SUN-222 Testosterone Treatment in Men with Classical vs. Functional Hypogonadism: A 9-Year Registry

Abstract

Introduction and Objective Longterm data of Testosterone (T) substitution in hypogonadal men are scarce and clinical value of this treatment is especially debated in men with functional (so called “late-onset”) hypogonadism. A long-term registry comprising various groups of patients provides an efficient tool to approach this issue. Methods Registry data of max. 9 years comprising 650 patients with hypogonadism including 266 men with primary forms (mean age 34.0±11.7 years), 196 with secondary origin (mean age 31.9±12.0 years) and 188 with functional hypogonadism (mean age 42.3±11.3 years) all receiving uniform treatment using intramuscular T undecanoate (1000 mg). Results The registry contained 8358 time points with a subset of metabolic and safety parameters each. Serum T concentrations increased from 5.7±2.3 nmol/L to 19.4±2.8 nmol/L in men with classical hypogonadism and from 7.8±2.4 nmol/L to 19.2±3.1 nmol/L in men with functional hypogonadism (difference in delta T: p<0.0001). There was an initial difference in the distribution of body mass index (BMI): 35.6% of men with classical hypogonadism and 51.6% of men with functional hypogonadism were obese (BMI>30 kg/m2, p=0.0006). Changes over time using Kaplan-Meier models revealed fundamental differences in inter-individual effects: men with functional hypogonadism were more likely to lose 10% weight and 5% of waist circumference (WC) than men with classical hypogonadism (hazard ratio 1.3 [1.1-1.4], p=0.008 and hazard ratio 1.4 [1.3-1.5], p=0.001). There was no difference for increase in hematocrit. Changes in PSA levels were more likely to occur in functional hypogonadism (hazard ratio 1.3 [1.1-1.6], p=0.003). Significantly more pronounced effects of T substitution in functional hypogonadism could also be attributed to changes in parameters of lipid metabolism (levels of total cholesterol, triglycerides, LDL- and HDL-cholesterol and glucose metabolism). Stepwise multiple Cox regression models could attribute these differences to the initial higher values in BMI, WC, lipids, glucose and age found in functional hypogonadism. The condition as such rather attenuated the effects of testosterone treatment compared to those seen in classical forms of hypogonadism, due to the lower increase of testosterone concentrations during treatment. Conclusions Major new findings regarding effects and safety of T substitution in different groups of hypogonadal men are provided. Effects on factors influencing cardiovascular health are modulated by diagnosis and age. Patients with functional hypogonadism seem to benefit to a larger extent from T substitution, this being a function of their initially worse status in cardiovascular risk factors compared to men with classical forms of hypogonadism.