Men with untreated hypogonadism at risk of long-term morbidity, death

Untreated hypogonadism in men appears to elevate the risk of morbidity in the long term and early mortality based on time-related measures of risk only, according to a study.

This finding stresses the clinical importance and safety of testosterone therapy (TTh) in true hypogonadal men, as well as the need to obtain long-term follow-up data.

“In the context of established male hypogonadism, TTh has been employed to regain physiologic levels of circulating testosterone and improve sexual function and overall quality of life,” said the researchers.

The team conducted this study to assess the risk of cardiovascular disease and mortality as time-dependent outcomes in TTh-treated vs untreated hypogonadal men. They performed a meta-analysis using weighted time-related measures of risk for each of the outcome for all eligible studies.

Studies were included if they enrolled male adults (≥18 years old) diagnosed with hypogonadism who were divided into two arms—a treatment arm (any TTh) and a control arm (observation or placebo)—and assessed the risk of death or cardiovascular events. Single-arm, noncomparative studies, as well as those that did not report the hazard ratios (HRs) for the chosen outcomes, were excluded.

The researchers registered this systematic review on PROSPERO (CRD42022301592) and performed it according to MOOSE and PRISMA guidelines.

Ten studies, involving a total of 179,631 hypogonadal men, met the eligibility criteria for the meta-analysis. Treatment with TTh resulted in a reduced mortality risk from all cause compared with observation or placebo (HR, 0.70, 95 percent confidence interval [CI], 0.54‒0.90; p<0.01).

However, the researchers found an unfavourable effect of TTh in hypogonadal men in terms of cardiovascular evens when compared to untreated/observed counterparts (HR, 0.98, 95 percent CI, 0.73‒1.33; p=0.89).

“TTh in hypogonadal men might play a role in reducing the overall risk of death without increasing cardiovascular events risk,” the researchers said.