Baseline testosterone levels as a predictor of hypogonadism resolution in male patients with isolated hyperprolactinemia

Purpose: To evaluate the prevalence and the timing of gonadal axis restoration in men with hypogonadism secondary to hyperprolactinemia after prolactin (PRL) normalization, and to identify factors associated with testosterone (TT) recovery to normal values. Methods: We retrospectively analyzed clinical records of male patients with central hypogonadism and successfully treated isolated hyperprolactinemia. Data on PRL, TT, gonadotropins levels were retrieved for different time points: diagnosis, PRL normalization, gonadal axis restoration (if achieved) and last follow-up. Testosterone replacement therapy within 6 months of PRL normalization was an exclusion criterion. Results: Twenty-nine patients, median age 50 years (IQR 41-58), were included. The etiology of hyperprolactinemia included: prolactinoma (n = 23, 79%), non-functioning pituitary adenoma causing stalk effect (n = 5, 17%) and idiopathic cause (n = 1, 4%). After successful treatment of hyperprolactinemia, 20 patients (69%) spontaneously recovered the gonadal axis, achieving normal TT levels. Ten patients normalized PRL and TT values concurrently, while the other 10 exhibited a median delay of 6.5 months (4-9.25) after PRL normalization; the former group showed lower baseline PRL levels at diagnosis compared to the latter (p = 0.007). Patients who recovered the gonadal axis had higher baseline TT values compared to those with persistent hypogonadism (p = 0.02). At ROC curve analysis, baseline TT was a good predictor of spontaneous gonadal axis recovery after PRL normalization (AUC 0.869, p = 0.002). Conclusion: In patients with hypogonadism secondary to isolated hyperprolactinemia, gonadal axis recovery occurs frequently, particularly in those with higher baseline TT. Lower PRL levels at diagnosis are associated with a faster recovery of gonadal axis.