Serum Prolactin Levels and Mortality in Adults Without Prolactinoma: A Meta-Analysis

Context Prolactin (PRL) is a highly versatile, multifunctional hormone synthesized and secreted by lactotroph cells of the anterior pituitary. Its metabolic role has been extensively studied even in normoprolactinemic populations. Recently, a wealth of observational data have outlined the potential prognostic value of PRL in various clinical settings.Objective This systematic review aims to systematically evaluate and quantitatively synthesize the association between serum PRL levels and risk of mortality in adults without prolactinoma.Methods A systematic literature search was conducted up to June 10, 2023, to identify studies reporting the association of serum PRL levels with clinical outcomes of adults without prolactinoma. A random-effects meta-analysis was conducted to quantify the adjusted hazard ratios [(a)HRs] for all-cause and cardiovascular death (CVD) during follow-up.Results Twenty-eight studies were deemed eligible reporting the outcomes of adults without prolactinoma, in whom serum PRL levels were measured for risk-stratification. Fourteen studies reported appropriate data for meta-analysis encompassing a total of 23 596 individuals. Each unit of PRL increase was independently associated with increased risk of all-cause (pooled aHR = 1.17 [1.08-1.27]; I2 = 48%) and CV mortality (pooled aHR = 1.54 [1.14-2.09]; I2 = 89%). Individuals belonging to the highest PRL category had significantly higher risk for all-cause (pooled aHR = 1.81 [1.43-2.30]; I2 = 65%) and CV (pooled aHR = 1.59 [1.04-2.42]; I2 = 82%) mortality compared to their lowest-PRL category counterparts. The association between PRL levels and in-hospital death did not reach statistical significance.Conclusion PRL levels seem to be an independent predictor for mortality. Further validation is warranted before its role as a risk-stratification tool can be delineated in clinical practice.