Approach to the patient: low testosterone concentrations in men with obesity

Pathologic hypogonadism occurs when serum testosterone is significantly and persistently reduced by irreversible organic (structural, genetic) disorders of the hypothalamic pituitary testicular axis. Men with pathologic hypogonadism require lifelong testosterone replacement. In contrast, mild or moderate reductions in serum testosterone frequently accompany obesity, and its numerous comorbidities in men are best considered nongonadal illness syndromes, wherein reduction in serum testosterone is usually reversible upon amelioration of the underlying nongonadal illness. Obesity can result in nonspecific symptoms in conjunction with reduced serum testosterone and serum SHBG. Obesity-related reductions in SHBG, testosterone's principal circulating carrier protein, are primarily responsible for measured reductions in testosterone. However, obesity is not a cause of pathological hypogonadism, and proportionately reduced testosterone and SHBG concentrations accompanied by normal serum LH and FSH concentrations confirm a eugonadal state, best described as the pseudo-hypogonadism of obesity. Herein we demonstrate how clinically significant weight loss substantially reverses obesity-related reductions in serum testosterone and ameliorates nonspecific symptoms resembling, but not due to, androgen deficiency. The important reversible steps include weight reduction and optimizing management of type 2 diabetes mellitus, obstructive sleep apnea, depression, and other obesity-related comorbidities as well as rationalizing concomitant drug regimens. In the absence of pathological hypogonadism, testosterone treatment is less effective than a diet and lifestyle intervention to rectify the reversible conditions responsible for the nonspecific symptoms and associated reduced serum testosterone concentrations observed in men with obesity. As such, testosterone treatment is not indicated, and unwarranted off-label testosterone treatment can lead to adverse effects such as infertility, elevated hematocrit requiring venesection, a prothrombotic state, and testosterone dependence.