The International Journal of Romanian Society of Endocrinology / Registered in 1938

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July - September 2005, Volume 1, Issue 3
Endocrine Care

Gheorghiu ML, Gussi I, Lutescu I, Galoiu S, Hortopan D, Caragheorgheopol A, Coculescu M

Mantaining physiological levels of serum prolactin in prolactinomas treated with dopamine agonists throughout pregnancy prevents tumor growth

Acta Endo (Buc) 2005, 1 (3): 281-298
doi: 10.4183/aeb.2005.281

Introduction: Prolactinomas may grow during pregnancy. Dopamine agonists (DA) prevent tumor growth, but usually suppress prolactin (PRL) both in mother and fetus. Possible long-term consequences on fetal development remain unknown.\r\nAim: to assess whether DA treatment throughout pregnancy in a dosage able to maintain physiological gestational serum levels of prolactin (PRL) still prevents prolactinoma growth.\r\nPatients and methods: We evaluated 68 pregnancies in 49 women with prolactinoma (PRM) and 46 pregnancies in healthy women as controls. Thirty-three pregnancies were recorded in 27 women treated throughout pregnancy with bromocriptine (BRC) (n = 25) or cabergoline (CAB) (n = 2) divided in 2 groups: group A (22 pregnancies in 18 patients) had suppressed serum PRL (below the 5th percentile of the control group Z during the last trimester); group B (11 pregnancies in 10 patients) had physiological serum PRL levels. Other 26 pregnancies in 21 patients were incompletely evaluated and included only in the pregnancy outcome and cure rate analysis. Treated patients were compared with the control group Y 8 women with PRM who discontinued DA after pregnancy induction (9 pregnancies) and a control group Z of 46 healthy pregnant women, randomly selected from two departments of Obstetrics. Patients with multiple pregnancies were recorded in each corresponding study group.\r\nResults: In the control group Y, tumor size showed an increase in 2 (intrasellar macroPRM) out of 8 cases (25%). DA treatment throughout gestation in 27 women with PRM prevented the growth in all cases and induced a shrinkage of more than 30% of tumor mass in 8/14 macroPRM (57.1%), i.e., in 4/7 (57.1%) of macroPRM with physiological serum PRL levels during pregnancy, and in 5/8 (62.5%) of macroPRM with suppressed PRL levels (p = NS) (1 patient had pregnancies in both groups). Low dose DA (BRC 2.5 ? 5 mg/day or CAB 0.5 mg/week) maintains physiological PRL levels in 6/12 (50%) macroPRM, but suppressed PRL in 80% of microPRM. Cure was recorded in 6/49 (12.2%) of patients. Two patients with PRM-induced neuroophthalmic syndrome were successfully treated with DA throughout 1 and respectively 3 pregnancies.\r\nConclusions: Some women with prolactinomas showed a tumour size increase if they were not treated with dopamine agonists throughout pregnancy. Maintaining physiological serum PRL levels during pregnancy (frequently with low doses of DA) prevented tumor growth, avoiding a PRL suppression that may have subtle influence on long-term foetal development.

Keywords: prolactinoma, pregnancy, prolactin, dopamine agonists, bromocriptine

Correspondence: M. Coculescu, ?C. I. Parhon? Institute of Endocrinology, Bd Aviatorilor 34-36, sector 1, Bucharest, fax:+4021.319.87.18, email:


1. Sobrinho LG, Nunes MC, Santos MA, Mauricio JC. Radiological evidence for regression of prolactinoma after treatment with bromocriptine. Lancet 1978; 2(8083):257-258. [CrossRef]
2. McGregor AM, Scanlon MF, Hall R, Hall K. Effects of bromocriptine on pituitary tumour size. Br Med J 1979; 2(6192):700-703. [CrossRef]
3. Colao A, Annunziato L, Lombardi G. Treatment of prolactinomas. Ann Med 1998; 30(5):452-459. [CrossRef]
4. Coculescu M, Simionescu N, Oprescu M, Alessandrescu D. Bromocriptine treatment of pituitary adenomas. Evaluation of withdrawal effect. Endocrinologie 1983; 21(3):157-168.
5. Schlechte JA. Clinical practice. Prolactinoma. N Engl J Med 2003; 349(21):2035-2041. [CrossRef]
6. Passos VQ, Souza JJ, Musolino NR, Bronstein MD. Long-term follow-up of prolactinomas: normoprolactinemia after bromocriptine withdrawal. J Clin Endocrinol Metab 2002; 87(8):3578-3582. [CrossRef]
7. Coculescu M, Anghel R, Badiu C, Caragheorgheopol A, Hortopan D, Dumitrascu A et al. Additional effects of radiotherapy to dopamine agonists in the treatment of macroprolactinomas. Acta Endocrinologica (Buc) 2005; 1(1):43-60. [CrossRef]
8. Colao A, Di Sarno A, Cappabianca P, Di Somma C, Pivonello R, Lombardi G. Withdrawal of longterm cabergoline therapy for tumoral and nontumoral hyperprolactinemia. N Engl J Med 2003; 349(21):2023-2033. [CrossRef]
9. Robert E, Musatti L, Piscitelli G, Ferrari CI. Pregnancy outcome after treatment with the ergot derivative, cabergoline. Reprod Toxicol 1996; 10(4):333-337. [CrossRef]
10. Ricci E, Parazzini F, Motta T, Ferrari CI, Colao A, Clavenna A et al. Pregnancy outcome after cabergoline treatment in early weeks of gestation. Reprod Toxicol 2002; 16(6):791-793. [CrossRef]
11. Ricci E, Parazzini F, Motta T, Ferrari CI, Colao A, Clavenna A et al. Pregnancy outcome after cabergoline treatment in early weeks of gestation. Reprod Toxicol 2002; 16(6):791-793. [CrossRef]
12. Alessandrescu D, Coculescu M, Oprescu M, Brotea G, Zagrean L, Petrenciuc O. Pregnancy induced and maintained under 2-Br-alfa-ergocryptin in a patient with evolutive prolactinoma (in Romanian). Obstetrica si Ginecologia 1981; 29:209-215.
13. Briggs GG, Freeman RK, Yaffe SJ. Bromocriptine. Drugs in pregnancy and lactation. Philadelphia: Lippincott Williams & Wilkins, 2002: 143-145.
14. Kletzky OA, Rossman F, Bertolli SI, Platt LD, Mishell DR, Jr. Dynamics of human chorionic gonadotropin, prolactin, and growth hormone in serum and amniotic fluid throughout normal human pregnancy. Am J Obstet Gynecol 1985; 151(7):878-884.
15. Ben Jonathan N, Hnasko R. Dopamine as a prolactin (PRL) inhibitor. Endocr Rev 2001; 22(6):724-763. [CrossRef]
16. Bigazzi M, Ronga R, Lancranjan I, Ferraro S, Branconi F, Buzzoni P et al. 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 Me [CrossRef]
17. Handwerger S, Freemark M. Role of placental lactogen and prolactin in human pregnancy. Adv Exp Med Biol 1987; 219:399-420.
18. American College of Obstetricians and Gynecologists CoTB. Early pregnancy loss. ACOG Technical Bulletin 212. 1995.
19. Elster AD, Sanders TG, Vines FS, Chen MY. Size and shape of the pituitary gland during pregnancy and post partum: measurement with MR imaging. Radiology 1991; 181(2):531-535.
20. Gonzalez JG, Elizondo G, Saldivar D, Nanez H, Todd LE, Villarreal JZ. Pituitary gland growth during normal pregnancy: an in vivo study using magnetic resonance imaging. Am J Med 1988; 85(2):217-220. [CrossRef]
21. Scheithauer BW, Sano T, Kovacs KT, Young WF, Jr., Ryan N, Randall RV. The pituitary gland in pregnancy: a clinicopathologic and immunohistochemical study of 69 cases. Mayo Clin Proc 1990; 65(4):461-474.
22. Kupersmith MJ, Rosenberg C, Kleinberg D. Visual loss in pregnant women with pituitary adenomas. Ann Intern Med 1994; 121(7):473-477.
23. Molitch ME. Pregnancy and the hyperprolactinemic woman. N Engl J Med 1985; 312(21):1364-1370. [CrossRef]
24. Crosignani P, Ferrari C, Mattei AM. Visual field defects and reduced visual acuity during pregnancy in two patients with prolactinoma: rapid regression of symptoms under bromocriptine. Case reports. Br J Obstet Gynaecol 1984; 91(8):821-823.
25. 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(8):935-938.
26. Coculescu M, Hudita D, Gussi I, Gheorghiu M, Hortopan D, Caragheorgheopol A. Tumor size changes in prolactinomas treated with minimum bromocriptine throughout gestation . Gynecological Endocrinology 2000; 14(suppl 2):50.
27. Canales ES, Garcia IC, Ruiz JE, Zarate A. Bromocriptine as prophylactic therapy in prolactinoma during pregnancy. Fertil Steril 1981; 36(4):524-526.
28. Shanis BS, Check JH. Relative resistance of a macroprolactinoma to bromocriptine therapy during pregnancy. Gynecol Endocrinol 1996; 10(2):91-94. [CrossRef]
29. Liu C, Tyrrell JB. Successful treatment of a large macroprolactinoma with cabergoline during pregnancy. Pituitary 2001; 4(3):179-185. [CrossRef]
30. de Turris P, Venuti L, Zuppa AA. [Long-term treatment with cabergoline in pregnancy and neonatal outcome: report of a clinical case]. Pediatr Med Chir 2003; 25(3):178-180.
31. Verhelst J, Abs R, Maiter D, van den BA, Vandeweghe M, Velkeniers B et al. Cabergoline in the treatment of hyperprolactinemia: a study in 455 patients. J Clin Endocrinol Metab 1999; 84(7):2518-2522. [CrossRef]
32. 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(5):354-359.
33. Ciccarelli E, Grottoli S, Razzore P, Gaia D, Bertagna A, Cirillo S et al. Long-term treatment with cabergoline, a new long-lasting ergoline derivate, in idiopathic or tumorous hyperprolactinaemia and outcome of drug-induced pregnancy. J Endocrinol Inves
34. Jones J, Bashir T, Olney J, Wheatley T. Cabergoline treatment for a large macroprolactinoma throughout pregnancy. J Obstet Gynaecol 1997; 17(4):375-376.
35. Divers WA, Jr., Yen SS. Prolactin-producing microadenomas in pregnancy. Obstet Gynecol 1983; 62(4):425-429.
36. Luthman M, Bremme K, Eneroth P, Werner S. Women with prolactin-producing pituitary adenoma show decreased serum placental lactogen during pregnancy. Gynecol Obstet Invest 1993; 35(2):80-85. [CrossRef]
37. Kubota T, Nagae M, Yaoi Y, Kumasaka T, Saito M. Prolactin-releasing system in maternal, fetal, and amniotic compartments during labor. Obstet Gynecol 1986; 68(1):80-85.
38. Yuen BH, Moon YS, Shin DH. Inhibition of human chorionic gonadotropin production by prolactin from term human trophoblast. Am J Obstet Gynecol 1986; 154(2):336-340.
39. Leav I, Merk FB, Lee KF, Loda M, Mandoki M, McNeal JE et al. Prolactin receptor expression in the developing human prostate and in hyperplastic, dysplastic, and neoplastic lesions. Am J Pathol 1999; 154(3):863-870. [CrossRef]
40. Gussi I, Gheorghiu M, Lutescu I, Hortopan D, Caragheorgheopol A, Hudita D et al. Maintaining physiological profile of prolactin throughout pregnancy in women with prolactinomas on dopamine agonists. Rom J Endocrinol Metab 2002; 1(suppl 4):23.
41. Molitch ME. Pituitary tumors and pregnancy. Growth Horm IGF Res 2003; 13 Suppl A:S38-S44.
42. Ahmed M, al Dossary E, Woodhouse NJ. Macroprolactinomas with suprasellar extension: effect of bromocriptine withdrawal during one or more pregnancies. Fertil Steril 1992; 58(3):492-497.
43. Daya S, Shewchuk AB, Bryceland N. The effect of multiparity on intrasellar prolactinomas. Am J Obstet Gynecol 1984; 148(5):512-515.
44. Fujimoto M, Yoshino E, Mizukawa N, Hirakawa K. Spontaneous reduction in size of prolactinproducing adenoma after delivery. Case report. J Neurosurg 1985; 63(6):973-974. [CrossRef]
45. Hammond CB, Haney AF, Land MR, van der Merwe JV, Ory SJ, Wiebe RH. The outcome of pregnancy in patients with treated and untreated prolactin-secreting pituitary tumors. Am J Obstet Gynecol 1983; 147(2):148-157.
46. Yamada M, Miyake A, Koike K, Ikegami H, Aono T, Tanizawa O. Spontaneous pregnancy after a pregnancy induced by treatment in hyperprolactinemic women. Eur J Obstet Gynecol Reprod Biol 1990; 35(2-3):125-129. [CrossRef]
47. Bergh T, Nillius SJ, Larsson SG, Wide L. Effects of bromocriptine-induced pregnancy on prolactin-secreting pituitary tumours. Acta Endocrinol (Copenh) 1981; 98(3):333-338.