Skip to main content

Advertisement

Log in

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

  • Original Article
  • Published:
Neurological Sciences Aims and scope Submit manuscript

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 meta-analysis.

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 I2% 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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Cuvellier J-C (2019) Pediatric vs. adult prodrome and postdrome: a window on migraine pathophysiology? Front Neurol 10:199

  2. Ambrosini A (2018) Neurophysiology of migraine. Neurol Sci 39(1):59–60

    Article  PubMed  Google Scholar 

  3. Hoffmann J, Baca SM, Akerman S (2019) Neurovascular mechanisms of migraine and cluster headache. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 39(4):573–594

    Article  Google Scholar 

  4. Giani L, Corno S, Laganà MM, Baglio F, Lovati C (2019) Cerebral venous outflow in migraine. Neurol Sci 40(1):181–182

    Article  PubMed  Google Scholar 

  5. Guidetti V, Cerutti R, Faedda N, Natalucci G (2019) Migraine in childhood: an organic, biobehavioral, or psychosomatic disorder? Neurol Sci 40(1):93–98

    Article  PubMed  Google Scholar 

  6. Grazzi L, D’Amico D (2019) Chronic migraine and medication overuse: which strategy for a complex scenario. Neurol Sci 40(1):175–176

    Article  PubMed  Google Scholar 

  7. Pavlovic JM, Akcali D, Bolay H, Bernstein C, Maleki N (2017) Sex-related influences in migraine. J Neurosci Res 95(1–2):587–593

    Article  CAS  PubMed  Google Scholar 

  8. Allais G, Chiarle G, Sinigaglia S, Airola G, Schiapparelli P, Bergandi F, Benedetto C (2019) Acupuncture treatment of migraine, nausea, and vomiting in pregnancy. Neurol Sci 40(1):213–215

    Article  PubMed  Google Scholar 

  9. Freeman ME, Kanyicska B, Lerant A, Nagy G (2000) Prolactin: structure, function, and regulation of secretion. Physiol Rev 80(4):1523–1631

    Article  CAS  PubMed  Google Scholar 

  10. Moher D, Liberati A, Tetzlaff J, Altman DG, The PG (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 6(7):e1000097

    Article  PubMed  PubMed Central  Google Scholar 

  11. Higgins JPT, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21(11):1539–1558

    Article  PubMed  Google Scholar 

  12. Faraone SV (2008) Interpreting estimates of treatment effects: implications for managed care. P T 33(12):700–711

    PubMed  PubMed Central  Google Scholar 

  13. Cassidy EM, Tomkins E, Dinan T, Hardiman O, O'Keane V (2003) Central 5-HT receptor hypersensitivity in migraine without aura. Cephalalgia 23(1):29–34

    Article  CAS  PubMed  Google Scholar 

  14. Cassidy EM, Tomkins E, Sharifi N, Dinan T, Hardiman O, O'Keane V (2003) Differing central amine receptor sensitivity in different migraine subtypes? A neuroendocrine study using buspirone. Pain 101(3):283–290

    Article  CAS  PubMed  Google Scholar 

  15. Fava A, Pirritano D, Consoli D, Plastino M, Casalinuovo F, Cristofaro S, Colica C, Ermio C, De Bartolo M, Opipari C, Lanzo R, Consoli A, Bosco D (2014) Chronic migraine in women is associated with insulin resistance: a cross-sectional study. Eur J Neurol 21(2):267–272

    Article  CAS  PubMed  Google Scholar 

  16. Peres MF, Sanchez del Rio M, Seabra ML, Tufik S, Abucham J, Cipolla-Neto J, Silberstein SD, Zukerman E (2001) Hypothalamic involvement in chronic migraine. J Neurol Neurosurg Psychiatry 71(6):747–751

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Parashar R, Bhalla P, Rai N K, Pakhare A, Babbar R (2014) Migraine: is it related to hormonal disturbances or stress? International journal of women's health 6:921–5

  18. Guldiken S, Guldiken B, Demir M, Kabayel L, Ozkan H, Turgut N, Hunkar R, Kat S (2011) Soluble CD40 ligand and prolactin levels in migraine patients during interictal period. J Headache Pain 12(3):355–360

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Solmaz V, Ceviz A, Aksoy D, Cevik B, Kurt S, Gencten Y, Erdemir F (2016) Sexual dysfunction in women with migraine and tension-type headaches. Int J Impot Res 28(6):201–204

    Article  CAS  PubMed  Google Scholar 

  20. Dogan VB, Dagdeviren H, Dirican A, Dirican AC, Tutar NK, Yayla VA, Cengiz H (2017) Hormonal effect on the relationship between migraine and female sexual dysfunction. Neurol Sci 38(9):1651–1655

    Article  PubMed  Google Scholar 

  21. Awaki E, Takeshima T, Takahashi K (1989) A neuroendocrinological study in female migraineurs: prolactin and thyroid stimulating hormone responses. Cephalalgia 9(3):187–193

    Article  CAS  PubMed  Google Scholar 

  22. D'Andrea G, Cananzi AR, Grigoletto F, Meneghini F, Cortesi S, Soffiati G, Joseph R, Nordera G, Ferro-Milone F (1988) The effect of dopamine receptor agonists on prolactin secretion in childhood migraine. Headache 28(5):354–359

    Article  CAS  PubMed  Google Scholar 

  23. Gavaghan DJ, Moore RA, McQuay HJ (2000) An evaluation of homogeneity tests in meta-analyses in pain using simulations of individual patient data. Pain 85(3):415–424

    Article  CAS  PubMed  Google Scholar 

  24. Higgins JPT, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327(7414):557–560

    Article  PubMed  PubMed Central  Google Scholar 

  25. Sabharwal P, Glaser R, Lafuse W, Varma S, Liu Q, Arkins S, Kooijman R, Kutz L, Kelley KW, Malarkey WB (1992) Prolactin synthesized and secreted by human peripheral blood mononuclear cells: an autocrine growth factor for lymphoproliferation. Proc Natl Acad Sci U S A 89(16):7713–7716

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Kiefer KA, Malarkey WB (1978) Size heterogeneity of human prolactin in CSF and serum: experimental conditions that alter gel filtration patterns. J Clin Endocrinol Metab 46(1):119–124

    Article  CAS  PubMed  Google Scholar 

  27. Teive HAG, Munhoz RP, Camargo CHF, Walusinski O (2018) Yawning in neurology: a review. Arq Neuropsiquiatr 76(7):473–480

    Article  PubMed  Google Scholar 

  28. Güven B, Güven H, Çomoğlu SS (2018) Migraine and yawning. Headache 58(2):210–216

    Article  PubMed  Google Scholar 

  29. Granata R, Sabine E, Tilg H, Wenning G (2017) Gastrointestinal dysfunction, Bedside approach to autonomic disorders. Springer, pp 101–116

  30. Bussone G, Usai S, Moschiano F (2012) How to investigate and treat: headache and hyperprolactinemia. Curr Pain Headache Rep 16(4):365–370

    Article  PubMed  Google Scholar 

  31. Gudelsky GA, Nansel DD, Porter JC (1981) Role of estrogen in the dopaminergic control of prolactin secretion. Endocrinology 108(2):440–444

    Article  CAS  PubMed  Google Scholar 

  32. Villegas-Gabutti C, Pennacchio GE, Jahn GA, Soaje M (2016) Role of estradiol in the regulation of prolactin secretion during late pregnancy. Neurochem Res 41(12):3344–3355

    Article  CAS  PubMed  Google Scholar 

  33. Wang C, Chan V (1982) Divergent effects of prolactin on estrogen and progesterone production by granulosa cells of rat Graafian follicles. Endocrinology 110(4):1085–1093

    Article  CAS  PubMed  Google Scholar 

  34. Chang AS, Grant R, Tomita H, Kim H-S, Smithies O, Kakoki M (2016) Prolactin alters blood pressure by modulating the activity of endothelial nitric oxide synthase. Proc Natl Acad Sci U S A 113(44):12538–12543

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Zhang L, Curhan GC, Forman J (2010) Plasma prolactin level and risk of incident hypertension in postmenopausal women. J Hypertens 28(7):1400–1405

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Peterlin BL, Gupta S, Ward TN, Macgregor A (2011) Sex matters: evaluating sex and gender in migraine and headache research. Headache 51(6):839–842

    Article  PubMed  PubMed Central  Google Scholar 

  37. Vega CB, Quigley L, Patel M, Price T, Arkopian A, Dussor G (2017) (137) Meningeal application of prolactin and CGRP produces female specific migraine-related behavior in rodents. J Pain 18(4):S11

    Article  Google Scholar 

  38. Fedak KM, Bernal A, Capshaw ZA, Gross S (2015) Applying the Bradford Hill criteria in the 21st century: how data integration has changed causal inference in molecular epidemiology. Emerging themes in epidemiology 12:14

  39. Rainero I, Valfre W, Savi L, Gentile S, Pinessi L, Gianotti L, Arvat E, Ghigo E, Del Rizzo P, Calvelli P, Limone P (2001) Neuroendocrine effects of subcutaneous sumatriptan in patients with migraine. Journal of endocrinological investigation 24(5):310–4

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ali Seidkhani-Nahal.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethics

The present study was approved by the Ethics Committee of Ilam University of Medical Sciences.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Article highlights

• Association between blood prolactin and migraine pathogenesis was investigated using meta-analysis.

• The included studies (systematic review) were heterogeneous and random-effects model was applied.

• The pooled SMD for prolactin blood levels was 1.435 (95% confidence interval, 0.854 - 2.015). P value for the z-test was 0.000.

• Based on the findings, hyperprolactinemia is associated with migraine pathogenesis.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Noori-Zadeh, A., Karamkhani, M., Seidkhani-Nahal, A. et al. Evidence for hyperprolactinemia in migraineurs: a systematic review and meta-analysis. Neurol Sci 41, 91–99 (2020). https://doi.org/10.1007/s10072-019-04035-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10072-019-04035-7

Keywords

Navigation