Testosterone Recovery after Androgen Deprivation Therapy in Prostate Cancer: Differential Effects of Gonadotropin-Releasing Hormone Agonist Monotherapy and Maximal Androgen Blockade.

Purpose

Testosterone recovery after androgen deprivation therapy (ADT) cessation is clinically important because prolonged hypogonadism may affect metabolic, cardiovascular, skeletal, and quality-of-life outcomes in prostate cancer. Although predictors of testosterone recovery have been reported, most studies focused on gonadotropin-releasing hormone agonist monotherapy; comparative data with maximal androgen blockade (MAB) remain limited.

Materials And Methods

We retrospectively analyzed patients with prostate cancer who received ADT for ≥3 months between 2016 and 2024, had ≥3 months of follow-up after ADT cessation, and had at least two post-cessation testosterone measurements. Testosterone recovery was defined as the first testosterone level ≥3.0 ng/mL after discontinuation. Time to recovery was assessed using Cox proportional hazards regression, with the number of testosterone measurements included as a log-transformed variable. Propensity score-matched analysis addressed treatment-arm imbalance, and recursive partitioning analysis was used for risk stratification.

Results

Among 502 patients, testosterone recovery occurred in 177 (35.3%), with a median time to recovery of 15 months (interquartile range 10-19). In multivariable Cox analysis, longer ADT duration (hazard ratio [HR] 0.904, 95% confidence interval [CI] 0.884-0.926, p<0.001), older age (HR 0.894, 95% CI 0.870-0.918, p<0.001), and higher body mass index (BMI) (HR 0.909, 95% CI 0.858-0.963, p=0.001) were associated with delayed recovery, whereas higher baseline testosterone predicted faster recovery (HR 1.081, 95% CI 1.010-1.157, p=0.025). MAB was associated with delayed recovery in the full cohort (HR 0.557, 95% CI 0.360-0.862, p=0.009), but this was attenuated after propensity score matching (HR 0.690, 95% CI 0.378-1.258, p=0.226).

Conclusions

Testosterone recovery after ADT cessation occurred in approximately one-third of patients. Younger age, shorter ADT duration, lower BMI, and higher baseline testosterone were associated with faster recovery. The association between MAB and delayed recovery was attenuated after matching and should be interpreted cautiously.