Sexual dysfunction and low libido are among the most easily reversible symptoms of hypogonadism. Systematic reviews of randomized, placebo-controlled clinical trials of testosterone in men, including older men (aged 60 years and over) and middle-aged men, with sexual dysfunction and hypogonadism have shown large favourable effects on libido and moderate effects on satisfaction with erectile function.7-11 In men who do not respond sufficiently to testosterone therapy alone, the combination of phosphodiesterase 5-inhibitors and testosterone may be indicated, as there are suggestions that the combination may be synergistic.7
Alterations in mood and depression are a symptom of, but not confined to, hypogonadism.1,7 Outcomes in clinical trials of the effect of testosterone treatment on mood have varied. However, there is evidence that testosterone treatment results in improvements in mood, particularly in older men with hypogonadism.12-13 Similarly, although there is an established association between measures of cognitive ability and serum levels of testosterone, the benefits of testosterone treatment on cognition are less clearly established, with some studies reporting improvements in some measures of cognitive function and others failing to detect benefits.1,14-16 Although a potential role for testosterone in protecting cognitive function and preventing Alzheimer’s disease has been proposed by some researchers, confirmation from appropriately-designed clinical trials is awaited.
Testosterone therapy improves body composition (increase in lean body mass, decrease in fat mass) in men with hypogonadism.7 There is a supplementary improvement in muscle strength and physical function. The benefits of testosterone treatment on body composition have consistently been demonstrated in clinical studies of testosterone therapy in hypogonadal men or men with borderline low testosterone levels,1,2,7,13,17 and confirmed by systematic reviews or meta-analyses of randomized controlled trials.1,10,11,17
There is a large body of evidence linking the onset and/or progression of cardiovascular disease to low testosterone levels in men. It is now apparent that an increased cardiovascular risk and accelerated development of atherosclerosis occurs not only in elderly men or men with obesity or type 2 diabetes mellitus, but also in non-obese men with hypogonadism.18 Current best evidence from systematic review of randomized controlled trials suggests that testosterone use in hypogonadal men is relatively safe in terms of cardiovascular health and do not produce unfavorable elevations in blood pressure or glycemic control, and does not adversely effect lipid profiles.10,19
In fact, there is increasing evidence of the potential benefits of testosterone replacement therapy on multiple cardiovascular risk factors. This evidence recently has been comprehensively reviewed by Traish et al. in the Journal of Andrology.20 Although the full effects of testosterone replacement therapy on cardiovascular risk are yet to be established, the balance of emerging evidence from clinical studies suggests that testosterone replacement therapy in hypogonadal men may improve endothelial function, reduce proinflammatory factors, reduce hypertension, and improve the lipid profile.
Hypogonadism is highly prevalent amongst men with diabetes mellitus type 2 or symptoms of the metabolic syndrome, including insulin resistance, impaired glucose regulation, obesity, and hypertension.1,7,17,18,21,22 Low testosterone in many men with diabetes remains undiagnosed and untreated, and current guidelines recommend measurement of testosterone levels in such patients and, equally, that such chronic diseases should be investigated and treated in men with hypogonadism.1,7 It is not yet fully known whether diabetes is a cause or a consequence of low testosterone, and the full effects of testosterone administration on glycemic control in hypogonadal men with diabetes are unclear. However, there are indications that treating hypogonadism may have benefits on metabolic status in men with diabetes, and there is evidence that testosterone replacement therapy has a beneficial effect on risk factors for diabetes such as central obesity, insulin sensitivity, glucose control and blood lipid profiles in hypogonadal men with type 2 diabetes.18,23,24
Low testosterone can lead to reduced bone mineral density and osteoporosis, and men with hip fractures tend to have low testosterone.1,7 For example, in a matched case-control study at a hospital orthopedic service, 71% of men with hip fractures had low testosterone levels, compared with 32% of age-matched controls.25
A large number of trials have shown the positive effects of testosterone treatment on markers of bone formation and increased bone density in hypogonadal men treated with testosterone.1,7,10,13,17 Not surprisingly, the effects may take several years to fully develop. At present no data on the role of testosterone in preventing fracture in men with hypogonadism are available.
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