Morteza Taghavi Corresponding Author
- Endocrine Research Center, Faculty of Medicine, Mashad University of Medical Sciences, Mashad, Iran
Hossein Ayat-Allahi
- Department of Pathology, Faculty of Medicine, Mashad University of Medical Sciences, Mashad, Iran
Mohammad Khadjeh Dalouie
- Department of Biostatistics, Faculty of Medicine, Mashad University of Medical Sciences, Mashad, Iran

Received: 7/1/2007 Accepted: 7/1/2007 - Publisher : Avicenna Research Institute

Related Articles


Other Format



Introduction: Prolactin exists in three different molecular forms, i.e., monomeric, big and big big (macroprolactin) in human serum. Macroprolactin is a complex of prolactin and IgG and may account for a significant proportion of idiopathic hyperprolactinemia. Its biological activity is considered low or absent, but it is measured alongside free prolactin in common immunoassay methods, thus can wrongly lead to high prolactin detection, expensive explorations and ineffec-tive treatments. Conventionally, the diagnosis of macroprolactinemia has been done by gel filtra-tion chromatography, which could not be used routinely. Recently polyethylene glycol (PEG) has been employed to precipitate macroprolactin, allowing its detection rapidly, trustworthily and inexpensively. The objectives of the present study have been to evaluate the prevalence of macroprolactinemia in infertile women with hyperprolactinemia through identification with PEG and to compare the clinical (Galactorrhea and oligomenorrhea) and radiological findings (Sella turcica MRI). Materials & Methods: 17 infertile women with hyperprolactinemia were investigated for macro-prolactin by using PEG. Prolactin was measured before and after precipitation of macroprolactin by PEG. A prolactin recovery >60% after precipitation was an indicator of macroprolactinemia. The results were analyzed by SPSS software and p<0.05 was considered significant. results: macroprolactinemia was diagnosed in six (35%) women. in true hyperprolactinemic women (11women), galactorrhea occurred in 81.8% and oligomenorrhea in 90.9% of them, but in macroprolactinemic women galactorrhea occurred in 33.3% and oligomenorrhea in 16.6%. in addition, normal pituitary images were found in 45.5% of the patients who had true hyperpro-lactinemia; however, 100% of the women with macroprolactinemia had normal pituitary images. conclusion: macroprolactinemia evaluation by peg in infertile women with hyperprolactinemia is recommended before extensive diagnostic and therapeutic procedures.< pan>

Keywords: Prolactin, Macroprolactin, Hyperprolactinemia, Macroprolactinemia, Polyethylene glycol, Infertility, Galactorrhea, Oligomenorrhea

To cite this article:


  1. Luciano AA. Clinical presentation of hyperprolactine-mia. J Reprod Med. 1999;44:1085-90.   [PubMed]
  2. Suliman AM, Smith TP, Gibney Y, Mc Kenna TJ. Frequent misdiagnosis and mismanagement of hyper-prolactinemic patients before the introduction of macroprolactin screening: application of a new strict laboratory definition of macroprolactinemia. Clin Chem. 2003;49(9):1504-9.   [PubMed]
  3. Fahie-Wilson MN, John R, Ellis AR. Macroprolactin; high molecular mass forms of circulating prolactin. Ann Clin Biochem. 2005;42(pt 3):175-92.   [PubMed]
  4. Leite V, Cosby H, Sobrinho LG, Fresnoza A, Amparo Santos M, Friesen HG. Characterisation of big, big prolactin in patients with hyperprolactinaemia. Clin Endocrinol. 1992;37:365-72.   [PubMed]
  5. Bonhoff A, Vuille JC, Gomez F, Gellersen B. Identi-fication of macroprolactin in a patient with asympto-matic hyperprolactinaemia as a stable PRL-IgG comp-lex. Exp Cin Endocrinol Diabetes. 1995;103:252-5.   [PubMed]
  6. Carlson HC, Markoff E, Lee W. On the nature of serum prolactin in two patients with macroprolactinaemia. Similar results in fresh serum (chromatography within 2 hours of phlebotomy) and after storage at -20°C for 12 months. Fertil Steril. 1992;58:78-87.   [PubMed]
  7. Cavaco B, Leite V, Amparo Santos M, Arranhado E, Sobrinho LG. Some forms of big big prolactin behave as a complex of monomeric prolactin with an immuno-globulin G in patients with macroprolactinaemia or prolactinoma. J Clin Endocrinol Metab. 1995;80:2342-6.   [PubMed]
  8. Hattori N, lkekubo K, lshihara T, Moridera K, Hino M, Kurahacki H. A normal ovulatory woman with hyper-prolactinaemia: presence of anti-prolactin autoantibody and the regulation of prolactin secretion. Acta Endo-crinol. 1992;126:497-500.   [PubMed]
  9. Heaney AP, Laing I, Walton L, Self MW, Beardwell CG, Davis JRE. Misleading hyperprolactinaemia in pregnancy. Lancet. 1999;353:720.   [PubMed]
  10. Andersen AN, Pedersen H, Djursing H, Andersen BN, Friesen HG. Bioactivity of prolactin in a woman with an excess of large molecular size prolactin, persistent hyperprolactinaemia and spontaneous conception. Fertil Steril. 1982;38:625-8.   [PubMed]
  11. Hattori N, lnagaki C. Anti-prolactin autoantibodies cause asymptomatic hyperprolactinaemia: bioassay and clearance studies of PRL-immunoglobulin G complex. J Clin Endocrinol Metab. 1997;82:3107-10.   [PubMed]
  12. Fraser IS, Lun ZG, Zhou JP, Herington AC, Mc Carron G, Caterson I, et al. Detailed assessment of big big prolactin in women with hyperprolactinemia and normal ovarian function. J Clin Endocrinol Metab. 1989;69:585-92.   [PubMed]
  13. Hattori N, Ikekubo K, Ishihara T, Moridera K, Hino M, Kurahachi H. A normal ovulatory woman with hyperprolactinemia: presence of anti-prolactin auto-antibody and the regulation of prolactin secretion. Acta Endocrinol. 1992;126:497-500.   [PubMed]
  14. Ismail AAA, Walker PL, Fahie-wilson MN, Jassam N, Barth JH. Prolactin and macroprolactin: a case report of hyperprolactinaemia highlighting the interpre-tation of discrepant results. Ann Clin Biochem. 2003; 40(pt 3):298-300.   [PubMed]
  15. Hattori N. The frequency of macroprolactinaemia in pregnant women and the heterogeneity of its etiologies. J. Clin Endocrinol Metab. 1996;81:586-90.   [PubMed]
  16. Hattori N, lkekubo T, lkekubo K, Moridera K, Hino M, Kurahachi H. Autoantibody to human prolactin in patients with idiopathic hyperprolactinemia. J Clin Endocrinol Metab. 1992;75:1226-9.   [PubMed]
  17. Freeman ME, Kanyicska B, Levant A, Nabgy G. Prolactin: structure, function and regulation of secre-tion. Physiol Rev. 2000;80:1523-631.   [PubMed]
  18. Bjoro T, Johansen E, Frey HH, Turter A, Torjesen PA. Different responses in little and bigbig prolactin to metoclopramide in subjects with hyperprolactinemia due to 150-170 kD (bigbig) prolactin. Endocrinol (copenh). 1993;128:308-12.   [PubMed]
  19. Atha DH, lngham KC. Mechanism of precipitation of proteins by polyethylene glycols. J Biol Chem. 1981; 256:12108-7.   [PubMed]
  20. Fahie-Wilson MN, Soule SG. Macroprolactinaemia: contribution to hyperprolactinaemia in a district gene-ral hospital and evaluation of a screening test based on precipitation with polyethylene glycol. Ann Clin Biochem. 1997;34:252-8.   [PubMed]
  21. Toldy E, Locsei Z, Szabolcs I, Kneffel P, Goth M, Szoke D, et al. Macroprolactinemia in the differential diagnosis of hyperprolactinemia. Orv Hetil. 2003;144 (43):2121-7.   [PubMed]
  22. Fahie-Wilson MN, Soule SG. Macroprolactinaemia: contribution to hyperprolactinaemia in a district gene-ral hospital and evaluation of a screening test based on precipitation with polyethylene glycol. Ann Clin Biochem. 1997;34: 252-8.   [PubMed]
  23. Whitaker MD, Klee GG, Kao PC, Randall RV, Heser DW. Demonstration of biological activity of prolactin molecular weight variants in human sera. J Clin Endocrinol Metab. 1983;58:826-30.   [PubMed]
  24. Hauche OM, Rocha AJ, Maia ACM, Maciel RMB, Vieira GH. Screening for macroprolactinaemia and pituitary imaging studies. Clin Endocrinol. 2002;57: 327-31.   [PubMed]
  25. Olukoga AO, Kane JW. Macroprolactinaemia: valida-tion and application of the polyethylene glycol precipi-tation test and clinical characterization of the condition. Clin Endocrinol. 1999;51:119-26.   [PubMed]
  26. Olukoga AO, Dornan TL, Kane JW. Three cases of macroprolactinaemia. J R Soc Med. 1999;92:342-4.   [PubMed]
  27. Guay AT, Sabharwal P, Varma S, Malarkey WB. Delayed diagnosis of psychological erectile dysfunc-tion because of the presence of macroprolactinemia. J Clin Endocrinol Metab. 1996;81:2512-4.   [PubMed]
  28. Toldy E, Locsei Z, Szabolcs I, Goth MI, Kneffel P, Szoke D ,et al. Macroprolactinemia: the consequences of a laboratory pitfall. Endocrine. 2003;22(3):267-73.   [PubMed]
  29. Garcia Menendez L, Diez Hernandez A, Ciriza de los Rios C, Delgado Gomez M, Orejas Garcia A, Fernan-dez Erales AL,et al. Macroprolactin as etiology of hyperprolactinemia. Method for detection and clinical characterization of the entity in 39 patients.Rev Clin Esp. 2003;203(10):459-64.   [PubMed]
  30. Strachan MW, Teoh WL, Don-Wauchope AC, Seth J, Stoddart M, Beckett GJ.Clinical and radiological features of patients with macroprolactinaemia. Clin Endocrinol. 2003;59(3):339-46.   [PubMed]
  31. Smith TP, Suliman AM, Fahie-Wilson MN, McKenna TJ. Gross variability in the detection of prolactin in sera containing big big prolactin (macroprolactin) by commercial immunoassays. J Clin Endocrinol Metab. 2002;87(12):5410-5.   [PubMed]
  32. Hauache OM, Rocha AJ, Maia AC, Maciel RM, Vieira JG. Screening for macroprolactinaemia and pituitary imaging studies. Clin Endocrinol. 2002;57(3): 327-31.   [PubMed]
  33. Sophie Vallette-Kasic, Isabelle Morange-Ramos, Adel Selim, Ginette Gunz, Sophie Morange, et al. Macro-prolactinemia Revisited: A Study on 106 Patients. J Clin Endocrinol Metab. 2002;87(2):581-8.   [PubMed]
  34. Khandwala HM. Macroprolactinemia in a patient with infertility and hyperprolactinemia.South Med J. 2006; 99(11):1282-4.   [PubMed]


Home | About Us | Current Issue | Past Issues | Submit a Manuscript | Instructions for Authors | Subscribe | Search | Contact Us

"Journal of Reproduction & Infertility" is owned, published, and managed by Avicenna Research Institute .
Creative Commons License

This work is licensed under a Creative Commons Attribution –NonCommercial 4.0 International License which allows users to read, copy, distribute and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited properly.

Journal of Reproductoin and Infertility (JRI) is a member of COMMITTEE ON PUBLICATION ETHICS . Verify here .

©2024 - eISSN : 2251-676X, ISSN : 2228-5482, For any comments and questions please contact us.