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The Rationale, Efficacy and Safety of Androgen Therapy in Older Men: Future Research and Current Practice Recommendations

Division of Endocrinology, Department of Internal Medicine, Endocrine Research Unit, Mayo Clinic, Mayo Medical and Graduate Schools of Medicine (P.Y.L., J.D.V.), Rochester, Minnesota 55905; and Division of Endocrinology, Department of Medicine, Harbor-University of California-Los Angeles, Research and Education Institute (R.S.S.), Torrance, California 90502

Address all correspondence and requests for reprints to: Dr. Peter Y. Liu, Division of Endocrinology, Department of Internal Medicine, Endocrine Research Unit, Mayo Clinic, Mayo Medical and Graduate Schools of Medicine, 200 First Street SW, Rochester, Minnesota 55905. E-mail: liu.peter{at}mayo.edu.

Epidemiological studies indicate that normal male aging is associated with a gradual and variable decline in blood testosterone concentrations and unfavorable changes in muscle, bone, and fat that mimic those of androgen deficiency in young men. These age-related reductions in muscle and bone mass and increased fat mass may be responsible for other age-related changes, including decreased muscle strength and physical function, changes in metabolic function, and increased falls, fractures, and disability. Whether age-related relative androgen deficiency truly causes any of these features requires interventional studies specifically in older men, because aged tissues may not remain androgen sensitive nor is such treatment necessarily safe. A Medline search (years 1966 through January 2004, using search terms random and androgen), supplemented by subsequent reference searches of retrieved articles, identified randomized placebo-controlled studies of androgen therapy. These studies show that androgen replacement in older men increases muscle and reduces fat mass to a small degree, but to date has not improved muscle strength, physical function, or insulin sensitivity, nor does it convincingly improve bone density, although the latter effect is particularly dose responsive. However, idiosyncratic adverse effects, such as disordered sleep and breathing as well as polycythemia, are also dose responsive, suggesting that dose escalation to increase efficacy may create or aggravate undesirable side effects. Furthermore, the clinical safety of androgen therapy for cardiovascular and prostatic disease is uncertain. Under these circumstances, androgen supplementation is not recommended in healthy older men. However, interim recommendations are available to help guide appropriate and curb unnecessary androgen prescription for symptomatic older men with low serum testosterone levels.

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