Testosterone therapy in older men with late-onset hypogonadism: a counter-rationale

The past decade has seen a surge in referrals of older men for consideration of testosterone therapy for late-onset hypogonadism (LOH) to treat symptoms such as fatigue, sexual dysfunction and decreased vitality. Prescription sales of testosterone have accordingly increased by 20-fold over the same period, due mainly to marketing campaign as well as to the failure of clinicians to distinguish organic hypogonadism from LOH. This review seeks to provide a counter-rationale for testosterone therapy in LOH.

A retrospective review of English-language epidemiologic studies, clinical trials and their relevant cited studies related to testosterone and older men was carried out.

Shortcomings of population studies on LOH include use of multiple numeric definitions and non-standard testosterone assays, and measurement of testosterone at a single time point. In contrast to higher estimates of prevalence based solely on numeric values, the syndromic prevalence of LOH is only 2%. Although attrition of testicular Leydig cells and slowing of gonadotropin-releasing hormone neurons both contribute to LOH, obesity and other comorbidities strongly influence testosterone levels, suggesting that testosterone is a biomarker of health. Testosterone therapy in LOH has consistently resulted in improvements in muscle mass and strength, although data regarding effects on physical function and improvements in fall and fracture rates remain unknown. Eythrocytosis is the most common adverse effect of testosterone therapy in older men, while long-term risks in the prostate and cardiovascular system remain unclear.

Considering the paucity of data on clinically meaningful outcomes, the number of uncertain risks, and the fact that modifiable risk factors adversely influence testosterone levels, healthy lifestyle and treatment of comorbidities might attenuate age-related declines in testosterone levels.