Testosterone replacement therapy (TRT) should be considered only in men with clinically significant **androgen deficiency** (eg, low libido, erectile dysfunction, loss of body hair, gynecomastia, decreased bone density, testicular atrophy) and an ==unequivocally low morning serum testosterone level== (eg, <200-300 ng/dL, depending on the reference). Nonspecific symptoms (eg, fatigue, weakness, weight changes) do not usually respond to TRT and do not warrant testing or treatment in most cases. Testosterone levels show significant variability; if the initial testosterone level is low, it should be confirmed on repeat testing. In addition, providers should consider measuring free testosterone levels, as variations in the levels of sex hormone–binding globulin, which may be decreased in certain conditions (eg, obesity, diabetes), can cause misleading total testosterone results.
Contraindications to TRT include breast or prostate cancer, polycythemia, severe lower urinary tract symptoms (ie, American Urological Association score >19), unstable heart failure, PSA >4 ng/mL (>3 ng/mL in high-risk patients), and untreated obstructive sleep apnea (OSA). This patient has an elevated hematocrit, hypertension, obesity, and a large neck circumference, which together suggest possible OSA. TRT can worsen OSA and exacerbate erythrocytosis, with a possible increased risk of venous thromboembolism. The patient also has multiple risk factors for cardiovascular disease, and some evidence suggests that TRT may increase this risk. As a result, the risks likely outweigh the benefits of TRT in this patient. In addition, TRT is indicated for specific disorders of gonadal function (eg, chemotherapy-induced hypogonadism), but TRT for age-related declines in serum testosterone is considered an off-label use.
Although erectile dysfunction is a significant symptom in men with hypogonadism, TRT has shown inconsistent benefits in the treatment of erectile dysfunction in older men. Phosphodiesterase inhibitors (eg, sildenafil) are more likely to be effective.