Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Drug Insight: cabergoline and bromocriptine in the treatment of hyperprolactinemia in men and women

Nature Clinical Practice Endocrinology & Metabolism volume 2, pages 200–210 (2006)Cite this article

Abstract

Prolactinoma is the most frequent pituitary tumor histotype. Men generally have macroadenomas whereas women generally have microadenomas. The major objectives of treating prolactinomas are to suppress excessive hormone secretion and its clinical consequences, to remove the tumor mass while preserving the residual pituitary function, and possibly to prevent disease recurrence or progression. Primary therapy of prolactinomas is based on use of dopamine-receptor agonists. Bromocriptine induces normalization of prolactin levels in 80–90% of patients with microprolactinomas and approximately 70% of those with macroprolactinomas. Tumor-mass shrinkage and improvement of visual-field defects are found in the majority of treated macroprolactinomas, but bromocriptine often causes side effects. Cabergoline is very effective and well tolerated in more than 90% of patients with either microprolactinomas or macroprolactinomas. Cabergoline treatment also induces tumor shrinkage in the majority of patients with macroprolactinomas. Tumor shrinkage is more evident if patients have not previously been treated with other dopamine agonists. Fewer results are available for men than for women, but there is no evidence that men are less responsive to dopamine agonists than are women.

Key Points

  • Prolactinomas are the most common pituitary tumors in humans

  • Microprolactinomas are more frequent than macroprolactinomas in women and are more frequent in the fertile age-group

  • Bromocriptine has been used for longer than cabergoline and is effective in normalizing prolactin levels and in reducing tumor mass but more frequently induces side effects

  • Cabergoline is a very efficient therapy for both macroadenomas and microadenomas

  • Cabergoline withdrawal has a high success rate in patients with either microprolactinomas or macroprolactinomas if serial MRI scans during treatment show that the tumor has disappeared

  • In men, cabergoline treatment restores erectile function and normalizes seminal-fluid characteristics

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Prevalence of nontumoral hyperprolactinemia, microprolactinomas and macroprolactinomas in 219 men and women with hyperprolactinemia who were treated in our unit between 1996 and 2000
Figure 2: Baseline prolactin levels (top) and maximal tumor diameter (bottom) in men and women
Figure 3: Decrease of tumor size after cabergoline treatment in men and women
Figure 4: Correlation study showing the relationship between the last prolactin level after cabergoline withdrawal and the nadir prolactin level during treatment, in 200 consecutive patients with hyperprolactinemia undergoing cabergoline withdrawal, in a prospective study
Figure 5: Total sperm count and forward motility of sperm from 31 men with prolactinoma undergoing 24 months of cabergoline treatment
Figure 6: Nocturnal penile tumescence in men with prolactinoma at diagnosis and 6 months after treatment with cabergoline

Similar content being viewed by others

References

  1. Mindermann T and Wilson CH (1994) Age-related and gender-related occurrence of pituitary tumors. Clin Endocrinol 41: 359–364

    Article  CAS  Google Scholar 

  2. Partington MD et al. (1994) Pituitary adenomas in childhood and adolescence. Results of transsphenoidal surgery. J Neurosurg 80: 209–216

    Article  CAS  PubMed  Google Scholar 

  3. Colao A (2003) Pituitary tumors in childhood. In Pediatric Endocrinology, chapter 3 (Ed. New MI) Endotext.com [http://www.endotext.org/pediatrics/pediatrics3/pediatricsframe3.htm] (accessed 20 January 2006)

    Google Scholar 

  4. Colao A and Lombardi G (1998) Growth-hormone and prolactin excess. Lancet 352: 1455–1461

    Article  CAS  PubMed  Google Scholar 

  5. Beckers A et al. Approaching the true prevalence of pituitary tumors. ENEA (The European Neuroendocrine Association) Meeting (NA): 2004 24–27 April; Sorrento, Italy, 23, [Abstract #1.1]

  6. Colao A et al. (2003) Gender differences in the prevalence, clinical features and response to cabergoline in hyperprolactinemia. Eur J Endocrinol 148: 325–331

    Article  CAS  PubMed  Google Scholar 

  7. Ambrosi B et al. (1980) Prolactin and sexual function. JAMA 244: 2608

    Article  CAS  PubMed  Google Scholar 

  8. Carter JN et al. (1978) Prolactin-secreting tumors and hypogonadism in 22 men. N Engl J Med 299: 847–852

    Article  CAS  PubMed  Google Scholar 

  9. Koppelman MC et al. (1984) Hyperprolactinemia, amenorrhea, and galactorrhea. A retrospective assessment of twenty-five cases. Ann Intern Med 100: 115–121

    Article  CAS  PubMed  Google Scholar 

  10. March CM et al. (1981) Longitudinal evaluation of patients with untreated prolactin-secreting pituitary adenomas. Am J Obstet Gynecol 139: 835–844

    Article  CAS  PubMed  Google Scholar 

  11. Schlechte J et al. (1989) The natural history of untreated hyperprolactinemia: a prospective analysis. J Clin Endocrinol Metab 68: 412–418

    Article  CAS  PubMed  Google Scholar 

  12. Sisam DA et al. (1987) The natural history of untreated microprolactinomas. Fertil Steril 48: 67–71

    Article  CAS  PubMed  Google Scholar 

  13. Von Werder K et al. (1982) Development of hyperprolactinemia in patients with adenomas with and without prior operative treatment. Excerpta Med Int Congr Ser 584: 175–188

    Google Scholar 

  14. Weiss MH et al. (1983) Natural history of microprolactinomas: six-year follow-up. Neurosurgery 12: 180–183

    Article  CAS  PubMed  Google Scholar 

  15. Molitch ME et al. (1997) Management of prolactinomas. J Clin Endocrinol Metab 82: 996–1000

    Article  CAS  PubMed  Google Scholar 

  16. Vance ML et al. (1984) Bromocriptine. Ann Intern Med 100: 78–91

    Article  CAS  PubMed  Google Scholar 

  17. Molitch ME et al. (1985) Bromocriptine as primary therapy for prolactin-secreting macroadenomas: results of a prospective multicenter study. J Clin Endocrinol Metab 60: 698–705

    Article  CAS  PubMed  Google Scholar 

  18. Bevan JS et al. (1992) Dopamine agonists and pituitary tumour shrinkage. Endocr Rev 13: 220–240

    Article  CAS  PubMed  Google Scholar 

  19. Webster J et al. (1994) A comparison of cabergoline and bromocriptine in the treatment of hyperprolactinemic amenorrhoea. N Engl J Med 331: 904–909

    Article  CAS  PubMed  Google Scholar 

  20. Ferrari CI et al. (1997) Treatment of macroprolactinoma with cabergoline: a study of 85 patients. Clin Endocrinol 46: 409–413

    Article  CAS  Google Scholar 

  21. Verhelst J et al. (1999) Cabergoline in the treatment of hyperprolactinemia: a study in 455 patients. J Clin Endocrinol Metab 84: 2518–2522

    Article  CAS  PubMed  Google Scholar 

  22. Colao A et al. (2000) Macroprolactinoma shrinkage during cabergoline treatment is greater in naive patients than in patients pre-treated with other dopamine agonists: a prospective study in 110 patients. J Clin Endocrinol Metab 85: 2247–2252

    CAS  PubMed  Google Scholar 

  23. Di Sarno A et al. (2001) Resistance to cabergoline as compared with bromocriptine in hyperprolactinemia: prevalence, clinical definition and therapeutic strategy. J Clin Endocrinol Metab 86: 5256–5261

    Article  CAS  PubMed  Google Scholar 

  24. Liuzzi A et al. (1985) Low doses of dopamine agonists in the long-term treatment of macroprolactinomas. N Engl J Med 313: 656–659

    Article  CAS  PubMed  Google Scholar 

  25. Eguchi K et al. (1995) In vivo effect of cabergoline, a dopamine agonist, on estrogen-induced rat pituitary tumors. Endocr J 42: 153–161

    Article  CAS  PubMed  Google Scholar 

  26. Eguchi K et al. (1995) Effect of cabergoline, a dopamine agonist, on estrogen-induced rat pituitary tumors: in vitro culture studies. Endocr J 42: 413–420

    Article  CAS  PubMed  Google Scholar 

  27. Pontiroli AE et al. (1987) Selective and extremely long inhibition of prolactin release in man by 1-ethyl-3-(3′-dimethylaminopropyl)-3-(6′ allylergoline-8′-β-carbonyl)urea-diphosphate (fce 21336). Br J Clin Pharmacol 23: 433–438

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Andreotti AC et al. (1995) Pharmacokinetics, pharmacodynamics, and tolerability of cabergoline, a prolactin-lowering drug, after administration of increasing oral doses (0.5, 1.0, and 1.5 milligrams) in healthy male volunteers. J Clin Endocrinol Metab 80: 841–845

    CAS  PubMed  Google Scholar 

  29. Melis GB et al. (1987) Dose related prolactin-inhibitory effect of the new long-acting dopamine receptor agonist cabergoline in normal cycling, puerperal and hyperprolactinemic women. J Clin Endocrinol Metab 65: 541–545

    Article  CAS  PubMed  Google Scholar 

  30. Johnston DG et al. (1983) Hyperprolactinemia. Long-term effects of bromocriptine. Am J Med. 75: 868–874

    Article  CAS  PubMed  Google Scholar 

  31. Johnston DG et al. (1984) Effect of dopamine agonist withdrawal after long-term therapy in prolactinomas. Studies with high-definition computerized tomography. Lancet 2: 187–192

    Article  CAS  PubMed  Google Scholar 

  32. Bergh T et al. (1982) Menstrual function and prolactin levels after long-term bromocriptine treatment of prolactinaemic amenorrhea. Clin Endocrinol 16: 587–593

    Article  CAS  Google Scholar 

  33. Maxson WS et al. (1984) Hyperprolactinemic response after bromocriptine withdrawal in women with prolactin-secreting pituitary tumors. Fertil Steril 41: 218–223

    Article  CAS  PubMed  Google Scholar 

  34. Zarate A et al. (1983) Follow-up of patients with prolactinoma after discontinuation of long-term therapy with bromocriptine. Acta Endocrinol 104: 139–142

    Article  CAS  Google Scholar 

  35. Moriondo P et al. (1985) Bromocriptine treatment of microprolactinomas: evidence of stable prolactin decrease after drug withdrawal. J Clin Endocrinol Metab 60: 764–772

    Article  CAS  PubMed  Google Scholar 

  36. Winkelmann W et al. (1985) Persisting normoprolactinemia after withdrawal of bromocriptine long-term therapy in patients with prolactinomas. In Prolactin. Basic and Clinical Correlates, 817–822 (Eds MacLeod RM et al.) Padova, Italy: Liviana Press

    Google Scholar 

  37. Wang C et al. (1987) Long-term treatment of hyperprolactinemia with bromocriptine: effect of drug withdrawal. Clin Endocrinol 27: 363–371

    Article  CAS  Google Scholar 

  38. Passos VQ et al. (2002) Long-term follow-up of prolactinomas: normoprolactinemia after bromocriptine withdrawal. J Clin Endocrinol Metab 87: 3578–3582

    Article  CAS  PubMed  Google Scholar 

  39. Biswas M et al. (2005) Long-term remission following withdrawal of dopamine agonist therapy in subjects with microprolactinomas. Clin Endocrinol 63: 26–31

    Article  CAS  Google Scholar 

  40. van't Verlaat JW and Croughs RJ (1991) Withdrawal of bromocriptine after long-term therapy for macroprolactinomas: effect on plasma prolactin and tumour size. Clin Endocrinol 34: 175–178

    Article  Google Scholar 

  41. Thorner MO et al. (1981) Rapid changes of prolactinoma volume after withdrawal and reinstitution of bromocriptine. J Clin Endocrinol Metab 53: 480–483

    Article  CAS  PubMed  Google Scholar 

  42. Vance ML et al. (1984) Drugs five years later. Bromocriptine. Ann Intern Med 100: 78–91

    Article  CAS  PubMed  Google Scholar 

  43. Orrego JJ et al. (2000) Rapid re-expansion of a macroprolactinoma after early discontinuation of bromocriptine. Pituitary 3: 189–192

    Article  CAS  PubMed  Google Scholar 

  44. Landolt AM and Osterwalder V (1984) Perivascular fibrosis in prolactinomas: is it increased by bromocriptine? J Clin Endocrinol Metab 58: 1179–1183

    Article  CAS  PubMed  Google Scholar 

  45. Krupp P and Monka C (1987) Bromocriptine in pregnancy: safety aspects. Klin Wochenschr 65: 823–827

    Article  CAS  PubMed  Google Scholar 

  46. Turkalj I et al. (1982) Surveillance of bromocriptine in pregnancy. JAMA 247: 1589–1591

    Article  CAS  PubMed  Google Scholar 

  47. Klibanski A and Greenspan SL (1986) Increase in bone mass after treatment of hyperprolactinemic amenorrhea. N Engl J Med 315: 542–546

    Article  CAS  PubMed  Google Scholar 

  48. Webster J et al. (1993) The efficacy and tolerability of long-term cabergoline therapy in hyperprolactinemic disorders: an open, uncontrolled, multicentre study. Clin Endocrinol 39: 323–329

    Article  CAS  Google Scholar 

  49. Biller BMK et al. (1996) Treatment of prolactin-secreting macroadenomas with the once-weekly dopamine agonist cabergoline. J Clin Endocrinol Metab 81: 2338–2343

    CAS  PubMed  Google Scholar 

  50. Colao A et al. (1997) Long-term and low-dose treatment with cabergoline induces macroprolactinoma shrinkage. J Clin Endocrinol Metab 82: 3574–3579

    Article  CAS  PubMed  Google Scholar 

  51. Cannavò S et al. (1999) Shrinkage of a PRL-secreting pituitary macroadenoma resistant to cabergoline. J Endocrinol Invest 22: 306–309

    Article  PubMed  Google Scholar 

  52. Ferrari C et al. (1995) Cabergoline: a new drug for the treatment of hyperprolactinaemia. Hum Reprod 10: 1647–1652

    Article  CAS  PubMed  Google Scholar 

  53. Colao A et al. (2003) Withdrawal of long-term cabergoline therapy for tumoral and nontumoral hyperprolactinemia. N Engl J Med 349: 2023–2033

    Article  CAS  PubMed  Google Scholar 

  54. Ferrari C et al. (1992) Cabergoline in the long-term therapy of hyperprolactinemic disorders. Acta Endocrinol 126: 589–594

    Article  Google Scholar 

  55. Muratori M et al. (1997) Use of cabergoline in the long-term treatment of hyperprolactinemic and acromegalic patients. J Endocrinol Invest 20: 537–546

    Article  CAS  PubMed  Google Scholar 

  56. Cannavò S et al. (1999) Cabergoline: a first-choice treatment in patients with previously untreated prolactin-secreting pituitary adenomas. J Endocrinol Invest 22: 354–359

    Article  PubMed  Google Scholar 

  57. Biswas M et al. (2005) Long-term remission following withdrawal of dopamine agonist therapy in subjects with microprolactinomas. Clin Endocrinol 63: 26–31

    Article  CAS  Google Scholar 

  58. Robert E et al. (1996) Pregnancy outcome after treatment with the ergot derivative, cabergoline. Reprod Toxicol 10: 333–337

    Article  CAS  PubMed  Google Scholar 

  59. Ricci E et al. (2002) Pregnancy outcome after cabergoline treatment in early weeks of gestation. Reprod Toxicol 16: 791–793

    Article  CAS  PubMed  Google Scholar 

  60. Pinzone JJ et al. (2000) Primary medical therapy of micro- and macroprolactinomas in men. J Clin Endocrinol Metab 85: 3053–3057

    CAS  PubMed  Google Scholar 

  61. Berezin M et al. (1995) Prolactinoma in 53 men: clinical characteristics and modes of treatment (male prolactinoma). J Endocrinol Invest 18: 436–441

    Article  CAS  PubMed  Google Scholar 

  62. Walsh JP and Pullan PT (1997) Hyperprolactinaemia in males: a heterogeneous disorder. Austr NZ J Med 27: 385–390

    Article  CAS  Google Scholar 

  63. Somma M et al. (1981) Prolactinoma in the male. Preoperative evaluation of 40 patients [French]. Neurochirurgie 27: 37–39

    PubMed  Google Scholar 

  64. Eversmann T et al. (1981) Hyperprolactinemia in the male: clinical aspects and therapy [German]. Schweiz Med Wochenschr 111: 1782–1789

    CAS  PubMed  Google Scholar 

  65. Spark RF et al. (1982) Hyperprolactinaemia in males with and without pituitary macroadenomas. Lancet 2: 129–132

    Article  CAS  PubMed  Google Scholar 

  66. Hulting AL et al. (1985) Prolactinomas in men: clinical characteristics and the effect of bromocriptine treatment. Acta Med Scand 217: 101–109

    Article  CAS  PubMed  Google Scholar 

  67. Grisoli F et al. (1980) Prolactin secreting adenoma in 22 men. Surg Neurol 13: 241–247

    CAS  PubMed  Google Scholar 

  68. Chattopadhyay A et al. (2005) Long-term efficacy of bromocriptine in macroprolactinomas and giant prolactinomas in men. Pituitary 8: 147–154

    Article  CAS  PubMed  Google Scholar 

  69. Di Somma C et al. (1998) Bone markers and bone density responses to dopamine agonist therapy in hyperprolactinemic males. J Clin Endocrinol Metab 83: 807–813

    Article  CAS  PubMed  Google Scholar 

  70. Colao A et al. (1996) Chronic treatment with CV 205-52 restores the gonadal function in hyperprolactinemic males. Eur J Endocrinol 135: 548–552

    Article  CAS  PubMed  Google Scholar 

  71. De Rosa M et al. (1998) Cabergoline treatment rapidly improves gonadal function in hyperprolactinemic males: a comparison with bromocriptine. Eur J Endocrinol 138: 286–293

    Article  CAS  PubMed  Google Scholar 

  72. Colao A et al. (2004) Outcome of cabergoline treatment in men with prolactinoma: effects of a 24-month treatment on prolactin levels, tumor mass, recovery of pituitary function, and semen analysis. J Clin Endocrinol Metab 89: 1704–1711

    Article  CAS  PubMed  Google Scholar 

  73. De Rosa M et al. (2006) The treatment with cabergoline for 24 month normalizes the quality of seminal fluid in hyperprolactinaemic males. Clin Endocrinol 64: 307–313

    Article  CAS  Google Scholar 

  74. De Rosa M et al. (2004). Six months of treatment with cabergoline restores sexual potency in hyperprolactinemic males: an open longitudinal study monitoring nocturnal penile tumescence. J Clin Endocrinol Metab 89: 621–625

    Article  CAS  PubMed  Google Scholar 

  75. Calle-Rodrigue RD et al. (1998) Prolactinomas in male and female patients: a comparative clinico-pathology study. Mayo Clin Proc 73: 1046–1052

    Article  CAS  PubMed  Google Scholar 

  76. Delgrange E et al. (1997) Sex-related difference in the growth of prolactinomas: a clinical and proliferation marker study. J Clin Endocrinol Metab 82: 2102–2107

    CAS  PubMed  Google Scholar 

  77. Parkes D (1980) Side effects of bromocriptine. N Engl J Med 302: 749–750

    Article  Google Scholar 

  78. Webster J (1996) A comparative review of the tolerability profiles of dopamine agonists in the treatment of hyperprolactinaemia and inhibition of lactation. Drug Saf 14: 228–238

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Associate Professor of Endocrinology, University Federico II, Naples

    Annamaria Colao

  2. Full Professor of Endocrinology, University Federico II, Naples

    Gaetano Lombardi

  3. are students in the Department of Molecular and Clinical Endocrinology and Oncology, University Federico II, Naples

    Ermelinda Guerra, Monica De Leo & Alberto Mentone

  4. Senior Doctor at the Department of Liver Diseases at the Cotugno Hospital, Naples, Italy

    Antonella Di Sarno

Authors
  1. Annamaria Colao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Antonella Di Sarno
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ermelinda Guerra
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Monica De Leo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Alberto Mentone
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Gaetano Lombardi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Annamaria Colao.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Colao, A., Di Sarno, A., Guerra, E. et al. Drug Insight: cabergoline and bromocriptine in the treatment of hyperprolactinemia in men and women. Nat Rev Endocrinol 2, 200–210 (2006). https://doi.org/10.1038/ncpendmet0160

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ncpendmet0160

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing