Current drug withdrawal strategy in prolactinoma patients treated with cabergoline: a systematic review and meta-analysis

Cabergoline is a recommended first-line dopamine agonist for prolactinoma treatment, which is withdrawable for some cases. However, the optimal withdrawal strategy and the accurate recurrence rate associated with cabergoline withdrawal remains uncertain. To assess the current recurrence rate of hyperprolactinemia and possible favorable factors associated with cabergoline withdrawal in prolactinoma patients. The databases of PubMed, EMBASE, and Web of Science were searched up to May 2014 to identify studies containing data of recurrent hyperprolactinemia in prolactinoma patients after cabergoline withdrawal. Meta-analysis, including sensitivity analysis, meta-regression analysis, and subgroup analysis were performed. When the patients who received cabergoline withdrawal were pooled, it was found that the hyperprolactinemia recurrence rate was 65 % by a random effects meta-analysis [95 % confidence interval 55-74 %]. In a random effects meta-regression adjusting for optimal withdrawal strategies, CAB dose reduced to the lowest level before withdrawal was associated with treatment success (p = 0.006), whereas CAB treatment longer than 2 years showed no trend of effect (p = 0.587). Patients who received the lowest CAB dose and presented a significant reduction in tumor size before withdrawal were more likely to achieve the best success (p < 0.001). Our meta-analysis shows that hyperprolactinemia recurs after cabergoline withdrawal in a majority of patients. The probability of success favors patients who have achieved normoprolactinemia and considerable reduction in tumor size by low dose of cabergoline treatment. In addition, our study further suggests that a beneficial strategy is associated with tapering CAB dose before withdrawal but not with CAB treatment duration longer than 2 years.