FLUOXYMESTERONE

US Previously Marketed

First approved in 1956

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C20H29FO3
Molecular Weight	336.4409
Optical Activity	UNSPECIFIED
Defined Stereocenters	7 / 7
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@@]12CC[C@](C)(O)[C@@]1(C)C[C@H](O)[C@@]3(F)[C@@]2([H])CCC4=CC(=O)CC[C@]34C

InChI

InChIKey=YLRFCQOZQXIBAB-RBZZARIASA-N

InChI=1S/C20H29FO3/c1-17-8-6-13(22)10-12(17)4-5-15-14-7-9-19(3,24)18(14,2)11-16(23)20(15,17)21/h10,14-16,23-24H,4-9,11H2,1-3H3/t14-,15-,16-,17-,18-,19-,20-/m0/s1

HIDE SMILES / InChI

Molecular Formula	C20H29FO3
Molecular Weight	336.4409
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	7 / 7
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.drugs.com/ppa/fluoxymesterone.html
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/17439112 | http://reference.staging.medscape.com/drug/androxy-fluoxymesterone-342776

Fluoxymesterone, sold under the brand names Halotestin and Ultandren among others, is a synthetic, orally active androgenic-anabolic steroid (AAS) and a 17α-alkylated derivative of testosterone developed by Pharmacia & Upjohn Company LLC, approved by FDA at 1956. Fluoxymesterone is used in the treatment of hypogonadism in males and breast cancer in women. Fluoxymesterone has a relatively high ratio of androgenic to anabolic activity similarly to testosterone. Like many 17α-alkylated AAS, it has a relatively low affinity for the androgen receptor (AR). However, its actions are mediated by the AR, most likely due to its relatively long elimination half-life of approximately 9.2 hours.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Androgen Receptor 167 Target ID: CHEMBL1871 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17439112	Agonist 2678		0.3 nM [EC50]

Conditions

Condition	Modality	Highest Phase	Product
Male hypogonadism 1 Sources: https://www.drugs.com/ppa/fluoxymesterone.html	Primary	Approved 8429	HALOTESTIN Approved Use Males ANDROXY™ Tablets are indicated for replacement therapy in conditions associated with a deficiency or absence of endogenous testosterone. Primary hypogonadism (congenital or acquired) Testicular failure due to cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome, or orchidectomy. Hypogonadotropic hypogonadism (congenital or acquired) Idiopathic gonadotropin or luteinizing hormone-releasing hormone (LHRH) deficiency, or pituitary-hypothalamic injury from tumors, trauma, or radiation. (Appropriate adrenal cortical and thyroid hormone replacement therapy are still necessary, however, and are actually of primary importance.) If the above conditions occur prior to puberty, androgen replacement therapy will be needed during the adolescent years for development of secondary sexual characteristics. Prolonged androgen treatment will be required to maintain sexual characteristics in these and other males who develop testosterone deficiency after puberty. Delayed puberty ANDROXY™ (Fluoxymesterone Tablets, USP) may be used to stimulate puberty in carefully selected males with clearly delayed puberty. These patients usually have a familial pattern of delayed puberty that is not secondary to a pathological disorder; puberty is expected to occur spontaneously at a relatively late date. Brief treatment with conservative doses may occasionally be justified in these patients if they do not respond to psychological support. The potential adverse effect on bone maturation should be discussed with the patient and parents prior to androgen administration. An X-ray of the hand and wrist to determine bone age should be obtained every six months to assess the effect of treatment on the epiphyseal centers (see WARNINGS). Females Metastatic mammary cancer ANDROXY™ (Fluoxymesterone Tablets, USP) may be used secondarily in women with advancing inoperable metastatic (skeletal) mammary cancer who are one to five years postmenopausal. Primary goals of therapy in these women include ablation of the ovaries. Other methods of counteracting estrogen activity are adrenalectomy, hypophysectomy, and/or antiestrogen therapy. This treatment has been used in premenopausal women with breast cancer who have benefited from oophorectomy and are considered to have a hormone-responsive tumor. Judgment concerning androgen therapy should be made by an oncologist with expertise in this field. Launch Date 1956
Delayed male puberty 1 Sources: https://www.drugs.com/ppa/fluoxymesterone.html	Primary	Approved 8429	HALOTESTIN Approved Use Males ANDROXY™ Tablets are indicated for replacement therapy in conditions associated with a deficiency or absence of endogenous testosterone. Primary hypogonadism (congenital or acquired) Testicular failure due to cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome, or orchidectomy. Hypogonadotropic hypogonadism (congenital or acquired) Idiopathic gonadotropin or luteinizing hormone-releasing hormone (LHRH) deficiency, or pituitary-hypothalamic injury from tumors, trauma, or radiation. (Appropriate adrenal cortical and thyroid hormone replacement therapy are still necessary, however, and are actually of primary importance.) If the above conditions occur prior to puberty, androgen replacement therapy will be needed during the adolescent years for development of secondary sexual characteristics. Prolonged androgen treatment will be required to maintain sexual characteristics in these and other males who develop testosterone deficiency after puberty. Delayed puberty ANDROXY™ (Fluoxymesterone Tablets, USP) may be used to stimulate puberty in carefully selected males with clearly delayed puberty. These patients usually have a familial pattern of delayed puberty that is not secondary to a pathological disorder; puberty is expected to occur spontaneously at a relatively late date. Brief treatment with conservative doses may occasionally be justified in these patients if they do not respond to psychological support. The potential adverse effect on bone maturation should be discussed with the patient and parents prior to androgen administration. An X-ray of the hand and wrist to determine bone age should be obtained every six months to assess the effect of treatment on the epiphyseal centers (see WARNINGS). Females Metastatic mammary cancer ANDROXY™ (Fluoxymesterone Tablets, USP) may be used secondarily in women with advancing inoperable metastatic (skeletal) mammary cancer who are one to five years postmenopausal. Primary goals of therapy in these women include ablation of the ovaries. Other methods of counteracting estrogen activity are adrenalectomy, hypophysectomy, and/or antiestrogen therapy. This treatment has been used in premenopausal women with breast cancer who have benefited from oophorectomy and are considered to have a hormone-responsive tumor. Judgment concerning androgen therapy should be made by an oncologist with expertise in this field. Launch Date 1956
Inoperable metastatic female breast cancer 1 Sources: https://www.drugs.com/ppa/fluoxymesterone.html	Primary	Approved 8429	HALOTESTIN Approved Use Males ANDROXY™ Tablets are indicated for replacement therapy in conditions associated with a deficiency or absence of endogenous testosterone. Primary hypogonadism (congenital or acquired) Testicular failure due to cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome, or orchidectomy. Hypogonadotropic hypogonadism (congenital or acquired) Idiopathic gonadotropin or luteinizing hormone-releasing hormone (LHRH) deficiency, or pituitary-hypothalamic injury from tumors, trauma, or radiation. (Appropriate adrenal cortical and thyroid hormone replacement therapy are still necessary, however, and are actually of primary importance.) If the above conditions occur prior to puberty, androgen replacement therapy will be needed during the adolescent years for development of secondary sexual characteristics. Prolonged androgen treatment will be required to maintain sexual characteristics in these and other males who develop testosterone deficiency after puberty. Delayed puberty ANDROXY™ (Fluoxymesterone Tablets, USP) may be used to stimulate puberty in carefully selected males with clearly delayed puberty. These patients usually have a familial pattern of delayed puberty that is not secondary to a pathological disorder; puberty is expected to occur spontaneously at a relatively late date. Brief treatment with conservative doses may occasionally be justified in these patients if they do not respond to psychological support. The potential adverse effect on bone maturation should be discussed with the patient and parents prior to androgen administration. An X-ray of the hand and wrist to determine bone age should be obtained every six months to assess the effect of treatment on the epiphyseal centers (see WARNINGS). Females Metastatic mammary cancer ANDROXY™ (Fluoxymesterone Tablets, USP) may be used secondarily in women with advancing inoperable metastatic (skeletal) mammary cancer who are one to five years postmenopausal. Primary goals of therapy in these women include ablation of the ovaries. Other methods of counteracting estrogen activity are adrenalectomy, hypophysectomy, and/or antiestrogen therapy. This treatment has been used in premenopausal women with breast cancer who have benefited from oophorectomy and are considered to have a hormone-responsive tumor. Judgment concerning androgen therapy should be made by an oncologist with expertise in this field. Launch Date 1956

C_max

Value	Dose	Co-administered	Analyte	Population
80 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/4009439	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:		FLUOXYMESTERONE serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
100 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/4009439	10 mg single, buccal dose: 10 mg route of administration: Buccal experiment type: SINGLE co-administered:		FLUOXYMESTERONE serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
306 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/4009439	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:		FLUOXYMESTERONE serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
391 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/4009439	10 mg single, buccal dose: 10 mg route of administration: Buccal experiment type: SINGLE co-administered:		FLUOXYMESTERONE serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/4009439	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:		FLUOXYMESTERONE serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

Doses

Dose	Population	Adverse events
40 mg 1 times / day multiple, oral (max) Recommended Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=5328c194-5650-4d1f-9e28-8cea038cce81&type=display https://pubmed.ncbi.nlm.nih.gov/577673	unhealthy Health Status: unhealthy Condition: Conditions associated with a deficiency or absence of endogenous testosterone\|Metastatic mammary cancer Sources: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=5328c194-5650-4d1f-9e28-8cea038cce81&type=display https://pubmed.ncbi.nlm.nih.gov/577673	Disc. AE: Peliosis hepatis... AEs leading to discontinuation/dose reduction: Peliosis hepatis (grade 4-5) Sources: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=5328c194-5650-4d1f-9e28-8cea038cce81&type=display https://pubmed.ncbi.nlm.nih.gov/577673

AEs

AE	Significance	Dose	Population
Peliosis hepatis	grade 4-5 Disc. AE	40 mg 1 times / day multiple, oral (max) Recommended Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=5328c194-5650-4d1f-9e28-8cea038cce81&type=display https://pubmed.ncbi.nlm.nih.gov/577673	unhealthy Health Status: unhealthy Condition: Conditions associated with a deficiency or absence of endogenous testosterone\|Metastatic mammary cancer Sources: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=5328c194-5650-4d1f-9e28-8cea038cce81&type=display https://pubmed.ncbi.nlm.nih.gov/577673

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:5120	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:5120
ChemicalBook	CB9258118	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB9258118
ZINC	ZINC000003875484	http://zinc15.docking.org/substances/ZINC000003875484

PubMed

Title	Date	PubMed
Impotence therapy and cancer of the prostate.	1976 May	58562
Ataxia caused by fluoxymesterone therapy in breast cancer.	1981 Jun	7235823
Hormone stimulation and chemotherapy in advanced prostate cancer: preliminary results of a prospective controlled clinical trial.	1985 Mar-Apr	3888046
Peliosis hepatis after long-term androgen therapy.	1985 May	3992778
Hormone stimulation and chemotherapy in advanced prostate cancer: interim analysis of an ongoing randomized trial.	1986 Mar-Apr	3518596
Androgen depletion and repletion as a means of potentiating the effect of cytotoxic chemotherapy in advanced prostate cancer.	1987	3695494
Splenic and hepatic peliosis: MR findings.	1992 Jan	1727362
Sample size calculations for the two-sample problem using the multiplicative intensity model.	2001 Feb 28	11223901
Androgen responsiveness of the pituitary gonadotrope cell line LbetaT2.	2001 Sep	11524240
A49T, V89L and TA repeat polymorphisms of steroid 5alpha-reductase type II and breast cancer risk in Japanese women.	2002	12100746
Factors affecting progression-free survival in hormone-dependent metastatic breast cancer patients receiving high-dose chemotherapy and hematopoietic progenitor cell transplantation: role of maintenance endocrine therapy.	2002 May	12058236
The androgen-regulated gene human kallikrein 15 (KLK15) is an independent and favourable prognostic marker for breast cancer.	2002 Nov 18	12439720
Optimization and validation of conventional and micellar LC methods for the analysis of methyltestosterone in sugar-coated pills.	2003 Feb 5	12560066
Screening of free 17-alkyl-substituted anabolic steroids in human urine by liquid chromatography-electrospray ionization tandem mass spectrometry.	2004 Feb	15013688
Analysis of anabolic steroids by partial filling micellar electrokinetic capillary chromatography and electrospray mass spectrometry.	2004 Jun 18	15248432
Mitochondrial function in diaphragm of emphysematous hamsters after treatment with nandrolone.	2006	18046906
Randomized trial of tamoxifen alone or combined with fluoxymesterone as adjuvant therapy in postmenopausal women with resected estrogen receptor positive breast cancer. North Central Cancer Treatment Group Trial 89-30-52.	2006 Jul	16538529
[Secondary hypogonadism].	2006 Jun 28	16817386
Partial filling micellar electrokinetic chromatography analysis of androgens and testosterone derivatives using two sequential pseudostationary phases.	2006 Oct 27	16949594
Testosterone depot injection in male hypogonadism: a critical appraisal.	2007	18225458
Letrozole in advanced breast cancer: the PO25 trial.	2007	17333340
Phase III study of standard combination versus rotating regimen of induction chemotherapy in patients with hormone insensitive metastatic breast cancer: an Eastern Cooperative Oncology Group Intergroup Study (E3185).	2007 Apr	17414459
Mini-dose of thalidomide for treatment of primary myelofibrosis. Report of a case with complete reversal of bone marrow fibrosis and splenomegaly.	2007 Feb	17405746
How do distress and well-being relate to medical student empathy? A multicenter study.	2007 Feb	17356983
An orally active selective androgen receptor modulator is efficacious on bone, muscle, and sex function with reduced impact on prostate.	2007 Jan	17023534
Liquid chromatographic method development for steroids determination (corticoids and anabolics). Application to animal feed samples.	2007 Jul 13	17451720
Novel series of potent, nonsteroidal, selective androgen receptor modulators based on 7H-[1,4]oxazino[3,2-g]quinolin-7-ones.	2007 May 17	17439112
Determination of association constants between steroid compounds and albumins by partial-filling ACE.	2007 Oct	17893945
Pharmacogenetics and pharmacogenomics of endocrine agents for breast cancer.	2008	19128430
1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE) disrupts the estrogen-androgen balance regulating the growth of hormone-dependent breast cancer cells.	2008	18275596
Characterization and quantification of fluoxymesterone metabolite in horse urine by gas chromatography/mass spectrometry.	2008 Jul	18614835
Elucidation of urinary metabolites of fluoxymesterone by liquid chromatography-tandem mass spectrometry and gas chromatography-mass spectrometry.	2008 Mar	18035854
Efficient approach for the comprehensive detection of unknown anabolic steroids and metabolites in human urine by liquid chromatography-electrospray-tandem mass spectrometry.	2008 Mar 1	18220370
Liquid chromatographic method development for anabolic androgenic steroids using a monolithic column Application to animal feed samples.	2008 Mar 17	18298974
Systematic review of the clinical effect of glucocorticoids on nonhematologic malignancy.	2008 Mar 28	18373855
The development of multiple drug use among anabolic-androgenic steroid users: six subjective case reports.	2008 Nov 28	19040748
Simultaneous doping analysis of main urinary metabolites of anabolic steroids in horse by ion-trap gas chromatography-tandem mass spectrometry.	2008 Sep	18781036
Development of a rapid method for the analysis of synthetic growth promoters in bovine muscle using liquid chromatography tandem mass spectrometry.	2009 Apr 1	19286019
Megestrol acetate versus metronomic cyclophosphamide in patients having exhausted all effective therapies under standard care.	2010 Apr 13	20354522
Treatment of cachexia in oncology.	2010 Sep	21218002
The anabolic androgenic steroid fluoxymesterone inhibits 11β-hydroxysteroid dehydrogenase 2-dependent glucocorticoid inactivation.	2012 Apr	22273746

Patents

Sample Use Guides

In Vivo Use Guide

Hypogonadism (Males): 5-20 mg daily Delayed puberty (Males): 2.5-20 mg daily for 4-6 months Inoperable breast carcinoma (Females): 10-40 mg daily in divided doses for ≥3 months

Route of Administration: Oral

In Vitro Use Guide

MDA-MB-453 cells were used for Androgen Receptor binding assays. Media containing 0.3 nM [3H]DHT and Fluoxymesterone in concentrations ranging from 10-10 to 10-6 M were added to the cells. Three replicates were used for each sample. After 3 h at 37 C, an aliquot of the total binding media at each concentration was removed to determine the amount of free [3H]DHT.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 14:58:49 GMT 2023` Edited by `admin` on `Fri Dec 15 14:58:49 GMT 2023`
Record UNII	9JU12S4YFY
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

FLUOXYMESTERONE

Official Name

English

9-Fluoro-11β,17β-dihydroxy-17-methylandrost-4-en-3-one

Common Name

English

ANDROST-4-EN-3-ONE, 9-FLUORO-11,17-DIHYDROXY-17-METHYL-, (11.BETA.,17.BETA.)-

Common Name

English

FLUOXYMESTERONE [HSDB]

Common Name

English

FLUOXYMESTERONE [VANDF]

Common Name

English

FLUOXYMESTERONE CIII

Common Name

English

ANDROID-F

Brand Name

English

FLUOXYMESTERONE [USP MONOGRAPH]

Common Name

English

FLUOXYMESTERONE [MI]

Common Name

English

NSC-12165

Code

English

ORA-TESTRYL

Brand Name

English

FLUOXYMESTERONE CIII [USP-RS]

Common Name

English

FLUOXYMESTERONE [JAN]

Common Name

English

NSC-10704

Code

English

Fluoxymesterone [WHO-DD]

Common Name

English

FLUOXYMESTERONE [ORANGE BOOK]

Common Name

English

HALOTESTIN

Brand Name

English

FLUOXYMESTERONE [MART.]

Common Name

English

fluoxymesterone [INN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C243