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A Brazilian multicentre study evaluating pregnancies induced by cabergoline in patients harboring prolactinomas

  • B. G. Sant’ AnnaEmail author
  • N. R. C. Musolino
  • M. R. Gadelha
  • C. Marques
  • M. Castro
  • P. C. L. Elias
  • L. Vilar
  • R. Lyra
  • M. R. A. Martins
  • A. R. P. Quidute
  • J. Abucham
  • D. Nazato
  • H. M. Garmes
  • M. L. C. Fontana
  • C. L. Boguszewski
  • C. B. Bueno
  • M. A. Czepielewski
  • E. S. Portes
  • V. S. Nunes-Nogueira
  • A. Ribeiro-OliveiraJr.
  • R. P. V. Francisco
  • M. D. Bronstein
  • A. Glezer



To evaluate the maternal–fetal outcomes of CAB-induced pregnancies in patients with prolactinoma in a large cohort.


The prevalence of tumor growth, miscarriage, preterm, low birth weight, congenital malformations and impairment in neuropsychological development in children among women treated with CAB were assessed in a Brazilian multicentre retrospective observational study,


We included 194 women with a mean age of 31 (17–45) years, 43.6% presenting microadenomas and 56.4% macroadenomas, at prolactinoma diagnosis. In 233 pregnancies, CAB was withdrawn in 89%, after pregnancy confirmation. Symptoms related to tumor growth occurred in 25 cases, more frequently in macroadenomas. The overall miscarriage rate was 11%, although higher in the subgroup of patients with CAB maintainance after pregnancy confirmation (38% vs. 7.5%). Amongst the live-birth deliveries, preterm occurred in 12%, low birth weight in 6% and congenital malformations in 4.3%. Neuropsychological development impairment was reported in 7% of cases.


Our findings confirm previous results of safety in maternal and fetal outcomes in CAB-induced pregnancies; nevertheless, CAB maintenance after pregnancy confirmation was associated with higher miscarriage rate; result that must be further confirmed.


Prolactinoma Pregnancy Dopamine agonist Cabergoline Miscarriage Malformation 



No financial support.

Compliance with ethical standards

Conflict of interest

Musolino NRC. received fees as a speaker for Pfizer. Ribeiro-Oliveira Júnior A. received fees as a speaker for Novartis and IPSEN. He is currently an employee of IPSEN Biosciences in the USA, and data was generated before his joining to IPSEN. We certify that nor other co-authors have a conflict of interest as described above that is relevant to the subject matter or materials included in this Work.


  1. 1.
    Miyai K, Ichihara K, Kondo K, Mori S (1986) Asymptomatic hyperprolactinaemia and prolactinoma in the general population–mass screening by paired assays of serum prolactin. Clin Endocrinol 25(5):549–554CrossRefGoogle Scholar
  2. 2.
    Hardy J (1969) Transphenoidal microsurgery of the normal and pathological pituitary. Clin Neurosurg. 16:185–217PubMedCrossRefGoogle Scholar
  3. 3.
    Colao A, Sarno AD, Cappabianca P, Briganti F, Pivonello R, Somma CD et al (2003) Gender differences in the prevalence, clinical features and response to cabergoline in hyperprolactinemia. Eur J Endocrinol 148(3):325–331PubMedCrossRefGoogle Scholar
  4. 4.
    Robert E, Musatti L, Piscitelli G, Ferrari CI (1996) Pregnancy outcome after treatment with the ergot derivative, cabergoline. Reprod Toxicol 10(4):333–337PubMedCrossRefGoogle Scholar
  5. 5.
    Webster J, Piscitelli G, Polli A, Ferrari CI, Ismail I, Scanlon MF (1994) A comparison of cabergoline and bromocriptine in the treatment of hyperprolactinemic amenorrhea. Cabergoline Comparative Study Group. N Engl J Med 331(14):904–909PubMedCrossRefGoogle Scholar
  6. 6.
    Ferrari C, Barbieri C, Caldara R, Mucci M, Codecasa F, Paracchi A et al (1986) Long-lasting prolactin-lowering effect of cabergoline, a new dopamine agonist, in hyperprolactinemic patients. J Clin Endocrinol Metab 63(4):941–945PubMedCrossRefGoogle Scholar
  7. 7.
    Molitch ME (2002) Medical management of prolactin-secreting pituitary adenomas. Pituitary 5(2):55–65PubMedCrossRefGoogle Scholar
  8. 8.
    Melmed S, Casanueva FF, Hoffman AR, Kleinberg DL, Montori VM, Schlechte JA et al (2011) Diagnosis and treatment of hyperprolactinemia: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 96(2):273–288PubMedCrossRefGoogle Scholar
  9. 9.
    Mehta AE, Tolis G (1979) Pharmacology of bromocriptine in health and disease. Drugs 17(5):313–325PubMedCrossRefGoogle Scholar
  10. 10.
    Krupp P, Monka C (1987) Bromocriptine in pregnancy: safety aspects. Klin Wochenschr 65(17):823–827PubMedCrossRefGoogle Scholar
  11. 11.
    Molitch ME (2015) Endocrinology in pregnancy: management of the pregnant patient with a prolactinoma. Eur J Endocrinol 172(5):R205–R213PubMedCrossRefGoogle Scholar
  12. 12.
    Gonzalez JG, Elizondo G, Saldivar D, Nanez H, Todd LE, Villarreal JZ (1988) Pituitary gland growth during normal pregnancy: an in vivo study using magnetic resonance imaging. Am J Med 85(2):217–220PubMedCrossRefGoogle Scholar
  13. 13.
    Hu Y, Ding Y, Yang M, Xiang Z (2018) Serum prolactin levels across pregnancy and the establishment of reference intervals. Clin Chem Lab Med 56(5):803–807PubMedCrossRefGoogle Scholar
  14. 14.
    Scheithauer BW, Sano T, Kovacs KT, Young WF, Ryan N, Randall RV (1990) The pituitary gland in pregnancy: a clinicopathologic and immunohistochemical study of 69 cases. Mayo Clin Proc 65(4):461–474PubMedCrossRefGoogle Scholar
  15. 15.
    Persiani S, Sassolas G, Piscitelli G, Bizollon CA, Poggesi I, Pianezzola E et al (1994) Pharmacodynamics and relative bioavailability of cabergoline tablets vs solution in healthy volunteers. J Pharm Sci 83(10):1421–1424PubMedCrossRefGoogle Scholar
  16. 16.
    Bigazzi M, Ronga R, Lancranjan I, Ferraro S, Branconi F, Buzzoni P et al (1979) A pregnancy in an acromegalic woman during bromocriptine treatment: effects on growth hormone and prolactin in the maternal, fetal, and amniotic compartments. J Clin Endocrinol Metab 48(1):9–12PubMedCrossRefGoogle Scholar
  17. 17.
    Beltrame D, Longo M, Mazué G (1996) Reproductive toxicity of cabergoline in mice, rats, and rabbits. Reprod Toxicol 10(6):471–483PubMedCrossRefGoogle Scholar
  18. 18.
    Molitch ME (1999) Management of prolactinomas during pregnancy. J Reprod Med 44(12 Suppl):1121–1126PubMedGoogle Scholar
  19. 19.
    Lebbe M, Hubinont C, Bernard P, Maiter D (2010) Outcome of 100 pregnancies initiated under treatment with cabergoline in hyperprolactinaemic women. Clin Endocrinol 73(2):236–242Google Scholar
  20. 20.
    Stalldecker G, Mallea-Gil MS, Guitelman M, Alfieri A, Ballarino MC, Boero L et al (2010) Effects of cabergoline on pregnancy and embryo-fetal development: retrospective study on 103 pregnancies and a review of the literature. Pituitary 13(4):345–350PubMedCrossRefGoogle Scholar
  21. 21.
    Bronstein MD (2005) Prolactinomas and pregnancy. Pituitary 8(1):31–38PubMedCrossRefGoogle Scholar
  22. 22.
    Ono M, Miki N, Amano K, Kawamata T, Seki T, Makino R et al (2010) Individualized high-dose cabergoline therapy for hyperprolactinemic infertility in women with micro- and macroprolactinomas. J Clin Endocrinol Metab 95(6):2672–2679PubMedCrossRefGoogle Scholar
  23. 23.
    Raymond JP, Goldstein E, Konopka P, Leleu MF, Merceron RE, Loria Y (1985) Follow-up of children born of bromocriptine-treated mothers. Horm Res 22(3):239–246PubMedCrossRefGoogle Scholar
  24. 24.
    Bronstein MD, Salgado LR, de Castro Musolino NR (2002) Medical management of pituitary adenomas: the special case of management of the pregnant woman. Pituitary 5(2):99–107PubMedCrossRefGoogle Scholar
  25. 25.
    Karaca Z, Yarman S, Ozbas I, Kadioglu P, Akturk M, Kilicli F et al (2018) How does pregnancy affect the patients with pituitary adenomas: a study on 113 pregnancies from Turkey. J Endocrinol Investig 41(1):129–141CrossRefGoogle Scholar
  26. 26.
    Rastogi A, Bhadada SK, Bhansali A (2017) Pregnancy and tumor outcomes in infertile women with macroprolactinoma on cabergoline therapy. Gynecol Endocrinol 33(4):270–273PubMedCrossRefGoogle Scholar
  27. 27.
    Galvão A, Gonçalves D, Moreira M, Inocêncio G, Silva C, Braga J (2017) Prolactinoma and pregnancy—a series of cases including pituitary apoplexy. J Obstet Gynaecol 37(3):284–287PubMedCrossRefGoogle Scholar
  28. 28.
    Araujo B, Belo S, Carvalho D (2017) Pregnancy and Tumor Outcomes in Women with Prolactinoma. Exp Clin Endocrinol Diabetes 125(10):642–648PubMedCrossRefGoogle Scholar
  29. 29.
    Lambert K, Rees K, Seed PT, Dhanjal MK, Knight M, McCance DR et al (2017) Macroprolactinomas and nonfunctioning pituitary adenomas and pregnancy outcomes. Obstet Gynecol 129(1):185–194PubMedCrossRefGoogle Scholar
  30. 30.
    Glezer A, Bronstein MD (2017) Prolactinomas: how to handle prior to and during pregnancy? Minerva Endocrinol 43(4):423–429PubMedGoogle Scholar
  31. 31.
    Molitch ME (1985) Pregnancy and the hyperprolactinemic woman. N Engl J Med 312(21):1364–1370PubMedCrossRefGoogle Scholar
  32. 32.
    Gemzell C, Wang CF (1979) Outcome of pregnancy in women with pituitary adenoma. Fertil Steril 31(4):363–372PubMedCrossRefGoogle Scholar
  33. 33.
    Holmgren U, Bergstrand G, Hagenfeldt K, Werner S (1986) Women with prolactinoma–effect of pregnancy and lactation on serum prolactin and on tumour growth. Acta Endocrinol 111(4):452–459PubMedCrossRefGoogle Scholar
  34. 34.
    Wilcox AJ, Weinberg CR, O'Connor JF, Baird DD, Schlatterer JP, Canfield RE et al (1988) Incidence of early loss of pregnancy. N Engl J Med 319(4):189–194PubMedCrossRefGoogle Scholar
  35. 35.
    Hemminki E, Forssas E (1999) Epidemiology of miscarriage and its relation to other reproductive events in Finland. Am J Obstet Gynecol 181(2):396–401PubMedCrossRefGoogle Scholar
  36. 36.
    Cecatti JG, Guerra GV, Sousa MH, Menezes GM (2010) Abortion in Brazil: a demographic approach. Rev Bras Ginecol Obstet 32(3):105–111PubMedCrossRefGoogle Scholar
  37. 37.
    Sedgh G, Bearak J, Singh S, Bankole A, Popinchalk A, Ganatra B et al (2016) Abortion incidence between 1990 and 2014: global, regional, and subregional levels and trends. Lancet 388(10041):258–267PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Hurault-Delarue C, Montastruc JL, Beau AB, Lacroix I, Damase-Michel C (2014) Pregnancy outcome in women exposed to dopamine agonists during pregnancy: a pharmacoepidemiology study in EFEMERIS database. Arch Gynecol Obstet 290(2):263–270PubMedCrossRefGoogle Scholar
  39. 39.
    Bachelot A, Binart N (2007) Reproductive role of prolactin. Reproduction 133(2):361–369PubMedCrossRefGoogle Scholar
  40. 40.
    Iwama S, Welt CK, Romero CJ, Radovick S, Caturegli P (2013) Isolated prolactin deficiency associated with serum autoantibodies against prolactin-secreting cells. J Clin Endocrinol Metab 98(10):3920–3925PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Vila G, Akerblad AC, Mattsson AF, Riedl M, Webb SM, Hána V et al (2015) Pregnancy outcomes in women with growth hormone deficiency. Fertil Steril 104(5):1210–7.e1PubMedCrossRefGoogle Scholar
  42. 42.
    Betrán AP, Ye J, Moller AB, Zhang J, Gülmezoglu AM, Torloni MR (2016) The increasing trend in caesarean section rates: global, regional and national estimates: 1990–2014. PLoS ONE 11(2):e0148343PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Ferreira EC, Pacagnella RC, Costa ML, Cecatti JG (2015) The Robson ten-group classification system for appraising deliveries at a tertiary referral hospital in Brazil. Int J Gynaecol Obstet 129(3):236–239PubMedCrossRefGoogle Scholar
  44. 44.
    Bolognani CV, Reis LBSM, Dias A, Calderon IMP (2018) Robson 10-groups classification system to access C-section in two public hospitals of the Federal District/Brazil. PLoS ONE 13(2):e0192997PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Ricci E, Parazzini F, Motta T, Ferrari CI, Colao A, Clavenna A et al (2002) Pregnancy outcome after cabergoline treatment in early weeks of gestation. Reprod Toxicol 16(6):791–793PubMedCrossRefGoogle Scholar
  46. 46.
    Colao A, Abs R, Bárcena DG, Chanson P, Paulus W, Kleinberg DL (2008) Pregnancy outcomes following cabergoline treatment: extended results from a 12-year observational study. Clin Endocrinol 68(1):66–71CrossRefGoogle Scholar
  47. 47.
    Domingue ME, Devuyst F, Alexopoulou O, Corvilain B, Maiter D (2014) Outcome of prolactinoma after pregnancy and lactation: a study on 73 patients. Clin Endocrinol 80(5):642–648CrossRefGoogle Scholar
  48. 48.
    Blencowe H, Cousens S, Oestergaard MZ, Chou D, Moller AB, Narwal R et al (2012) National, regional, and worldwide estimates of preterm birth rates in the year 2010 with time trends since 1990 for selected countries: a systematic analysis and implications. Lancet 379(9832):2162–2172PubMedCrossRefGoogle Scholar
  49. 49.
    Blanc AK, Wardlaw T (2005) Monitoring low birth weight: an evaluation of international estimates and an updated estimation procedure. Bull World Health Organ 83(3):178–185PubMedPubMedCentralGoogle Scholar
  50. 50.
    Kalter H, Warkany J (1983) Medical progress. Congenital malformations: etiologic factors and their role in prevention (first of two parts). N Engl J Med 308(8):424–431PubMedCrossRefGoogle Scholar
  51. 51.
    Glezer A, Bronstein MD (2014) Prolactinomas, cabergoline, and pregnancy. Endocrine 47(1):64–69PubMedCrossRefGoogle Scholar
  52. 52.
    Mitsiakos G (2019) A possible role of GDNF expression by which cabergoline use affects corpus callosum. J Pediatr Neonatal Individ Med 8:e080112Google Scholar
  53. 53.
    van Gool JD, Hirche H, Lax H, De Schaepdrijver L (2018) Folic acid and primary prevention of neural tube defects: a review. Reprod Toxicol 80:73–84PubMedCrossRefGoogle Scholar
  54. 54.
    Zárate A, Canales ES, Alger M, Forsbach G (1979) The effect of pregnancy and lactation on pituitary prolactin-secreting tumours. Acta Endocrinol 92(3):407–412PubMedCrossRefGoogle Scholar
  55. 55.
    Auriemma RS, Perone Y, Di Sarno A, Grasso LF, Guerra E, Gasperi M et al (2013) Results of a single-center observational 10-year survey study on recurrence of hyperprolactinemia after pregnancy and lactation. J Clin Endocrinol Metab 98(1):372–379PubMedCrossRefGoogle Scholar
  56. 56.
    Rjosk HK, Fahlbusch R, von Werder K (1982) Influence of pregnancies on prolactinomas. Acta Endocrinol 100(3):337–346PubMedCrossRefGoogle Scholar
  57. 57.
    Crosignani PG, Mattei AM, Scarduelli C, Cavioni V, Boracchi P (1989) Is pregnancy the best treatment for hyperprolactinaemia? Hum Reprod 4(8):910–912PubMedCrossRefGoogle Scholar
  58. 58.
    Crosignani PG, Mattei AM, Severini V, Cavioni V, Maggioni P, Testa G (1992) Long-term effects of time, medical treatment and pregnancy in 176 hyperprolactinemic women. Eur J Obstet Gynecol Reprod Biol 44(3):175–180PubMedCrossRefGoogle Scholar
  59. 59.
    Huda MS, Athauda NB, Teh MM, Carroll PV, Powrie JK (2010) Factors determining the remission of microprolactinomas after dopamine agonist withdrawal. Clin Endocrinol 72(4):507–511CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • B. G. Sant’ Anna
    • 1
    Email author
  • N. R. C. Musolino
    • 2
  • M. R. Gadelha
    • 3
  • C. Marques
    • 3
  • M. Castro
    • 4
  • P. C. L. Elias
    • 4
  • L. Vilar
    • 5
  • R. Lyra
    • 5
  • M. R. A. Martins
    • 6
  • A. R. P. Quidute
    • 6
  • J. Abucham
    • 7
  • D. Nazato
    • 7
  • H. M. Garmes
    • 8
  • M. L. C. Fontana
    • 8
  • C. L. Boguszewski
    • 9
  • C. B. Bueno
    • 10
  • M. A. Czepielewski
    • 11
  • E. S. Portes
    • 12
  • V. S. Nunes-Nogueira
    • 13
  • A. Ribeiro-OliveiraJr.
    • 14
  • R. P. V. Francisco
    • 15
  • M. D. Bronstein
    • 1
  • A. Glezer
    • 1
  1. 1.Division of Endocrinology and Metabolism, Hospital das ClinicasNeuroendocrine Unit, University of Sao Paulo Medical SchoolSao PauloBrazil
  2. 2.Division of Neurosurgery, Institute of PsychiatryUniversity of Sao Paulo Medical SchoolSao PauloBrazil
  3. 3.Federal University of Rio de JaneiroRio de JaneiroBrazil
  4. 4.University of Sao Paulo Medical School of Ribeirao PretoRibeirao PretoBrazil
  5. 5.Federal University of PernambucoRecifeBrazil
  6. 6.Federal University of CearaFortalezaBrazil
  7. 7.Escola Paulista de Medicina, Universidade Federal de São PauloSao PauloBrazil
  8. 8.State University of CampinasCampinasBrazil
  9. 9.Endocrine Division (SEMPR), Department of Internal MedicineFederal University of ParanaCuritibaBrazil
  10. 10.Irmandade da Santa Casa de Misericórdia de São PauloSao PauloBrazil
  11. 11.Division of EndocrinologyHospital de Clinicas de Porto Alegre (UFRGS)Porto AlegreBrazil
  12. 12.Institute of Medical Assistance to the State Public HospitalSao PauloBrazil
  13. 13.São Paulo State University (UNESP), Medical SchoolBotucatuBrazil
  14. 14.Federal University of Minas GeraisBelo HorizonteBrazil
  15. 15.Disciplina de Obstetrícia, Departamento de Obstetrícia e GinecologiaFaculdade de Medicina (FMUSP), Universidade de São PauloSao PauloBrazil

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