The age-related decline of serum testosterone is reported in about 20 to 35% of men, and may be due to an increase in sex hormone-binding globulin. For this reason the biochemical diagnosis of androgen deficiency should be confirmed twice along with the measurement of SHBG and, whenever possible, bioavailable testosterone. Ongoing studies suggest that testosterone may have a role as an anti-atherogenic therapy by preserving endothelial and smooth muscle cells integrity. Furthermore, the recent finding that androgen may also directly control the expression and activity of phosphodiesterase type-5 (PDE5) in human genital tissues opens a new scenario for its use in selected patients in whom total testosterone below 10 nmol/L and/or free testosterone below 0.250 nmol/L may directly determine a failure of men with ED in the clinical response to PDE5-inhibitors. The possibility to challenge these men with TRT to improve their erectile function and sexual satisfaction in the absence of contraindications to testosterone administration, may represent a “salvage” for subjects that would be otherwise referred for less satisfactory or more invasive alternatives. Because ED shares the same risk factors and may be a sentinel of cardiovascular disease, in the future TRT will offer the potential to enhance men’s motivation for prevention and treatment of cardiovascular disease associated with disorders of erection. For present, the beneficial effects of testosterone administration on body composition, bone density and sexual function have been recently reviewed using the powerful techniques of meta-analyses, providing a summary of the known effects that can be expected. Whether such changes justify a trial or a life-long treatment with one of the several androgen preparations now available, should be evaluated individually for each patient by a physician knowledgeable in the field, in respect of published guidelines, while awaiting for adequate safety data to become available.
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