safety and efficacy of methyltestosterone in men with “age-related hypogonadism” (also referred to as “late-onset hypogonadism”) have not been established. androgens 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 6 months to assess the effect of treatment on the epiphyseal centers (see warnings ). 2. females androgens may be used secondarily in women with advancing inoperable metastatic (skeletal) mammary cancer who are 1 to 5 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 also been used in premenopausal women with breast cancer who have benefitted 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.

t is lacking. there have been postmarketing reports of venous thromboembolic events, including deep vein thrombosis (dvt) and pulmonary embolism (pe), in patients using testosterone products, such as methyltestosterone. evaluate patients who report symptoms of pain, edema, warmth and erythema in the lower extremity for dvt and those who present with acute shortness of breath for pe. if a venous thromboembolic event is suspected, discontinue treatment with methyltestosterone and initiate appropriate workup and management. long term clinical safety trials have not been conducted to assess the cardiovascular outcomes of testosterone replacement therapy in men. to date, epidemiologic studies and randomized controlled trials have been inconclusive for determining the risk of major adverse cardiovascular events (mace), such as non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death, with the use of testosterone compared to non-use. some studies, but not all, have reported an increased risk of mace in association with use of testosterone replacement therapy in men. patients should be informed of this possible risk when deciding whether to use or to continue to use methyltestosterone. testosterone has been subject to abuse, typically at doses higher than recommended for the approved indication and in combination with other anabolic androgenic steroids. anabolic androgenic steroid abuse can lead to serious cardiovascular and psychiatric adverse reactions (see drug abuse and dependence ). if testosterone abuse is suspected, check serum testosterone concentrations to ensure they are within therapeutic range. however, testosterone levels may be in the normal or subnormal range in men abusing synthetic testosterone derivatives. counsel patients concerning the serious adverse reactions associated with abuse of testosterone and anabolic androgenic steroids. conversely, consider the possibility of testosterone and anabolic androgenic steroid abuse in suspected patients who present with serious cardiovascular or psychiatric adverse events. edema with or without congestive heart failure may be a serious complication in patients with pre-existing cardiac, renal or hepatic disease. in addition to discontinuation of the drug, diuretic therapy may be required. gynecomastia frequently develops and occasionally persists in patients being treated for hypogonadism. androgen therapy should be used cautiously in healthy males with delayed puberty. the effect on bone maturation should be monitored by assessing bone age of the wrist and hand every 6 months. in children, androgen treatment 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 compromising final mature height. this drug has not been shown to be safe and effective for the enhancement of athletic performance. because of the potential risk of serious adverse health effects, this drug should not be used for such purpose.

t higher dosages are needed to induce pubertal changes and lower dosages can be used for maintenance after puberty. the chronological and skeletal ages must be taken into consideration, both in determining the initial dose and in adjusting the dose. dosages used in delayed puberty generally are in the lower ranges of those given above, and are for limited duration, for example, 4 to 6 months. females: women with metastatic breast carcinoma must be followed closely because androgen therapy occasionally appears to accelerate the disease. thus, many experts prefer to use the shorter acting androgen preparations rather than those with prolonged activity for treating breast carcinoma particularly during the early stages of androgen therapy. guideline dosages of androgens for use in the palliative treatment of women with metastatic breast cancer are 50 mg to 200 mg daily.

ogic: suppression of clotting factors ii, v, vii, and x, bleeding in patients on concomitant anticoagulant therapy, and polycythemia. nervous system: increased or decreased libido, headache, anxiety, depression, and generalized paresthesia. metabolic: increased serum cholesterol. vascular disorders: venous thromboembolism. miscellaneous: rarely, anaphylactoid reactions. to report suspected adverse reactions, contact amneal pharmaceuticals at 1-877-835-5472 or fda at 1-800-fda-1088 or www.fda.gov/medwatch.

near growth rates, but may cause a disproportionate advancement in bone maturation. use over long periods may result in fusion of the epiphyseal growth centers and termination of growth process. androgens have been reported to stimulate the production of red blood cells by enhancing the production of erythropoietic stimulating factor. during exogenous administration of androgens, endogenous testosterone release is inhibited through feedback inhibition of pituitary luteinizing hormone (lh). with large doses of exogenous androgens, spermatogenesis may also be suppressed through feedback inhibition of pituitary follicle stimulating hormone (fsh). there is a lack of substantial evidence that androgens are effective in fractures, surgery, convalescence, and functional uterine bleeding. pharmacokinetics testosterone given orally is metabolized by the gut and 44% is cleared by the liver in the first pass. oral doses as high as 400 mg per day are needed to achieve clinically effective blood levels for full replacement therapy. the synthetic androgen (methyltestosterone) is less extensively metabolized by the liver and has a longer half-life. it is more suitable than testosterone for oral administration. testosterone in plasma is 98% bound to a specific testosterone-estradiol binding globulin, and about 1% is free. generally, the amount of this sex-hormone binding globulin in the plasma will determine the distribution of testosterone between free and bound forms, and the free testosterone concentration will determine its half-life. about 90% of a dose of testosterone is excreted in the urine as glucuronic and sulfuric acid conjugates of testosterone and its metabolites; about 6% of a dose is excreted in the feces, mostly in the unconjugated form. inactivation of testosterone occurs primarily in the liver. testosterone is metabolized to various 17-keto steroids through two different pathways. as reported in the literature, the half-life of testosterone varies considerably, ranging from 10 to 100 minutes. in many tissues the activity of testosterone appears to depend on reduction to dihydrotestosterone, which binds to cytosol receptor proteins. the steroid-receptor complex is transported to the nucleus where it initiates transcription events and cellular changes related to androgen action.