Hypothesis / aims of study
According to current EAU (1) and AUA (2) guidelines, there is no evidence for an increased risk for prostate diseases with testosterone therapy (TTh). However, concerns in general as well as urological clinical practice are still common. To provide more data from clinical experience, we updated analyses of a registry database of men with functional hypogonadism which we had last published in 2018 (3).
Study design, materials and methods
A urological registry study of men with hypogonadism, defined by two morning total testosterone levels ≤12.1 nmol/L, was initiated in 2004 in a single urology office in Germany. After exclusion of men with primary hypogonadism (for instance, Klinefelter’s syndrome, orchiectomy following testicular cancer), 779 men were classified as having functional hypogonadism. Of these men, 723 (92.8%) had overweight or obesity. 367 men received testosterone undecanoate injections 1000 mg every 12 weeks following an initial 6-week interval (T-group), 356 opted against TTh and served as controls (CTRL). 12-year results were analyzed. Changes over time between groups were compared and adjusted for age, weight, waist circumference, fasting glucose, blood pressure, lipids, and quality of life to account for baseline differences between groups.
Results
Mean age at baseline: 58.8±5.9 years (T-group) and 63.1±4.9 (CTRL) (p<0.0001). Mean (median) follow-up: T-group 9.3±3.0 (10), CTRL 9.8±2.6 (11) years. Alphablockers were used at baseline by 46.0% in the T-group and 52.8% in CTRL (p=0.1223). 5-alpha reductase inhibitors were used at baseline by 2.7% in the T-group and 9.3% in CTRL (p=0.0002). PDE5 inhibitors were used at baseline by 24.0% in the T-group and 23.0% in CTRL (p=0.7646).
The International Prostate Symptom Score (IPSS) at baseline was 7.2±3.5 (mean±SD) in the T-group and 4.9±1.9 in CTRL (p<0.0001). In the T-group, IPSS declined by 5.2±0.2 (least squares means±SE) in year 12. In CTRL, IPSS increased by 4.5±1.2. Estimated adjusted difference between groups at 12 years: -9.7 [95% confidence interval (CI): -10.2;-9.2] (p<0.0001 for all).
Post-voiding residual bladder volume (RBS) at baseline was 57.1±23.8 mL (mean±SD) in the T-group and 51.3±16.1 in CTRL (p=0.0001). In the T-group, RBS declined by 44.4±1.5 mL (least squares means±SE) in year 12. In CTRL, RBS increased by 38.8±1.5. Estimated adjusted difference between groups at 12 years: -83.2 mL [95% CI: -87.9;-78.5] (p<0.0001 for all).
Prostate volume (PV) at baseline was 32.4±9.2 mL (mean±SD) in the T-group and 35.4±6.1 in CTRL (p=0.0001). In the T-group, PV increased by 3.5±0.2 mL (least squares means±SE) in year 12 (p<0.0001). In CTRL, PV increased by 4.1±0.2 (p<0.0001). Estimated adjusted difference between groups at 12 years: -0.5 [95% CI: -1.1;0.1] (p=0.09529).
The Aging Males’ Symptoms scale (AMS) at baseline was 53.4±9.3 (mean±SD) in the T-group and 40.2±5.5 in CTRL (p<0.0001). In the T-group, AMS declined by 29.7±0.4 (least squares means±SE) in year 12. In CTRL, AMS increased by 21.6±0.4. Estimated adjusted difference between groups at 12 years: -51.4 [95% CI: -51.4;-52.7] (p<0.0001 for all).
Cases of acute urinary retention occurred in 16 patients in CTRL. There were no cases in the T-group.
Interpretation of results
While baseline mean IPSS was in the mild to moderate category and there were no patients with severe symptoms, one would expect IPPS to worsen with advancing age. We found this to be the natural development in patients with hypogonadism and overweight or obesity who were not treated with testosterone. However, in those patients who received long-term TTh we could show that urinary function, measured by IPSS and RBV, improved over time. This seemed to be independent of prostate volume because the age-related increase in PV was not different between the T-group and CTRL.