Prolactinoma-associated headache: Clinical and radiological correlates and long-term outcomes

While headache is frequently encountered in patients with prolactinomas, data on its determinants and long-term outcome following upfront medical versus upfront surgical treatment are limited. We aimed to identify clinical and radiological determinants of prolactinoma-associated headache (PAH) and to evaluate long-term headache outcomes according to the primary treatment strategy.

We retrospectively analyzed 145 prolactinoma patients treated at a tertiary center. Headache at presentation, endocrine parameters, tumor size, and cavernous sinus involvement were assessed. Independent determinants of PAH at diagnosis were identified using multivariable logistic regression. Long-term headache status and prolactin outcomes were evaluated according to upfront dopamine agonist (DA) therapy or transsphenoidal surgery (TSS).

At diagnosis, 42 of 145 patients (28.9%) presented with PAH. Compared with patients without PAH, those with PAH were older, more often male, and more likely to harbor macroadenomas and tumors with cavernous sinus involvement. In multivariable analysis, cavernous sinus involvement was the only independent factor associated with PAH (adjusted OR, 7.8; 95% CI, 1.2-48.7; p = 0.03), whereas baseline prolactin levels were not independently associated. After a median follow-up of 80 months, headache prevalence declined from 28.9% to 2.8% (p < 0.001). Durable headache improvement was observed after both DA therapy and transsphenoidal surgery, with no significant difference between treatment modalities.

PAH is most strongly linked to tumor invasiveness rather than to prolactin levels alone. Durable headache relief is achieved with both upfront surgical and medical therapy, suggesting that effective tumor control, rather than the specific initial treatment approach, is the key determinant of headache improvement. These findings support careful patient counseling and underscore the importance of an individualized multidisciplinary approach in prolactinoma patients presenting with headache.