VA Class:HS100
ATC Class:G03BA01
Fluoxymesterone is a synthetic androgenic anabolic steroid hormone.
Fluoxymesterone is used mainly for replacement or substitution of diminished or absent endogenous testicular hormone.
In males, fluoxymesterone is used for the management of congenital or acquired primary hypogonadism such as that resulting from orchiectomy or from testicular failure caused by cryptorchidism, bilateral torsion, orchitis, or vanishing testis syndrome. Fluoxymesterone also is used in males for the management of congenital or acquired hypogonadotropic hypogonadism such as that resulting from idiopathic gonadotropin or gonadotropin releasing hormone (luteinizing hormone releasing hormone) deficiency or from pituitary-hypothalamic injury caused by tumors, trauma, or radiation. If any of these conditions occur before puberty, androgen replacement therapy will be necessary during adolescence for the development of secondary sexual characteristics and prolonged therapy will be required to maintain these characteristics. Prolonged androgen therapy also is required to maintain sexual characteristics in other males who develop testosterone deficiency after puberty.
When the diagnosis is well established, fluoxymesterone may be used to stimulate puberty in carefully selected males with delayed puberty. These males usually have a family history of delayed puberty that is not caused by a pathologic disorder. Brief treatment with conservative doses of an androgen occasionally may be justified in these males if they do not respond to psychologic support. Because androgens may adversely affect bone maturation in these prepubertal males, this potential risk should be fully discussed with the patient and his parents prior to initiation of androgen therapy. (See Cautions: Pediatric Precautions.) If androgen therapy is initiated in these prepubertal males, radiographs of the hand and wrist should be obtained at 6-month intervals to determine the effect of therapy on the epiphyseal centers.
In females, fluoxymesterone is used for the palliative treatment of androgen-responsive, advanced, inoperable, metastatic (skeletal) carcinoma of the breast in women who are 1-5 years postmenopausal. Primary goals of therapy in these women include ablation of the ovaries. Other methods of counteracting estrogen activity include adrenalectomy, hypophysectomy, and/or antiestrogen therapy (e.g., tamoxifen). Androgen therapy also has been used in premenopausal women with carcinoma of the breast who have benefited from oophorectomy and are considered to have a hormone-responsive tumor. The decision to use androgen therapy in women with carcinoma of the breast should be made by an oncologist with expertise in the treatment of this carcinoma.
Fluoxymesterone also has been used for the prevention of postpartum breast pain and engorgement†; however, the drug does not appear to prevent or suppress lactation.
In females, fluoxymesterone has been used concomitantly with estrogens (i.e., ethinyl estradiol) for the management of moderate to severe vasomotor symptoms associated with menopause in patients who do not respond adequately to estrogens alone†. Estrogens do not appear to be effective for the management of nervous symptoms or depression associated with menopause†, and the drugs should not be used in the management of such conditions in these patients.
Although fluoxymesterone also has been used in other conditions (e.g., fractures, surgery, convalescence, functional uterine bleeding), there is lack of substantial evidence that androgens are effective in these conditions.
Because of their anabolic and androgenic effects on performance (ergogenic potential) and physique, androgens have been misused and abused by athletes, bodybuilders, weightlifters, and others, including high school- and college-aged individuals engaged in sports.193, 194 Following review of data from published literature and case reports in October 2016, the FDA concluded that misuse and abuse of androgens are associated with serious adverse cardiovascular, hepatic, endocrine, and mental health effects.193, 194 (See Cautions; see also Uses: Misuse, Abuse, and Dependence, in Testosterone 68:08.)
Serum testosterone concentrations should be evaluated in patients who may be misusing or abusing androgens (e.g., patients experiencing serious adverse cardiovascular or psychiatric effects); however, serum testosterone concentrations may be below or within the normal range in patients abusing synthetic derivatives of testosterone.135, 194
Fluoxymesterone is administered orally; the drug may be given as a single daily dose or in 3 or 4 divided doses.
Dosage of fluoxymesterone is variable and should be individualized according to the condition being treated, the severity of symptoms, and the patient's age, gender, and history of prior androgenic therapy.
For complete replacement of endogenous testicular hormone in androgen-deficient males, the usual dosage of fluoxymesterone is 5-20 mg daily. This dosage will provide complete replacement in most patients. In general, therapy is initiated at a higher level within the range (e.g., 10 mg daily); subsequent dosage adjustment should be made according to the patient's tolerance and therapeutic response. If priapism occurs, the drug should be temporarily discontinued and subsequently reinstituted at a lower dosage.
Various dosage regimens have been used to induce pubertal changes in hypogonadal males. Some clinicians recommend that lower dosages be used initially, followed by gradual increases in dosage as puberty progresses; subsequently, the dosage may be decreased to maintenance levels. Other clinicians state that higher dosages are required initially to induce pubertal changes and lower dosages can then be used for maintenance therapy after puberty. The chronologic and skeletal ages of the patient must be considered when determining the initial dosage and subsequent dosage adjustment. In general, short-term administration (e.g., 4-6 months) of fluoxymesterone and dosages in the lower range for replacement are used for the treatment of delayed puberty in males; dosage should be titrated carefully using low doses. Dosage for the treatment of delayed puberty in males ranges from 2.5-20 mg daily, although most patients respond to dosages of 2.5-10 mg daily.
Inoperable Carcinoma of the Breast
For the palliative treatment of advanced, inoperable carcinoma of the breast in women, the usual dosage of fluoxymesterone is 10-40 mg daily. Because of fluoxymesterone's short duration of action, the drug should be administered in divided, rather than single, daily doses to maintain more stable blood concentrations in these patients.
In general, it appears that at least 1 month of therapy is necessary to obtain a satisfactory subjective response, and at least 2-3 months of continuous therapy is required to obtain a satisfactory objective response.
Postpartum Breast Pain and Engorgement
For the prevention of postpartum breast pain and engorgement†, an initial fluoxymesterone dose of 2.5 mg has been recommended to be given shortly after parturition; thereafter, a dosage of 5-10 mg daily has been recommended, preferably to be given in divided doses, for 4-5 days.
Vasomotor Symptoms Associated with Menopause
When fluoxymesterone is used concomitantly with ethinyl estradiol for the short-term management of moderate to severe vasomotor symptoms associated with menopause†, the lowest possible effective dosage should be used and therapy should be discontinued as soon as possible. Attempts to reduce dosage or discontinue the drugs should be made at 3- to 6-month intervals. The usual recommended dosage of fluoxymesterone is 1 or 2 mg given concomitantly with 0.02 or 0.04 mg of ethinyl estradiol, respectively, twice daily. The drugs are administered twice daily for 21 consecutive days, followed by 7 days without the drugs, and then this regimen is repeated as necessary. Women with an intact uterus receiving fluoxymesterone concomitantly with ethinyl estradiol should be closely monitored for signs of endometrial carcinoma, and appropriate diagnostic measures to rule out malignancy should be employed if persistent or recurring abnormal vaginal bleeding occurs during therapy with the drugs.
Adverse effects associated with fluoxymesterone are similar to those of other synthetic or natural androgens and include acne, gynecomastia, and edema. If edema is present before or develops during therapy, administration of diuretics may be required. Gynecomastia frequently develops and occasionally persists in patients being treated for hypogonadism.
Oligospermia and decreased ejaculatory volume may occur in male patients receiving excessive dosage or prolonged administration of the drug. Priapism or excessive sexual stimulation in males, especially geriatric patients, also may occur. If priapism or excessive sexual stimulation develops during fluoxymesterone therapy, the drug should be discontinued temporarily, since these are signs of excessive dosa if therapy with fluoxymesterone is reinstituted, a lower dosage should be used. Male pattern of baldness also may occur.
Amenorrhea and other menstrual irregularities and inhibition of gonadotropin secretion occur commonly in females. Virilization, including deepening of the voice, hirsutism, and clitoral enlargement, also occur commonly in females; these changes may not be reversible following discontinuance of the drug.
Hypersensitivity reactions, including skin manifestations and anaphylactoid reactions, have occurred with fluoxymesterone.
Hypercalcemia resulting from osteolysis, especially in immobile patients and those with metastatic carcinoma of the breast, has been reported in patients receiving fluoxymesterone. The drug should be discontinued if hypercalcemia occurs in patients with cancer since this may indicate progression of metastases to the bone. Retention of water, sodium, chloride, potassium, and inorganic phosphates also has occurred in patients receiving the drug.
Cholestatic hepatitis and jaundice and abnormal liver function test results may occur in patients receiving 17-α-alkylandrogens such as fluoxymesterone. These adverse hepatic effects may occur at relatively low doses of the drug. Drug-induced jaundice usually is reversible following discontinuance of the drug. Fluoxymesterone should be discontinued if cholestatic jaundice or hepatitis occurs, or if liver function test results become abnormal during therapy with the drug; the etiology of these disorders should be determined. Peliosis of the liver and hepatocellular neoplasms, including hepatocellular adenoma and carcinoma, have been reported rarely in patients receiving long-term administration of androgenic anabolic steroids. Peliosis of the liver can be a life-threatening or fatal complication of androgen therapy.
Serious adverse effects (e.g., increased aggression, antisocial behavior, manic episode, hostility, depression, changes in libido, increased risk of cardiovascular events, hepatotoxicity, testicular atrophy, sperm abnormalities) are associated with misuse and abuse of androgens (see Uses: Misuse, Abuse, and Dependence). Fluoxymesterone preparations currently are subject to control under the Federal Controlled Substances Act of 1970, as amended by the Anabolic Steroids Control Act of 1990 and 2004, as schedule III (C-III) drugs.135, 193, 194, 195 Manifestations of withdrawal (e.g., depressed mood, major depression, fatigue, cravings, restlessness, irritability, anorexia, insomnia, decreased libido, hypogonadotropic hypogonadism) may occur if androgens are discontinued abruptly or dosage is substantially reduced in physically dependent patients or in those taking supratherapeutic dosages of such drugs; withdrawal symptoms may persist for weeks or months.135
Other adverse effects associated with fluoxymesterone therapy include nausea, polycythemia, headache, anxiety, mental depression, generalized paresthesia, and suppression of clotting factors II, V, VII, and X. Serum cholesterol concentration may increase during androgen therapy.
Precautions and Contraindications
Fluoxymesterone shares the toxic potentials of other androgens, and the usual precautions of androgen therapy should be observed.
Fluoxymesterone should be used with caution in patients with cardiac, renal, or hepatic dysfunction, since edema, with or without congestive heart failure, may occur as a result of sodium and water retention. If edema occurs during fluoxymesterone therapy and it is considered a serious complication, the drug should be discontinued; diuretic therapy may also be necessary. Liver function should be evaluated periodically during use of fluoxymesterone.
Females should be carefully monitored for signs of virilization (e.g., deepening of the voice, hirsutism, clitoromegaly, menstrual irregularities) during fluoxymesterone therapy. The drug generally should be discontinued when mild virilization is evident, since some adverse androgenic effects (e.g., voice changes) may not subside following discontinuance of the drug. The woman and physician may decide that some virilization is acceptable during treatment for carcinoma of the breast.
Males should be carefully monitored for the development of priapism or excessive sexual stimulation since these are signs of excessive dosage. Males, especially geriatric patients, may become overly stimulated. (See also Cautions: Adverse Effects.) Geriatric males may be at increased risk of developing prostatic hypertrophy and carcinoma during androgen therapy.
Adult or adolescent males should be advised to report too frequent or persistent penile erections to their clinician. Females should be advised to report hoarseness, acne, menstrual changes, or the growth of facial hair to their clinician. All patients should be advised to report nausea, vomiting, changes in skin color, or ankle swelling to their physician.
Patients receiving high dosages of or long-term therapy with fluoxymesterone should have periodic hemoglobin and hematocrit determinations, since polycythemia may occur.
Fluoxymesterone is contraindicated in males with carcinoma of the breast or known or suspected carcinoma of the prostate. The manufacturers state that the drug also is contraindicated in patients with serious cardiac, renal, or hepatic disease and in patients with known hypersensitivity to the drug. Because of the potential risk of serious adverse health effects, fluoxymesterone should not be used for enhancement of athletic performance or physique. (See Uses: Misuse, Abuse, and Dependence in Testosterone 68:08.) Patients should be informed of the serious adverse effects associated with misuse and abuse of androgens.135
Androgens should be used with extreme caution in children and only by specialists who are aware of the adverse effects of these drugs on bone maturation. Fluoxymesterone should be used cautiously to stimulate puberty, and only in carefully selected males with delayed puberty. (See Uses: Uses in Males.) In children, fluoxymesterone may accelerate bone maturation without producing compensatory gain in linear growth. This adverse effect may result in compromised adult stature. The younger the child, the greater the risk of fluoxymesterone compromising final mature stature. If fluoxymesterone is administered to prepubertal children (e.g., to stimulate puberty in males), the drug should be used with extreme caution, and radiographic examination of the hand and wrist should be performed every 6 months to determine the rate of bone maturation and to assess the effect of treatment on the epiphyseal centers. If fluoxymesterone is to be used to stimulate puberty in a male with delayed puberty, the potential risk of therapy should be fully discussed with the patient and his parents prior to initiation of the drug.
Mutagenicity and Carcinogenicity
Studies to evaluate the mutagenic potential of fluoxymesterone have not been performed to date. Hepatocellular carcinoma has reportedly occurred in patients receiving long-term therapy with high dosages of androgens. Regression of the tumor does not always occur following discontinuance of androgen therapy. Geriatric patients may be at increased risk of developing prostatic hypertrophy and carcinoma during androgen therapy. The carcinogenic potential of fluoxymesterone appears to be associated with the androgenic effects of the drug.
Following implantation of testosterone in mice, cervical-uterine tumors developed which occasionally metastasized. There is some evidence to suggest that injection of testosterone into some strains of female mice increases their susceptibility to hepatomas. Testosterone also has been shown to increase the number of tumors and decrease the degree of differentiation of chemically induced tumors in rats.
Pregnancy, Fertility, and Lactation
Fluoxymesterone may cause fetal harm when administered to pregnant women. Androgenic effects including clitoral hypertrophy, labial fusion of the external genitalia to form a scrotal-like structure, and persistence of a urogenital sinus have occurred in the female offspring of women who were given androgens during pregnancy. Since the risks clearly outweigh the possible benefits in women who are or may become pregnant, fluoxymesterone is contraindicated in such women.
Although the effect of fluoxymesterone on fertility in humans has not been conclusively determined, the drug produces oligospermia and decreased ejaculatory volume in males. Priapism and excessive sexual stimulation also have occurred in males receiving the drug. (See Cautions: Adverse Effects.) Increased or decreased libido also has been reported.
It is not known whether fluoxymesterone is distributed into milk. Because of the potential for serious adverse reactions to androgens in nursing infants, a decision should be made whether to discontinue nursing or to not use fluoxymesterone, taking into account the importance of the drug to the woman.
Fluoxymesterone may potentiate the action of oral anticoagulants, causing bleeding in some patients. When fluoxymesterone therapy is initiated in patients receiving oral anticoagulants, dosage reduction of the anticoagulant may be required to prevent an excessive hypoprothrombinemic response. Patients receiving oral anticoagulants also should be closely monitored when androgen therapy is discontinued.
The metabolic effects of androgens may decrease blood glucose concentrations and insulin requirements in patients with diabetes.
Protein bound iodine (PBI) concentrations may be decreased in some patients during fluoxymesterone therapy; however, this does not appear to be clinically important. Androgens may decrease thyroxine-binding globulin concentrations, resulting in decreased total serum thyroxine (T4) concentrations and increased resin uptake of triiodothyronine (T3) and T4. Free thyroid hormone concentrations remain unchanged, and there is no clinical evidence of thyroid dysfunction.
Endogenous androgens are essential hormones that are responsible for the normal growth and development of the male sex organs and for maintenance of secondary sex characteristics, including the growth and maturation of the prostate, seminal vesicles, penis, and scrotum; development of male hair distribution, such as beard, pubic, chest, and axillary hair; laryngeal enlargement and thickening of the vocal cords; and alterations in body musculature and fat distribution. Fluoxymesterone is approximately 5 times as potent as methyltestosterone and has androgenic activity equal to parenterally administered testosterone.
Like testosterone and other androgenic anabolic hormones, fluoxymesterone produces retention of nitrogen, potassium, and phosphorus; increases protein anabolism; and decreases amino acid catabolism. Weight gain is usually promoted. Fluoxymesterone decreases urinary concentrations of calcium, and causes recalcification of osseous metastases and regression of soft tissue lesions.
Androgens are responsible for the growth spurt that occurs during adolescence and for the eventual termination of linear growth that results from fusion of the epiphyseal growth centers. Although exogenous androgens accelerate linear growth rates in children, the drugs may cause a disproportionate advancement in bone maturation, and long-term administration of the drugs in prepubertal children may result in fusion of the epiphyseal growth centers and premature termination of the growth process.
Exogenous administration of androgens inhibits the release of endogenous testosterone via feedback inhibition of pituitary luteinizing hormone (LH). Following administration of large doses of exogenous androgens, spermatogenesis also may be suppressed as a result of feedback inhibition of pituitary follicle-stimulating hormone (FSH).
Androgens reportedly stimulate the production of erythrocytes, apparently by enhancing the production of erythropoietic stimulating factor.
Fluoxymesterone is a synthetic androgenic anabolic steroid hormone. The drug is a halogenated derivative of 17-α-methyltestosterone.
Fluoxymesterone occurs as a white or practically white, odorless, crystalline powder and is practically insoluble in water and sparingly soluble in alcohol.
Commercially available fluoxymesterone tablets should be protected from light and stored in well-closed containers at 20-25°C.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Fluoxymesterone is subject to control under the Federal Controlled Substances Act of 1970, as amended by the Anabolic Steroids Control Act of 1990 and 2004, as a schedule III (C-III) drug. (See the introductory paragraph under Preparations, in Testosterone 68:08.)
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Tablets | 10 mg* | Androxy® (C-III) | |
Fluoxymesterone Tablets (C-III) |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Only references cited for selected revisions after 1984 are available electronically.
135. Abbvie. AndroGel® 1% (testosterone) topical gel prescribing information. North Chicago, IL; 2016 Oct.
193. Christou MA, Christou PA, Markozannes G et al. Effects of Anabolic Androgenic Steroids on the Reproductive System of Athletes and Recreational Users: A Systematic Review and Meta-Analysis. Sports Med . 2017; 47:1869-83. [PubMed 28258581]
194. Food and Drug Administration. Testosterone and other anabolic androgenic steroids (AAS): FDA statement - risks associated with abuse and dependence. Silver Spring, MD; 2016 Oct 25. From the FDA website. Accessed 2017 Apr 7. [Web]
195. Drug Enforcement Administration (DEA), Department of Justice. Implementation of the Anabolic Steroid Control Act of 2004. Final rule. [21 CFR Part 1300 and 1308] Fed Regist . 2005; 70:74653-8.