Dopamine agonists in prolactinomas: when to withdraw?

Abstract

Dopamine agonists (DAs) are well recognized as the first-line therapy for prolactinomas due to their efficacy in achieving tumoral shrinkage and normoprolactinemia. However, it remains to be established the best timing to withdraw DAs and in which patients this should be attempted. Studies in the 1980s, mainly using bromocriptine, started to defy the concept that DAs should be regarded as a lifelong therapy considering that sustained normoprolactinemia was attained in a small subset of patients after drug withdrawal. The introduction of the more effective agent cabergoline led to an increase in the percentages of remission. The most recent meta-analysis on the topic stated than remission rates after withdrawal can range from 15% in macroprolactinoma patients treated with bromocriptine to 41% in those with microprolactinomas previously treated with cabergoline. When more stringent criteria were applied before attempting withdrawal, sustained remission ensued in more than 50% of the individuals. Treatment duration for more than 24months, the achievement of normoprolactinemia, marked reduction (≥ 50%) in tumoral size and DAs tapering till a low maintenance dose (e.g. cabergoline 0.5mg/week) have been the most consistently identified predictors of success. In addition, a growing amount of evidence suggests that the post-pregnancy/breastfeeding period and menopause are reasonable timings to re-access the need for continuing DAs therapy. Considering that the achievement of sustained normoprolactinemia is still far from being universal after the withdrawal, even in highly selected cohorts, future larger prospective studies should continue to address this issue.