Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-78c5997874-mlc7c Total loading time: 0 Render date: 2024-11-13T10:39:46.815Z Has data issue: false hasContentIssue false

Chapter 8 - Prolactin, Prolactinoma, and Pregnancy

from Section II - Hormones and Gestational Disorders

Published online by Cambridge University Press:  09 November 2022

By
Dominique Maiter  and
Philippe Chanson
Edited by
Felice Petraglia ,
Mariarosaria Di Tommaso  and
Federico Mecacci
Felice Petraglia
Affiliation:
Università degli Studi, Florence
Mariarosaria Di Tommaso
Affiliation:
Università degli Studi, Florence
Federico Mecacci
Affiliation:
Università degli Studi, Florence
Get access

Summary

Prolactin (PRL) is a key player in normal physiology and pathophysiology of reproduction. Although not indispensable to achieve gestation in humans (as opposed to rodents), PRL is essential for the development of the mammary gland and for lactation. On the other hand, hyperprolactinemia is a frequent cause of infertility and needs to be corrected in a young woman who actively seeks pregnancy. Dopamine agonists (DA) represent the first-line treatment of prolactinomas, but transsphenoidal surgery may be considered in selected cases. Among DA, preference should be given to cabergoline over bromocriptine, due to its higher efficacy and better tolerance. Both drugs are safe to use during early gestation. In most cases, however, drug withdrawal is advised as soon as the pregnancy is confirmed. Symptomatic tumor growth is a rare event in microprolactinomas (2–3 percent) but more frequent in large macroprolactinomas without previous ablative therapy (15–20 percent). Symptomatic tumor enlargement will usually be successfully treated with resumption of the DA. Breastfeeding is not contra-indicated in women with a prolactinoma. In addition, pregnancy may have a beneficial effect on further endocrine outcome, inducing early remission of hyperprolactinemia in about 40 percent of these women. Data are much less robust in men in whom PRL concentrations are less prone to increase. The male reproductive axis is also less sensitive to the effects of hyperprolactinemia. Nevertheless, significant hyperprolactinemia in men may also cause hypogonadism and infertility and must be treated as in women.

Keywords

hyperprolactinaemiapituitary tumorscabergolinebromocriptinegestationinfertility
Type
Chapter
Information
Hormones and Pregnancy
Basic Science and Clinical Implications
 , pp. 73 - 86
Publisher: Cambridge University Press
Print publication year: 2022

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Bachelot, A, and Binart, N. Reproductive role of prolactin. Reproduction. 2007, 133(2):361–369.Google Scholar
Bernard, V, Young, J, Chanson, P, et al. New insights in prolactin: Pathological implications. Nat Rev Endocrinol. 2015, 11(5):265–275.Google Scholar
Binart, N. Prolactin. In: Melmed, S, editor. The Pituitary. 2017; 129–161. London: Elsevier.Google Scholar
Bernard, V, Young, J, and Binart, N. Prolactin – A pleiotropic factor in health and disease. Nat Rev Endocrinol. 2019, 15(6):356–365.Google Scholar
Horseman, ND. Physiological actions and receptors. In: Tritos, NA, Klibanski, A, editors. Prolactin disorders from basic science to clinical management. 2019; 79–94. Springer Nature Switzerland AG: Humana Press.Google Scholar
Newey, PJ, Gorvin, CM, and Thakker, RV. Mutant prolactin receptor and familial hyperprolactinemia. N Engl J Med. 2014, 370(10):977–978.Google Scholar
Kobayashi, T, Usui, H, Tanaka, H, et al. Variant prolactin receptor in agalactia and hyperprolactinemia. N Engl J Med. 2018, 379(23):2230–2236.CrossRefGoogle ScholarPubMed
Molitch, ME. Endocrinology in pregnancy: Management of the pregnant patient with a prolactinoma. Eur J Endocrinol. 2015, 172(5):R205–13.Google Scholar
Kaiser, UB. Hyperprolactinemia and infertility: New insights. J Clin Invest. 2012, 122(10):3467–3468.Google Scholar
Sonigo, C, Bouilly, J, Carre, N, et al. Hyperprolactinemia-induced ovarian acyclicity is reversed by kisspeptin administration. J Clin Invest. 2012, 122(10):3791–3795.Google Scholar
Demura, R, Ono, M, Demura, H, et al. Prolactin directly inhibits basal as well as gonadotropin-stimulated secretion of progesterone and 17 beta-estradiol in the human ovary. J Clin Endocrinol Metab. 1982, 54(6):1246–1250.Google Scholar
Dorrington, JH, and Gore-Langton, RE. Antigonadal action of prolactin: Further studies on the mechanism of inhibition of follicle-stimulating hormone-induced aromatase activity in rat granulosa cell cultures. Endocrinology. 1982, 110(5):1701–1707.Google Scholar
McNatty, KP. Relationship between plasma prolactin and the endocrine microenvironment of the developing human antral follicle. Fertil Steril. 1979, 32(4):433–438.CrossRefGoogle ScholarPubMed
Seppala, M, Ranta, T, and Hirvonen, E. Hyperprolactinaemia and luteal insufficiency. Lancet. 1976, 1(7953):229–230.Google Scholar
Maiter, D. Prolactinoma and pregnancy: From the wish of conception to lactation. Ann Endocrinol (Paris). 2016, 77(2):128–134.Google Scholar
Chanson, P, and Maiter, D. Prolactinoma. In: Melmed, S, editor. The Pituitary. 4th ed. 2017; 467–514. London: Elsevier.Google Scholar
Chanson, P, and Maiter, D. The epidemiology, diagnosis and treatment of prolactinomas: The old and the new. Best Pract Res Clin Endocrinol Metab. 2019:101290.Google Scholar
Souter, I, Baltagi, LM, Toth, TL, et al. Prevalence of hyperprolactinemia and abnormal magnetic resonance imaging findings in a population with infertility. Acta Obstet Gynecol Scand. 2010, 94(3):1159–1162.Google Scholar
Maiter, D. Prolactinomas in men. In: Tritos, NA, Klibanski, A, editors. Prolactin Disorders from Basic Science to Clinical Management. 2019; 189–204. Springer Nature Switzerland AG: Humana Press.Google Scholar
Ambulkar, SS, Darves-Bornoz, AL, Fantus, RJ, et al. Prevalence of hyperprolactinemia and clinically apparent prolactinomas in men undergoing fertility evaluation. Urology. 2021.Google Scholar
Ben-Jonathan, N, and Hnasko, R. Dopamine as a prolactin (PRL) inhibitor. Endocr Rev. 2001, 22(6):724–763.CrossRefGoogle ScholarPubMed
Schuff, KG, Hentges, ST, Kelly, MA, et al. Lack of prolactin receptor signaling in mice results in lactotroph proliferation and prolactinomas by dopamine-dependent and -independent mechanisms. J Clin Invest. 2002, 110(7):973–981.CrossRefGoogle ScholarPubMed
Freeman, ME, Kanyicska, B, Lerant, A, et al. Prolactin: Structure, function, and regulation of secretion. Physiol Rev. 2000;80(4):1523–1631.CrossRefGoogle ScholarPubMed
Boockfor, FR, Hoeffler, JP, and Frawley, LS. Estradiol induces a shift in cultured cells that release prolactin or growth hormone. Am J Physiol. 1986, 250(1 Pt 1):E103–105.Google Scholar
Ben-Jonathan, N, LaPensee, CR, and LaPensee, EW. What can we learn from rodents about prolactin in humans? Endocr Rev. 2008, 29(1):1–41.Google Scholar
Dinc, H, Esen, F, Demirci, A, et al. Pituitary dimensions and volume measurements in pregnancy and post partum. MR assessment. Acta Radiol. 1998, 39(1):64–69.Google Scholar
Gonzalez, JG, Elizondo, G, Saldivar, D, et al. Pituitary gland growth during normal pregnancy: An in vivo study using magnetic resonance imaging. Am J Med. 1988, 85(2):217–220.Google Scholar
Knuth, UA, and Friesen, HG. Prolactin and pregnancy. In: Martini, L, James, VHT, editors. Current Topics in Experimental Endocrinology. 1983. 69–96. 4: Elsevier.Google Scholar
Biswas, S. Prolactin in amniotic fluid: Its correlation with maternal plasma prolactin. Clin Chim Acta. 1976, 73(2):363–367.Google Scholar
Rigg, LA, Lein, A, and Yen, SS. Pattern of increase in circulating prolactin levels during human gestation. Am J Obstet Gynecol. 1977, 129(4):454–456.Google Scholar
Grattan, DR, and Kokay, IC. Prolactin: A pleiotropic neuroendocrine hormone. J Neuroendocrinol. 2008, 20(6):752–763.Google Scholar
Recent advances in medically assisted conception. Report of a WHO Scientific Group. 1992, 820:1-. Geneva: WHO; 1992.Google Scholar
Soto-Pedre, E, Newey, PJ, Bevan, JS, et al. The epidemiology of hyperprolactinaemia over 20 years in the Tayside region of Scotland: The Prolactin Epidemiology, Audit and Research Study (PROLEARS). Clin Endocrinol. 2017, 86(1):60–67.Google Scholar
Huang, KE, Bonfiglio, TA, and Muechler, EK. Transient hyperprolactinemia in infertile women with luteal phase deficiency. Obstet Gynecol. 1991, 78(4):651–655.Google Scholar
Molitch, ME, and Reichlin, S. Hyperprolactinemic disorders. Dis Mon. 1982, 28(9):1–58.CrossRefGoogle ScholarPubMed
Touraine, P, Plu-Bureau, G, Beji, C, et al. Long-term follow-up of 246 hyperprolactinemic patients. Acta Obstet Gynecol Scand. 2001, 80(2):162–168.CrossRefGoogle ScholarPubMed
Lee, DY, Oh, YK, Yoon, BK, et al. Prevalence of hyperprolactinemia in adolescents and young women with menstruation-related problems. Am J Obstet Gynecol. 2012, 206(3):213 e1–5.CrossRefGoogle Scholar
Binart, N, Young, J, and Chanson, P. Prolactin assays and regulation of secretion: animal and human data. In: Tritos, NA, Klibanski, A (Eds.) Prolactin Disorders from Basic Science to Clinical Management. Contemporary Endocrinology 2019; 55–78. Springer Nature Switzerland AG: Humana Press.Google Scholar
Fahie-Wilson, M, and Smith, TP. Determination of prolactin: The macroprolactin problem. Best Pract Res Clin Endocrinol Metab. 2013, 27(5):725–742.Google Scholar
Kalsi, AK, Halder, A, Jain, M, et al. Prevalence and reproductive manifestations of macroprolactinemia. Endocrine. 2019, 63(2):332–340.Google Scholar
Karavitaki, N, Thanabalasingham, G, Shore, HC, et al. Do the limits of serum prolactin in disconnection hyperprolactinaemia need re-definition? A study of 226 patients with histologically verified non-functioning pituitary macroadenoma. Clin Endocrinol (Oxf). 2006, 65(4):524–529.CrossRefGoogle ScholarPubMed
Dohle, GR, Colpi, GM, Hargreave, TB, et al. EAU guidelines on male infertility. Eur Urol. 2005, 48(5):703–711.Google Scholar
Patel, DP, Chandrapal, JC, and Hotaling, JM. Hormone-Based Treatments in Subfertile Males. Curr Urol Rep. 2016, 17(8):56.CrossRefGoogle ScholarPubMed
Iglesias, P, Bernal, C, Villabona, C, et al. Prolactinomas in men: A multicentre and retrospective analysis of treatment outcome. Clin Endocrinol (Oxf). 2012, 77(2):281–287.Google Scholar
Shimon, I, and Benbassat, C. Male prolactinomas presenting with normal testosterone levels. Pituitary. 2014;17(3):246–250.Google Scholar
Colao, A, Vitale, G, Cappabianca, P, et al. 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. 2004, 89(4):1704–1711.Google Scholar
De Rosa, M, Ciccarelli, A, Zarrilli, S, et al. The treatment with cabergoline for 24 month normalizes the quality of seminal fluid in hyperprolactinaemic males. Clin Endocrinol (Oxf). 2006, 64(3):307–313.Google Scholar
De Rosa, M, Zarrilli, S, Di Sarno, A, et al. Hyperprolactinemia in men: clinical and biochemical features and response to treatment. Endocrine. 2003, 20(1-2):75–82.Google Scholar
Pinzone, JJ, Katznelson, L, Danila, DC, et al. Primary medical therapy of micro- and macroprolactinomas in men. J Clin Endocrinol Metab. 2000, 85(9):3053–3057.Google Scholar
Molitch, M. Prolactin and pregnancy. In: Tritos, NA, Klibanski, A (Eds.), Prolactin Disorders from Basic Science to Clinical Management. Contemporary Endocrinology. 2019; 161–174. Springer Nature Switzerland AG: Humana Press.Google Scholar
Gillam, MP, Molitch, ME, Lombardi, G, et al. Advances in the treatment of prolactinomas. Endocr Rev. 2006, 27(5):485–534.Google Scholar
Melmed, S, Casanueva, FF, Hoffman, AR, et al. Diagnosis and treatment of hyperprolactinemia: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011, 96(2):273–288.Google Scholar
Glezer, A, and Bronstein, MD. Prolactinomas, cabergoline, and pregnancy. Endocrine. 2014, 47(1):64–69.Google Scholar
Webster, J. A comparative review of the tolerability profiles of dopamine agonists in the treatment of hyperprolactinaemia and inhibition of lactation. Drug Saf. 1996, 14(4):228–238.CrossRefGoogle ScholarPubMed
Webster, J, Piscitelli, G, Polli, A, et al. A comparison of cabergoline and bromocriptine in the treatment of hyperprolactinemic amenorrhea. Cabergoline Comparative Study Group (see comments). N Engl J Med. 1994, 331(14):904–909.Google Scholar
Wang, AT, Mullan, RJ, Lane, MA, et al. Treatment of hyperprolactinemia: a systematic review and meta-analysis. Syst Rev. 2012, 1:33.Google Scholar
Ono, M, Miki, N, Amano, K, et al. Individualized high-dose cabergoline therapy for hyperprolactinemic infertility in women with micro- and macroprolactinomas. J Clin Endocrinol Metab. 2010.Google Scholar
Verhelst, J, Abs, R, Maiter, D, et al. Cabergoline in the treatment of hyperprolactinemia: a study in 455 patients. J Clin Endocrinol Metab. 1999, 84(7):2518–2522.Google Scholar
Laws, ER, Jr., Fode, NC, Randall, RV, et al. Pregnancy following transsphenoidal resection of prolactin-secreting pituitary tumors. J Neurosurg. 1983, 58(5):685–688.Google Scholar
Buchfelder, M, Zhao, Y, and Schlaffer, SM. Surgery for prolactinomas to date. Neuroendocrinology. 2019.Google Scholar
Zamanipoor Najafabadi, AH, Zandbergen, IM, de Vries, F, et al. Surgery as a viable alternative first-line treatment for prolactinoma patients. A systematic review and meta-analysis. J Clin Endocrinol Metab. 2020, 105(3).Google Scholar
Primeau, V, Raftopoulos, C, and Maiter, D. Outcomes of transsphenoidal surgery in prolactinomas: improvement of hormonal control in dopamine agonist-resistant patients. Eur J Endocrinol. 2012, 166(5):779–786.Google Scholar
McGarrigle, HH, Sarris, S, Little, V, et al. Induction of ovulation with clomiphene and human chorionic gonadotrophin in women with hyperprolactinaemic amenorrhoea. Br J Obstet Gynaecol. 1978, 85(9):692–697.CrossRefGoogle ScholarPubMed
Lebbe, M, Hubinont, C, Bernard, P, et al. Outcome of 100 pregnancies initiated under treatment with cabergoline in hyperprolactinaemic women. Clin Endocrinol (Oxf). 2010, 73(2):236–242.CrossRefGoogle ScholarPubMed
Casanueva, FF, Molitch, ME, Schlechte, JA, et al. Guidelines of the pituitary society for the diagnosis and management of prolactinomas. Clin Endocrinol (Oxf). 2006, 65(2):265–273.CrossRefGoogle ScholarPubMed
Ray, JG, Vermeulen, MJ, Bharatha, A, et al. Association between MRI exposure during pregnancy and fetal and childhood outcomes. JAMA. 2016, 316(9):952–961.Google Scholar
Proenca, F, Guerreiro, C, Sa, G, et al Neuroimaging safety during pregnancy and lactation: a review. Neuroradiology. 2021.Google Scholar
Sant’ Anna, BG, Musolino, NRC, Gadelha, MR, et al. A Brazilian multicentre study evaluating pregnancies induced by cabergoline in patients harboring prolactinomas. Pituitary. 2020, 23(2):120–128.Google Scholar
Lambert, K, Rees, K, Seed, PT, et al. Macroprolactinomas and nonfunctioning pituitary adenomas and pregnancy outcomes. Obstet Gynecol. 2017, 129(1):185–194.Google Scholar
Barraud, S, Guedra, L, Delemer, B, et al. Evolution of macroprolactinomas during pregnancy: A cohort study of 85 pregnancies. Clin Endocrinol (Oxf). 2020, 92(5):421–427.Google Scholar
Huang, W, and Molitch, ME. Pituitary tumors in pregnancy. Endocrinol Metab Clin North Am. 2019, 48(3):569–581.Google Scholar
Araujo, B, Belo, S, and Carvalho, D. Pregnancy and tumor outcomes in women with prolactinoma. Exp Clin Endocrinol Diabetes. 2017, 125(10):642–648.Google Scholar
Galvao, A, Goncalves, D, Moreira, M, et al. Prolactinoma and pregnancy – A series of cases including pituitary apoplexy. J Obstet Gynaecol. 2017;37(3):284–287.Google Scholar
Karaca, Z, Yarman, S, Ozbas, I, et al. How does pregnancy affect the patients with pituitary adenomas: a study on 113 pregnancies from Turkey. J Endocrinol Invest. 2018, 41(1):129–141.Google Scholar
O’Sullivan, SM, Farrant, MT, Ogilvie, CM, et al. An observational study of pregnancy and post-partum outcomes in women with prolactinoma treated with dopamine agonists. Aust N Z J Obstet Gynaecol. 2020, 60(3):405–411.Google Scholar
Schlechte, JA. Clinical practice. Prolactinoma. N Engl J Med. 2003, 349(21):2035–2041.Google Scholar
Divers, WA, Jr., and Yen, SS. Prolactin-producing microadenomas in pregnancy. Obstet Gynecol. 1983, 62(4):425–429.Google Scholar
Rastogi, A, Bhansali, A, Dutta, P, et al. A comparison between intensive and conventional cabergoline treatment of newly diagnosed patients with macroprolactinoma. Clin Endocrinol (Oxf). 2013, 79(3):409–415.Google Scholar
Graillon, T, Cuny, T, Castinetti, F, et al. Surgical indications for pituitary tumors during pregnancy: a literature review. Pituitary. 2020, 23(2):189–199.Google Scholar
Grand’Maison, S, Weber, F, Bedard, MJ, et al. Pituitary apoplexy in pregnancy: A case series and literature review. Obstet Med. 2015, 8(4):177–183.Google Scholar
Kuhn, E, Weinreich, AA, Biermasz, NR, et al. Apoplexy of microprolactinomas during pregnancy. Eur J Endocrinol. 2021.Google Scholar
Bronstein, MD. Prolactinomas and pregnancy. Pituitary. 2005, 8(1):31–38.Google Scholar
Molitch, ME. Prolactinoma in pregnancy. Best Pract Res Clin Endocrinol Metab. 2011, 25(6):885–896.Google Scholar
Auriemma, RS, Perone, Y, Di Sarno, A, Grasso, LF, Guerra, E, Gasperi, M, et al. Results of a single-center observational 10-year survey study on recurrence of hyperprolactinemia after pregnancy and lactation. J Clin Endocrinol Metab. 2013, 98(1):372–379.Google Scholar
Domingue, ME, Devuyst, F, Alexopoulou, O, et al. Outcome of prolactinoma after pregnancy and lactation: a study on 73 patients. Clin Endocrinol (Oxf). 2014, 80(5):642–648.Google Scholar
Ikegami, H, Aono, T, Koizumi, K, et al. Relationship between the methods of treatment for prolactinomas and the puerperal lactation. Fertil Steril. 1987, 47(5):867–869.CrossRefGoogle ScholarPubMed
Bern, HA, and Nicoll, CS. The comparative endocrinology of prolactin. Recent Prog Horm Res. 1968, 24:681–720.Google Scholar
Biswas, S, and Rodeck, CH. Plasma prolactin levels during pregnancy. Br J Obstet Gynaecol. 1976, 83(9):683–687.Google Scholar
Karunakaran, S, Page, RC, and Wass, JA. The effect of the menopause on prolactin levels in patients with hyperprolactinaemia. Clin Endocrinol (Oxf). 2001, 54(3):295–300.Google Scholar
Huda, MS, Athauda, NB, Teh, MM, et al. Factors determining the remission of microprolactinomas after dopamine agonist withdrawal. Clin Endocrinol (Oxf). 2010, 72(4):507–511.Google Scholar

Save book to Kindle

To save this book to your Kindle, first ensure coreplatform@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×