The Differences Between Dopamine Agonist-Resistant and -Non-Resistant Prolactinomas: Are There Any Predictors of a Good Response?

<b>Background/Objectives</b>: Dopamine agonists (DAs) are the first-line therapy for prolactinomas; however, a subset of patients exhibits resistance or incomplete response. <b>Methods</b>: This retrospective study included 85 of 125 eligible consecutive patients with prolactinoma who were treated with DA, followed for a median of 52.0 (31.5-86.8) months. Clinical, biochemical, and radiological parameters were analyzed at baseline and at 6 and 12 months. Resistance was defined as failure to normalize serum prolactin concentration (PRL) or achieve ≥ 30% reduction in tumor maximal diameter after standard DA therapy. Logistic regression analyses were performed to identify predictors of DA resistance and treatment response. <b>Results</b>: The cohort comprised 54 males (63.5%) and 31 females (36.1%), with a mean age of 41.5 ± 17.2 years. In total, 22.4% had giant prolactinomas. After 6 months of treatment, 24.7% achieved PRL normalization, and 29.4% demonstrated ≥ 50% reduction in tumor volume. At 12 months, PRL normalized in 40% of patients, and a ≥50% volume reduction was observed in 41.2%. DA-resistant patients, compared to DA-non-resistant, were predominantly men (80.0% vs. 56.7%, <i>p</i> = 0.042), with a higher proportion of giant adenomas (44.0% vs. 13.3%, <i>p</i> = 0.002) and significantly higher baseline PRL (2000.000 ng/mL vs. 478.985 ng/mL, <i>p</i> = 0.012). Early reduction in maximal tumor diameter at 6 months predicted a favorable therapeutic response at 12 months (aOR = 1.156; 95% CI = 1.001-1.335, <i>p</i> = 0.049). <b>Conclusions</b>: Male sex, higher baseline PRL, and larger tumor size can be predictors of DA resistance. On the other hand, early radiological tumor shrinkage may predict favorable treatment outcomes. However, new markers of DA resistance, particularly molecular ones, should be identified.