Testosterone therapy demonstrated heterogeneous responses across distinct hypogonadal populations, with functional hypogonadism patients showing higher propensity for weight reduction and metabolic improvements but also greater PSA increments compared to classical hypogonadism, with outcomes significantly influenced by diagnostic categorization, age, and baseline risk factor profiles.
Key Findings
Results
Testosterone therapy significantly increased serum testosterone levels across the entire cohort.
Serum testosterone levels increased from 6.6 ± 2.4 to 19.3 ± 2.9 nmol/L (p < 0.001)
Treatment involved uniform intramuscular administration of testosterone undecanoate (1,000 mg)
The registry encompassed 650 patients equivalent to 4,362 cumulative years of treatment over 9 years
Results
Testosterone therapy was associated with weight reduction and decreased waist circumference in both classical hypogonadism and functional hypogonadism cohorts.
Weight reduction and decreased waist circumference were observed in both CH and FH cohorts (both p < 0.001)
Men with FH demonstrated a higher propensity for losing >10% body weight compared to CH (HR 1.3 [1.1-1.4], p = 0.008)
Men with FH demonstrated a higher propensity for losing >5% waist circumference compared to CH (HR 1.4 [1.3-1.5], p = 0.001)
Results
Increases in hematocrit above 50% were uniform across hypogonadal groups, but amelioration of anemia was more pronounced in functional hypogonadism.
Hematocrit increases >50% were described as 'uniform across groups'
Amelioration of anemia was more pronounced in FH versus CH (p = 0.002)
Results
Increments in prostate-specific antigen levels were more likely to occur in functional hypogonadism patients than in classical hypogonadism patients.
PSA level increments were more likely in FH compared to CH (HR 1.3 [1.1-1.6], p = 0.003)
Results
Functional hypogonadism patients exhibited pronounced improvements in metabolic parameters and symptom scores compared to classical hypogonadism patients.
FH patients showed pronounced improvements in metabolic parameters
FH patients showed improvements in aging male symptom (AMS) score and IIEF-EF questionnaire scores
These effects were markedly modulated by age and initial weight
FH patients had a mean age of 42.3 ± 11.3 years, older than both PH (34.0 ± 11.7 years) and SH (31.9 ± 12.0 years) subgroups
Results
In age-matched obese patients, the impact of testosterone therapy was accentuated in classical hypogonadism compared to functional hypogonadism.
Subgroup analysis of age-matched obese patients revealed an accentuated impact of TTh in CH compared to FH
This finding contrasts with the overall cohort results where FH showed greater anthropometric improvements
The study included 188 FH patients and 462 CH patients (266 primary, 196 secondary hypogonadism)
Methods
The study population consisted of three distinct hypogonadal groups with differing demographic profiles.
188 patients were diagnosed with functional hypogonadism (FH), mean age 42.3 ± 11.3 years
266 men had primary hypogonadism (PH), mean age 34.0 ± 11.7 years
196 men had secondary hypogonadism (SH), mean age 31.9 ± 12.0 years
Total cohort of 650 patients was followed over 9 years (4,362 cumulative treatment years)
Zitzmann M, Cremers J, Krallmann C, Soave A, Kliesch S. (2024). TRACK_9: Testosterone replacement assessment: Classical vs. functional hypogonadism-knowledge from a 9-year study.. Andrology. https://doi.org/10.1111/andr.13626