‘’ When Treatment Backfires: Dopamine Agonist-Induced CSF Leaks in Prolactinomas – Case Series and Systematic Review.’’

Cerebrospinal fluid (CSF) rhinorrhea is a rare but potentially life-threatening complication of dopamine agonist (DA) therapy in patients with invasive macroprolactinomas. To identify clinical and anatomical risk factors for DA-induced CSF rhinorrhea and to evaluate effective surgical management strategies in patients with prolactinomas. We retrospectively reviewed two adult male patients treated at our center who developed CSF rhinorrhea following cabergoline therapy for prolactinomas. In parallel, a systematic literature review was conducted following PRISMA guidelines, including 105 patients from 38 studies published between 1982 and 2025. Data on demographics, tumor characteristics, prolactin levels, timing of CSF leak, and management strategies were analyzed. Both patients developed CSF rhinorrhea 7–12 months after initiation of DA therapy. Imaging revealed sellar floor erosion. Endoscopic transsphenoidal surgery (ETSS) with sellar reconstruction using a vascularized nasoseptal flap was successfully performed. The postoperative course was uneventful, and no recurrence of CSF leak was observed during follow-up. Literature review confirmed a male predominance, a mean age of 45.6 years, frequent sphenoid sinus or sellar floor involvement and onset of CSF leaks predominantly within the first year of therapy. Endoscopic transsphenoidal multilayer reconstruction was the most employed and effective treatment modality across reported cases. DA-induced CSF rhinorrhea is associated with invasive tumor features and sphenoid sinus involvement. Early recognition and timely surgical intervention in specialized centers are critical to prevent serious complications. Patients receiving DAs should be counseled regarding this risk, and standardized endoscopic skull base reconstruction provides a safe and effective management strategy. • Dopamine agonist therapy may precipitate cerebrospinal fluid (CSF) rhinorrhea in patients with invasive macroprolactinomas. • Most CSF leaks occurred after treatment initiation, with 71.6% presenting within 6 months and 86.8% within 1 year. • The most frequent anatomical defect sites were the sellar floor (78%) and the sphenoid sinus (47.6%). • Endoscopic endonasal transsphenoidal repair using standardized multilayer reconstruction and a vascularized nasoseptal flap resulted in durable CSF leak closure.