Background

Testosterone deficiency is a poorly understood entity among many physicians and patients. In order to provide an evidence-based foundation for diagnosis and management, the Endocrine Society published an updated guideline on this condition early this year.

Conclusions

The symptoms of androgen deficiency in men vary with the age of onset and degree of testosterone deficiency.

William E. Golden (left) and Robert H. Hopkins

The signs and symptoms most consistent with testosterone deficiency include decreased libido, erectile dysfunction, gynecomastia, loss of body hair, hot flushes/sweats, bone loss and/or low-impact fractures, azoospermia/infertility, and incomplete sexual development. A variety of less-specific symptoms also may be attributable to testosterone deficiency: decreased energy or mood, sleep disturbance, poor concentration, modest anemia, and increased body fat with decreased muscle bulk/mass.

Testosterone deficiency can result from defects in testicular production of androgens (primary testicular failure), at the hypothalamic-pituitary level (secondary failure), or from combined mechanisms. The distinction is important because combined and secondary defects might be caused by specific diseases that may require treatment; and the potential to restore fertility in some patients with secondary testicular failure with correct hormone stimulation. Testosterone levels decline by 1%-2% per year in older men, and the circadian variability of levels present in younger men is also commonly lost with aging.

Randomized trials of testosterone replacement in men with testosterone deficiency have shown consistent improvement in bone density, lean body mass with concomitant reduction in fat mass, and sense of physical well-being; the trials were less consistent in effects on muscle strength, libido, erectile function, quality of life, depression, cognition, and muscle strength. Testosterone replacement has not been demonstrated to reduce fractures. Many of the trials are limited by small sample size and short follow-up.

Implementation

Androgen deficiency should not be diagnosed without the presence of both symptoms and low testosterone levels.

Screening is not indicated in the general population or in men who are being evaluated for unrelated health issues. There is not a consensus case definition for androgen deficiency; there are few data on the performance of screening criteria; and the long-term implications of replacement is unclear in the most commonly affected populations: older men and men with chronic illness.

Patients should not be evaluated for androgen deficiency during an acute illness because illness can suppress testosterone levels.

High-dose glucocorticoids, opiates (particularly methadone and long-acting opiates), eating disorders, and excessive exercise can affect testosterone levels and should be asked about in the evaluation of a patient who is potentially androgen deficient.

A morning total testosterone level is the recommended initial test for androgen deficiency; this should be repeated to confirm deficiency.

Patients who have total testosterone levels near the lower limit of normal and in whom protein binding may be abnormal, such as those who have concomitant obesity, diabetes, chronic illness, or thyroid disease, might require measurement of free testosterone levels in their evaluation.

Luteinizing hormone and follicle-stimulating hormone levels should be measured in patients found to be testosterone deficient in order to distinguish primary from secondary testicular failure. Those men found to have secondary androgen deficiency should be evaluated further to assess for systemic disease (for example, hyperprolactinemia or hemochromatosis) and/or pituitary tumor.

Testosterone replacement is recommended to maintain secondary sex characteristics, improve sexual function and sense of well being, and improve bone density in patients who have androgen deficiency and who do not have identified contraindications. The choice of replacement medication and delivery system will depend on individual patient factors and preference.

Testosterone treatment is not recommended in men with breast or prostate cancer, elevated PSA, and/or unevaluated prostate abnormality, those at high risk for prostate cancer, those with severe lower urinary tract symptoms, or in men with hematocrit greater than 50 %, untreated sleep apnea or poorly controlled heart failure.

Men treated with testosterone replacement should be evaluated 3-6 months after it is initiated, and then annually thereafter. This follow-up should include measurement of testosterone, hematocrit and PSA levels, and a prostate exam. Bone density should be measured 1-2 years after initiation of testosterone replacement in patients with low bone density or fragility fracture; the subsequent interval of remeasurement of bone density remains controversial.

Urologic consultation is recommended when prostate abnormalities or rising PSA is detected while a man is taking testosterone.

Dr. Golden is professor of medicine and public health and Dr. Hopkins is program director for the internal medicine/pediatrics combined residency program at the University of Arkansas, Little Rock.

Reference

Testosterone Therapy in Men With Androgen Deficiency Syndromes: An Endocrine Society Clinical Practice Guideline (J. Clin. Endo. Metab. 2010;95:2536-59).

Perspective: Managing Testosterone Deficiency in Men