Potential benefits

of testosterone therapy are wide-ranging

Potential secondary health benefits of testosterone therapy in men with hypogonadism

Testosterone, historically believed to be important only for male sexual function, has over the past decades transformed from niche hormone to multi-system player.¹⁹ There is increasing recognition of the harmful consequences of hypogonadism (also known as testosterone deficiency) and the potential, beneficial health effects of testosterone therapy.^20,²¹

A growing number of studies have provided evidence that it takes several years for many of the beneficial health effects of testosterone therapy to manifest fully²², and that for most men maintenance of these health benefits requires lifelong testosterone therapy, as explained in the FAQ section.

Figure: Potential secondary health benefits of testosterone therapy in men with hypogonadism (low testosterone).

Blood

Prevents anemia

Sexual

Controls sexual function (sex drive, erectile function, orgasm)
Reduces lower urinary tract symptoms (LUTS)

Psychological

Improves mood, energy, wellbeing and quality of life
Prevents depression

Physical symptoms

Increases muscle mass
Increases strength
Decreases overall body fat mass
Decreases belly (visceral) fat mass
Increases bone mineral density

Sexual
function

Sexual dysfunction and low libido may be among the most easily reversed symptoms of hypogonadism. Systematic reviews of randomised, placebo-controlled clinical trials of testosterone in men, including older men (aged 60 years and over) and middleaged men, with sexual dysfunction and hypogonadism have shown large favourable effects on libido and moderate effects on satisfaction with erectile function.^1-4 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.¹

Depression, well-being, cognitive function

Alterations in mood and depression are a symptom of, but not confined to, hypogonadism.^1,⁶ 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 with hypogonadism.^7,⁸ 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.^6,^9-11 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.

Body
composition

Testosterone therapy may improve body composition (increase in lean body mass, decrease in fat mass) in men with hypogonadism.¹ There may also be improvements in muscle strength and physical function.¹² 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,^6,^8,^13,¹⁴ and confirmed by systematic reviews or meta-analyses of randomised controlled trials.^4,^5,^6,¹⁴

Diabetes and metabolic syndrome

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,^6,¹⁴ 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.^1,⁶ 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.

Bone
health

Low testosterone can lead to reduced bone mineral density and osteoporosis, and men with hip fractures tend to have low testosterone.^1,6,18 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.¹⁸

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.^1,4,6,8,14 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.

Cardiovascular
risk

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 hypogonadism¹⁵

Recommendations

Symptoms of hypogonadism

Safety of testosterone therapy