Advances in Drug Treatments for Male Patients with Prolactinomas

Background: Pituitary adenomas (PAs), the most common intracranial neuroendocrine tumors, are typically benign. Among them, prolactinomas – tumors that secrete prolactin – account for approximately 60% of all PAs and are characterized by hyperprolactinemia and potential mass effects. Significant epidemiological and clinical differences exist between male and female prolactinoma patients. Summary: Prolactinomas in male patients tend to be larger and more aggressive, presenting unique challenges in treatment and management. Although dopamine agonists (DAs) remain the first-line therapy, men exhibit higher rates of DA resistance compared to women. For refractory prolactinomas in males, alternative treatments include temozolomide (TMZ), immune checkpoint inhibitors (anti-PD-1/PD-L1 and anti-CTLA4), somatostatin receptor analogs, mTOR inhibitors, tyrosine kinase inhibitors, bevacizumab, and aromatase inhibitors. These therapies may provide greater benefits to men with refractory prolactinomas than to women. Key Messages: Despite advancements, significant challenges and opportunities persist in managing male prolactinoma patients. Key areas requiring attention include early diagnosis, predicting drug responsiveness, understanding sex-specific molecular mechanisms, and developing novel therapeutic strategies. Large-scale clinical trials are crucial to further assess the efficacy and safety of these treatments in men. This review consolidates recent progress in medical therapies and management approaches for male prolactinoma patients.