Endocrine Abstracts (2011) 26 PL7

Androgen use and misuse: a 2011 view

David Handelsman

ANZAC Research Institute, Sydney, Australia.

Testosterone is a well established, safe, effective and affordable hormone for use in androgen replacement therapy (ART) for androgen deficiency (AD) due to pathology of the hypothalamo-pituitary testicular axis. Newer testosterone products provide short-acting (transdermal) or long-acting (depot injectable) delivery with enhanced convenience to improve long-term compliance during life-long ART. Yet there is a striking disparity between major under-diagnosis of authentic AD (e.g. Klinefelter’s syndrome) and the steeply increasing overuse of androgens in ageing men and women as well as abuse for bodybuilding and sports doping. Within the accepted framework of the pathological basis of disease, AD remains a clinical diagnosis with a pathological basis and confirmed by hormone assays. Biochemical confirmation of AD remains hampered by the unreliability (method-dependent bias, non-specificity) of direct testosterone immunoassays which are still universal in clinical pathology labs although almost completely supplanted by mass spectrometry in clinical research labs. The epidemic use of (meaning)-free testosterone, elevating an outdated heuristic concept (‘free hormone hypothesis’) into an unquestioned quasi–axiom, usually calculated by inaccurate formulae only adds confusion. Readily available, affordable testosterone assays used in a form of ad hoc population screening together with the pathologising of ageing by invention of ‘andropause’ as a disease, have created a ‘eugonadal sick syndrome’, analogous to what is now known as ‘non-thyroidal illness syndrome’, a reversible, non-specific pan-hypothalamic reaction to systemic illness. These factors have converged to foster a striking upsurge in testosterone prescribing, a marketing-driven distortion threatening to derail endocrinology practice from a needed focus on improving underdiagnosis of genuine AD into a lifestyle consultancy treating pseudo-AD of ageing. Whether testosterone can ameliorate any biological aspect of ageing (obesity, pre-diabetes, cardiovascular disease) remains to be established by adequately powered, placebo-controlled RCTs but the prospects of a WHI-style study focussed on male ageing per se seems a remote prospect of doubtful value.

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