Age-related changes in testosterone and the role of replacement therapy in older men.

Abstract

Western populations represent an ageing society with continuing gains being made in life expectancy; a male born in Australia has a healthy life expectancy of 70 years with slightly lower expectations for those born in the UK and USA (WHO, 2001). The search for ways to maintain and enhance physical health and well-being is endless. Rather than aiming to simply live longer, people aspire to undertake ‘active ageing’ (WHO, 2002), with an emphasis on quality of life. Attention has been focussed on the possibility that testosterone replacement therapy may be beneficial to the quality of life of men in middle age and beyond, akin to that of the role of oestrogen replacement for symptomatic peri- and postmenopausal women (Hlatky et al ., 2002). Although the clinical presentation of androgen deficiency in men with primary or secondary testicular failure is well recognized and the benefits of treatment well established (Allan & McLachlan, 2003), whether testosterone replacement therapy is beneficial for older men with more subtle age-associated declines in serum testosterone levels is beneficial remains uncertain. Ill-defined terms such as ‘andropause’ or ‘partial androgen deficiency of ageing men’ have been popularized and underscore the increasing use of testosterone treatment for a range of ailments prevalent in older men. In the USA, the market for testosterone therapies has increased from US$49 million to almost US$400 million between 1997 and , with the majority of prescribing being for men 40 years and older. No matter how well-intentioned, such treatment cannot escape evaluation according to the modern principles of evidence-based medicine. Recent experiences in the field of female HRT (Hulley et al ., 1998; Rossouw et al ., 2002) serve to remind us of the need for properly designed and powered randomized, placebo-controlled data, and for caution in extrapolating cross-sectional or surrogate end-point data. We will discuss the extent of age-related decline in testosterone and the confounding effects of concomitant illness, the physiology of the changes in the hypothalamo‐pituitary‐testicular (HPT) axis, and the approaches to the laboratory assessment of hypoandrogenism in older men. The effects of androgens on key target tissues and the existing data from the limited number of placebo-controlled trials regarding the benefits and potential risks of its usage will be discussed.