Testosterone – not just a replacement therapy

Most of us associate testosterone with normal male development – the voice deepens, the energy levels are sustained, muscle mass and strength is increased and sex drive is maintained. In addition, testosterone causes the growth of pubic and body hair (though it can also lead to baldness) and benefits bone strength, but can also decrease high-density lipoprotein (HDL) cholesterol. However, the impact of a reduction in HDL cholesterol only appears to affect HDL3c, which is the least antiatherogenic subfraction, and overall no atherogenic or antiatherogenic effects have been recorded (1). There are, however, several reports of a link between low testosterone levels and coronary artery disease as well as the more predictable reduction in libido, increased fatigue, muscle weakness, osteoporosis, depression, poor concentration and erectile dysfunction (ED) (2,3). In this issue, Shabsigh et al. provide an overall review of the role of testosterone in the treatment of ED (4). In addition to taking a thorough history clarifying whether the problem is sex drive (libido), ED or both (important because men may equate ED with sex drive in their minds when their drive is normal), there is a recommendation to screen all men with ED from 50 years of age for hypogonadism. Testosterone is at its highest in the morning and samples should be obtained before 10 AM. Shabsigh et al. (4) emphasise the importance of testosterone replacement therapy with regard to treating ED usually in combination with a phosphodiesterase type 5 inhibitor (sildenafil, tadalafil, vardenafil), especially in those at risk for hypogonadism and ED, such as type 2 diabetics, and those with multiple risk factors for vascular disease which may be clustered as the metabolic syndrome (1,4). One of the problems with testosterone levels is the variability between laboratories in the definition of the normal range. However, if we accept a range from 8–12 to 35–45 nmol/L this still presents a problem because of the width of the range. A level of 12 nmol/L may be perfectly normal for most men but not adequate for some, so there needs to be a clinical and biochemical correlation. If a man with ED and low normal testosterone is not responding fully to a phosphodiesterase type 5 inhibitor, he may benefit from testosterone replacement therapy in a similar manner to those in Shabsigh et al.’s paper (4). Hypogonadism in men over 50 years is often known as the ‘andropause’ though technically the terms are late onset hypogonadism (LOH) or androgen decline in the ageing male (ADAM). Treatment improves physical and mental well-being, quality of life (including sex life), bone density increases and there may be an overall vascular benefit. Negatives include aggravating existing prostate cancer but not causing prostate cancer, reducing sperm count so a check needs to be made on family intentions regarding children, and increasing haematocrit (polycythaemic men need careful monitoring). In the review of testosterone therapy in hypogonadism and the metabolic syndrome, an argument was made to not only treat the hypogonadism with testosterone, but also in doing so, the metabolic syndrome’s progression to overt diabetes or cardiovascular disease could be slowed or stopped (1). The link between a low testosterone and aortic atherosclerosis in men was found to be independent of other risk factors but not in women, and the authors raised the tantalising question of using testosterone to protect against atherogenesis in men (1). When English et al. challenged the concept that physiologically high levels of androgens accounted for men’s increased relative risk for coronary disease, reporting lower levels of androgens when compared to men with normal coronary arteries, they pointed out the potential benefit of replacement therapy on quality of life with no increased cardiovascular risk and a potential benefit (3). More recently testosterone administration has been shown to have anti-ischaemic potential in men with angina and the LOH with cardiovascular risks reversed by testosterone replacement (5–7). In men presenting with coronary disease, measuring testosterone should be part of the assessment, especially if ED and/or diabetes coexist. Replacement can only be advocated if there are clear signs or symptoms of androgen deficiency including ED, but the long-term cardiovascular risk reduction and symptom management potential merits further study. Replacing testosterone can lead to a lifelong benefit on quality of life but the detection of a low testosterone should also trigger a search for other vascular risk factors whilst treatment progresses.