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Antipsychotic-Induced Hyperprolactinaemia

Mechanisms, Clinical Features and Management

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Abstract

Hyperprolactinaemia is an important but neglected adverse effect of antipsychotic medication. It occurs frequently with conventional antipsychotics and some atypical antipsychotics (risperidone and amisulpride) but is rare with other atypical antipsychotics (aripiprazole, clozapine, olanzapine, quetiapine, ziprasidone). For this reason the terms ‘prolactin-sparing’ and ‘prolactin-raising’ are more useful than ‘atypical’ and ‘conventional’ when considering the effect of antipsychotic drugs on serum prolactin.

During antipsychotic treatment prolactin levels can rise 10-fold or more above pretreatment values. In a recent study approximately 60% of women and 40% of men treated with a prolactin-raising antipsychotic had a prolactin level above the upper limit of the normal range. The distinction between asymptomatic and symptomatic hyperprolactinaemia is important but is often not made in the literature. Some symptoms of hyperprolactinaemia result from a direct effect of prolactin on target tissues but others result from hypogonadism caused by prolactin disrupting the normal functioning of the hypothalamic-pituitary-gonadal axis.

Symptoms of hyperprolactinaemia include gynaecomastia, galactorrhoea, sexual dysfunction, infertility, oligomenorrhoea and amenorrhoea. These symptoms are little researched in psychiatric patients. Existing data suggest that they are common but that clinicians underestimate their prevalence. For example, well conducted studies of women treated with conventional antipsychotics have reported prevalence rates of approximately 45% for oligomenorrhoea/amenorrhoea and 19% for galactorrhoea. An illness-related under-function of the hypothalamic-pituitary-gonadal axis in female patients with schizophrenia may also contribute to menstrual irregularities. Long-term consequences of antipsychotic-related hypogonadism require further research but are likely and include premature bone loss in men and women. There are conflicting data on whether hyperprolactinaemia is associated with an increased risk of breast cancer in women.

In patients prescribed antipsychotics who have biochemically confirmed hyperprolactinaemia it is important to exclude other causes of prolactin elevation, in particular tumours in the hypothalamic-pituitary area. If a patient has been amenorrhoeic for 1 year or more, investigations should include bone mineral density measurements. Management should be tailored to the individual patient. Options include reducing the dose of the antipsychotic, switching to a prolactin-sparing agent, prescribing a dopamine receptor agonist and prescribing estrogen replacement in hypoestrogenic female patients. The efficacy and risks of the last two treatment options have not been systematically examined.

Antipsychotic-induced hyperprolactinaemia should become a focus of interest in the drug treatment of psychiatric patients, particularly given the recent introduction of prolactin-sparing antipsychotics. Appropriate investigations and effective management should reduce the burden of adverse effects and prevent long-term consequences.

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References

  1. Beumont PJV, Gelder MG, Friesen HG, et al. The effects of phenothiazines on endocrine function: I. Patients with inappropriate lactation and amenorrhoea. Br J Psychiatry 1974; 124: 413–9

    CAS  Google Scholar 

  2. Hellewell JSE. Antipsychotic tolerability: the attitudes and perceptions of medical professionals, patients and caregivers towards side-effects of antipsychotic therapy [abstract]. Eur Neuropsychopharmacol 1998; 8: S248

    Google Scholar 

  3. Veldhuis JD, Johnson ML. Operating characteristics of the hypothalamo-pituitary-gonadal axis in men: circadian, ultradian, and pulsatile release of prolactin and its temporal coupling with luteinizing hormone. J Clin Endocrinol Metab 1988; 67: 116–23

    Article  PubMed  CAS  Google Scholar 

  4. Frantz AG. Prolactin. N Engl J Med 1978; 198: 201–7

    Article  Google Scholar 

  5. Molitch ME. Prolactin. In: Melmed S, editor. The pituitary. Cambridge (MA): Blackwell Science, 1995: 136–86

    Google Scholar 

  6. Bevan JS. Interpreting prolactin levels: implications for the management of large pituitary lesions. Br J Neurosurg 1991; 5: 3–6

    Article  PubMed  CAS  Google Scholar 

  7. Marken PA, Haykal RF, Fisher JN. Management of psychotropic-induced hyperprolactinaemia. Clin Pharm 1992; 11: 851–6

    PubMed  CAS  Google Scholar 

  8. Lenton EA, Brook LM, Sobowale O, et al. Prolactin concentrations in normal menstrual cycles and conception cycles. Clin Endocrinol (Oxf) 1979; 10: 383–91

    Article  CAS  Google Scholar 

  9. Liddle GW, Liddle LA. Endocrinology. In: Smith LH, Their SO, editors. The biological principles of disease. Philadelphia (PA): Saunders, 1981: 653–754

    Google Scholar 

  10. Freeman ME, Kanyicska B, Lerant A, et al. Prolactin: structure, function and regulation of secretion. Physiol Rev 2000; 80: 1523–31

    PubMed  CAS  Google Scholar 

  11. Gudelsky GA. Tuberoinfundibular dopamine neurons and the regulation of prolactin secretion. Psychoneuroendocrinology 1981; 6: 3–16

    Article  PubMed  CAS  Google Scholar 

  12. Tuomisto J, Mannisto P. Neurotransmitter regulation of anterior pituitary hormones. Pharmacol Rev 1985; 37: 249–301

    PubMed  CAS  Google Scholar 

  13. Arita J, Kimura F. Direct inhibitory effect of long term estradiol treatment on dopamine synthesis in tuberoinfundibular dopa-minergic neurons: in vitro studies using hypothalamic slices. Endocrinology 1987; 121: 692–8

    Article  PubMed  CAS  Google Scholar 

  14. Kukstas LA, Domec C, Bascles L, et al. Different expression of the two dopaminergic D2 receptors, D2415 and D2444, in two types of lactotroph each characterised by their response to dopamine, and modification of expression by sex steroids. Endocrinology 1991; 129: 1101–3

    Article  PubMed  CAS  Google Scholar 

  15. Cavagnini F, Benetti G, Invitti C, et al. Effects of gamma amino butyric acid on growth hormone and prolactin secretion in man; influence of pimozide and domperidone. J Clin Endocrinol Metab 1980; 51: 789–92

    Article  PubMed  CAS  Google Scholar 

  16. Rao ML, Gross G, Halaris A, et al. Hyperdopaminergia in schizophreniform psychosis: a chronobiological study. Psychiatry Res 1993; 47: 187–203

    Article  PubMed  CAS  Google Scholar 

  17. Rao ML, Gross G, Strebel B, et al. Circadian rhythm of tryptophan, serotonin, melatonin, and pituitary hormones in schizophrenia. Biol Psychiatry 1994; 35: 151–63

    Article  PubMed  CAS  Google Scholar 

  18. Meltzer HY, Sachar EJ, Frantz AG. Serum prolactin levels in unmedicated schizophrenic patients. Arch Gen Psychiatry 1974; 31: 564–9

    Article  PubMed  CAS  Google Scholar 

  19. Keks NA, Copolov DL, Singh BS. Abnormal prolactin response to haloperidol challenge in men with schizophrenia. Am J Psychiatry 1987; 144: 1335–7

    PubMed  CAS  Google Scholar 

  20. Kuruvilla A, Peedicayil J, Srikrishna G, et al. A study of serum prolactin levels in schizophrenia: comparison of males and females. Clin Exp Pharmacol Physiol 1992; 19: 603–6

    Article  PubMed  CAS  Google Scholar 

  21. Linkwork P, Van Acuter E, L’Hermite-Baleriaux M, et al. The 24-hour profile of plasma prolactin in men with major endogenous depressive illness. Arch Gen Psychiatry 1989; 46: 813–9

    Article  Google Scholar 

  22. Beck-Friis J, Ljunggren JG, Thoren M, et al. Melatonin,cortisol and ACTH in patients with major depressive disorder and healthy humans with special reference to the outcome of the dexamethasone suppression test. Psychoneuroendocrinology 1985; 10: 173–86

    Article  PubMed  CAS  Google Scholar 

  23. Goetze U, Tolle R. Circadian rhythm of free urinary cortisol, temperature and heart rate in endogenous depressives and under antidepressant therapy. Neuropsychobiology 1987; 18: 175–84

    Article  PubMed  CAS  Google Scholar 

  24. Meltzer HY, Fang VS. The effect of neuroleptics on serum prolactin in schizophrenic patients. Arch Gen Psychiatry 1976; 33: 279–86

    Article  PubMed  CAS  Google Scholar 

  25. Gruen PH, Sachar EJ, Altman N, et al. Relation of plasma prolactin to clinical response in schizophrenic patients. Arch Gen Psychiatry 1978; 35: 1222–7

    Article  PubMed  CAS  Google Scholar 

  26. Oseko F, Morikawa K, Motohashi T, et al. Effects of chronic sulpiride-induced hyperprolactinemia on menstrual cycles of normal women. Obstet Gynecol 1988; 72: 267–71

    PubMed  CAS  Google Scholar 

  27. Kuruvilla A, Peedicayil J, Srikrishna G, et al. A study of serum prolactin levels in schizophrenia: comparison of males and females. Clin Exp Pharmacol Physiol 1992; 19: 603–6

    Article  PubMed  CAS  Google Scholar 

  28. Arvanitis LA, Miller BG, and the Seroquel Trial 13 Study Group. Multiple fixed doses of ‘Seroquel’ (quetiapine) in patients with acute exacerbations of schizophrenia: a comparison with haloperidol and placebo. Biol Psychiatry 1997; 42: 233–46

    Article  PubMed  CAS  Google Scholar 

  29. Crawford AM, Beasley Jr CM, Tollefson GD. The acute and long-term effect of olanzapine compared with placebo and haloperidol on serum prolactin concentrations. Schizophr Res 1997; 26: 41–54

    Article  PubMed  CAS  Google Scholar 

  30. Meltzer HY, Kane JM, Kolakowska T. Plasma levels of neuroleptics, prolactin levels, and clinical response. In: Coyle JT, Enna SJ, editors. Neuroleptics: neurochemical, behavioural and clinical perspectives. New York: Raven Press, 1983: 255–79

    Google Scholar 

  31. Green AL, Brown WA. Prolactin and neuroleptic drugs. Endocrinol Metab Clin North Am 1988; 17: 213–23

    PubMed  CAS  Google Scholar 

  32. Smith S, Wheeler MJ, Murray R, et al. The effects of anti-psychotic-induced hyperprolactinaemia on the hypothalamic-pituitary-gonadal axis. J Clin Psychopharmacol 2002; 22: 109–14

    Article  PubMed  CAS  Google Scholar 

  33. Brown WA, Laughren T. Tolerance to the prolactin-elevating effect of neuroleptics. Psychiatry Res 1981; 5: 317–22

    Article  PubMed  CAS  Google Scholar 

  34. Checkley S. Neuroendocrine effects of psychotropic drugs. Baillieres Clin Endocrinol Metab 1991; 5(1): 15–33

    Article  PubMed  CAS  Google Scholar 

  35. Rivera JL, Lal S, Ettigi P, et al. Effect of acute and chronic neuroleptic therapy on serum prolactin levels in men and women of different age groups. Clin Endocrinol 1976; 5: 273–82

    Article  CAS  Google Scholar 

  36. Zelaschi NM, Delucchi GA, Rodriguez JL. High plasma prolactin levels after long-term neuroleptic treatment. Biol Psychiatry 1996; 39: 900–1

    Article  PubMed  CAS  Google Scholar 

  37. Kinon B, Gilmore JA, Liu H, et al. Prevalence of hyperprolactinemia in schizophrenic patients treated with conventional antipsychotic medications or risperidone. Psychoendocrinology 2003; 28 Suppl. 2: 55–68

    Article  CAS  Google Scholar 

  38. Smith SM, O’Keane V, Murray R, et al. Sexual dysfunction in patients taking conventional antipsychotic medication. Br J Psychiatry 2002; 181: 49–55

    Article  PubMed  CAS  Google Scholar 

  39. Langer G, Sachar EJ. Dopaminergic factors in human prolactin regulation: effects of neuroleptics and dopamine. Psychoneuroendocrinology 1997; 2: 373–8

    Article  Google Scholar 

  40. Turkington RW. Prolactin secretion in patients treated with various drugs. Arch Intern Med 1972; 130: 349–54

    Article  PubMed  CAS  Google Scholar 

  41. Wistedt B, Wiles D, Kolakowska T. Slow decline of plasma drug and prolactin levels after discontinuation of chronic treatments with depot neuroleptics [letter]. Lancet 1981; I: 1 63

  42. Meltzer HY, Goode DJ, Schyve PM, et al. Effect of clozapine on human serum prolactin levels. Am J Psychiatry 1979; 136: 1550–5

    PubMed  CAS  Google Scholar 

  43. Small JG, Hirsch SR, Arvanitis LA, et al. Quetiapine in patients with schizophrenia: a high- and low-dose double-blind comparison with placebo. Arch Gen Psychiatry 1997; 54: 549–57

    Article  PubMed  CAS  Google Scholar 

  44. Tollefson GD, Kuntz AJ. Review of recent clinical studies with olanzapine. Br J Psychiatry 1999; 174 Suppl. 37: 30–5

    Google Scholar 

  45. Peuskens J. Risperidone in the treatment of patients with chronic schizophrenia: a multi-national, multi-centre, double-blind, parallel-group study versus haloperidol. Br J Psychiatry 1995; 166: 712–26

    Article  PubMed  CAS  Google Scholar 

  46. Grander G, Wetzel H, Schloesser R, et al. Neuroendocrine response to antipsychotics: effects of drag type and gender. Biol Psychiatry 1999; 45: 89–97

    Article  Google Scholar 

  47. Kleinberg DL, Davis JM, De Coster R, et al. Prolactin levels and adverse effects in patients treated with risperidone. J Clin Psychopharmacol 1999; 19: 57–61

    Article  PubMed  CAS  Google Scholar 

  48. Breier AF, Malhotra AK, Tung-Ping S, et al. Clozapine and risperidone in chronic schizophrenia: effects on symptoms, parkinsonian side-effects, and neuroendocrine response. Am J Psychiatry 1999; 156: 294–8

    PubMed  CAS  Google Scholar 

  49. David SR, Taylor CC, Kinon BJ, et al. The effects of olanzapine, risperidone, and haloperidol on plasma prolactin levels in patients with schizophrenia. Clin Ther 2000; 22: 1085–96

    Article  PubMed  CAS  Google Scholar 

  50. Kim KS, Pae CU, Chae JH, et al. Effects of olanzapine on prolactin levels of female patients with schizophrenia treated with risperidone. J Clin Psychiatry 2002; 63: 408–13

    Article  PubMed  CAS  Google Scholar 

  51. Von Bardeleben U, Benkert O, Holsboer F. Clinical and neuroendocrine effects of zotepine: a new neuroleptic drug. Pharmacopsychiatry 1987; 20: 28–34

    Article  Google Scholar 

  52. Otani K, Kondo T, Kaneko S, et al. Correlation between prolactin response and therapeutic effects of zotepine in schizophrenic patients. Int Clin Psychopharmacol 1994; 9: 287–9

    Article  PubMed  CAS  Google Scholar 

  53. Kondo T, Otani K, Ishida M, et al. Adverse effects of zotepine and their relationship to serum concentrations of the drug and prolactin. Ther Drag Monit 1994; 16: 120–4

    Article  CAS  Google Scholar 

  54. Goff DC, Posever T, Herz L, et al. An exploratory haloperidol-controlled dose-finding study of ziprasidone in hospitalized patients with schizophrenia or schizoaffective disorder. J Clin Psychopharmacol 1998; 18: 296–304

    Article  PubMed  CAS  Google Scholar 

  55. Miceli JJ, Wilner KD, Hansen RA, et al. Single- and multiple-dose pharmacokinetics of ziprasidone under non-fasting conditions in healthy male volunteers. Br J Clin Pharmacol 2000; 49 Suppl. 1: 5S–13S

    Article  PubMed  CAS  Google Scholar 

  56. Goodnick PJ, Jerry JM. Aripiprazole; profile on efficacy and safety. Expert Opin Pharmacother 2002; 3: 1773–81

    Article  PubMed  CAS  Google Scholar 

  57. McGavin JK, Goa KL. Aripiprazole. CNS Drags 2002; 16: 779–86

    Article  CAS  Google Scholar 

  58. Kane JM, Carson WH, Saha AR, et al. Efficacy and safety of aripiprazole and haloperidol versus placebo in patients with schizophrenia and schizoaffective disorder. J Clin Psychiatry 2002; 63: 763–71

    Article  PubMed  CAS  Google Scholar 

  59. Kohler C, Karlsson-Boethius G. In vivo labelling of pituitary dopamine D2 receptors in the male rat using [3H]-raclopride. J Neural Transm 1989; 76: 13–28

    Article  PubMed  CAS  Google Scholar 

  60. Baron JC, Martinot JL, Cambon H, et al. Striatal dopamine receptor occupancy during and following withdrawal from neuroleptic treatment: correlative evaluation by positron emission tomography and plasma prolactin levels. Psychopharmacology 1989; 99: 463–72

    Article  PubMed  CAS  Google Scholar 

  61. Nordstrom AL, Farde L. Plasma prolactin and central D2 receptor occupancy in antipsychotic drug-treated patients. J Clin Psychopharmacol 1998; 18: 305–10

    Article  PubMed  CAS  Google Scholar 

  62. Kapur S, Zipursky R, Jones C, et al. Relationship between dopamine D2 occupancy, clinical response, and side effects: a double-blind PET study of first-episode schizophrenia. Am J Psychiatry 2000; 157: 514–20

    Article  PubMed  CAS  Google Scholar 

  63. Farde L, Nordstrom AL, Wiesel FA, et al. Positron emission tomographic analysis of central D1 and D2 dopamine receptor occupancy in patients treated with classical neuroleptics and clozapine. Arch Gen Psychiatry 1992; 49: 538–44

    Article  PubMed  CAS  Google Scholar 

  64. Nordstrom AL, Farde L, Nyberg S, et al. D1, D2, and 5-HT2 receptor occupancy in relation to clozapine serum concentration: a PET study of schizophrenic patients. Am J Psychiatry 1995; 152: 1444–9

    PubMed  CAS  Google Scholar 

  65. Gefvert O, Bergstrom M, Langstrom B, et al. Time course of central nervous dopamine-D2 and 5-HT2 receptor blockade and plasma drug concentrations after discontinuation of quetiapine (seroquel) in patients with schizophrenia. Psycho-pharmacology 1998; 135: 119–26

    CAS  Google Scholar 

  66. Kapur S, Zipursky RB, Remington G. Clinical and theoretical implications of 5-HT2 and D2 receptor occupancy of clozapine, risperidone, and olanzapine in schizophrenia. Am J Psychiatry 1999; 156: 286–93

    PubMed  CAS  Google Scholar 

  67. Pilowsky LS, Bussatto GF, Taylor M, et al. Dopamine D2 receptor occupancy in vivo by the novel atypical antipsychotic olanzapine: a 123I IBZM single photon emission tomography (SPET) study. Psychopharmacology 1996; 124: 148–53

    Article  PubMed  CAS  Google Scholar 

  68. Kapur S, Seeman P. Does fast dissociation from the dopamine d(2) receptor explain the action of atypical antipsychotics? A new hypothesis. Am J Psychiatry 2001; 158: 360–9

    Article  PubMed  CAS  Google Scholar 

  69. Van de Kar LD. Neuroendocrine pharmacology of serotonergic (5-HT) neurones. Annu Rev Pharmacol Toxicol 1991; 31: 289–320

    Article  PubMed  Google Scholar 

  70. Mizuchi A, Kitagawa N, Miyachi Y. Regional distribution of sultopride and sulpiride in rat brain measured by radioimmunoassay. Psychopharmacology 1983; 81: 195–8

    Article  PubMed  CAS  Google Scholar 

  71. Haddad P, Wieck A. Antidepressant induced hyperprolactinaemia [abstract]. J Psychopharmacol 2000; 14 Suppl. 3: A28

    Google Scholar 

  72. Wode-Helgodt B, Eneroth P, Fryo B, et al. Effect of chlorpromazine treatment on prolactin levels in cerebrospinal fluid and plasma of psychotic patients. Acta Psychiatr Scand 1977; 56: 280–93

    Article  PubMed  CAS  Google Scholar 

  73. Davis JRE. Prolactin and related peptides in pregnancy. Baillieres Clin Endocrinol Metab 1990; 4: 273–90

    Article  PubMed  CAS  Google Scholar 

  74. Goode DJ, Meltzer HY, Fang VS. Increased serum prolactin levels during phenothiazine and butyrophenone treatment of six postpartum women. Psychoneuroendocrinology 1980; 5: 345–51

    Article  PubMed  CAS  Google Scholar 

  75. Wudarsky M, Nicolson R, Hamburger SD, et al. Elevated prolactin in paediatric patients on typical and atypical antipsy-chotics. J Child Adolesc Psychopharmacol 1999; 9: 239–45

    Article  PubMed  CAS  Google Scholar 

  76. Shaw JA, Lewis JE, Pascal S, et al. A study of quetiapine: efficacy and tolerability in psychotic adolescents. J Child Adolesc Psychopharmacol 2001; 11: 415–24

    Article  PubMed  CAS  Google Scholar 

  77. Kaneda Y, Fujii A. Effects of chronic neuroleptic administration on the hypothalamo-pituitary-gonadal axis of male schizophrenics. Prog Neuropsychopharmacol Biol Psychiatry 2000; 24: 251–8

    Article  PubMed  CAS  Google Scholar 

  78. Bole-Feysot C, Goffin V, Edery M, et al. Prolactin (PRL) and its receptor: actions, signal transduction pathways and phenotypes observed in PRL receptor knockout mice. Endocr Rev 1998; 9: 225–68

    Article  Google Scholar 

  79. Sobrinho LG. The psychogenic effects of prolactin. Acta Endocrinol 1993; 29 Suppl. 1: 38–40

    Google Scholar 

  80. Reavley A, Fisher AD, Owen D, et al. Psychological distress in patients with hyperprolactinaemia. Clin Endocrinol 1997; 47: 343–8

    Article  CAS  Google Scholar 

  81. Kaneda Y, Fujii A, Yamaoka T, et al. Neither gynaecomastia nor galactorrhea is a common side effect of neuroleptics in male patients. Neuroendocrinol Lett 2000; 21: 447–51

    PubMed  CAS  Google Scholar 

  82. Windgassen K, Wesselmann U, Schulze Monking H. Galactor-rhoea and hyperprolactinaemia in schizophrenic patients on neuroleptics: frequency and etiology. Neuropsychobiology 1996; 33: 142–6

    Article  PubMed  CAS  Google Scholar 

  83. Kaneda Y, Fujii A. Gynaecomastia with sulphide. J Clin Pharm Ther 2002; 27: 75–7

    Article  PubMed  CAS  Google Scholar 

  84. Haddad PM, Hellewell JSE, Wieck A. Antipsychotic-induced hyperprolactinaemia: a series of illustrative case reports. J Psychopharmacol 2001; 15: 293–5

    Article  PubMed  CAS  Google Scholar 

  85. Peters F, Del Pozo E, Conti A, et al. Inhibition of lactation by a long-acting bromocriptine. Obstet Gynecol 1986; 67: 82–5

    PubMed  CAS  Google Scholar 

  86. Wesselmann U, Windgassen K. Galactorrhea: subjective response by schizophrenic patients. Acta Psychiatr Scand 1995; 91: 152–5

    Article  PubMed  CAS  Google Scholar 

  87. Ghadirian AM, Chouinard G, Annable L. Sexual dysfunction and plasma prolactin levels in neuroleptic-treated schizophrenic outpatients. J Nerv Ment Dis 1982; 170: 463–7

    Article  PubMed  CAS  Google Scholar 

  88. Finn SE, Bailey JM, Schultz RT, et al. Subjective utility ratings of neuroleptics in treating schizophrenia. Psychol Med 1990; 20: 843–8

    Article  PubMed  CAS  Google Scholar 

  89. Weiden PJ, Mackell JA, McDonnell DD. Sexual dysfunction and adherence to antipsychotic therapy in schizophrenia [abstract]. Eur Neuropsychopharmacol 2002; 12 Suppl. 13: S316

    Article  Google Scholar 

  90. Barnes TRE, Harvey CA. Psychiatric drugs and sexuality. In: Riley AJ, Peet M, Wilson C, editors. Sexual pharmacology. Oxford: Clarendon Press, 1993: 176–96

    Google Scholar 

  91. Lundberg PO, Hulter B. Sexual dysfunction in patients with hypothalamo-pituitary disorders. Exp Clin Endocrinol 1991; 98: 81–8

    Article  PubMed  CAS  Google Scholar 

  92. Arato M, Erdos A, Polgar M. Endocrinological changes in patients with sexual dysfunction under long-term neuroleptic treatment. Pharmakopsychiatr Neuropsychopharmakol 1979; 12: 426–31

    PubMed  CAS  Google Scholar 

  93. Burke MA, McEvoy JP, Ritchie JC. A pilot study of a structured interview addressing sexual function in men with schizophrenia. Biol Psychiatry 1994; 35: 32–5

    Article  PubMed  CAS  Google Scholar 

  94. Aizenberg D, Modai I, Landa A, et al. Comparison of sexual dysfunction in male schizophrenic patients maintained on treatment with classical antipsychotics versus clozapine. J Clin Psychiatry 2001; 62: 541–4

    Article  PubMed  CAS  Google Scholar 

  95. Wirshing DA, Pierre JM, Marder SR, et al. Sexual side effects of novel antipsychotic medications. Schizophr Res 2002; 56: 25–30

    Article  PubMed  Google Scholar 

  96. Dickson RA, Glazer WM. Hyperprolactinaemia and male sexual dysfunction [letter]. J Clin Psychiatry 1999; 60: 125

    Article  PubMed  CAS  Google Scholar 

  97. Polishuk JL, Kulcsar S. Effects of chlorpromazine on pituitary function. J Clin Endocrinol 1956; 16: 292–3

    Article  CAS  Google Scholar 

  98. Prentice DS, Deakin JFW. Role of neuroleptic drugs and organic mechanisms in the aetiology of menstrual irregularities in schizophrenic women [abstract]. Schizophr Res 1992; 6 (2 Special Issue): 114

    Article  Google Scholar 

  99. Magharious W, Goff DC, Amico E. Relationship of gender and menstrual status to symptoms and medication side effects in patients with schizophrenia. Psychiatry Res 1998; 77: 159–66

    Article  PubMed  CAS  Google Scholar 

  100. Nonacs RM. Antipsychotic treatment and menstrual irregularity [abstract]. 153rd Annual Meeting of the American Psychiatric Association, New Research Abstracts; 2000 May 13–18; Chicago, 245

  101. Wieck A, Haddad PM. Antipsychotic-induced hyperprolactinaemia in women: pathophysiology, severity and consequences: selective literature review. Br J Psychiatry 2003; 182: 199–204

    Article  PubMed  CAS  Google Scholar 

  102. Gregory BA. The menstrual cycle and its disorders in psychiatric patients: II. J Psychosom Res 1957; 2: 199–224

    Article  PubMed  CAS  Google Scholar 

  103. Bergemann N. Hypooestrogenism in schizophrenic women [abstract]. Arch Women Ment Health 2001; 3 Suppl. 2: S154

    Google Scholar 

  104. Kim YK, Kim L, Lee MS. Risperidone and associated amenorrhea: a report of 5 cases. J Clin Psychiatry 1999; 60: 315–7

    Article  PubMed  CAS  Google Scholar 

  105. World Health Organization. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. WHO Technical Report Series 843. Geneva: WHO, 1994

    Google Scholar 

  106. Royal College of Physicians. Osteoporosis: clinical guidelines for prevention and treatment. London: Royal College of Physicians, 1999

    Google Scholar 

  107. Kiel DP, Felson DT, Andersen JJ, et al. Hip fractures and the use of estrogen in postmenopausal women: the Framingham Study. N Engl J Med 1987; 317: 1169–74

    Article  PubMed  CAS  Google Scholar 

  108. Sowers MF, Corton G, Shapiro B, et al. Changes in bone density with lactation. JAMA 1993; 269: 3130–5

    Article  PubMed  CAS  Google Scholar 

  109. Rigotti NA, Nussbaum SR, Herzog DB, et al. Osteoporosis in women with anorexia nervosa. N Engl J Med 1984; 311: 1601–6

    Article  PubMed  CAS  Google Scholar 

  110. Klibanski A, Biller BM, Rosenthal DI, et al. Effects of prolactin and estrogen deficiency in amenorrheic bone loss. J Clin Endocrinol Metab 1988; 67: 124–30

    Article  PubMed  CAS  Google Scholar 

  111. Biller BMK, Baum HBA, Rosenthal DI, et al. Progressive trabecular osteopenia in women with hyperprolactinaemic amenorrhoea. J Clin Endocrinol Metab 1992; 75: 692–7

    Article  PubMed  CAS  Google Scholar 

  112. Klibanski A, Neer RM, Beitins IZ, et al. Decreased bone mineral density in hyperprolactinaemic women. N Engl J Med 1980; 303: 1511–4

    Article  PubMed  CAS  Google Scholar 

  113. Koppelman MCS, Kurtz DW, Morrish KA, et al. Vertebral bone mineral density content in hyperprolactinemic women. J Clin Endocrinol Metab 1984; 59: 1050–3

    Article  PubMed  CAS  Google Scholar 

  114. Schlechte J, El-Khoury G, Kathol M, et al. Forearm and vertebral bone mineral density in treated and untreated hyperprolactinemic amenorrhea. J Clin Endocrinol Metab 1987; 64: 1021–6

    Article  PubMed  CAS  Google Scholar 

  115. Klibanski A, Greenspan SL. Increase in bone mass after treatment of hyperprolactinemic amenorrhea. N Engl J Med 1986; 315: 542–6

    Article  PubMed  CAS  Google Scholar 

  116. Finkelstein JS, Klibanski A, Neer RM, et al. Osteoporosis in men with idiopathic hypogonadotropic hypogonadism. Ann J Med 1983; 75: 977–83

    Article  Google Scholar 

  117. Greenspan SL, Neer RM, Ridgway EL, et al. Osteoporosis in men with hyperprolactinemic hypogonadism. Ann Intern Med 1986; 104: 777–82

    PubMed  CAS  Google Scholar 

  118. Greenspan SL, Oppenheim DS, Klibanski A. Importance of gonadal steroids to bone mass in men with hyperprolactinemic hypogonadism. Ann Intern Med 1989; 110: 526–31

    PubMed  CAS  Google Scholar 

  119. De Leon J, Dadvand M, Canuso C, et al. Schizophrenia and smoking: an epidemiological survey in a state hospital. Am J Psychiatry 1995; 152: 453–5

    PubMed  Google Scholar 

  120. Hopper JL, Seeman E. The bone density of female twins discordant for tobacco use. N Engl J Med 1994; 330: 387–92

    Article  PubMed  CAS  Google Scholar 

  121. Menezes PR, Johnson S, Thornicroft G, et al. Drug and alcohol problems among individuals with severe mental illness in south London. Br J Psychiatry 1996; 168: 612–9

    Article  PubMed  CAS  Google Scholar 

  122. Peris P, Pares A, Guanabens N, et al. Reduced spinal bone mass and deranged bone mineral metabolism in chronic alcoholics. Alcohol Alcohol 1992; 27: 619–25

    PubMed  CAS  Google Scholar 

  123. Delva NJ, Crammer JL, Jarzylo SV, et al. Osteopenia, pathological fractures, and increased urinary calcium excretion in schizophrenic patients with polydipsia. Biol Psychiatry 1989; 26: 781–93

    Article  PubMed  CAS  Google Scholar 

  124. Ataya K, Mercado A, Kartaginer J, et al. Bone density and reproductive hormones in patients with neuroleptic-induced hyperprolactinemia. Fertil Steril 1988; 50: 876–81

    PubMed  CAS  Google Scholar 

  125. Halbreich U, Rojansky N, Palter S, et al. Decreased bone mineral density in medicated psychiatric patients. Psychosom Med 1995; 57: 485–91

    PubMed  CAS  Google Scholar 

  126. Akande B, Wieck A, Haddad PM. Bone mineral density in premenopausal women with antipsychotic-induced hyperprolactinaemia. Eur Neuropsychopharmacol 2002; 12 Suppl. 3: S311–2

    Article  Google Scholar 

  127. Meaney AM, Smith S, Howes OD, et al. Effects of long term prolactin-raising antipsychotic medication on bone mineral density in patients with schizophrenia. Br J Psychiatry 2004; 184: 503–8

    Article  PubMed  CAS  Google Scholar 

  128. Dinan TG. The physical consequences of depressive illness. BMJ 1999; 318: 826

    Article  PubMed  CAS  Google Scholar 

  129. Rao ML, Strebel B, Halaris A, et al. Orcadian rhythm of vital signs, norepinephrine, epinephrine, thyroid hormone, and cortisol in schizophrenia. Psychiatry Res 1995; 57: 21–39

    Article  PubMed  CAS  Google Scholar 

  130. Ismail K, Murra RM, Wheele MJ, et al. The dexamethasone suppression test in schizophrenia. Psychol Med 1998; 28: 311–7

    Article  PubMed  CAS  Google Scholar 

  131. Welsch CW, Nagasawa H. Prolactin and murine mammary tumorigenesis: a review. Cancer Res 1977; 37: 951–63

    PubMed  CAS  Google Scholar 

  132. Pearson OH, Llerena O, Llerena L. Prolactin-dependent rat mammary cancer: a model for man? Trans Assoc Am Physicians 1969; 82: 225–38

    PubMed  CAS  Google Scholar 

  133. Kanhouwa S, Gowdy JM, Solomon JD. Phenothiazines and breast cancer. J Natl Med Assoc 1984; 76: 785–8

    PubMed  CAS  Google Scholar 

  134. Gulbinat W, Dupont A, Jablensky A, et al. Cancer incidence of schizophrenic patients: results of record-linkage studies in three countries. Br J Psychiatry 1992; 161 Suppl. 18: 75–85

    Google Scholar 

  135. Halbreich U, Shen J, Panaro V. Are chronic psychiatric patients at increased risk for developing breast cancer? Am J Psychiatry 1996; 153: 559–60

    PubMed  CAS  Google Scholar 

  136. Wang PS, Walker AM, Tsuang MT, et al. Dopamine antagonists and the development of breast cancer. Arch Gen Psychiatry 2002; 59: 1147–54

    Article  PubMed  CAS  Google Scholar 

  137. Cheung AP. Ultrasound and menstrual history in predicting endometrial hyperplasia in polycystic ovary syndrome. Obstet Gynecol 2001; 98: 325–31

    Article  PubMed  CAS  Google Scholar 

  138. Jenkins PJ, Besser GM. Disorders of the anterior pituitary. In: Warrell D, Cox TM, Firth JD, et al., editors. Oxford textbook of medicine. 4th ed. Oxford: Oxford University Press, 2004

    Google Scholar 

  139. Jeffcoate SL, Bacon RRA, Beastall GH, et al. Assays for prolactin: guidelines for the provision of a clinical biochemistry service. Ann Clin Biochem 1986; 23: 638–51

    PubMed  CAS  Google Scholar 

  140. Pollock A, McLaren EH. Serum concentration in patients taking neuroleptic drugs. Clin Endocrinol 1998; 49: 513–6

    Article  CAS  Google Scholar 

  141. Levy A, Lightman SL. Diagnosis and treatment of pituitary tumours. BMJ 1994; 308: 1087–91

    Article  PubMed  CAS  Google Scholar 

  142. Beumont P, Bruwer J, Pimstone B, et al. Brom-ergocryptine in the treatment of phenothiazine-induced galactorrhea. Br J Psychiatry 1975; 126: 285–8

    Article  PubMed  CAS  Google Scholar 

  143. Siever L. The effect of amantadine on prolactin levels and galactorrhea in neuroleptic-treated patients. J Clin Psychopharmacol 1981; 1: 2–7

    Article  PubMed  CAS  Google Scholar 

  144. Matsuoka I, Nakai T, Miyaki M, et al. Effects of bromocriptine on neuroleptic-induced amenorrhea, galactorrhea and impotence. Jpn J Psychiatry Neurol 1986; 40: 639–46

    PubMed  CAS  Google Scholar 

  145. Smith S. Neuroleptic-associated hyperprolactinaemia: can it be treated with bromocriptine? J Reprod Med 1992; 37: 737–40

    PubMed  CAS  Google Scholar 

  146. Perovitch RM, Lieberman JA, Fleischhacker WW, et al. The behavioural toxicity of bromocriptine in patients with psychiatric illness. J Clin Psychopharmacol 1989; 9: 417–22

    Google Scholar 

  147. Haggstrom JE, Andersson U, Gunne IM. Bromocriptine in tardive dyskinesia. Pharmacopsichiatrica 1982; 15: 161–3

    Article  CAS  Google Scholar 

  148. Tollin SR. Use of the dopamine agonists bromocriptine and cabergoline in the management of risperidone-induced hyperprolactinaemia in patients with psychotic disorders. J Endocrinol Invest 2000; 23: 765–70

    PubMed  CAS  Google Scholar 

  149. Pymar HC, Creinin MD. The risks of oral contraceptive pills. Semin Reprod Med 2001; 19: 305–12

    Article  PubMed  CAS  Google Scholar 

  150. Molitch ME. Antipsychotic drug-induced hyperprolactinemia: clinical implications. Endocr Pract 2000; 6: 479–81

    PubMed  CAS  Google Scholar 

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Acknowledgements

Both authors have received lecture fees and conference expenses from the manufacturers of several atypical antipsychotics and funding for a small investigator-initiated study from Astra-Zeneca, the manufacturers of quetiapine.

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  1. Bolton, Salford & Trafford Mental Health NHS Trust, Cromwell House, Cromwell Road, Eccles, Salford, M30 0GT, UK

    Peter M. Haddad

  2. Department of Psychiatry, University of Manchester, Manchester, UK

    Peter M. Haddad & Angelika Wieck

  3. Manchester Mental Health and Social Care Trust, Manchester, UK

    Angelika Wieck

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  1. Peter M. Haddad
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Haddad, P.M., Wieck, A. Antipsychotic-Induced Hyperprolactinaemia. Drugs 64, 2291–2314 (2004). https://doi.org/10.2165/00003495-200464200-00003

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