If testosterone abuse is suspected, check serum testosterone concentrations to ensure they are within therapeutic range. Testosterone has been subject to abuse, typically at doses higher than recommended for the approved indication and in combination with other anabolic androgenic steroids. If a venous thromboembolic event is suspected, discontinue treatment with AXIRON and initiate appropriate workup and management see ADVERSE REACTIONS. An increase in red blood cell mass may increase the risk of thromboembolic events. If hematocrit becomes elevated, stop therapy until hematocrit decreases to an acceptable level. In women, testosterone can produce hirsutism (excessive facial/body hair growth), deepening of the voice, and other signs of virilization. These include the testosterone/epitestosterone ratio (normally less than 6), the testosterone/luteinizing hormone ratio and the carbon-13/carbon-12 ratio (pharmaceutical testosterone contains less carbon-13 than endogenous testosterone). Anabolic–androgenic steroids (AAS), including testosterone and its esters, have also been taken to enhance muscle development, strength, or endurance. There are many known cases of doping in sports with testosterone and its esters by professional athletes. In the United States, they are Schedule III drugs under the Controlled Substances Act, in Canada, they are Schedule IV drugs under the Controlled Drugs and Substances Act, and in the United Kingdom, they are Class C drugs under the Misuse of Drugs Act. Unlike in Europe, Canada, and much of the rest of the world, oral testosterone undecanoate is not available in the United States. Unmodified testosterone was also formerly available for intramuscular injection but was discontinued. Intramuscular testosterone undecanoate was not introduced in Europe and the United States until much later (in the early to mid 2000s and 2014, respectively). In the 1970s, testosterone undecanoate was introduced for oral use in Europe, although intramuscular testosterone undecanoate had already been in use in China for several years. They largely superseded testosterone propionate and became the major testosterone esters used medically for over half a century. In addition to ester and ether prodrugs, androgen prohormones or precursors of testosterone, such as dehydroepiandrosterone (DHEA), androstenediol, and androstenedione, exist as well, and convert into testosterone to variable extents upon oral ingestion. Another C17β ether prodrug of testosterone, silandrone, also exists but was never marketed, and is notable in that it is orally active. A C17β ether prodrug of testosterone, cloxotestosterone acetate, has also been marketed, although it is little known and is used very rarely or no longer. Major testosterone esters include testosterone cypionate, testosterone enanthate, testosterone propionate, and testosterone undecanoate. The ARs are expressed widely throughout the body, including in the penis, testicles, epididymides, prostate gland, seminal vesicles, fat, skin, bone, bone marrow, muscle, larynx, heart, liver, kidneys, pituitary gland, hypothalamus, and elsewhere throughout the brain. In contrast to the case of testosterone, such potentiation occurs to a reduced extent or not at all with most synthetic AAS (as well as with DHT), and this is primarily responsible for the dissociation of anabolic and androgenic effects with these agents. People with diabetes may find it necessary to monitor their blood sugar more frequently while using this medication. The following side effects have been reported by at least 1% of people taking this medication. If you are concerned about side effects, discuss the risks and benefits of this medication with your doctor. The side effects listed below are not experienced by everyone who takes this medication. Testosterone therapy should be promptly discontinued at least until the cause of virilization has been identified. Abuse and misuse of testosterone are seen in male and female adults and adolescents. AXIRON contains testosterone, a Schedule III controlled substance in the Controlled Substances Act. Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. At the end of the 180 day extension clinical trial, there was an overall increase in mean PSA values of 0.1 ± 0.54 ng/mL. During the 120 day clinical trial there was an increase in mean PSA values of 0.13 ± 0.68 ng/mL from baseline.
