Failure of testosterone replacement therapy to improve symptoms correlates with burden of systemic conditions

BACKGROUND: The symptoms of hypogonadism are non-specific and restoring testosterone (T) to physiologic levels may not lead to clinical improvement. In men with a high burden of systemic illness, it is difficult to assess whether hypogonadism is a primary contributing factor of their symptoms. Given that testosterone replacement therapy (TRT) is not without risk, it is important to understand which patients will benefit from treatment. Therefore, we hypothesize that men with a higher burden of systemic illness would be less likely to continue with TRT. METHODS: We performed a retrospective review of our men’s health registry for men who started TRT and adhered to follow up labs and visits within the first year. We restricted treatment to Testopel pellets due to reliable early T levels. Men were classified as yes/no for continued TRT based on whether they felt their presenting symptoms improved on therapy and they chose to continue TRT. The previously validated ACTIONS men’s health phenotype was calculated as a composite systemic disease score grading severity [0–2] for each of anxiety, cardiovascular disease, low testosterone, diabetes, obesity, neurologic disease and obstructive sleep apnea (total score 0–14). RESULTS: Sixty men were identified with a mean age of 59.5 (range, 33–81) years and mean starting total testosterone of 215 [48–332] ng/dL. Thirty-nine men (65%) felt symptomatic benefit and continued therapy for a median of 40.4 (20.5–76.4) months vs. 21 men without benefit treated for a median of 4.1 months (2.9–10.7, P<0.0001). Those who stopped TRT had a higher ACTIONS score than those who continued (8±2.5 vs. 4.1±1.6, P<0.0001). Age weakly correlated with total ACTIONS score (r=0.28, P=0.03) but age had no impact on continuing TRT and the relationship between continuing TRT and ACTIONS score held true regardless of age. CONCLUSIONS: Patients with a greater burden of systemic disease were less likely to have symptomatic improvement with TRT and more likely to stop therapy within a year. As several hypogonadal symptoms are non-specific, it is imperative that patients be counseled on the likelihood of success with TRT, particularly if they have multiple comorbidities. Ideal outcomes may come from multimodal therapy that includes lifestyle modification, and optimization of conditions such as diabetes, cardiovascular disease and sleep apnea.