Androstanolone

{{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 | image_class = skin-invert-image | width = 225px | image2 = Dihydrotestosterone molecule ball.png | image_class2 = bg-transparent | width2 = 225px

| tradename = Andractim, others | pregnancy_category = X | routes_of_administration = Transdermal (gel), in the cheek, under the tongue, intramuscular injection (as esters) | class = Androgen; Anabolic steroid

| 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: Very low<ref name="Llewellyn2011" /> Transdermal: 10%<ref name="Llewellyn2011" /><ref name="pmid9365393" /> {{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: 2.8 hours<ref name="MozayaniRaymon2003" /> | excretion = Urine

| CAS_number_Ref = {{cascite|correct|CAS}} | CAS_number = 521-18-6 | ATC_prefix = A14 | ATC_suffix = AA01 | PubChem = 10635 | IUPHAR_ligand = 2856 | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank = DB02901 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 10189 | 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

| 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 }}  '''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 hormone which is used mainly in the treatment of 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 breast development and small penis in males.<ref name="Llewellyn2011" /> Compared to testosterone, androstanolone (DHT) is less likely to aromatize into estrogen, and therefore it shows less pronounced estrogenic side effects, such as gynecomastia and 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 androgenic effects and muscle-building effects, as well as relatively weak estrogenic effects.<ref name="Llewellyn2011" />

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

Side effects of androstanolone include symptoms of masculinization like acne, increased hair growth, voice changes, and increased sexual desire.<ref name="Llewellyn2011" /> The medication is a 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>

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 not permitted.<ref name="Llewellyn2011" />

==Medical uses== Androstanolone is available in pharmaceutical formulations for 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 |date=2019 |location=Singapore | publisher = Springer | doi = 10.1007/978-981-13-1226-7_8 | isbn = 978-981-13-1225-0 | doi-access = free }}</ref> Topical androstanolone is useful in the treatment of gynecomastia.<ref name="AgrawalGanie2017">{{cite book |title=Basics of Human Andrology |vauthors=Agrawal S, Ganie MA, Nisar S |date=2017 |publisher=Springer |isbn=978-981-10-3694-1 |location=Singapore |pages=451–458 |chapter=Gynaecomastia |doi=10.1007/978-981-10-3695-8_26}}</ref>{{Additional citation needed|date=June 2025|reason=This claim is unsupported by the primary sources this secondary source cites.}} Similarly, androstanolone enanthate via intramuscular injection has been found to be effective in the treatment persistent 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 small penis in pre- and peripubertal boys with 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 |author=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 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}}

===Available forms=== Androstanolone is available as a 2.5% hydroalcoholic gel given transdermally in doses of 5 or 10 g/day (brand name Andractim).<ref name="RastrelliReisman2019" /> The medication was previously available as a 10 mg oral tablet with 300 mg L-lysine (brand name Lysinex) and as a 25 mg 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 esters, 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 solutions for intramuscular injection at regular intervals.<ref name="Elks2014" />

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

Adverse effects of androstanolone are similar to those of other AAS and include androgenic side effects like oily skin, acne, seborrhea, increased facial/body hair growth, 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 disturbances 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 thrombic events such as embolism and stroke.<ref name="Llewellyn2009" /> Unlike many other AAS, androstanolone is not aromatized into estrogens and hence has no risk of estrogenic side effects like gynecomastia, 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 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 potent agonist of the AR. It has an affinity (Kd) of 0.25 to 0.5 nM for the human AR, which is about 2- to 3-fold higher than that of testosterone (Kd = 0.4 to 1.0 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 of androstanolone for activation of the AR is 0.13 nM, which is about 5-fold stronger than that of testosterone (EC50 = 0.66 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 bioassays, 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 aromatized, and for this reason, poses no risk of estrogenic side effects 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 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 follicles, and prostate gland, thereby improving its ratio of anabolic to androgenic 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=978-0-9679304-7-3|pages=19,163}}</ref> This is attributed to its high affinity as a 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 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 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 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 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 minutes) is longer than that of testosterone (34 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 | url-access = subscription }}</ref> A study of transdermal androstanolone and testosterone therapy reported terminal half-lives of 2.83 hours and 1.29 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 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 derivative of testosterone in which the double bond between the C4 and C5 positions has been reduced or hydrogenated.<ref name="Elks2014" /><ref name="IndexNominum2000" />

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

Several C17β ester prodrugs 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 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 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 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 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 European 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=https://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 European 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 or sublingual tablets (Anabolex, Stanolone), topical gels (Andractim, Gelovit, Ophtovital), and, as esters in oil, injectables 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 prodrugs of androstanolone in the body and have a long-lasting depot effect when given via intramuscular injection.<ref name="HydeGengenbach2007" />

===Legal status=== Androstanolone, along with other AAS, is a 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 phase II clinical trials for hypogonadism and BPH and 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 orally active synthetic 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 hyperandrogenic women have higher amounts of abdominal fat than healthy women, and androgen therapy has been found to increase abdominal fat in 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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