Medical Abstract:

                    Mayo Clinic Proceedings January, 2000, Vol.75(Suppl)   J. Lisa Tenover, M.D., Ph.D.  Symposium Article

      Experience with Testosterone Replacement in the Elderly

      To date, most of the studies of androgen replacement have been done with healthy older men (age > 55 years), and almost no data are available for frail elderly individuals. Treatment effects that make a relatively small difference in younger, more robust individuals may have a greater effect on the elderly, whose improvement in functioning and level of activity may be more dramatic. However, the frail elderly individual is also more vulnerable to adverse effects from treatment and these potential risks and benefits must be weighed.

       Potential Benefits

     Clinical Findings For older men, the potential benefits of androgen therapy include maintenance or  improvement in bone density, improved body composition (i.e., ratio of fat to lean muscle mass), strength,    libido and sexual function, mood, and improvement or maintenance of cognitive function. This discussion  will focus on treatment for maintenance or improvement of bone density or for improved body composition and strength.

     Effects on bone mineral density (BMD) and muscle mass have been the outcomes most studied. However, only limited data have been published on treatment in middle-aged and older men. Several studies are available only in abstract form.

      Effects on Bone BMD of the lumbar spine increased in all studies for which data were available.

      Effects on Body Composition The study by Katznelson et. al., was longest in duration and produced the largest decrease in body fat. Lean body mass also changed favorably, increasing in three of the five studies, although not to the same degree as body fat decreased.

     Effects on Strength Grip strength was shown to improve in nearly all of the studies that measured it, and it can serve as a fairly accurate predictor of overall strength.

     Potential Risks

     Liver Toxicity Liver toxicity has not been seen with the types of parenteral testosterone administered in clinical studies to older men.

      Gynecomastia Breast enlargement or tenderness occasionally occurs (in < 2% of subjects), more frequently with administration of injectable testosterone. It usually can be resolved by lowering the dosage.

      Fluid retention has not been a problem in the healthy men who have been treated with testosterone to date.

      Effects on Prostate Health Currently, there is no evidence that, in an older man with a pretreatment testosterone level in the range of 200 to 400 ng/dL, raising the level to approximately 800 ng/dL will affect    prostate mass.

      Since PSA is made by androgen-dependent cells, one might expect an increase in PSA levels with replacement. However, only a few studies have resulted in data that reflect any change in PSA levels, and those studies show only small changes within the normal range. Uroflow rate, prostate size, prostate symptom scores, and other assessed factors showed no major effects in most studies.

      Cardiovascular Risk Current data on cardiovascular risk suggest that it is better for men to have a high rather than a low testosterone level. In general , higher serum testosterone levels correlate with lower metabolic  cardiovascular risk factors, including higher high-density lipoprotein (HDL) cholesterol levels, lower blood pressure, and lower levels of plasma fibrinogen, fasting insulin, and lipoprotien. Nonetheless, concerns about   this issue tend to raise basic questions about why men have more cardiovascular disease than premenopausal women: Are estrogens protective, are androgens causative, or both? Recent well-controlled data are insufficient to provide a definitive answer.

     In general, parenteral testosterone therapy in older men results in a decline in serum levels of total cholesterol and low-density lipoprotein (LDL) cholesterol, and no change in HDL cholesterol, although a few new studies show a decline in HDL cholesterol with treatment. Perhaps various subfractions should be investigated further, but little evidence suggests that this particular aspect of cardiovascular risk represents a   major problem.

      Conclusion

     Most of the available evidence suggests that testosterone replacement is potentially beneficial to aging men, particularly in the areas of bone density and body composition. The magnitude and longevity of the beneficial effects are not known, however.

      The short-term treatment risks of adverse effects over three to four years of treatment appear to be predictable and easy to monitor and manage. To date, most of the studies of treatment benefits and risks    have been performed on healthy older men.