Gender differences in prolactin thresholds and their association with lactotroph adenoma invasiveness for potential treatment considerations

Recent trends in first-line transsphenoidal surgery (TSS) for prolactinoma patients aim to reduce long-term dependence on dopamine agonists (DA). Key factors linked to poor surgical outcomes include cavernous sinus invasiveness and high baseline serum prolactin (PRL) levels. Defining simple PRL threshold values to indicate invasiveness and inform treatment strategy is crucial. In this retrospective cohort study of 149 prolactinoma patients treated with first-line transsphenoidal surgery (TSS) or dopamine agonist (DA) therapy, we evaluated preoperative prolactin (PRL) levels and cavernous sinus invasion as factors associated with long-term remission. Bayesian modeling identified cohort-wide and gender-specific PRL thresholds associated with invasiveness. Preoperative PRL values strongly correlated with cavernous sinus invasion (AUROC = 0.95; 95% CI: 0.90-0.98). The cohort-wide PRL threshold was 431.9 µg/L (95% CI: 181.1-708.3 µg/L), with gender-specific thresholds of 280.8 µg/L (95% CI: 51.0-528.2 µg/L) for women and 1325.0 µg/L (95% CI: 667.2-2582.9 µg/L) for men. Female thresholds were lower and less affected by age and obesity, while male thresholds were influenced by these factors, particularly in young, obese men. These findings suggest that gender-specific PRL thresholds may be useful for improving specificity and sensitivity in identifying invasiveness, potentially aiding clinical decisions. Personalized treatment informed by preoperative biomarkers is essential for optimizing outcomes and reducing DA reliance, but it should be considered in conjunction with a comprehensive clinical evaluation.