Optimal timing of dopamine agonist withdrawal in patients with hyperprolactinemia: a systematic review and meta-analysis
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Dopamine agonists (DAs) are recommended as first-line treatment for patients with hyperprolactinemia. Generally, it is accepted that patients with hyperprolactinemia do not need lifelong medication, but the optimal timing for DA withdrawal has not been determined. The aim of this systematic review and meta-analysis is to assess the impact of DA withdrawal on the clinical outcomes of patients with hyperprolactinemia, and to explore possible factors affecting successful DA withdrawal.
The databases of PubMed, Cochrane and EMBASE were searched up to May 2016.
The proportion of patients with persisting normoprolactinemia after DA withdrawal reached 36.6% in a random effects model (95% CI, 29.4–44.2%; I-squared: 82.5%). Data of stratified analysis showed that the success rate of drug withdrawal was high in patients using cabergoline (CAB) as the only treatment (41.2%; 95% CI 32.3–50.4%) and those using CAB over 24 months (48.7%; 95% CI 38.9–58.5%), especially in patients with idiopathic hyperprolactinemia (73.2%; 95% CI 55.6–87.7%). In addition, patients who received a low maintenance dose of CAB, and had a significant reduction in tumor size (over 50%) before withdrawal, were more likely to achieve success (51.5 and 49.4%, respectively).
The success rate of DA withdrawal has increased in recent years. Further, the success rate of CAB withdrawal was higher than that of bromocriptine, especially in patients with a duration of treatment longer than 24 months. Conclusively, the probability of success was higher in patients who received low-dose CAB maintenance treatment and those who achieved a significant reduction in tumor size before withdrawal.
KeywordsDopamine agonists Withdrawal Hyperprolactinemia Prolactinoma Cabergoline Bromocriptine
We thank Ms. Erin M. Botticelli of Massachusetts General Hospital for her careful reading and editing of the manuscript.
This work was supported by Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support (Grant No. 20161407), and the National Natural Science Foundation of China (Grant No. 81471392, 81271523).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no competing interests.
- 1.S. Melmed, F.F. Casanueva, A.R. Hoffman, D.L. Kleinberg, V.M. Montori, J.A. Schlechte, J.A. Wass, Diagnosis and treatment of hyperprolactinemia: an Endocrine Society clinical practice guideline. J. Clin. Endocrinol. Metab. 96(2), 273–288 (2011). https://doi.org/10.1210/jc.2010-1692 PubMedCrossRefGoogle Scholar
- 8.M.O. Thorner, R.L. Perryman, A.D. Rogol, B.P. Conway, R.M. Macleod, I.S. Login, J.L. Morris, Rapid changes of prolactinoma volume after withdrawal and reinstitution of bromocriptine. J. Clin. Endocrinol. Metab. 53(3), 480–483 (1981). https://doi.org/10.1210/jcem-53-3-480 PubMedCrossRefGoogle Scholar
- 9.F.F. Casanueva, M.E. Molitch, J.A. Schlechte, R. Abs, V. Bonert, M.D. Bronstein, T. Brue, P. Cappabianca, A. Colao, R. Fahlbusch, H. Fideleff, M. Hadani, P. Kelly, D. Kleinberg, E. Laws, J. Marek, M. Scanlon, L.G. Sobrinho, J.A. Wass, A. Giustina, Guidelines of the Pituitary Society for the diagnosis and management of prolactinomas. Clin. Endocrinol. 65(2), 265–273 (2006). https://doi.org/10.1111/j.1365-2265.2006.02562.x CrossRefGoogle Scholar
- 10.O.M. Dekkers, J. Lagro, P. Burman, J.O. Jorgensen, J.A. Romijn, A.M. Pereira, Recurrence of hyperprolactinemia after withdrawal of dopamine agonists: systematic review and meta-analysis. J. Clin. Endocrinol. Metab. 95(1), 43–51 (2010). https://doi.org/10.1210/jc.2009-1238 PubMedCrossRefGoogle Scholar
- 11.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(1), 25–29 (2012). https://doi.org/10.1007/s11102-011-0303-6 PubMedCrossRefGoogle Scholar
- 16.L. Vilar, J.L. Albuquerque, P.S. Gadelha, F. Rangel Filho, A.M. Siqueira, M.M. da Fonseca, K.F. Viana, B.S. Gomes, R. Lyra, Second attempt of cabergoline withdrawal in patients with prolactinomas after a failed first attempt: is it worthwhile? Front. Endocrinol. 6, 11 (2015). https://doi.org/10.3389/fendo.2015.00011 CrossRefGoogle Scholar
- 20.W. Winkelmann, B. Allolio, U. Deuss, D. Heesen, D. Kaulen, in Persisting Normoprolactinemia After Withdrawal of Bromocriptine Long-term Therapy in Patients with Prolactinomas, (ed.), by R.M. Macleod, M.O. Thorner, U. Scapagnini. Basic and Clinical Correlates (Liviana Press, Padova, 1985), pp. 817–822Google Scholar
- 27.T.M. Barber, J. Kenkre, C. Garnett, R.V. Scott, J.V. Byrne, J.A. Wass, Recurrence of hyperprolactinaemia following discontinuation of dopamine agonist therapy in patients with prolactinoma occurs commonly especially in macroprolactinoma. Clin. Endocrinol. 75(6), 819–824 (2011). https://doi.org/10.1111/j.1365-2265.2011.04136.x CrossRefGoogle Scholar
- 28.E.E. Buyukbayrak, A.Y. Karageyim Karsidag, B. Kars, O. Balcik, M. Pirimoglu, O. Unal, C. Turan, Effectiveness of short-term maintenance treatment with cabergoline in microadenoma-related and idiopathic hyperprolactinemia. Arch. Gynecol. Obstet. 282(5), 561–566 (2010). https://doi.org/10.1007/s00404-010-1562-6 PubMedCrossRefGoogle Scholar
- 30.M. Biswas, J. Smith, D. Jadon, P. McEwan, D.A. Rees, L.M. Evans, M.F. Scanlon, J.S. Davies, Long-term remission following withdrawal of dopamine agonist therapy in subjects with microprolactinomas. Clin. Endocrinol. 63(1), 26–31 (2005). https://doi.org/10.1111/j.1365-2265.2005.02293.x CrossRefGoogle Scholar
- 34.A.M. Mattei, C. Ferrari, G. Ragni, R. Benco, M.C. Picciotti, P. Rampini, R. Caldara, P.G. Crosignani, Serum prolactin and ovarian function after discontinuation of drug treatment for hyperprolactinaemia: a study with bromocriptine and metergoline. Br. J. Obstet. Gynaecol. 91(3), 244–250 (1984)PubMedCrossRefGoogle Scholar
- 37.E. Sala, P. Bellaviti Buttoni, E. Malchiodi, E. Verrua, G. Carosi, E. Profka, G. Rodari, M. Filopanti, E. Ferrante, A. Spada, G. Mantovani, Recurrence of hyperprolactinemia following dopamine agonist withdrawal and possible predictive factors of recurrence in prolactinomas. J. Endocr. Investig. (2016). https://doi.org/10.1007/s40618-016-0483-z
- 38.A. Colao, A. Di Sarno, E. Guerra, R. Pivonello, P. Cappabianca, F. Caranci, A. Elefante, L.M. Cavallo, F. Briganti, S. Cirillo, G. Lombardi, Predictors of remission of hyperprolactinaemia after long-term withdrawal of cabergoline therapy. Clin. Endocrinol. 67(3), 426–433 (2007). https://doi.org/10.1111/j.1365-2265.2007.02905.x CrossRefGoogle Scholar