Testosterone and Ageing: What Have We Learned Since the Institute of Medicine Report and What Lies Ahead?

M. M. Miner; A. D. Seftel


Int J Clin Pract. 2007;61(4):622-632. 

In This Article

Summary and Introduction


A 2003 report by the Institute of Medicine (IOM) surveyed the literature on the benefits and risks of testosterone replacement therapy in older men and identified knowledge gaps and research needs. This review summarises some key studies published since the IOM report. The possible relationship of testosterone to risk of prostate cancer remains a concern; however, no new evidence has emerged to suggest that testosterone replacement therapy increases the risk. Recent studies have demonstrated that hypogonadism in men may be more prevalent than previously thought, is strongly associated with metabolic syndrome, and may be a risk factor for type 2 diabetes and cardiovascular disease. Clinical studies have shown that testosterone replacement therapy in hypogonadal men improves metabolic syndrome indicators and cardiovascular risk factors. Maintaining testosterone concentrations in the normal range has been shown to contribute to bone health, lean muscle mass, and physical and sexual function, suggesting that testosterone replacement therapy may help to prevent frailty in older men. Based on current knowledge, testosterone replacement therapy is unlikely to pose major health risks in patients without prostate cancer and may offer substantial health benefits. Larger, longer-term randomised studies are needed to fully establish the effects of testosterone replacement therapy.


In 2002, the National Institute on Aging and the US National Cancer Institute asked the Institute of Medicine (IOM) to assess existing evidence regarding testosterone replacement in older men.[1] The resulting IOM report, published in 2003, considered the following: (i) epidemiological data on normal testosterone concentrations during the lifespan; (ii) associations between testosterone concentration and morbidity/mortality; (iii) risks and benefits of testosterone replacement therapy; (iv) the potential public impact of testosterone replacement therapy in the USA and (v) ethical issues related to the conduct of clinical trials of testosterone replacement therapy.[1] On the basis of its findings, the IOM panel also recommended future research directions for testosterone therapy in older men.[1]

The IOM report identified critical gaps in knowledge. A clear decline was found in testosterone concentrations as men aged, but it was unclear if lower testosterone concentrations affected health outcomes in older men.[1] The panel concluded that available evidence suggested potential benefits of testosterone replacement for older men, including improved body composition, strength, bone density, frailty, cognitive function, mood, sexual function and quality of life, but evidence of benefit for these health outcomes was generally mixed and inconclusive ( Table 1 ).[1] With the exception of increased haematocrit, no definitive evidence of risk was identified, and the report called for more research into the relationship between testosterone replacement therapy and prostate health in older men.[1] In the summary of its findings, the panel recommended longer-duration placebo-controlled trials with larger sample sizes to evaluate the efficacy and safety of testosterone therapy in older men.[1]

This review summarises key findings that have emerged since the publication of the IOM report. This analysis focuses on the following areas in which new evidence has been used to address questions raised by the IOM report: the prevalence of hypogonadism in ageing men; prostate health; metabolic syndrome/body composition; cardiovascular health; physical function and sexual health. It is beyond the scope of this review to consider differences between available testosterone replacement therapy products, or to review the IOM topics for which limited new evidence has been published. However, clinicians should become familiar with these issues prior to initiating testosterone replacement therapy.


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