A practical guide to male hypogonadism in the primary care setting

Abstract

There is a high prevalence of hypogonadism in the older adult male population and the proportion of older men in the population is projected to rise in the future. As hypogonadism increases with age and is significantly associated with various comorbidities such as obesity, type 2 diabetes, hypertension, osteoporosis and metabolic syndrome, the physician is increasingly likely to have to treat hypogonadism in the clinic. The main symptoms of hypogonadism are reduced libido/erectile dysfunction, reduced muscle mass and strength, increased adiposity, osteoporosis/low bone mass, depressed mood and fatigue. Diagnosis of the condition requires the presence of low serum testosterone levels and the presence of hypogonadal symptoms. There are a number of formulations available for testosterone therapy including intramuscular injections, transdermal patches, transdermal gels, buccal patches and subcutaneous pellets. These are efficacious in establishing eugonadal testosterone levels in the blood and relieving symptoms. Restoration of testosterone levels to the normal range improves libido, sexual function, and mood; reduces fat body mass; increases lean body mass; and improves bone mineral density. Testosterone treatment is contraindicated in subjects with prostate cancer or benign prostate hyperplasia and risks of treatment are perceived to be high by many physicians. These risks, however, are often exaggerated and should not outweigh the benefits of testosterone treatment.

Figure 1

The hypothalamic–pituitary–gonadal axis in men. GnRH, FSH, and LH have stimulatory effects on their targets. Testosterone inhibits their release from the hypothalamus and the pituitary. FSH, follicle-stimulating hormone; GnRH, gonadotropin-releasing hormone; LH, luteinizing hormone

Figure 2

The interrelationship between hypogonadism and insulin resistance (after (42,51)). LH, luteinizing hormone. Low testosterone stimulates an increase in adiposity. Adipose tissue contains high concentrations of aromatase, which reduces testosterone concentrations by converting it to estradiol. The estradiol negatively feeds back on the HPG system, reducing testosterone production in the Leydig cells. Increasing adipose tissue increases insulin resistance, which negatively impacts the Leydig cells as well as inhibiting the release of luteinizing hormone (LH) via the release of adipokines (inflammatory cytokines) such as TNF-α. Leptin, released in response to increased adiposity, also inhibits the release of LH via its effect on the release of gonadotropin-releasing hormone

Figure 3

An algorithm for the diagnosis of hypogonadism (2,76,77). TT, total testosterone