c.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 taken every 6 months to assess the effect of treatment on epiphyseal centers (see warnings ).

nt is suspected, discontinue treatment with testopel ® (testosterone pellets) and initiate appropriate workup and management [see adverse reactions . 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 testopel® (testosterone pellets). testosterone has been subject to abuse, typically at doses higher than recommended for the approved indication and in combination with other anabolic 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 preexisting cardiac, renal, or hepatic disease. in addition to discontinuation of the drug, diuretic therapy may be required. gynecomastia frequently develops in patients 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. post-marketing cases associate testopel ® pellet(s) insertion with implant site infection (cellulitis and abscess), and/or pellet extrusion at or near the implantation site. infection and extrusion may occur concurrently or separately. reported signs and symptoms of infection and/or extrusion at the implant site included induration, inflammation, fibrosis, bleeding, bruising, wound drainage, pain, itching, and pellet extrusion. although cases of infection and/or extrusion may occur at any time, most reported cases occurred within the first month after testopel ® implantation. infection and/or extrusion may require further treatment (see adverse reactions). this drug has not been shown to be safe and effective for the enhancement of athletic performance. because of the potential risk for serious adverse health effects, this drug should not be used for such purpose.

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 in delayed puberty generally are in the lower range of that listed above and, for a limited duration, for example 4 to 6 months. the number of pellets to be implanted depends upon the minimal daily requirements of testosterone propionate determined by a gradual reduction of the amount administered parenterally. the usual dosage is as follows: implant two 75mg pellets for each 25mg testosterone propionate required weekly. thus when a patient requires injections of 75mg per week, it is usually necessary to implant 450mg (6 pellets). with injections of 50mg per week, implantation of 300mg (4 pellets) may suffice for approximately three months. with lower requirements by injection, correspondingly lower amounts may be implanted. it has been found that approximately one-third of the material is absorbed in the first month, one-fourth in the second month and one-sixth in the third month. adequate effect of the pellets ordinarily continues for three to four months, sometimes as long as six months.

atologic. 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 (see warnings ) miscellaneous. rarely anaphylactoid reactions.

rate linear 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). at 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 in plasma is 98 percent bound to a specific testosterone-estradiol binding globulin, and about 2 percent is free. generally, the amount of this sex-hormone binding globulin in the plasma will determine the distribution of testosterone between the free and bound forms, and the free testosterone concentration will determine its half-life. about 90 percent of a dose of testosterone is excreted as glucuronic and sulfuric acid conjugates of testosterone and its metabolites; about 6 percent of a dose is excreted in 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. there are considerable variations of the half-life as reported in the literature, ranging from 10-100 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.