Introduction. Typical and atypical antipsychotic agent is currently used for treatment in the majority of patients with psychotic disorders. The aim of this review is to assess antipsychotic induced hyperprolactinaemia and the following menstrual dysfunction that affects fertility, quality of life, and therapeutic compliance of women. Method. For this purpose, Medline, PsychInfo, Cochrane library, and Scopus databases were accessed, with a focus on the publication dates between 1954 and 2012. Research of references was also performed and 78 studies were retrieved and used for the needs of this review. Results. A summary of several antipsychotics as well as frequency rates and data on hyperprolactinaemia and menstrual disorders for different agent is presented. Conclusion. Diverse prevalence rates of hyperprolactinaemia and menstrual abnormalities have been found about each medication among different studies. Menstruation plays an important role for women, thus, understanding, careful assessment, and management of hyperprolactinaemia could enhance their lives, especially when dealing with women that suffer from a psychotic disorder. 1. Introduction Acute psychotic episodes as well as psychotic relapses are treated effectively with antipsychotic drugs. Most patients with confirmed diagnoses of psychiatric disorders need to undergo antipsychotic drug therapy throughout their whole lives [1, 2]. Typical antipsychotic medications and some of the novel antipsychotics frequently cause an elevation of plasma prolactin levels. Among the several side reactions related with hyperprolactinaemia, are menstrual disorders such as amenorrhea or oligomenorrhea which have not been adequately evaluated. Menstrual dysfunction can be an important source of distress for women, as it influences their libido and fertility [1] and, thus, interferes with their quality of life, a consequence that should be taken into account by clinicians when antipsychotic treatment for each woman is chosen. This review aims to summarize the effects of antipsychotic agents on prolactin levels and menstruation and investigate the frequency of hyperprolactinaemia and menstrual abnormalities that affect female patients, depending on the selected antipsychotic therapy. It also indicates the need for further research on these adverse effects, the severity of which is not always reported in a clinically meaningful way to experts. 2. Background 2.1. How Do Antipsychotics Lead to Hyperprolactinaemia? A great number of studies have investigated antipsychotic medication and its important effects on human
References
[1]
R. A. Dickson and W. M. Glazer, “Neuroleptic-induced hyperprolactinaemia,” Schizophrenia Research, no. 35, pp. 575–586, 1999.
[2]
J. Peuskens, P. Sienaert, and M. de Hert, “Sexual dysfunction: the unspoken side effect of antipsychotics,” European Psychiatry, vol. 13, no. 1, pp. 23–30, 1998.
[3]
H. Knegtering, A. E. G. M. van der Moolen, S. Castelein, H. Kluiter, and R. J. van den Bosch, “What are the effects of antipsychotics on sexual dysfunctions and endocrine functioning?” Psychoneuroendocrinology, vol. 28, no. 2, pp. 109–123, 2003.
[4]
C. M. Canuso, J. M. Goldstein, J. Wojcik et al., “Antipsychotic medication, prolactin elevation, and ovarian function in women with schizophrenia and schizoaffective disorder,” Psychiatry Research, vol. 111, no. 1, pp. 11–20, 2002.
[5]
S. Brunelleschi, P. Zeppegno, F. Risso, C. I. Cattaneo, and E. Torre, “Risperidone-associated hyperprolactinemia: evaluation in twenty psychiatric outpatients,” Pharmacological Research, vol. 48, no. 4, pp. 405–409, 2003.
[6]
B. J. Kinon, J. A. Gilmore, H. Liu, and U. M. Halbreich, “Prevalence of hyperprolactinemia in schizophrenic patients treated with conventional antipsychotic medications or risperidone,” Psychoneuroendocrinology, vol. 28, no. 2, pp. 55–68, 2003.
[7]
B.-H. Lee and Y.-K. Kim, “The relationship between prolactin response and clinical efficacy of risperidone in acute psychotic inpatients,” Progress in Neuro-Psychopharmacology and Biological Psychiatry, vol. 30, no. 4, pp. 658–662, 2006.
[8]
M. J. Fell, J. C. Neill, and K. M. Marshall, “Effects of the classical antipsychotic haloperidol and atypical antipsychotic risperidone on weight gain, the oestrous cycle and uterine weight in female rats,” European Neuropsychopharmacology, vol. 14, no. 5, pp. 385–392, 2004.
[9]
U. Halbreich, B. J. Kinon, J. A. Gilmore, and L. S. Kahn, “Elevated prolactin levels in patients with schizophrenia: mechanisms and related adverse effects,” Psychoneuroendocrinology, vol. 28, no. 1, pp. 53–67, 2003.
[10]
V. K. B. Prabhakar and J. R. E. Davis, “Hyperprolactinaemia,” Best Practice and Research in Clinical Obstetrics and Gynaecology, vol. 22, no. 2, pp. 341–353, 2008.
[11]
P. G. Crosignani, “Current treatment issues in female hyperprolactinaemia,” European Journal of Obstetrics Gynecology and Reproductive Biology, vol. 125, no. 2, pp. 152–164, 2006.
[12]
H. Rosengarten and D. Quartermain, “The effect of chronic treatment with typical and atypical antipsychotics on working memory and jaw movements in three- and eighteen-month-old rats,” Progress in Neuro-Psychopharmacology and Biological Psychiatry, vol. 26, no. 6, pp. 1047–1054, 2002.
[13]
S. Melmed, The Pituitary, Blackwell Science, Cambridge, Mass, USA, 1995.
[14]
A. M. Meaney and V. O'Keane, “Prolactin and schizophrenia: clinical consequences of hyperprolactinaemia,” Life Sciences, vol. 71, no. 9, pp. 979–992, 2002.
[15]
H. S. Ripley and G. N. Papanikolaou, “The menstrual cycle with vaginal smear studies in schizophrenia, depression and elation,” American Journal of Psychiatry, vol. 98, pp. 567–573, 1942.
[16]
B. A. J. C. Gregory, “The menstrual cycle and its disorders in psychiatric patients-II. Clinical studies,” Journal of Psychosomatic Research, vol. 2, no. 3, pp. 199–224, 1957.
[17]
W. Magharious, D. C. Goff, and E. Amico, “Relationship of gender and menstrual status to symptoms and medication side effects in patients with schizophrenia,” Psychiatry Research, vol. 77, no. 3, pp. 159–166, 1998.
[18]
M. L. Barron, L. H. Flick, C. A. Cook, S. M. Homan, and C. Campbell, “Associations between psychiatric disorders and menstrual cycle characteristics,” Archives of Psychiatric Nursing, vol. 22, no. 5, pp. 254–265, 2008.
[19]
J. Aston, E. Rechsteiner, N. Bull, S. Borgwardt, U. Gschwandtner, and A. Riecher-R？ssler, “Hyperprolactinaemia in early psychosis-not only due to antipsychotics,” Progress in Neuro-Psychopharmacology and Biological Psychiatry, vol. 34, no. 7, pp. 1342–1344, 2010.
[20]
H. Y. Meltzer, E. J. Sachar, and A. G. Frantz, “Serum prolactin levels in unmedicated schizophrenic patients,” Archives of General Psychiatry, vol. 31, no. 4, pp. 564–569, 1974.
[21]
D. Owerbach, W. J. Rutter, and N. E. Cooke, “The prolactin gene is located on chromosome 6 in humans,” Science, vol. 212, no. 4496, pp. 815–816, 1981.
[22]
J. R. Davis, “Prolactin and reproductive medicine,” Current Opinion in Obstetrics and Gynecology, vol. 16, no. 4, pp. 331–337, 2004.
[23]
F. F. Casanueva, M. E. Molitch, J. A. Schlechte et al., “Guidelines of the Pituitary Society for the diagnosis and management of prolactinomas,” Clinical Endocrinology, vol. 65, no. 2, pp. 265–273, 2006.
[24]
S. D. Harlow, “Menstruation and menstrual disorders: the epidemiology of menstruation and menstrual dysfunction,” in Women and Health, M. B. Goldmam and M. C. Hatch, Eds., pp. 99–113, Academic Press, San Diego, Calif, USA, 2000.
[25]
L. Seshadri, S. John, S. S. George, and M. S. Seshardi, “Endocrine profile of women with amenorrhea and oligomenorrhea,” International Journal of Gynecology and Obstetrics, vol. 45, no. 3, pp. 247–255, 1995.
[26]
J. Skull, “Amenorrhoea,” Current Obstetrics and Gynaecology, vol. 11, no. 4, pp. 225–232, 2001.
[27]
C. Bushe, M. Shaw, and R. C. Peveler, “A review of the association between antipsychotic use and hyperprolactinaemia,” Journal of Psychopharmacology, vol. 22, no. 2, pp. 46–55, 2008.
[28]
J. Montgomery, E. Winterbottom, M. Jessani et al., “Prevalence of hyperprolactinemia in schizophrenia: association with typical and atypical antipsychotic treatment,” Journal of Clinical Psychiatry, vol. 65, no. 11, pp. 1491–1498, 2004.
[29]
W. Z. Polishuk and S. Kulcsar, “Effects of chlorpromazine on pituitary function,” Clinical Endocrinology, vol. 16, pp. 292–293, 1956.
[30]
P. J. V. Beaumont, M. G. Gelder, H. G. Friesen et al., “The effects of phenotheiazines on endocrine function: I,” The British Journal of Psychiatry, vol. 124, pp. 413–419, 1974.
[31]
A. M. Ghadirian, G. Chouinard, and L. Annable, “Sexual dysfunction and plasma prolactin levels in neuroleptic-treated schizophrenic outpatients,” Journal of Nervous and Mental Disease, vol. 170, no. 8, pp. 463–467, 1982.
[32]
J. P. Santoni and S. Saubadu, “Adverse events associated with neuroleptic drugs: focus on neuroendocrine reactions,” Acta Therapeutica, vol. 21, no. 3-4, pp. 193–204, 1995.
[33]
M. I. Crismon and P. G. Dorson, “Schizophrenia,” in Pharmacotherapy: A Pathophysiologic Approach, J. T. DiPiro, R. L. Talbert, G. C. Yee, G. R. Matzke, B. G. Wells, and L. M. Posey, Eds., pp. 1367–1394, Appleton and Lange, Standord, Conn, USA, 3rd edition, 1997.
[34]
P. A. Marken, R. F. Haykal, and J. N. Fisher, “Management of psychotropic-induced hyperprolactinemia,” Clinical Pharmacy, vol. 11, no. 10, pp. 851–856, 1992.
[35]
K. Sawamura, Y. Suzuki, N. Fukui, T. Sugai, and T. Someya, “Gender differences in prolactin elevation induced by olanzapine in Japanese drug-na？ve schizophrenic patients,” Progress in Neuro-Psychopharmacology and Biological Psychiatry, vol. 30, no. 8, pp. 1511–1514, 2006.
[36]
P. M. Haddad and A. Wieck, “Antipsychotic-induced hyperprolactinaemia: mechanisms, clinical features and management,” Drugs, vol. 64, no. 20, pp. 2291–2314, 2004.
[37]
J. Wong and M. V. Seeman, “Prolactin, menstrual irregularities, quality of life,” Schizophrenia Research, vol. 91, no. 1–3, pp. 270–271, 2007.
[38]
J. L. de Rivera, S. Lal, and P. Ettigi, “Effect of acute and chronic neuroleptic therapy on serum prolactin levels in men and women of different age groups,” Clinical Endocrinology, vol. 5, no. 3, pp. 273–282, 1976.
[39]
D.-U. Jung, Y.-S. Seo, J.-H. Park et al., “The prevalence of hyperprolactinemia after long-term haloperidol use in patients with chronic schizophrenia,” Journal of Clinical Psychopharmacology, vol. 25, no. 6, pp. 613–615, 2005.
[40]
S. M. Smith, M. J. Wheeler, V. O’Keane, and R. Murray, “Antipsychotics an Hypogonadism in patients with schizophrenia,” Schizophrenia Research, vol. 41, no. 1, article 218, 2000.
[41]
M. Spitzer, R. Sajjad, and F. Benjamin, “Pattern of development of hyperprolactinemia after initiation of haloperidol therapy,” Obstetrics and Gynecology, vol. 91, no. 5, part 1, pp. 693–695, 1998.
[42]
A. M. K. Crawford, C. M. Beasley Jr., and G. D. Tollefson, “The acute and long-term effect of olanzapine compared with placebo and haloperidol on serum prolactin concentrations,” Schizophrenia Research, vol. 26, no. 1, pp. 41–54, 1997.
[43]
H. Y. Meltzer, D. A. Busch, and V. S. Fang, “Serum neuroleptic and prolactin levels in schizophrenic patients and clinical response,” Psychiatry Research, vol. 9, no. 4, pp. 271–283, 1983.
[44]
R. M. Nonacs, “Antipsychotic treatment and menstrual irregularity,” in Proceedings of the 153rd Annual Meeting of the American Psychiatric Association, pp. 13–18, Chicago, Ill, USA, May 2000.
[45]
D. L. Kleinberg, J. M. Davis, R. de Coster, B. van Baelen, and M. Brecher, “Prolactin levels and adverse events in patients treated with risperidone,” Journal of Clinical Psychopharmacology, vol. 19, no. 1, pp. 57–61, 1999.
[46]
A. E. Kearns, D. C. Goff, D. L. Hayden, and G. H. Daniels, “Risperidone-associated hyperprolactinemia,” Endocrine Practice, vol. 6, no. 6, pp. 425–429, 2000.
[47]
S. R. David, C. C. Taylor, B. J. Kinon, and A. Breier, “The effects of olanzapine, risperidone, and haloperidol on plasma prolactin levels in patients with schizophrenia,” Clinical Therapeutics, vol. 22, no. 9, pp. 1085–1096, 2000.
[48]
S. Madhusoodanan, S. Parida, and C. Jimenez, “Hyperprolactinemia associated with psychotropics—a review,” Human Psychopharmacology, vol. 25, no. 4, pp. 281–297, 2010.
[49]
C. Bushe and M. Shaw, “Prevalence of hyperprolactinaemia in a naturalistic cohort of schizophrenia and bipolar outpatients during treatment with typical and atypical antipsychotics,” Journal of Psychopharmacology, vol. 21, no. 7, pp. 768–773, 2007.
[50]
D. Feldman and J. F. Goldberg, “A preliminary study of the relationship between clozapine-induced weight gain and menstrual irregularities in schizophrenic, schizoaffective, and bipolar women,” Annals of Clinical Psychiatry, vol. 14, no. 1, pp. 17–21, 2002.
[51]
A. F. Breier, A. K. Malhotra, T.-P. Su et al., “Clozapine and risperidone in chronic schizophrenia: effects on symptoms, parkinsonian side effects, and neuroendocrine response,” American Journal of Psychiatry, vol. 156, no. 2, pp. 294–298, 1999.
[52]
R. Knegtering, P. Baselmans, S. Castelein, F. Bosker, R. Bruggeman, and R. J. Van den Bosch, “Predominant role of the 9-hydroxy metabolite of risperidone in elevating blood prolactin levels,” American Journal of Psychiatry, vol. 162, no. 5, pp. 1010–1012, 2005.
[53]
M. Skopek and P. Manoj, “Hyperprolactinaemia during treatment with paliperidone,” Australasian Psychiatry, vol. 18, no. 3, pp. 261–263, 2010.
[54]
S. Kapur, R. B. Zipursky, G. Remington et al., “5-HT2 and D2 receptor occupancy of olanzapine in schizophrenia: a PET investigation,” American Journal of Psychiatry, vol. 155, no. 7, pp. 921–928, 1998.
[55]
K. Melkersson, “Differences in prolactin elevation and related symptoms of atypical antipsychotics in schizophrenic patients,” Journal of Clinical Psychiatry, vol. 66, no. 6, pp. 761–767, 2005.
[56]
B. J. Kinon, J. Ahl, H. Liu-Seifert, and G. A. Maguire, “Improvement in hyperprolactinemia and reproductive comorbidities in patients with schizophrenia switched from conventional antipsychotics or risperidone to olanzapine,” Psychoneuroendocrinology, vol. 31, no. 5, pp. 577–588, 2006.
[57]
H. Takahashi, H. Higuchi, M. Kamata et al., “Effectiveness of switching to quetiapine for neuroleptic-induced amenorrhea,” Journal of Neuropsychiatry and Clinical Neurosciences, vol. 15, no. 3, pp. 375–377, 2003.
[58]
J. M. Kane, H. Y. Meltzer, W. H. Carson Jr., R. D. McQuade, R. N. Marcus, and R. Sanchez, “Aripiprazole for treatment-resistant schizophrenia: results of a multicenter, randomized, double-blind, comparison study versus perphenazine,” Journal of Clinical Psychiatry, vol. 68, no. 2, pp. 213–223, 2007.
[59]
M. Saitis, G. Papazisis, K. Katsigiannopoulos, and D. Kouvelas, “Aripiprazole resolves amisulpride and ziprasidone-induced hyperprolactinemia,” Psychiatry and Clinical Neurosciences, vol. 62, no. 5, article 624, 2008.
[60]
M. Kopecek, M. Bares, J. Svarc, C. Dockery, and J. Horácek, “Hyperprolactinemia after low dose of amisulpride,” Neuroendocrinology Letters, vol. 25, no. 6, pp. 419–422, 2004.
[61]
S. Kapur, X. Langlois, P. Vinken, A. A. H. P. Megens, R. de Coster, and J. S. Andrews, “The differential effects of atypical antipsychotics on prolactin elevation are explained by their differential blood-brain disposition: a pharmacological analysis in rats,” Journal of Pharmacology and Experimental Therapeutics, vol. 302, no. 3, pp. 1129–1134, 2002.
[62]
T. Paparrigopoulos, J. Liappas, E. Tzavellas, I. Mourikis, and C. Soldatos, “Amisulpride-induced hyperprolactinemia is reversible following discontinuation,” Progress in Neuro-Psychopharmacology and Biological Psychiatry, vol. 31, no. 1, pp. 92–96, 2007.
[63]
B.-H. Lee, S.-G. Kang, T.-W. Kim, H.-J. Lee, H.-K. Yoon, and Y.-M. Park, “Hyperprolactinemia induced by low-dosage amisulpride in Korean psychiatric patients,” Psychiatry and Clinical Neurosciences, vol. 66, no. 1, pp. 69–73, 2012.
[64]
K.-Y. Mak and S. T.-K. Lai, “Use of amisulpride in a psychiatric outpatient clinic in Hong Kong,” Hong Kong Journal of Psychiatry, vol. 14, no. 2, pp. 2–27, 2004.
[65]
R. Rajnish and S. B. Singh, “Hyperprolactinaemia with amisulpride,” Indian Journal of Psychiatry, vol. 50, no. 1, pp. 54–56, 2008.
[66]
D. C. Goff, T. Posever, L. Herz et al., “An exploratory haloperidol-controlled dose-finding study of ziprasidone in hospitalized patients with schizophrenia or schizoaffective disorder,” Journal of Clinical Psychopharmacology, vol. 18, no. 4, pp. 296–304, 1998.
[67]
F.-G. Sun, R.-L. Dong, Z. Zhao, and M. Pan, “Efficacy and adverse reactions of ziprasidone in 30 female patients with schizophrenia,” Chinese Journal of New Drugs and Clinical Remedies, vol. 5, 2009.
[68]
K. Otani, T. Kondo, S. Kaneko, M. Ishida, and Y. Fukushima, “Correlation between prolactin response and therapeutic effects of zotepine in schizophrenic patients,” International Clinical Psychopharmacology, vol. 9, no. 4, pp. 287–289, 1994.
[69]
U. Von Bardeleben, O. Benkert, and F. Holsboer, “Clinical and neuroendocrine effects of zotepine—a new neuroleptic drug,” Pharmacopsychiatry, vol. 20, no. 1, pp. 28–34, 1987.
[70]
M. C. E. Do Amaral, E. Hardy, E. M. Hebling, and A. Faúndes, “Menstruation and amenorrhea: opinion of Brazilian women,” Contraception, vol. 72, no. 2, pp. 157–161, 2005.
[71]
E. Hardy, E. M. Hebling, M. H. de Sousa, E. Kneuper, and R. Snow, “Association between characteristics of current menses and preference for induced amenorrhea,” Contraception, vol. 80, no. 3, pp. 266–269, 2009.
[72]
W. L. Ledger and J. Skull, “Amenorrhoea: investigation and treatment,” Current Obstetrics and Gynaecology, vol. 14, no. 4, pp. 254–260, 2004.
[73]
A. F. Glasier, K. B. Smith, Z. M. van der Spuy et al., “Amenorrhea associated with contraception—an international study on acceptability,” Contraception, vol. 67, no. 1, pp. 1–8, 2003.
[74]
S. Ferrero, L. H. Abbamonte, M. Giordano et al., “What is the desired menstrual frequency of women without menstruation-related symptoms?” Contraception, vol. 73, no. 5, pp. 537–541, 2006.
[75]
V. Leite, H. Cosby, L. G. Sobrinho, A. Fresnoza, M. A. Santos, and H. G. Friesen, “Characterization of big, big prolactin in patients with hyperprolactinaemia,” Clinical Endocrinology, vol. 37, no. 4, pp. 365–372, 1992.
[76]
B. J. Kinon, B. R. Basson, J. A. Gilmore, S. Malcolm, and V. L. Stauffer, “Strategies for switching from conventional antipsychotic drugs or risperidone to olanzapine,” Journal of Clinical Psychiatry, vol. 61, no. 11, pp. 833–840, 2000.
[77]
G. B. Cassano, A. Fagiolini, L. Lattanzi et al., “Aripiprazole in the treatment of schizophrenia: a consensus report produced by schizophrenia experts in Italy,” Clinical Drug Investigation, vol. 27, no. 1, pp. 1–13, 2007.
[78]
J. Peuskens, A Literature Review of Prolactin in Schizophrenia, AstraZeneca, 1998.
