Secondary Hypogonadism and Effects of Testosterone Replacement Therapy on Cardiovascular Events

Context: The safety of testosterone replacement therapy (TRT) has generated some controversy during recent years. While untreated hypogonadism leads to diminished sexual characteristics, muscle weakness and osteoporosis, the cardiovascular safety of TRT has been vigorously debated. TRT remains the standard of care for those with secondary hypogonadism (SHG) due to structural pituitary disease, but long-term cardiovascular safety in this population remains unclear. Methods: We conducted a retrospective cohort study to investigate occurrence of major adverse cardiovascular events (MACE) in male patients with nonfunctioning pituitary adenomas and prolactinomas, with and without SHG. Demographic data, TRT treatment, stroke, myocardial infarction, and mortality data were retrieved from chart review as well as provincial cardiac and stroke registries. Results: There were 408 patients followed for a median 8.1 years (interquartile range 3.3-14.1); 150 (36.7%) did not have SHG, whereas 214 (52.5%) had SHG adequately treated with TRT and 44 (10.8%) had SHG that was untreated. Multivariable logistic regression analysis demonstrated no significant difference in MACE between groups. MACE outcomes were not impacted by size of adenoma, presence of other pituitary hormonal deficits, or testosterone levels. There was increased risk of mortality in untreated SHG compared to both TRT-treated SHG and those without SHG. Conclusion: TRT does not appear to increase risk of MACE in those with SHG related to pituitary disorders. Untreated SHG appears to convey increased risk of mortality though these patients were older and more comorbid.