, Volume 8, Issue 1, pp 31–38 | Cite as

Prolactinomas and Pregnancy

  • Marcello Delano BronsteinEmail author


Prolactinomas are the most frequent pituitary tumors. Treatment of infertility in such tumors usually is very successful. On the other hand, reports of pituitary tumor growth during pregnancy have been described since bromocriptine started to be used. Since then, dopamine agonists (DA) have been increasingly used as the first-choice treatment of prolactinomas, with surgery being reserved for resistance or persistent intolerance to DA or for special situations. More recently other DA, such as quinagolide and cabergoline have shown better tolerance than bromocriptine with similar or greater efficacy. Cabergoline is now the first choice drug but its use in pregnancy is still under evaluation. We followed 71 term pregnancies in women bearing microprolactinomas. Of the 22 patients with previous surgery, none presented symptoms of tumor growth. Of the 41 pregnant patients treated with bromocriptine alone, only one (2.4%) presented with headaches, which regressed with drug reintroduction. Fifty one term pregnancies in patients with macroprolactinomas were followed by us. Of those, 21 were in patients with previous surgery and none of them presented clinical evidence of tumor growth. On the other hand, of the 30 patients treated only with pre-gestational bromocriptine, 11 (37%) manifested complaints related to tumor growth. A non-hormonal contraceptive should be the use along with a DA drug until tumor shrinkage within sellar boundaries has been evidenced. After pregnancy has been confirmed, the DA can be withdrawn and the patient must be closely followed. If tumor expansion is suspected, confirmation can be made through MRI and by visual field testing. Reintroduction of bromocriptine in such cases can lead to tumor reduction and clinical improvement. Surgery can also be employed as treatment for symptomatic tumor growth in pregnancy.

Key Words

prolactin prolactinomas pituitary tumors pregnancy bromocriptine cabergoline 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Burrow GN, Wortzman G, Rewcastle HB, Holgate RC, Kovacs K. Microadenomas of the pituitary and abnormal sellar tomograms in an unselected autopsy. N Engl J Med 1981;304:156.PubMedCrossRefGoogle Scholar
  2. 2.
    Hardy J. Transsphenoidal surgery of hypersecreting pituitary tumors. In: Kohler PO and Ross GT (eds.), Diagnosis and treatment of Pituitary Tumors, Amsterdam: Excerpta Medica, 1973, p. 179.Google Scholar
  3. 3.
    Miyai K, Ichihara K, Kondo K, Mori S. Asymptomatic hyperprolactinaemia and prolactinoma in the general population-mass screening by paired assays of serum prolactin. Clin Endocrinol (Oxf) 1986;25:549–554.Google Scholar
  4. 4.
    Hardy J. Transsphenoidal microsurgery of the normal and pathological pituitary. Clin Neurosurg 1969;16:185–217.PubMedGoogle Scholar
  5. 5.
    Marino RJr, Bronstein MD. The role of pituitary surgery in the treatment of prolactinomas. In: Meireles RMR, Machado A, Póvoa LC (eds.), Clinical Endocrinology : Proceedings of the 18th Brazilian Congress of Endocrinology and Metabolism, Rio de Janeiro, Junho, 1988, pp. 12–17. Amsterdam-New York-Oxford Excepta Medica. 1988, pp. 53–56.Google Scholar
  6. 6.
    Molitch ME. Medical treatment of prolactinomas. Endocrinol Metab Clin North Am 1999;28:143–169.CrossRefPubMedGoogle Scholar
  7. 7.
    Berezin M, Avidan D, Baron E. Long-term pergolide treatment of hyperprolactinemic patients previously unsuccessfully treated with dipaminergic drugs. Isr J Med Sci 1991;27:375–379.PubMedGoogle Scholar
  8. 8.
    Webster J. A comparative review of the tolerability profiles of dopamine agonists in the treatment of hyperprolactinaemia and inhibition of lactation. Drug Saf 1996;14:228–238.PubMedGoogle Scholar
  9. 9.
    Musolino NRC, Cunha Neto MB, Bronstein MD. Cabergoline as an alternative for medical treatment of prolactinomas: Experience in bromocriptine intolerance/resistance. Arq Bras Endocrinol Metab 2000;44:139–143.CrossRefGoogle Scholar
  10. 10.
    Colao A, Di Sarno A, Sarnacchiaro F, Ferone D, Di Renzo G, Merola B, Annunziato L, Lombardi G. Prolactinomas resistant to standard dopamine agonists respond to chronic cabergoline treatment. J Clin Endocrinol Metab 1997;82:876–883.PubMedGoogle Scholar
  11. 11.
    Duranteau L, Chanson P, Lavoinne A, Horlait S, Lubetzki J, Kuhn JM. Effect of the new dopaminergic agonist CV 205–502 on plasma prolactin levels and tumour size in bromocriptine-resistant prolactinomas. Clin Endocrinol (Oxf) 1991;34:25–29.Google Scholar
  12. 12.
    Verhelst J, Abs R, Maiter D, van der Bruel A, Vandeweghe M, Velkeniers B, Mockel J, Lamberigts G, Petrossians P, Coremans P, Mahler C, Stevenaert A, Verlooy J, Raftopoulos C, Beckers A. Cabergoline in the treatment of hyperprolactinemia: A study in 455 patients. J Clin Endocrinol Metab 1999;784:2518–2522.Google Scholar
  13. 13.
    Cannavo S, Curto L, Squadrito S, Almoto B, Vieni A, Trimarchi F. Cabergoline: a first-choice treatment in patients with previously untreated prolactin-secreting pituitary adenoma. J Endocrinol Invest 1999;22:354–359.PubMedGoogle Scholar
  14. 14.
    Bronstein MD, Musolino NR, Benabou S, Marino R Jr. Cerebrospinal fluid rhinorrhea occurring in long-term bromocriptine treatment for macroprolactinomas. Surg Neurol 1989;32:346–349.PubMedGoogle Scholar
  15. 15.
    Jalali R, Brada M, Perks JR, Warrington AP, Traish D, Burchell L, McNair H, Thomas DG, Robinson S, Johnston DG. Stereotactic conformal radiotherapy for pituitary adenomas: technique and preliminary experience. Clin Endocrinol (Oxf) 2000;52:695–702.CrossRefGoogle Scholar
  16. 16.
    Inoue HK, Kohga H, Hirato M, Sasaki T, Shihara J, Shibazaki T, Ohye C, Andou Y. Pituitary adenomas treated by microsurgery with or without Gamma Knife surgery: Experience in 122 cases. Stereotact Funct Neurosurg 1999;72:125–131.CrossRefPubMedGoogle Scholar
  17. 17.
    Morange-Ramos I, Regis J, Dufor H, Andrieu JM, Grisoli F, Jaquet P, Peragaut JC. Short-term endocrinological results after gamma knife surgery of pituitary adenomas. Stereotact Funct Neurosurg 1998;70:127–138.PubMedGoogle Scholar
  18. 18.
    Elster AD, Sanders TG, Vines FS, Chen MY. Size and shape of the pituitary gland during pregnancy and post partum: Measurement with M R imaging. Radiology 1991;181:531–500.PubMedGoogle Scholar
  19. 19.
    Dinc H, Esen F, Demirci A, Sari A, Resit Gumele H. Pituitary dimensions and volume measurements in pregnancy and post partum M R assessment. Acta Radiol 1998;39:64–69.PubMedGoogle Scholar
  20. 20.
    Gonzalez JG, Elizondo G, Saldriar D, Nanez H, Todd LE, Vielarreal JZ. Pituitary gland growth during normal pregnancy: An in vivo study using magnetic resonance imaging. Am J Med 1988;85:217–220.PubMedCrossRefGoogle Scholar
  21. 21.
    Scheithauer BW, Sano T, Kovacs KT, Young WFJr, Ryan N, Randall RV. The pituitary gland in pregnancy: A clinicopathologic and immunohistochemical study of 69 cases. Mayo Clin Proc 1990;65:461–474.PubMedGoogle Scholar
  22. 22.
    Rigg LA, Lein A, Yen SSC. Pattern of increase in circulating prolactin levels during human gestation. Am J Obstet Gynecol 1977;129:454–456.PubMedGoogle Scholar
  23. 23.
    Ferriani RA, Silva de Sá MF, Lima Filho EC. A comparative study of longitudinal and cross-sectional changes in plasma levels of prolactin and estriol during normal pregnancy. Brazilian J Med Biol Res 1986;19:183–188.Google Scholar
  24. 24.
    Zegher F, Spitz B, Van der Berghe G, Lemmens D, Vanweser K, Keppens K, Bowers CY. Postpartum hyperprolactinemia and hyporesponsiveness of growth hormone to GH-releasing peptide. J Clin Endocrinol Metab 1998;83:103–106.PubMedGoogle Scholar
  25. 25.
    Delvoye P, Delogne-Desnoeck J, Robyn C. Hyperprolactinaemia during prolonged lactation: Evidence for anovulatory cycles and inadequate corpus luteum. Clin Endocrinol 1980;13:243–247.Google Scholar
  26. 26.
    Gemzell C, Wang CF. Outcome of pregnancy in women with pituitary adenoma. Fertil Steril 1979;31:363–372.PubMedGoogle Scholar
  27. 27.
    Krupp P, Monka C. Bromocriptine in Pregnancy: Safety Aspects. Klin Wochenschr 1987;65:823–827.CrossRefPubMedGoogle Scholar
  28. 28.
    Weil C. The safety of bromocriptine in long-term use: A review of the literature. Curr Res Opin 1986;10:25–51.Google Scholar
  29. 29.
    Krupp P, Monka C, Richter K. The safety aspects of infertility treatments. Program of the Second Word Congress of Gynecology and Obstetrics, Rio de Janeiro, Brazil, 1988.Google Scholar
  30. 30.
    Chiodini I, Liuzzi A. PRL-secreting adenomas in pregnancy. J Endocrinol Invest 2003;96–99.Google Scholar
  31. 31.
    Musolino NRC, Bronstein MD. Prolactinomas and Pregnancy. In: Bronstein MD (ed.), Pituitary Tumors in Pregnancy. Boston, Kluwer Academic Publishers, 2001, pp. 91–108.Google Scholar
  32. 32.
    Molitch ME. Pregnancy and the hyperprolactinemic woman. N Engl J Med 1985;312:1364–1370.PubMedCrossRefGoogle Scholar
  33. 33.
    Ferrer-Barriendos J, Millet A, Lucas-Pinilla E. Necrosis de un prolactinoma durante el embarazo. Rev Esp Obst Gin 1981;40:578–585.Google Scholar
  34. 34.
    Holmgren U, Bergstrand G, Hagenfeldt K, Werner S. Women with prolactinoma—effect of pregnancy and lactation on serum prolactin and on tumour growth. Acta Endocrinol (Copenh) 1986;111:452–459.Google Scholar
  35. 35.
    Shewchuk AB, Adamson GD, Lessard P, Ejrin C. The effect of pregnancy on suspected pituitary adenomas after conservative management of ovulation defects associated with galactorrhea. Am J Obstet Gynecol 1980;136:659–666.PubMedGoogle Scholar
  36. 36.
    Child DF, Gordon H, Mashiter K, Jopkin GF. Pregnancy, prolactin, and pituitary tumours. Br Med J 1975;4:87–89.PubMedGoogle Scholar
  37. 37.
    van Roon E, van der Vijver JCM, Gerretsen G, Hekster REM, Wattendorff RA. Rapid regression of a suprasellar extending prolactinoma after bromocriptine treatment during pregnancy. Fertil and Steril 1981;36:173–177.Google Scholar
  38. 38.
    Maeda T, Ushiroyama T, Okuda K, Fujimoto A, Ueki M, Sugimoto O. Effective bromocriptine treatment of a pituitary macroadenoma during pregnancy. Obstet Gynecol 1983;61:117–120.PubMedGoogle Scholar
  39. 39.
    Brodsky JB, Cohen EN, Brown BWJr, Wu ML, Whitcher C. Surgery during pregnancy and fetal outcome. Am J Obstet Gynecol 1980;138:1165–1167.PubMedGoogle Scholar
  40. 40.
    Bergh T, Nillius SJ, Wide L. Clinical course and outcome of pregnancies in amenorrhoeic women with hyperprolactinaemia and pituitary tumours. Br Med J 1978;1:875–880.PubMedCrossRefGoogle Scholar
  41. 41.
    Tan SL, Jacobs HS. Rapid regression through bromocriptine therapy of a suprasellar extending prolactinoma during pregnancy. Int J Gynaecol Obstet 1986;24:209–215.CrossRefPubMedGoogle Scholar
  42. 42.
    Canales ES, Garcia IC, Ruiz JE, Zarate A. X Bromocriptine as prophylactic therapy in prolactinoma during pregnancy. Fertil and Steril 1986;36:524–526.Google Scholar
  43. 43.
    Konopka P, Raymond JP, Merceron RE, Seneze J. Continuous administration of bromocriptine in the prevention of neurological complications in pregnant women with prolactinomas. Am J Obstet Gynecol 1983;146:935–938.PubMedGoogle Scholar
  44. 44.
    Molitch ME. Pituitary diseases in pregnancy. Semin Perinatol 1998;22:457–470.PubMedGoogle Scholar
  45. 45.
    Morange I, Barlier A, Pellegrini I, Brue T, Enjalbert A, Jaquet P. Prolactinomas resistant to bromocriptine: long-term efficacy of quinagolide and outcome of pregnancy. Eur J Endocrinol 1996;135:413–420.PubMedCrossRefGoogle Scholar
  46. 46.
    Robert E, Musatti L, Piscitelli G, Ferrari CI. Pregnancy outcome after treatment with the ergot derivative, cabergoline. Reprod Toxicol 1996;10:333–337.PubMedGoogle Scholar
  47. 47.
    Cannavo S, Curto L, Squadrito S, et al. Cabergoline: a first-choice treatment in patients with previously untreated prolactin-secreting pituitary adenoma. J Endocrinol Invest 1999;22:354–359.PubMedGoogle Scholar
  48. 48.
    Verhelst J, Abs R, Maiter D, et al. Cabergoline in the treatment of hyperprolactinemia: a study in 455 patients. J Clin Endocrinol Metab 1999;84:2518–2522.PubMedGoogle Scholar
  49. 49.
    Ricci E, Parazzini F, Motta T, Ferrari CI, Colao A, et al. Pregnancy outcome after cabergoline treatment in early weeks of gestation. Reprod Toxicol 2002;16:791–793.CrossRefPubMedGoogle Scholar
  50. 50.
    Liu C, Tyrrell JB. Successful treatment of a large macroprolactinoma with cabergoline during pregnancy. Pituitary 2001;4:179–185.CrossRefPubMedGoogle Scholar
  51. 51.
    Bronstein MD, Salgado LR, Musolino NR. Medical management of pituitary adenomas: The special case of the pregnant woman. Pituitary 2002;5:99–107.CrossRefPubMedGoogle Scholar
  52. 52.
    Zárate A, Canales ES, Alger M, Forsbach G. The effect of pregnancy and lactation on pituitary prolactin-secreting tumours. Acta Endocrinol (Copenh) 1979;92:407–412.Google Scholar
  53. 53.
    Bronstein MD, Musolino NR, Cardim CS, Marino RJr. Outcome of 52 pregnancies in hyperprolactinemic women. Rev Bras Ginecol Obstet 1988;10:175–178.Google Scholar
  54. 54.
    Bronstein MD, Musolino NR, Cardim C, Monteiro M, Marino RJr. Repeatable depot-bromocriptine treatment for prolactinomas. In: Meireles RMR, Machado A, Póvoa LC (eds.), Clinical Endocrinology: Proceedings of the 18th Brazilian Congress of Endocrinology and Metabolism, Rio de Janeiro, 1988;Junho pp. 12–17, Amsterdam-New York-Oxford: Excepta Medica. 1988, pp. 45–48.Google Scholar
  55. 55.
    Crosignani PG, Mattei AM, Severini V, Cavioni V, Maggioni P, Testa G. Long-term effects of time, medical treatment and pregnancy in 176 hyperprolactinemic women. Eur J Obstet Gynecol Reprod Biol 1992;44:175–180.PubMedCrossRefGoogle Scholar
  56. 56.
    Rjosk HK, Fahlbusch R, von Werder K. Influence of pregnancies on prolactinomas. Acta Endocrinol (Copenh) 1982;100:337–346.Google Scholar
  57. 57.
    Badawy SZ, Marziale JC, Rosenbaum AE, Chang JK, Joy SE. The long-term effects of pregnancy and bromocriptine treatment on prolactinomas—the value of radiologic studies. Early Pregnancy 1997;3:306–311.PubMedGoogle Scholar
  58. 58.
    Ahmed M, al-Dossary E, Woodhouse NJ. Macroprolactinomas with suprasellar extension: Effect of bromocriptine withdrawal during one or more pregnancies. Fertil Steril 1992;58:492–497.PubMedGoogle Scholar
  59. 59.
    Peillon F, Racadot J, Moussy D, Vila-Porcile E, Olivier L, Racadot O. Prolactin-secreting adenomas. A correlative study of morphological and clinical data. In: Fahlbusch R., Von Werder K. (eds.), Treatament of pituitary adenomas. Stuttgart: Thiemi, 1978, pp. 114.Google Scholar
  60. 60.
    Freeman R, Wezenter B, Silvestein M, Kuo D, Weiss KL, Kantrowitz AB, Schubart UK. Pregnancy-associated subacute hemorrhage into a prolactinoma resulting in diabetes insipidus. Fertil Steril 1992;58:427–429.PubMedGoogle Scholar

Copyright information

© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  1. 1.Neuroendocrine Unit, Division of Endocrinology and Metabolism, Hospital das ClínicasUniversity of S. Paulo Medical SchoolBrazil
  2. 2.Neuroendocrine Unit, Division of Endocrinology and Metabolism, Hospital das ClínicasUniversity of S. Paulo Medical SchoolS. PauloBrazil

Personalised recommendations