Abstract
The review article by Belchetz et al. 1 provides an in-depth review of the role of testosterone in the male, from the fetus to old age. This included a section on an area generating much current interest – the decline in circulating testosterone as men grow older. While most of the discussion appears balanced, the section ends with a statement that the article aims to be ‘in full accord’ with a consensus statement produced by a multinational panel from the International Society of Andrology, the International Society for the Study of the Aging Male, the European Academy of Urology and American Society of Andrology. This guideline promotes the use of testosterone therapy in men who have symptoms consistent with androgen deficiency, and a free testosterone of less than 225 pmol/L, irrespective of age.
The implications of being in full accord with that position must be carefully considered. In the more recent 2010 Endocrine Society guideline, 2 there is a clear statement of the differing views on this matter. The panellists could not reach agreement, some favouring treating symptomatic older men with a total testosterone level below the lower limit for healthy young men (around 10 nmol/L), others favouring a level below around 7 nmol/L. It was pointed out that a lack of definitive studies precludes an unequivocal recommendation and emphasizes the need for additional research. Publications in Nature Clinical Practice 3 and the Drugs and Therapeutics Bulletin 4 have argued that an adequately powered randomized placebo controlled clinical trial of testosterone on clinically important outcomes is needed to provide the evidence base to guide clinical practice. As far as we are aware, there is no such trial currently planned. Pharmaceutical companies may find it more profitable to facilitate the development of recommendations by international panels of experts and key opinion leaders. It may be that public funding will be required to pay for a trial. 5
It was estimated in 2009 that 1% of UK men aged greater than 50 were on testosterone replacement therapy. 6 In the USA, the figure was 8% and ‘rapidly rising’. If 10% of men over 50 in the UK were to receive testosterone replacement therapy, the annual cost for treatment alone might run into hundreds of millions of pounds. In addition to this, it has been recommended that elderly men being considered for testosterone replacement therapy should undergo a digital rectal examination prior to commencement of therapy, as well as baseline and regular prostate-specific antigen measurements, thus increasing costs substantially. It may be that this cost would be justifiable if the result was a reinvigoration of flagging sexual appetites, physical strength and general wellbeing of an ageing male population, as they face more years in the workforce before retirement. For now the case is far from proven.
Adopting a single cut-off for reporting serum testosterone in males, irrespective of age, may contribute substantially to the widespread use of an expensive treatment with unproven safety and efficacy. We believe that biochemistry departments should report age-related reference intervals for total and (calculated) free testosterone, thus enabling identification of individuals with significant testosterone deficiency who are likely to benefit from replacement therapy.
DECLARATIONS