 | doi = 10.2174/1381612805666230111201150 | url = https://books.google.com/books?id=9rfNZL6oEO0C&pg=PA708 }}</ref> A study of transdermal androstanolone and testosterone therapy reported terminal half-lives of 2.83&nbsp;hours and 1.29&nbsp;hours, respectively.<ref name="MozayaniRaymon2003">{{cite book | vauthors = von Deutsch DA, Abukhalaf IK, Lapu-Bula R | veditors = Mozayani A, Raymon L | chapter = Anabolic Doping Agents | title=Handbook of Drug Interactions: A Clinical and Forensic Guide | chapter-url = https://books.google.com/books?id=dwMyBwAAQBAJ&pg=PA510 | date = 15 October 2003 | publisher = Springer Science & Business Media | isbn = 978-1-59259-654-6 | pages = 510– | doi = 10.1007/978-1-61779-222-9_15 }}</ref>

==Chemistry==

{{Main|Dihydrotestosterone#Chemistry}}

{{See also|List of androgens/anabolic steroids|List of androgen esters#Dihydrotestosterone esters}}

Androstanolone, also known as 5α-androstan-17β-ol-3-one or as 5α-dihydrotestosterone (5α-DHT), is a [[natural product|naturally occurring]] [[androstane]] [[steroid]] with a [[ketone group]] at the C3 position and a [[hydroxyl group]] at the C17β position.<ref name="Elks2014" /><ref name="IndexNominum2000" /> It is the [[chemical derivative|derivative]] of testosterone in which the [[double bond]] between the C4 and C5 positions has been [[redox|reduced]] or [[hydrogenation|hydrogenated]].<ref name="Elks2014" /><ref name="IndexNominum2000" />

===Esters===

{{See also|List of androgen esters#Dihydrotestosterone esters}}

Several C17β [[ester]] [[prodrug]]s of androstanolone, including [[androstanolone benzoate]], [[androstanolone enanthate]], [[androstanolone propionate]], and [[androstanolone valerate]], have been developed and introduced for medical use as AAS. Conversely, [[dihydrotestosterone acetate]], [[dihydrotestosterone butyrate]], and [[dihydrotestosterone formate]] have been developed but have not been marketed.<ref name="Elks2014"/><ref name="MortonHall2012">{{cite book|url=https://books.google.com/books?id=tsjrCAAAQBAJ&pg=PA261|title=Concise Dictionary of Pharmacological Agents: Properties and Synonyms| vauthors = Morton IK, Hall JM |date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-94-011-4439-1|pages=261– }}</ref>

===Derivatives===

{{See also|List of androgens/anabolic steroids|List of androgen esters#Esters of synthetic AAS}}

[[Synthetic compound|Synthetic]] derivatives of androstanolone (DHT) that have been developed as AAS include:<ref name="Llewellyn2011" />

{{Col-begin}}

{{Col-break}}

; Non-17α-alkylated derivatives

* Marketed

** [[Bolazine]] (an [[azine]] [[dimer (chemistry)|dimer]] prodrug of drostanolone)

** [[Drostanolone]] (2α-methyl-DHT)

** [[Epitiostanol]] (2α,3α-epithio-DHT)

** [[Mepitiostane]] (a 17-[[ether]] [[prodrug]] of epitiostanol)

** [[Mesterolone]] (1α-methyl-DHT)

** [[Metenolone]] (1-methyl-δ¹-DHT)

** [[Stenbolone]] (2-methyl-δ¹-DHT)

* Never marketed

** [[1-Testosterone]] (dihydroboldenone; δ¹-DHT)

** [[Mesabolone]] (a 17-ether prodrug of δ¹-DHT)

** [[Prostanozol]] (a 17-ether prodrug of 17α-demethylstanozolol)

{{Col-break}}

; [[17α-Alkylated anabolic steroid|17α-Alkylated]] derivatives

* Marketed

** [[Androisoxazole]] (a 2,3-[[isoxazole]] A ring-fused derivative of 17α-methyl-DHT)

** [[Furazabol]] (a 2,3-[[furan]] A ring-fused derivative of 17α-methyl-DHT)

** [[Mebolazine]] (an azine dimer prodrug of methasterone)

** [[Mestanolone]] (17α-methyl-DHT)

** [[Oxandrolone]] (2-oxa-17α-methyl-DHT)

** [[Oxymetholone]] (2-hydroxymethylene-17α-methyl-DHT)

** [[Stanozolol]] (a 2,3-[[pyrazole]] A [[bicyclic molecule|ring-fused]] derivative of 17α-methyl-DHT)

* Never marketed

** [[Desoxymethyltestosterone]] (3-deketo-17α-methyl-δ²-DHT)

** [[Methasterone]] (2α,17α-dimethyl-DHT)

** [[Methyl-1-testosterone]] (methyldihydroboldenone; 17α-methyl-δ¹-DHT)

** [[Methylepitiostanol]] (2α,3α-epithio-17α-methyl-DHT)

** [[Methylstenbolone]] (2,17α-dimethyl-δ¹-DHT)

{{Col-end}}

==History==

Androstanolone was first discovered and synthesized in 1935 by [[Adolf Butenandt]] and his colleagues.<ref name="Schnitzer1967">{{cite book| vauthors = Schnitzer R |title=Experimental Chemotherapy|url=https://books.google.com/books?id=elAJWRnKqDEC&pg=PA156|date=1 January 1967|publisher=Elsevier Science|isbn=978-0-323-14611-1|pages=156–}}</ref><ref name="Krüskemper2013">{{cite book| vauthors = Krüskemper HL |title= Anabolic Steroids|url=https://books.google.com/books?id=4xIlBQAAQBAJ&pg=PA12|date=22 October 2013|publisher=Elsevier|isbn=978-1-4832-6504-9|pages=12–}}</ref> It was first introduced for medical use in 1953, under the brand name ''Neodrol'' in the [[United States]],<ref name="Publishing2007">{{cite book | vauthors = Sittig M | publisher = William Andrew Publishing|title=Pharmaceutical Manufacturing Encyclopedia|url=https://books.google.com/books?id=dXpUAAAAMAAJ|year=2007 |isbn=978-0-8155-1526-5}}</ref><ref name="Newsweek1953">{{cite book|title=Newsweek|url=https://books.google.com/books?id=tsALAQAAIAAJ|year=1953|publisher=Newsweek}}</ref><ref name="Lippincott1958">{{cite book|title=New and Nonofficial Drugs|url=https://books.google.com/books?id=eY4wAAAAIAAJ|year=1958|publisher=Lippincott}}</ref> and was subsequently marketed in the [[United Kingdom]] and other [[Europe]]an countries.<ref name="Publishing2007" /> Transdermal androstanolone gel has been available in [[France]] since 1982.<ref name="LunenfeldOettel2009">{{cite journal| vauthors = Lunenfeld B, Oettel M |title=Therapeutic potential of testosterone gels|journal=Aging Health|volume=5|issue=2|year=2009|pages=227–245|issn=1745-509X|doi=10.2217/ahe.09.6}}</ref>

==Society and culture==

===Generic names===

When used as a drug, androstanolone is referred to as ''androstanolone'' ({{abbrlink|INN|International Nonproprietary Name}}) or as ''stanolone'' ({{abbrlink|BAN|British Approved Name}}) rather than as DHT.<ref name="HydeGengenbach2007" /><ref name="Elks2014">{{cite book | vauthors = Elks J | title = The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies|url=https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA640|date=14 November 2014|publisher=Springer|isbn=978-1-4757-2085-3|pages=640–}}</ref><ref name="IndexNominum2000">{{cite book|title=Index Nominum 2000: International Drug Directory|url=https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA63|date=January 2000|publisher=Taylor & Francis|isbn=978-3-88763-075-1|pages=63–}}</ref><ref name="Drugs.com">{{cite web | url=https://www.drugs.com/international/androstanolone.html |title = Androstanolone}}</ref>

===Brand names===

Brand names of androstanolone include Anaboleen, Anabolex, Anaprotin ({{abbr|UK|United Kingdom}}), Andractim (formerly AndroGel-DHT) ({{abbr|FR|France}}, {{abbr|BE|Belgium}}, {{abbr|LU|Luxembourg}}), Androlone, Apeton, Gelovit ({{abbr|ES|Spain}}), Neodrol, Ophtovital ({{abbr|DE|Germany}}), Pesomax ({{abbr|IT|Italy}}), Stanaprol, and Stanolone, among others.<ref name="HydeGengenbach2007" /><ref name="Elks2014" /><ref name="IndexNominum2000" /><ref name="AdisInsight-HPG-CHX" /><ref name="ListHörhammer2013">{{cite book | vauthors = List PH, Hörhammer L| title = Chemikalien und Drogen: Teil B: R, S|url=https://books.google.com/books?id=VXutBgAAQBAJ&pg=PA523|date=12 March 2013|publisher=Springer-Verlag|isbn=978-3-642-66377-2|pages=523–}}</ref><ref name="Drugs.com" /><ref name="GoorenBunck2004" />

===Availability===

The availability of pharmaceutical androstanolone is limited; it is not available in the [[United States]] or [[Canada]],<ref name="Drugs@FDA">{{cite web |title=Drugs@FDA: FDA Approved Drug Products |publisher=United States Food and Drug Administration |access-date=16 November 2016 |url=http://www.accessdata.fda.gov/scripts/cder/daf/}}</ref><ref name="DPD@HealthCanada">{{cite web |title=Drug Product Database - Health Canada |date=18 March 2010 |publisher=Health Canada |url=http://www.hc-sc.gc.ca/dhp-mps/prodpharma/databasdon/index-eng.php |access-date=13 November 2016}}</ref> but it is or has been available in certain [[Europe]]an countries, including the [[United Kingdom]], [[Germany]], [[France]], [[Spain]], [[Italy]], [[Belgium]], and [[Luxembourg]].<ref name="IndexNominum2000" /><ref name="AdisInsight-HPG-CHX" /><ref name="Drugs.com" /><ref name="GoorenBunck2004" /><ref name="Brotherton1976" />

The available formulations of androstanolone include [[buccal administration|buccal]] or [[sublingual administration|sublingual]] [[tablet (pharmacy)|tablet]]s (Anabolex, Stanolone), [[topical gels]] (Andractim, Gelovit, Ophtovital), and, as [[ester]]s in [[oil]], [[injectable]]s like [[androstanolone propionate]] (Pesomax) and [[androstanolone valerate]] (Apeton).<ref name="HydeGengenbach2007" /><ref name="AdisInsight-HPG-CHX" /><ref name="ListHörhammer2013" /><ref name="Brotherton1976" /> [[Androstanolone benzoate]] (Ermalone-Amp, Hermalone, Sarcosan) and [[androstanolone enanthate]] (Anaboleen Depot) are additional androstanolone esters that are available for medical use in some countries.<ref name="Elks2014" /> Androstanolone esters act as [[prodrug]]s of androstanolone in the body and have a long-lasting [[depot injection|depot]] effect when given via [[intramuscular injection]].<ref name="HydeGengenbach2007" />

===Legal status===

Androstanolone, along with other AAS, is a [[Controlled Substances Act#Schedule III controlled substances|schedule III]] [[controlled substance]] in the [[United States]] under the [[Controlled Substances Act]].<ref name="FFFLM2006">{{cite book|vauthors = Karch S|title=Drug Abuse Handbook, Second Edition|url=https://books.google.com/books?id=ZjrMBQAAQBAJ&pg=PA30|date=21 December 2006|publisher=CRC Press|isbn=978-1-4200-0346-8|pages=30–}}</ref>

Androstanolone is on the [[World Anti-Doping Agency]]'s list of prohibited substances,<ref>{{cite web|url=https://www.wada-ama.org/sites/default/files/wada_2020_english_prohibited_list_0.pdf|title=The World Anti-Doping Code: The 2020 Prohibited List|publisher=[[World Anti-Doping Agency]]|access-date=28 December 2019}}</ref> and is therefore banned from use in most major sports.

==Research==

In the early- to mid-2000s, transdermal or topical androstanolone was under development in the [[United States]] for the treatment of [[hypogonadism]] (as a form of [[androgen replacement therapy]]), male [[osteoporosis]], and [[cachexia]] (in [[cancer]] patients) and in [[Australia]] for the treatment of [[benign prostatic hyperplasia]] (BPH).<ref name="AdisInsight-HPG-BPH">{{cite web | url=http://adisinsight.springer.com/drugs/800019178 |title = Androgen replacement therapy | work = AdisInsight | publisher = Springer Nature Switzerland AG }}</ref><ref name="AdisInsight-OSP">{{cite web | url=https://adisinsight.springer.com/drugs/800016161 | title=Dihydrotestosterone-transdermal | work = AdisInsight | publisher = Springer Nature Switzerland AG }}</ref><ref name="AdisInsight-HPG-CHX">{{cite web | url=http://adisinsight.springer.com/drugs/800011409 |title = Androstanolone | work = AdisInsight | publisher = Springer Nature Switzerland AG }}</ref> It reached [[Phases of clinical research#Phase II|phase II]] [[clinical trial]]s for hypogonadism and BPH and [[Phases of clinical research#Phase III|phase III]] clinical studies for cachexia but development was ultimately never completed for these indications in these specific countries.<ref name="AdisInsight-HPG-BPH" /><ref name="AdisInsight-OSP" /><ref name="AdisInsight-HPG-CHX" /> Although androstanolone itself has not been approved for cachexia in any country, an [[oral administration|orally active]] [[synthetic compound|synthetic]] [[chemical derivative|derivative]] of androstanolone, [[oxandrolone]] (2-oxa-17α-methylandrostanolone), is approved and used for this indication in the United States.<ref name="NelmsSucher2010">{{cite book | vauthors = Nelms M, Sucher KP, Lacey K, Roth SL | title = Nutrition Therapy and Pathophysiology|url=https://books.google.com/books?id=rSgIAAAAQBAJ&pg=PT766|date=16 June 2010|publisher=Cengage Learning|isbn=978-1-133-00809-5|pages=766–}}</ref><ref name="Mantovani2007">{{cite book | vauthors = Mantovani G | title = Cachexia and Wasting: A Modern Approach|url=https://books.google.com/books?id=lQyGxrmQ17AC&pg=PA673|date=6 October 2007|publisher=Springer Science & Business Media|isbn=978-88-470-0552-5|pages=673–}}</ref>

Topical androgens like androstanolone have been used and studied in the treatment of [[cellulite]] in women.<ref name="pmid12626029">{{cite journal | vauthors = Gruber CJ, Wieser F, Gruber IM, Ferlitsch K, Gruber DM, Huber JC | title = Current concepts in aesthetic endocrinology | journal = Gynecological Endocrinology | volume = 16 | issue = 6 | pages = 431–441 | date = December 2002 | pmid = 12626029 | doi = 10.1080/gye.16.6.431.441 | s2cid = 37424524 }}</ref> Topical androstanolone on the abdomen has also been found to significantly decrease subcutaneous abdominal fat in women, and hence may be useful for improving body silhouette.<ref name="pmid12626029" /> However, men and [[hyperandrogenism|hyperandrogenic]] women have higher amounts of abdominal fat than healthy women, and androgen therapy has been found to increase abdominal fat in [[postmenopause|postmenopausal]] women and [[transgender men]].<ref name="pmid25781555">{{cite journal | vauthors = Sam S | title = Adiposity and metabolic dysfunction in polycystic ovary syndrome | journal = Hormone Molecular Biology and Clinical Investigation | volume = 21 | issue = 2 | pages = 107–116 | date = February 2015 | pmid = 25781555 | doi = 10.1515/hmbci-2015-0008 | s2cid = 23592351 }}</ref>

== References ==

{{Reflist}}

== External links ==

*

* [https://adisinsight.springer.com/drugs/800011409 Androstanolone (for hypogonadism and cachexia) - AdisInsight]

* [https://adisinsight.springer.com/drugs/800019178 Androstanolone (for hypogonadism and BPH) - AdisInsight]

* [https://adisinsight.springer.com/drugs/800016161 Androstanolone (for male osteoporosis) - AdisInsight]

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