Total testosterone represents the sum of free, or bioavailable, testosterone and a more sizeable proportion bound to sex hormone-binding globulin (SHBG) and albumin. Total testosterone readings may therefore be misleading in circumstances that raise levels of SHBG (aging, liver disease, hyperthyroidism) or lower it (obesity, diabetes, kidney disease, hypothyroidism).

When total testosterone is close to the lower limits of normal in men in any of these groups, the follow-up with free testosterone assay is recommended. (This may require a reference laboratory.)

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Further evaluation. Once androgen deficiency is de­tected, assessment of serum luteinizing hormone and follicle-stimulating hormone is indicated to distinguish between primary and secondary hypogonadism. Measure BMD with dual-energy x-ray absorptiometry when deficiency is severe, particularly if the patient has a history of low-impact fracture, the guideline authors advise.

Treatment and its limits

Testosterone therapy aims to restore hormone levels to mid-normal range, resolve symptoms, and maintain secondary sexual characteristics, BMD, and muscle mass.

When symptoms are equivocal or testosterone levels borderline, “One has to use clinical judgment,” Dr. Cunningham says. “You may elect to treat empirically for three months to see whether the patients benefits.”

Not all men with even pronounced clinical androgen deficiency should be treated, however. The guideline recommends against testosterone therapy for those with breast or prostate cancer, hematocrit >50%, poorly controlled heart failure, or severe lower urinary tract symptoms associated with benign prostatic hyperplasia. Patients with severe sleep apnea, which may depress testosterone levels, should be treated and retested before a decision to initiate hormone therapy is made.