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| Clinical data | |
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| Trade names | Halotestin, Ora-Testryl, Ultandren, others |
| Other names | Fluoxymestrone; Androfluorene; NSC-12165; 9α-Fluoro-11β-hydroxy-17α-methyltestosterone; 9α-Fluoro-17α-methylandrost-4-en-11β,17β-diol-3-one |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a682690 |
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| Routes of administration | By mouth[1] |
| Drug class | Androgen;Anabolic steroid |
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| Pharmacokinetic data | |
| Bioavailability | Oral: 80%[3] |
| Metabolism | Liver (6β-hydroxylation,5α- and5β-reduction,3α- and3β-keto-oxidation,11β-hydroxy-oxidation)[4] |
| Metabolites | • 5α-Dihydrofluoxymesterone[4] •11-Oxofluoxymesterone[4] |
| Eliminationhalf-life | 9.2 hours[5][6] |
| Excretion | Urine (<5% unchanged)[3][4] |
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| ECHA InfoCard | 100.000.875 |
| Chemical and physical data | |
| Formula | C20H29FO3 |
| Molar mass | 336.447 g·mol−1 |
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Fluoxymesterone, sold under the brand namesHalotestin andUltandren among others, is anandrogen andanabolic steroid (AAS) medication which is used in the treatment oflow testosterone levels in men,delayed puberty in boys,breast cancer in women, andanemia.[1] It is takenby mouth.[1]
Side effects of fluoxymesterone includesymptoms ofmasculinization likeacne,increased hair growth,voice changes, and increasedsexual desire.[1] It can also causeliver damage andcardiovascular side effects likehigh blood pressure.[1][7][8] The drug is asynthetic androgen and anabolic steroid and hence is anagonist of theandrogen receptor (AR), thebiological target of androgens liketestosterone anddihydrotestosterone (DHT).[1][9] It has strongandrogenic effects and moderateanabolic effects, which make it useful for producing masculinization.[1][10]
Fluoxymesterone was first described in 1956 and was introduced for medical use in 1957.[1][11] In addition to its medical use, fluoxymesterone is used toimprove physique and performance.[1] The drug is acontrolled substance in many countries and so non-medical use is generally illicit.[1]
Fluoxymesterone is or has been used in the treatment ofhypogonadism,delayed puberty, andanemia in males and the treatment ofbreast cancer in women.[1][12] It is specifically approved in one or more countries for the treatment of hypogonadism in men, delayed puberty in boys, and breast cancer in women.[13] Current prescribing guidelines in theUnited States list only the treatment ofandrogen deficiency in males and breast cancer in females as indications.[1]
Fluoxymesterone is less effective in inducing masculinization than testosterone, but is useful for maintaining established masculinization in adults.[14]
| Route | Medication | Major brand names | Form | Dosage |
|---|---|---|---|---|
| Oral | Testosteronea | – | Tablet | 400–800 mg/day (in divided doses) |
| Testosterone undecanoate | Andriol, Jatenzo | Capsule | 40–80 mg/2–4× day (with meals) | |
| Methyltestosteroneb | Android, Metandren, Testred | Tablet | 10–50 mg/day | |
| Fluoxymesteroneb | Halotestin, Ora-Testryl, Ultandren | Tablet | 5–20 mg/day | |
| Metandienoneb | Dianabol | Tablet | 5–15 mg/day | |
| Mesteroloneb | Proviron | Tablet | 25–150 mg/day | |
| Sublingual | Testosteroneb | Testoral | Tablet | 5–10 mg 1–4×/day |
| Methyltestosteroneb | Metandren, Oreton Methyl | Tablet | 10–30 mg/day | |
| Buccal | Testosterone | Striant | Tablet | 30 mg 2×/day |
| Methyltestosteroneb | Metandren, Oreton Methyl | Tablet | 5–25 mg/day | |
| Transdermal | Testosterone | AndroGel, Testim, TestoGel | Gel | 25–125 mg/day |
| Androderm, AndroPatch, TestoPatch | Non-scrotal patch | 2.5–15 mg/day | ||
| Testoderm | Scrotal patch | 4–6 mg/day | ||
| Axiron | Axillary solution | 30–120 mg/day | ||
| Androstanolone (DHT) | Andractim | Gel | 100–250 mg/day | |
| Rectal | Testosterone | Rektandron, Testosteronb | Suppository | 40 mg 2–3×/day |
| Injection (IMTooltip intramuscular injection orSCTooltip subcutaneous injection) | Testosterone | Andronaq, Sterotate, Virosterone | Aqueous suspension | 10–50 mg 2–3×/week |
| Testosterone propionateb | Testoviron | Oil solution | 10–50 mg 2–3×/week | |
| Testosterone enanthate | Delatestryl | Oil solution | 50–250 mg 1x/1–4 weeks | |
| Xyosted | Auto-injector | 50–100 mg 1×/week | ||
| Testosterone cypionate | Depo-Testosterone | Oil solution | 50–250 mg 1x/1–4 weeks | |
| Testosterone isobutyrate | Agovirin Depot | Aqueous suspension | 50–100 mg 1x/1–2 weeks | |
| Testosterone phenylacetateb | Perandren, Androject | Oil solution | 50–200 mg 1×/3–5 weeks | |
| Mixed testosterone esters | Sustanon 100, Sustanon 250 | Oil solution | 50–250 mg 1×/2–4 weeks | |
| Testosterone undecanoate | Aveed, Nebido | Oil solution | 750–1,000 mg 1×/10–14 weeks | |
| Testosterone buciclatea | – | Aqueous suspension | 600–1,000 mg 1×/12–20 weeks | |
| Implant | Testosterone | Testopel | Pellet | 150–1,200 mg/3–6 months |
| Notes: Men produce about 3 to 11 mg of testosterone per day (mean 7 mg/day in young men).Footnotes:a = Never marketed.b = No longer used and/or no longer marketed.Sources: See template. | ||||
| Route | Medication | Major brand names | Form | Dosage |
|---|---|---|---|---|
| Oral | Testosterone undecanoate | Andriol, Jatenzo | Capsule | 40–80 mg 1x/1–2 days |
| Methyltestosterone | Metandren, Estratest | Tablet | 0.5–10 mg/day | |
| Fluoxymesterone | Halotestin | Tablet | 1–2.5 mg 1x/1–2 days | |
| Normethandronea | Ginecoside | Tablet | 5 mg/day | |
| Tibolone | Livial | Tablet | 1.25–2.5 mg/day | |
| Prasterone (DHEA)b | – | Tablet | 10–100 mg/day | |
| Sublingual | Methyltestosterone | Metandren | Tablet | 0.25 mg/day |
| Transdermal | Testosterone | Intrinsa | Patch | 150–300 μg/day |
| AndroGel | Gel, cream | 1–10 mg/day | ||
| Vaginal | Prasterone (DHEA) | Intrarosa | Insert | 6.5 mg/day |
| Injection | Testosterone propionatea | Testoviron | Oil solution | 25 mg 1x/1–2 weeks |
| Testosterone enanthate | Delatestryl, Primodian Depot | Oil solution | 25–100 mg 1x/4–6 weeks | |
| Testosterone cypionate | Depo-Testosterone, Depo-Testadiol | Oil solution | 25–100 mg 1x/4–6 weeks | |
| Testosterone isobutyratea | Femandren M, Folivirin | Aqueous suspension | 25–50 mg 1x/4–6 weeks | |
| Mixed testosterone esters | Climacterona | Oil solution | 150 mg 1x/4–8 weeks | |
| Omnadren, Sustanon | Oil solution | 50–100 mg 1x/4–6 weeks | ||
| Nandrolone decanoate | Deca-Durabolin | Oil solution | 25–50 mg 1x/6–12 weeks | |
| Prasterone enanthatea | Gynodian Depot | Oil solution | 200 mg 1x/4–6 weeks | |
| Implant | Testosterone | Testopel | Pellet | 50–100 mg 1x/3–6 months |
| Notes:Premenopausal women produce about 230 ± 70 μgtestosterone per day (6.4 ± 2.0 mg testosterone per 4 weeks), with a range of 130 to 330 μg per day (3.6–9.2 mg per 4 weeks).Footnotes:a = Mostly discontinued or unavailable.b =Over-the-counter.Sources: See template. | ||||
| Route | Medication | Form | Dosage | |
|---|---|---|---|---|
| Oral | Methyltestosterone | Tablet | 30–200 mg/day | |
| Fluoxymesterone | Tablet | 10–40 mg 3x/day | ||
| Calusterone | Tablet | 40–80 mg 4x/day | ||
| Normethandrone | Tablet | 40 mg/day | ||
| Buccal | Methyltestosterone | Tablet | 25–100 mg/day | |
| Injection (IMTooltip intramuscular injection orSCTooltip subcutaneous injection) | Testosterone propionate | Oil solution | 50–100 mg 3x/week | |
| Testosterone enanthate | Oil solution | 200–400 mg 1x/2–4 weeks | ||
| Testosterone cypionate | Oil solution | 200–400 mg 1x/2–4 weeks | ||
| Mixed testosterone esters | Oil solution | 250 mg 1x/week | ||
| Methandriol | Aqueous suspension | 100 mg 3x/week | ||
| Androstanolone (DHT) | Aqueous suspension | 300 mg 3x/week | ||
| Drostanolone propionate | Oil solution | 100 mg 1–3x/week | ||
| Metenolone enanthate | Oil solution | 400 mg 3x/week | ||
| Nandrolone decanoate | Oil solution | 50–100 mg 1x/1–3 weeks | ||
| Nandrolone phenylpropionate | Oil solution | 50–100 mg/week | ||
| Note: Dosages are not necessarily equivalent.Sources: See template. | ||||
Fluoxymesterone is available in the form of 2, 5, and 10 mgoraltablets.[15]
Fluoxymesterone is used forphysique- and performance-enhancing purposes bycompetitiveathletes,bodybuilders, andpowerlifters.[1]
Side effects that have been associated with fluoxymesterone includeacne,edema,seborrhea/seborrheic dermatitis,alopecia,hirsutism,voice deepening,virilization in general,flushing,gynecomastia,breast pain,menstrual disturbances,hypogonadism,testicular atrophy,clitoral enlargement,penile enlargement,priapism, increasedaggressiveness,prostate enlargement,cardiovascular toxicity, andhepatotoxicity, among others.[1][16]
| Medication | Ratioa |
|---|---|
| Testosterone | ~1:1 |
| Androstanolone (DHT) | ~1:1 |
| Methyltestosterone | ~1:1 |
| Methandriol | ~1:1 |
| Fluoxymesterone | 1:1–1:15 |
| Metandienone | 1:1–1:8 |
| Drostanolone | 1:3–1:4 |
| Metenolone | 1:2–1:3 |
| Oxymetholone | 1:2–1:9 |
| Oxandrolone | 1:13–1:3 |
| Stanozolol | 1:1–1:3 |
| Nandrolone | 1:3–1:16 |
| Ethylestrenol | 1:2–1:19 |
| Norethandrolone | 1:1–1:2 |
| Notes: In rodents.Footnotes:a = Ratio of androgenic to anabolic activity.Sources: See template. | |
As an AAS, fluoxymesterone is anagonist of theandrogen receptor (AR), similarly toandrogens liketestosterone and DHT.[1][17] It is asubstrate for5α-reductase like testosterone, and so is potentiated in so-called "androgenic" tissues like theskin,hair follicles, andprostate gland viatransformation into5α-dihydrofluoxymesterone.[1][17][4] As such, fluoxymesterone has a relatively poor ratio ofanabolic toandrogenic activity similarly to testosterone andmethyltestosterone.[1][17] However, fluoxymesterone is nonetheless proportionally less androgenic and more anabolic than methyltestosterone and testosterone.[10]
Fluoxymesterone has been reported to be non-aromatizable due tosteric hindrance by its C11βhydroxyl group,[18] and hence is not considered to have a propensity for producingestrogenic effects such asgynecomastia orfluid retention.[1][19] However, paradoxically, a case report of severe fluoxymesterone-induced gynecomastia exists, and gynecomastia associated with fluoxymesterone has also been reported in other publications, although this may not be due to estrogenic activity.[20] Fluoxymesterone is thought to possess little or noprogestogenic activity.[1][17]
Because of the presence of its 17α-methyl group, themetabolism of fluoxymesterone is impeded, resulting in it beingorally active, although alsohepatotoxic.[1][17]
Fluoxymesterone has been found to act as apotentinhibitor of11β-hydroxysteroid dehydrogenasetype 2 (11β-HSD2) (IC50Tooltip Half-maximal inhibitory concentration = 60–630 nM), with a potency comparable to that of the 11β-HSD2 inhibitorglycyrrhetinic acid.[7][8] This action of fluoxymesterone is unique among AAS and is likely related to its 11β-hydroxyl group.[7] 11β-HSD2 is responsible for theinactivation of theglucocorticoidscortisol andcorticosterone (intocortisone and11-dehydrocorticosterone, respectively).[7][8] Inhibition of 11β-HSD2 by fluoxymesterone may result inmineralocorticoid receptor overactivation and associated side effects such ashypertension andfluid retention, and has been hypothesized to be involved in thecardiovascular and otheradverse effects of fluoxymesterone.[7][8]
Unlike other AAS, fluoxymesterone has structural features in common withcorticosteroids, including its C9αfluoro and C11βhydroxylgroups.[21] In relation to this, it has weak (micromolar) but potentially clinically significantaffinity for theglucocorticoid receptor.[22]
Fluoxymesterone has approximately 80%oralbioavailability, unlike testosterone, as the C17αmethyl group of fluoxymesterone inhibitsfirst-pass metabolism.[3][1] It has very lowaffinity for human serumsex hormone-binding globulin (SHBG), less than 5% of that of testosterone and less than 1% of that of DHT.[23] The drug ismetabolized in theliver, mainly by 6β-hydroxylation,5α- and5β-reduction,3α- and3β-keto-oxidation, and11β-hydroxy-oxidation.[4] Its knownactive metabolites include5α-dihydrofluoxymesterone and11-oxofluoxymesterone.[4][7][24][10] Fluoxymesterone has anelimination half-life of approximately 9.2 hours, which is long relative to that of testosterone.[5] It iseliminated in theurine, with less than 5%excreted unchanged.[3][4]
Fluoxymesterone, also known as 9α-fluoro-11β-hydroxy-17α-methyltestosterone or as 9α-fluoro-17α-methylandrost-4-en-11β,17β-diol-3-one, is asyntheticandrostanesteroid and a17α-alkylatedderivative oftestosterone (androst-4-en-17β-ol-3-one).[25][26] It is specifically the derivative of testosterone with afluorine atom at the C9α position, ahydroxyl group at the C11β position, and amethyl group at the C17α position.[25][26]
Step one: The first step in the synthesis of fluoxymesterone is the microbiological oxidation of commercially available androstenedione (1.11) byActinomyces; this introduces a hydroxyl group to the 11α-position (1.12), which is then oxidised to a ketone using Jones' reagent, yielding the 3,11,17-triketone, adrenosterone (1.13). Pyrrolidine then reacts to form an enamine (1.14) by reaction with the 3α-keto group, protecting it from alkylation in a subsequent step. The regioselectivity of pyrrolidine for reaction at the 3α-position occurs inherently in the structure of adrenosterone, due to the position of the sterically bulky methyl groups. In subsequent steps, alkylation of the 17-keto group (1.14) using Grignard reagent, addition of hydride at the 11-position (1.15) and regeneration of the protected 3-keto group yields the starting material (1.16) for the final steps of the fluoxymesterone synthesis. This involves more standard synthetic transformations.
Step two:The 11α-hydroxyl of the starting material (1.16) is sulfonylated byp-toluenesulfonyl chloride; addition of trimethylamine (base) deprotonates the 11α-carbon, yielding an (E2) elimination of tosylate (pka - 5) to give olefin (1.17). Stereospecificity of reaction between olefin and hypobromous acid (HOBr) in base,N-bromosuccinimide (NBS), is determined by the formation of a bromonium intermediate; the electrophilic bromonium cation approaches the ring's less sterically hinderedα-face and is attacked by the π-electron density of the alkene. The hydroxide ion then attacks from above the ring (β-face) at the 11-carbon, resulting in a structure (1.18) by the stereospecific addition of hydroxyl and bromine across the double bond. Addition of sodium hydroxide results in deprotonation of the 11α-hydroxyl, and the subsequent structure undergoes an intramolecular SN2 epoxy ring formation. The epoxy ring of theβ-epoxide (1.19) is protonated to give an oxironium ion intermediate. In a concerted process, fluoride attacks the ring'sα-face from below, as one of the two oxygen-carbon bonds is broken on the opposite face; hence regenerating the 11α-hydroxyl trans to the fluorine substituent. The resulting structure (1.20) is the androgenic steroid, fluoxymesterone.
Detection of halotestin and other such illegal anabolic steroids in sports is achieved by GS-MS identification of urinary excreted anabolic steroids and their metabolites. In a test for halotestin, a dry residue obtained from a urine sample is dissolved in dimethylformamide and a sulfur trioxide-pyridine complex and is heated with 1% potassium carbonate solution. Halotestin and many of its metabolites contain two polar hydroxyl groups, leading to intermolecular hydrogen bonding that increases their boiling point and reduces volatility. In order to attain a gaseous sample for GC-MS, the products of hydrolysis are extracted, dissolved in methanol and derivatised to form volatile trimethylsilyl (TMS) esters by addingN-methyl-N-trimethylsilyl-trifluoroacetamide (MSTFA) and trimethylsilylimidazole (TMSImi).[27]
Fluoxymesterone was first described in 1956 and was introduced for medical use in theUnited States in 1957.[1][11] Over time the use of fluoxymesterone has become increasingly controversial and limited.[1]
Fluoxymesterone is thegeneric name of the drug and itsINNTooltip International Nonproprietary Name,USPTooltip United States Pharmacopeia,BANTooltip British Approved Name,DCITTooltip Denominazione Comune Italiana, andJANTooltip Japanese Accepted Name, whilefluoxymestérone is itsDCFTooltip Dénomination Commune Française.[25][26][28][29]
Brand names of fluoxymesterone include Android-F, Androxy, Halotestin, Ora-Testryl, and Ultandren among others.[25][26][28][29]
Fluoxymesterone is one of the few AAS that remains available for medical use in theUnited States.[30] The others (as of August 2023) aretestosterone,testosterone cypionate,testosterone enanthate,testosterone undecanoate,methyltestosterone, andoxymetholone.[30]
Availability of fluoxymesterone aside from the United States remains scarce, but it is marketed in some other countries such asMexico,Moldova, andTaiwan.[1][29]
Fluoxymesterone, along with other AAS, is aschedule IIIcontrolled substance in theUnited States under theControlled Substances Act.[31]
