5α-Reductase inhibitors like finasteride and dutasteride can slightly increase circulating levels of testosterone by inhibiting its metabolism. However, the association between testosterone supplementation and the development of prostate cancer is unproven. The FDA now requires warnings in the drug labeling of all approved testosterone products regarding deep vein thrombosis and pulmonary embolism. Due to an increased incidence of adverse cardiovascular events compared to a placebo group, a Testosterone in Older Men with Mobility Limitations (TOM) trial (a National Institute of Aging randomized trial) was halted early by the Data Safety and Monitoring Committee.
Four patients (4.1%) discontinued treatment with Striant due to gumor mouth-related adverse reactions including two with severe gum irritation,one with mouth irritation, and one with "bad taste in mouth." Gum irritationgenerally resolved in 1 to 8 days. A total of 16 patients reported 19 gum-related adverse reactions. Gum-related adverse reactions, including severe gum irritation, were reported in clinical trials of Striant. Striant therapy should be discontinued if serum testosterone concentrations are consistently outside of the normal range (300 to 1050 ng/dL) despite the use of one buccal system applied twice daily. Estrogens can reduce the effects of testosterone by increasing the hepatic production and in turn circulating levels of sex hormone-binding globulin (SHBG), a carrier protein that binds to and occupies androgens like testosterone and DHT, and thereby reducing free concentrations of these androgens. Adverse effects of testosterone supplementation may include increased cardiovascular events (including strokes and heart attacks) and deaths based on three peer-reviewed studies involving men taking testosterone replacement. Gum-related adverse reactions, including severe gumirritation, were reported in clinical trials of Striant.
The most common route of administration for testosterone is by intramuscular injection. Testosterone has been marketed for use by oral, sublingual, buccal, intranasal, transdermal (patches), topical (gels), intramuscular (injection), and subcutaneous (implant) administration. Testosterone pellet implants are approved for use in postmenopausal women in the United Kingdom.