Benefits of Testosterone Replacement Therapy in Hypogonadal Males

Hypogonadism is defined by consistently low serum testosterone levels in conjunction with clinical symptoms. Testosterone replacement therapy (TRT) can be used to achieve physiologic levels of testosterone. Testosterone deficiency is associated with increased mortality and poorer health outcomes.

To compare rates of mortality, atrial fibrillation (AF), stroke, myocardial infarction (MI), and prostate cancer in hypogonadal men who received TRT versus those who did not.

The TriNetX database was utilized to access deidentified, retrospective propensity matched EMR data from 57 participating health care organizations between 2005 to 2020. Cohorts included males 40 to 80 years old diagnosed with hypogonadism who were prescribed TRT versus no TRT. Propensity matching was performed to reduce bias and balance confounding factors between the 2 groups. The following 3-year outcomes were analyzed: mortality, AF, stroke, MI, and prostate cancer.

There were 163,456 male patients identified with hypogonadism, and 133,584 were included after propensity matching. There was a lower mortality rate, (3.1% vs 3.6%; RR, 0.886; P < .001), decreased risk of AF (3.6% vs 4.0%; RR 0.900; P < .001), less stroke (1.6% vs 1.8%; RR, 0.898; P < .011), and fewer cases of prostate cancer (1.9% vs 2.9%; RR 0.648; P < .001) for patients on TRT.

Using TRT is associated with moderately lower rates of mortality, atrial fibrillation, stroke, and prostate cancer in hypogonadal men versus no TRT. There is potential for missed cases of stroke, prostate cancer, and cardiovascular disease incidence not captured by the database. As prescriptions of TRT increase, understanding risks and benefits will help guide future practice.