Evidence for hyperprolactinemia in migraineurs: a systematic review and meta-analysis

Abstract

Background One of the hypothalamus-pituitary axis hormones which may play a crucial role in pathophysiology of migraine is prolactin which is secreted from anterior pituitary gland and synthesized by various immune system cells as well. Whether prolactin blood levels can affect the migraine pathogenesis is an open question. Therefore, investigating prolactin circulatory levels in migraineurs may pave the way to underpin the mechanisms of migraine pathophysiology at biochemical levels. In the current investigation, the prolactin blood levels in the migraine subjects were investigated using systematic review and metaanalysis. Methods Using online and specialized biomedical databases including Google Scholar, Medline, Pubmed, Pubmed Central, Embase, and Scopus, without the beginning date restriction until Feb 2019, the systematic review retrieved 11 publications in this systematic review after fulfilling for the inclusion and exclusion criteria. For heterogeneity, extent calculation statistical testing was applied. In the present study, the levels of circulatory prolactin in migraineurs assessed using standardized mean difference (SMD) as the effect size. Results Q quantity and I 2 % statistic index showed a high heterogeneity in the 13 selected publications (188.370 and 92.568, respectively) and random-effects model was chosen for further analyses. The meta-analysis on a total number of 460 migraineurs and 429 healthy controls found that the weighted pooled SMD for the effects of prolactin blood concentrations on migraine pathogenesis was as follows: SMD = 1.435 (95% confidence interval, 0.854-2.015). Conclusion The current investigation presents evidence that prolactin blood levels are higher in migraineurs than healthy subjects.

Prolactin in headache and migraine: A systematic review of clinical studies

“…Different methodological approaches, particularly, not differentiating in migraine types might explain this discrepancy. A systematic review and a meta-analysis of available studies measuring serum PRL levels included 460 migraine patients and 429 healthy controls and reported that serum PRL levels were higher in migraine patients compared to healthy controls (72).…”

Prolactin and oxytocin: potential targets for migraine treatment

“…Increased serum PRL levels have been described in patients with headaches, especially migraine [ 106 , 107 ]. A meta-analysis from 2019 showed higher PRL levels in the migraine patient group compared to controls based on 13 studies, although there was a high degree of heterogeneity among studies [ 16 , 107 ]. In comparison, a few studies showed that reduced PRL levels accompany migraine attacks [ 108 , 109 ].…”

A Link Between Migraine and Prolactin: the Way Forward

“…One line of evidence supporting the view that prolactin plays a crucial role in the pathophysiology of migraine is an investigation of prolactin circulatory levels in migraine [ 31 ]. A systematic review followed by a meta-analysis [ 11 ] summarized the available literature since the 1970s on prolactin blood levels in patients with migraine. In this systematic review, 13 studies were found to be relevant, with a total number of 460 migraineurs and 429 healthy controls, with a high heterogeneity among the studies.…”

“…In this systematic review, 13 studies were found to be relevant, with a total number of 460 migraineurs and 429 healthy controls, with a high heterogeneity among the studies. For the meta-analysis, a random effects model (i.e., variance components model) was preformed and the findings demonstrated that the blood levels of prolactin were higher in patients with migraine compared with healthy controls [ 11 ]. However, some studies have shown that prolactin level decreased during a migraine attack; for example, a study comparing 20 men with migraine with 20 men without migraine reported that prolactin levels were lower in patients with migraine [ 32 ].…”

“…First, in hyperprolactinemia, headaches with migraine characteristics have been described and normalization of the prolactin level has alleviated headaches [ 9 , 10 ]. Moreover, in migraine patients, higher levels of prolactin have been identified that were also responsive to drugs lowering the prolactin level [ 11 , 12 ]. Second, a new line of evidence has shown that prolactin receptor expression and neuronal responsiveness to external stimuli and stress are different in female and male laboratory animals, which can explain some mechanisms underlying sex-related differences in migraine, with a spotlight on prolactin [ 8 , 13–16 ].…”