, Volume 55, Issue 1, pp 223–230 | Cite as

10-year follow-up study comparing primary medical vs. surgical therapy in women with prolactinomas

  • Lukas Andereggen
  • Janine Frey
  • Robert H. Andres
  • Marwan El-Koussy
  • Jürgen Beck
  • Rolf W. Seiler
  • Emanuel ChristEmail author
Original Article


While dopamine-agonists are the first-line approach in treating prolactinomas, surgery can be considered in selected cases besides non-responders or patients with dopamine-agonist intolerance. The aim of the present study was to compare the long-term outcome in women with prolactinomas treated primarily either surgically or medically who had not had prior dopamine-agonist treatment. Retrospective case-note study of all consecutive women with prolactinomas primarily managed with medical therapy or surgery in a tertiary referral centre. The clinical, biochemical, and radiological responses to first-line treatment at early and long-term follow-up were analysed. The primary therapeutic strategy was dopamine-agonists for 36 (34 %) and surgery for 71 (66 %) of the women. Baseline clinical and biochemical characteristics were not significantly different between the primary surgical and medical cohort. Median follow-up time was 90 months (range 13–408). Following primary treatment, prolactin level significantly decreased in both cohorts, on average to 13.5 µg/L (IQR 7–21; p < 0.001), and was within the normal range in 82 % of all patients. No women in the surgical cohort demonstrated permanent sequelae and morbidity was low. At final follow-up, control of hyperprolactinaemia required dopamine-agonist therapy in 64 % of women who had undergone primary medical therapy vs. 32 % of those who had primary surgical therapy (p = 0.003). Logistic regression revealed that the primary therapeutic strategy, but not adenoma size, was an independent risk factor for long-term dependence on dopamine-agonists. The present data indicate that in a dedicated tertiary referral centre, long-term control of hyperprolactinaemia in women with prolactinomas is high. In selected cases, a primary neurosurgical approach might at least be interdisciplinarily discussed with the primary goal of minimizing long-term dependence on dopamine-agonists.


Long-term results Primary medical therapy Primary surgical therapy Prolactinoma Women 



We are grateful for the support of the Swiss National Science Foundation (PBBEB-146099, and -155299 to L.A.). We wish to thank Dr. Edward R. Laws, Jr., MD, FACS, Director, Pituitary and Neuroendocrine Centre, Brigham & Women’s Hospital, Boston, for his insightful suggestions. The assistance of Ms. Susan Kaplan in editing the manuscript is acknowledged.

Compliance with ethical standards

Competing interests

This work or part of this work has not been previously published and/or is not under consideration for publication anywhere else. The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

Ethical standards and patient consent

This study was approved by the Ethical Committee of Bern (Kantonale Ethikkommision, KEK, Bern, Switzerland), the Swiss Ethics Committee on research involving humans. The study was performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

Supplementary material

12020_2016_1115_MOESM1_ESM.docx (42 kb)
Supplementary Information


  1. 1.
    M.C. Oh, M.K. Aghi, Dopamine agonist-resistant prolactinomas. J. Neurosurg. 114, 1369–1379 (2011)CrossRefPubMedGoogle Scholar
  2. 2.
    M. Ono, N. Miki, T. Kawamata et al., Prospective study of high-dose cabergoline treatment of prolactinomas in 150 patients. J. Clin. Endocrinol. Metab. 93, 4721–4727 (2008)CrossRefPubMedGoogle Scholar
  3. 3.
    A.I. Green, M. Sherlock, P.M. Stewart, N.J. Gittoes, A.A. Toogood, Extensive experience in the management of macroprolactinomas. Clin. Endocrinol. 81, 85–92 (2014)CrossRefGoogle Scholar
  4. 4.
    M. Babey, R. Sahli, I. Vajtai, R.H. Andres, R.W. Seiler, Pituitary surgery for small prolactinomas as an alternative to treatment with dopamine agonists. Pituitary 14, 222–230 (2011)CrossRefPubMedGoogle Scholar
  5. 5.
    J. Kreutzer, R. Buslei, H. Wallaschofski et al., Operative treatment of prolactinomas: indications and results in a current consecutive series of 212 patients. Eur. J. Endocrinol. 158, 11–18 (2008)CrossRefPubMedGoogle Scholar
  6. 6.
    M. Loyo-Varela, T. Herrada-Pineda, F. Revilla-Pacheco, S. Manrique-Guzman, Pituitary tumor surgery: review of 3004 cases. World Neurosurg. 79, 331–336 (2013)CrossRefPubMedGoogle Scholar
  7. 7.
    V. Primeau, C. Raftopoulos, D. Maiter, Outcomes of transsphenoidal surgery in prolactinomas: improvement of hormonal control in dopamine agonist-resistant patients. Eur. J. Endocrinol. 166, 779–786 (2012)CrossRefPubMedGoogle Scholar
  8. 8.
    X. Qu, M. Wang, G. Wang et al., Surgical outcomes and prognostic factors of transsphenoidal surgery for prolactinoma in men: a single-center experience with 87 consecutive cases. Eur. J. Endocrinol. 164, 499–504 (2011)CrossRefPubMedGoogle Scholar
  9. 9.
    T.R. Smith, M.M. Hulou, K.T. Huang et al., Current indications for the surgical treatment of prolactinomas. J. Clin. Neurosci. 22, 1785–1791 (2015)CrossRefPubMedGoogle Scholar
  10. 10.
    L. Andereggen, G. Schroth, J. Gralla et al., Selective inferior petrosal sinus sampling without venous outflow diversion in the detection of a pituitary adenoma in Cushing’s syndrome. Neuroradiology 54, 495–503 (2012)CrossRefPubMedGoogle Scholar
  11. 11.
    J.P. Cottier, C. Destrieux, L. Brunereau et al., Cavernous sinus invasion by pituitary adenoma: MR imaging. Radiology 215, 463–469 (2000)CrossRefPubMedGoogle Scholar
  12. 12.
    Z.B. Wu, Z.P. Su, J.S. Wu, W.M. Zheng, Q.C. Zhuge, M. Zhong, Five years follow-up of invasive prolactinomas with special reference to the control of cavernous sinus invasion. Pituitary 11, 63–70 (2008)CrossRefPubMedGoogle Scholar
  13. 13.
    R.W. Seiler, L. Mariani, Sellar reconstruction with resorbable vicryl patches, gelatin foam, and fibrin glue in transsphenoidal surgery: a 10-year experience with 376 patients. J. Neurosurg. 93, 762–765 (2000)CrossRefPubMedGoogle Scholar
  14. 14.
    J.A. Wass, When to discontinue treatment of prolactinoma? Nat. Clin. Pract. Endocrinol. Metab. 2, 298–299 (2006)CrossRefPubMedGoogle Scholar
  15. 15.
    A. Colao, A. Di Sarno, P. Cappabianca, C. Di Somma, R. Pivonello, G. Lombardi, Withdrawal of long-term cabergoline therapy for tumoral and nontumoral hyperprolactinemia. N. Engl. J. Med. 349, 2023–2033 (2003)CrossRefPubMedGoogle Scholar
  16. 16.
    M. Losa, P. Mortini, R. Barzaghi, L. Gioia, M. Giovanelli, Surgical treatment of prolactin-secreting pituitary adenomas: early results and long-term outcome. J. Clin. Endocrinol. Metab. 87, 3180–3186 (2002)CrossRefPubMedGoogle Scholar
  17. 17.
    G. Raverot, A. Wierinckx, E. Dantony et al., Prognostic factors in prolactin pituitary tumors: clinical, histological, and molecular data from a series of 94 patients with a long postoperative follow-up. J. Clin. Endocrinol. Metab. 95, 1708–1716 (2010)CrossRefPubMedGoogle Scholar
  18. 18.
    Bloomgarden E., Molitch M.E. Surgical treatment of prolactinomas: cons. Endocrine 47, 730–733 (2014)Google Scholar
  19. 19.
    M.E. Molitch, Management of medically refractory prolactinoma. J. Neuro-oncol. 117, 421–428 (2014)CrossRefGoogle Scholar
  20. 20.
    M.E. Molitch, R.L. Elton, R.E. Blackwell et al., Bromocriptine as primary therapy for prolactin-secreting macroadenomas: results of a prospective multicenter study. J. Clin. Endocrinol. Metab. 60, 698–705 (1985)CrossRefPubMedGoogle Scholar
  21. 21.
    J. Webster, G. Piscitelli, A. Polli, C.I. Ferrari, I. Ismail, M.F. Scanlon, A comparison of cabergoline and bromocriptine in the treatment of hyperprolactinemic amenorrhea. Cabergoline Comparative Study Group. N. Engl. J. Med. 331, 904–909 (1994)CrossRefPubMedGoogle Scholar
  22. 22.
    I. Bancos, M.R. Nannenga, J.M. Bostwick, M.H. Silber, D. Erickson, T.B. Nippoldt, Impulse control disorders in patients with dopamine agonist-treated prolactinomas and nonfunctioning pituitary adenomas: a case-control study. Clin. Endocrinol. 80, 863–868 (2014)CrossRefGoogle Scholar
  23. 23.
    W.M. Drake, C.E. Stiles, T.A. Howlett, A.A. Toogood, J.S. Bevan, R.P. Steeds, A cross-sectional study of the prevalence of cardiac valvular abnormalities in hyperprolactinemic patients treated with ergot-derived dopamine agonists. J. Clin. Endocrinol. Metab. 99, 90–96 (2014)CrossRefPubMedGoogle Scholar
  24. 24.
    F. Galluzzi, R. Salti, S. Stagi, F. La Cauza, F. Chiarelli, Reversible weight gain and prolactin levels--long-term follow-up in childhood. J. Pediatr. Endocrinol. Metab. 18, 921–924 (2005)CrossRefPubMedGoogle Scholar
  25. 25.
    B.L. Roth, Drugs and valvular heart disease. N. Engl. J. Med. 356, 6–9 (2007)CrossRefPubMedGoogle Scholar
  26. 26.
    J. Verhelst, R. Abs, D. Maiter et al., Cabergoline in the treatment of hyperprolactinemia: a study in 455 patients. J. Clin. Endocrinol. Metab. 84, 2518–2522 (1999)CrossRefPubMedGoogle Scholar
  27. 27.
    J. Kharlip, R. Salvatori, G. Yenokyan, G.S. Wand, Recurrence of hyperprolactinemia after withdrawal of long-term cabergoline therapy. J. Clin. Endocrinol. Metab. 94, 2428–2436 (2009)CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    O. Cohen-Inbar, Z. Xu, D. Schlesinger, M.L. Vance, J.P. Sheehan, Gamma knife radiosurgery for medically and surgically refractory prolactinomas: long-term results. Pituitary 18, 820–830 (2015)CrossRefPubMedGoogle Scholar
  29. 29.
    M. Menucci, A. Quinones-Hinojosa, P. Burger, R. Salvatori, Effect of dopaminergic drug treatment on surgical findings in prolactinomas. Pituitary 14, 68–74 (2011)CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    C. Caputo, D. Prior, W.J. Inder, The need for annual echocardiography to detect cabergoline-associated valvulopathy in patients with prolactinoma: a systematic review and additional clinical data. Lancet Diabetes Endocrinol. 3, 906–913 (2015)CrossRefPubMedGoogle Scholar
  31. 31.
    A. Elenkova, R. Shabani, K. Kalinov, S. Zacharieva, Increased prevalence of subclinical cardiac valve fibrosis in patients with prolactinomas on long-term bromocriptine and cabergoline treatment. Eur. J. Endocrinol. 167, 17–25 (2012)CrossRefPubMedGoogle Scholar
  32. 32.
    V. Delgado, N.R. Biermasz, S.W. van Thiel et al., Changes in heart valve structure and function in patients treated with dopamine agonists for prolactinomas, a 2-year follow-up study. Clin. Endocrinol. 77, 99–105 (2012)CrossRefGoogle Scholar
  33. 33.
    R. Schade, F. Andersohn, S. Suissa, W. Haverkamp, E. Garbe, Dopamine agonists and the risk of cardiac-valve regurgitation. N. Engl. J. Med. 356, 29–38 (2007)CrossRefPubMedGoogle Scholar
  34. 34.
    P. Anagnostis, F. Adamidou, S.A. Polyzos, Z. Efstathiadou, E. Karathanassi, M. Kita, Long term follow-up of patients with prolactinomas and outcome of dopamine agonist withdrawal: a single center experience. Pituitary 15, 25–29 (2012)CrossRefPubMedGoogle Scholar
  35. 35.
    C. Schmid, D.L. Goede, R.S. Hauser, M. Brandle, Increased prevalence of high Body Mass Index in patients presenting with pituitary tumours: severe obesity in patients with macroprolactinoma. Swiss Med. Wkly. 136, 254–258 (2006)PubMedGoogle Scholar
  36. 36.
    C.M. dos Santos Silva, F.R. Barbosa, G.A. Lima et al., BMI and metabolic profile in patients with prolactinoma before and after treatment with dopamine agonists. Obesity 19, 800–805 (2011)CrossRefPubMedGoogle Scholar
  37. 37.
    R. Yermus, S. Ezzat, Does normalization of prolactin levels result in weight loss in patients with prolactin secreting pituitary adenomas? Clin. Endocrinol. 56, 562 (2002)CrossRefGoogle Scholar
  38. 38.
    Y. Greenman, K. Tordjman, N. Stern, Increased body weight associated with prolactin secreting pituitary adenomas: weight loss with normalization of prolactin levels. Clin. Endocrinol. 48, 547–553 (1998)CrossRefGoogle Scholar
  39. 39.
    A. Ciresi, M.C. Amato, V. Guarnotta, F. Lo Castro, C. Giordano, Higher doses of cabergoline further improve metabolic parameters in patients with prolactinoma regardless of the degree of reduction in prolactin levels. Clin. Endocrinol. 79, 845–852 (2013)CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Lukas Andereggen
    • 1
  • Janine Frey
    • 2
  • Robert H. Andres
    • 1
  • Marwan El-Koussy
    • 3
  • Jürgen Beck
    • 1
  • Rolf W. Seiler
    • 1
  • Emanuel Christ
    • 2
    Email author
  1. 1.Departments of NeurosurgeryBern University Hospital, University of BernBernSwitzerland
  2. 2.Endocrinology Diabetes and MetabolismBern University Hospital, University of BernBernSwitzerland
  3. 3.Neuroradiology, InselspitalBern University Hospital, University of BernBernSwitzerland

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