Testosterone

With increasing age, both cross-sectional and longitudinal data have shown that there is a small but significant decline in both total plasma and bioavailable/'free' testosterone concentrations. While some of these changes may be causally linked to the presence of other co-morbidities, the phenomenon is also evident in otherwise healthy males, although in this latter group, its clinical significance is currently unclear. The benefits of replacement therapy, to generate testosterone levels into the mid normal range for a younger group have not been been systematically evaluated in controlled longitudinal studies, and nor have the risk:benefit ratios.

In the presence of symptoms of androgen deficiency (loss of libido, erectile dysfunction, visceral weight gain, loss of body hair, lethargy, decreased strength and vitality, grumpiness), it is appropriate to measure a 09.00 testosterone level. If this is below the 8nmol/l mark, endocrine referral is appropriate (a value in the 8-10 nmol/l range may be worth investigating, depending on the assay), a full physical examination conducted, and specific investigations carried out to elucidate the cause.

It is unclear whether patients with symptoms of mild androgen deficiency, associated with borderline low testosterone levels will benefit from replacement therapy. Symptoms of mild androgen deficiency are notoriously non-specific, and there is no evidence that the symptoms scores derived from ADAM questionnaires bear any relationship to circulating testosterone levels in such patients. Thus presently available questionnaires have high sensitivity but low specificity, and may be useful only for screening prior to prompting more systematic endocrine investigation.

We therefore believe that initially, short to medium term placebo controlled studies are warranted to study the risk:benefit of testosterone replacement in this group of 'partial androgen deficiency of aging males (PADAM)'. Potential risks of treating a potentially large group of aging males - notably on prostatic cancer incidence, and on the cardiovascular system - are unknown, but studies on surrogate metabolic parameters (eg insulin resistance, lipids, body composition, DEXA scans) may provide useful pointers about potential benefit, and leading to longer term prospective placebo-controlled studies into harder end points.

P Bouloux
F Wu