Sabine Kliesch

Background and objective The longitudinal efficacy and clinical utility of Testosterone Therapy (TTh) in ameliorating functional hypogonadism (FH) remain contentious, with long‐term data being scarce. To address this lacuna, a comprehensive long‐term registry study, stratifying patients across a spectrum of hypogonadal etiologies, offers a robust investigative paradigm. Materials and methods This 9‐year registry, encompassing 650 patients (equivalent to 4,362 cumulative years of treatment), included 188 patients diagnosed with FH (mean age 42.3 ± 11.3 years) and 462 individuals with classical hypogonadism (CH). The cohort segregated into 266 men with primary hypogonadism (PH, mean age 34.0 ± 11.7 years) and 196 with secondary hypogonadism (SH, mean age 31.9 ± 12.0 years). Uniform treatment across the cohort involved intramuscular administration of testosterone undecanoate (1,000 mg). A comparative analysis was conducted focusing on anthropometric, metabolic, and safety parameters. Results Serum testosterone levels increased from 6.6 ± 2.4 to 19.3 ± 2.9 nmol/L ( p < 0.001). TTh was linked with weight reduction and decreased waist circumference (WC) in both CH and FH cohorts (both p < 0.001). Cox regression and Kaplan–Meier analyses delineated disparities: men with FH demonstrated a higher propensity for losing > 10% body weight and > 5% WC compared to CH (hazard ratio [HR] 1.3 [1.1–1.4], p = 0.008 and HR 1.4 [1.3–1.5], p = 0.001). Increases in hematocrit > 50% were uniform across groups, albeit amelioration of anemia was more pronounced in FH versus CH ( p = 0.002). Increments of prostate‐specific antigen (PSA) levels were more likely to occur in FH (HR 1.3 [1.1–1.6], p = 0.003). FH patients exhibited pronounced improvements in metabolic parameters and in aging male symptom score (AMS) and IIEF‐EF questionnaire scores. These effects were markedly modulated by age and initial weight. Subgroup analysis of age‐matched obese patients revealed an accentuated impact of TTh in CH compared to FH. Discussion and conclusion The therapeutic outcomes of TTh across distinct hypogonadal populations demonstrate heterogeneous responses, significantly influenced by diagnostic categorization, age, and baseline risk factor profiles.