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Lithium Therapy Effects on the Reproductive System

  • Verónica Palmira Filippa
  • Fabián Heber MohamedEmail author
Chapter

Abstract

The chemical properties of lithium (Li) make it an extremely active substance in the body. It is active in the form of Li+ ion, so all salts have the same pharmacological action. Li salts are used to treat manic-depressive disorders (bipolar affective disorders), depressive manic symptoms that include hurried speech, hyperactivity, little need for sleep, aggression, and cholera. Li is a mood stabilizer and reduces extreme behaviors by restoring the balance of neurotransmitters in the brain. The modifications of the cAMP signaling pathway, alterations in the phosphoinositol pathway, and variations in the availability of GABA and glutamate are some described mechanisms of action of Li to achieve its antimanic and mood-stabilizing effects. Thus, Li exerts modifications on the circadian rhythm, neurotransmission processes in the central nervous system, and neuroendocrine functions.

Li therapies have benefits that have not yet been overtaken by other drugs. However, there is also some resistance to using these drugs, partly due to the lack of knowledge of the real impact of its adverse effects although some of them are reversible with the discontinuation of treatment. However, less known and more controversial are the toxic effects of Li therapy on the reproductive system and, therefore, on human sexual functions. Studies in human and laboratory animals on the effects of Li have demonstrated significant effects on the functioning of the hypothalamic-pituitary-gonadal axis. Therefore, this ion may alter human reproduction.

Keywords

Lithium Hypothalamic-pituitary-gonadal axis Human reproduction 

References

  1. 1.
    Goodwin FK. Rationale for using lithium in combination with other mood stabilizers in the management of bipolar disorder. J Clin Psychiatry. 2003;64:18–24.PubMedGoogle Scholar
  2. 2.
    Lin D, Mok H, Yatham LN. Polytherapy in bipolar disorder. CNS Drugs. 2006;20:29–42.PubMedGoogle Scholar
  3. 3.
    Merikangas KR, Jin R, He JP, Kessler RC, Lee S, Sampson NA, Viana MC, Andrade LH, Hu C, Karam EG, Ladea M, Medina-Mora ME, Ono Y, Posada-Villa J, Sagar R, Wells JE, Zarkov Z. Prevalence and correlates of bipolar spectrum disorder in the world mental health survey initiative. Arch Gen Psychiatry. 2011;68(3):241–51.PubMedPubMedCentralGoogle Scholar
  4. 4.
    Murru A, Popovic D, Pacchiarotti I, Hidalgo D, León-Caballero J, Vieta E. Management of adverse effects of mood stabilizers. Curr Psychiatry Rep. 2015;17:66.Google Scholar
  5. 5.
    Kenna HA, Jiang B, Rasgon NL. Reproductive and metabolic abnormalities associated with bipolar disorder and its treatment. Harv Rev Psychiatry. 2009;17(2):138–46.PubMedGoogle Scholar
  6. 6.
    Kesebir S, Toprak B, Baykaran B, Hariri A, Bilici M. Comparison of sexual function and hormonal parameters between mood stabilizer treatment modalities in bipolar disorder. Arch Neuropsychiatry. 2014;51:242–7.Google Scholar
  7. 7.
    Manisto PT. Endocrine side-effects of lithium. In: Johnson FN, editor. Handbook of lithium therapy. Baltimore: New York University Park Press; 1980.Google Scholar
  8. 8.
    Ghosh D, Biswas NM. Effect of lithium chloride on the activities of ovarian delta 5-3 beta and 17b-hydroxysteroid dehydrogenase and histology of ovary in albino rats. Med Sci Res. 1991;19:703.Google Scholar
  9. 9.
    Ghosh S, Misro M, Baran D, Maiti U, Mohan R, Debnath J, Ghosh D. Effect of human chorionic gonadotrophin coadministration on ovarian steroidogenic and folliculogenic activities in cyclophosphamide treated albino rats. Reprod Toxicol. 2001;15:221–5.PubMedGoogle Scholar
  10. 10.
    Joffe M. Semen quality analysis and the idea of normal fertility. Asian J Androl. 2010;12:79–82.PubMedPubMedCentralGoogle Scholar
  11. 11.
    Kusalic M, Engelsmann F. Effect of lithium maintenance treatment on hypothalamic pituitary gonadal axis in bipolar men. J Psychiatry Neurosci. 1996;21(3):181–6.PubMedPubMedCentralGoogle Scholar
  12. 12.
    El-Mallakh RS. Ion homeostasis and the mechanism of action of lithium. Clin Neurosci Res. 2004;4:227–31.Google Scholar
  13. 13.
    Martín B, López-Muñoz F, Alamo C, Cuenca E. Litio: otras indicaciones terapéuticas. 2001. Available from: http://www.psiquiatria.com/tratamientos/litio-otras-indicaciones-terapeuticas/.
  14. 14.
    Mármol F. Lithium: bipolar disorder and neurodegenerative diseases possible cellular mechanisms of the therapeutic effects of lithium. Prog Neuropsychopharmacol Biol Psychiatry. 2008;32(8):1761–71.PubMedGoogle Scholar
  15. 15.
    Mitchell PB. On the 50th anniversary of John Cade’s discovery of the anti-manic effect of lithium. Aust N Z J Psychiatry. 1999;33:623–8.PubMedGoogle Scholar
  16. 16.
    López-Muñoz F, Alamo C, Cuenca E. Sales de litio y otros reguladores del humor. In: López-Muñoz F, Alamo C, editors. Historia de la Neuropsicofarmacología. Madrid: Ediciones Eurobook S.L; 1998. p. 305–16.Google Scholar
  17. 17.
    Malgor V. Farmacología de las sales de litio. Usos terapéuticos en trastornos bipolares y en la depresión mayor recurrente. In: Temas de Farmacología. 2nd ed. 2000. 5 cap 15:153–161. Available from: http://med.unne.edu.ar/farmaco.html.
  18. 18.
    Scott IM. The determination of lithium in blood serum by atomic absorption spectrophotometry. J Forensic Sci. 1982;22:41–2.Google Scholar
  19. 19.
    Mármol F. Litio: 55 años de historia en el tratamiento del trastorno bipolar. Med Clin (Barc). 2006;127(5):189–95.Google Scholar
  20. 20.
    Lima TZ, Blanco MM, Santos Júnior JG, Coelho CT, Mello LE. Staying at the crossroads: assessment of the potential of serum lithium monitoring in predicting an ideal lithium dose. Rev Bras Psiquiatr. 2008;30(3):215–21.PubMedGoogle Scholar
  21. 21.
    Severus WE, Kleindienst N, Seemüller F, Frangou S, Möller HJ, Greil W. What is the optimal serum lithium level in the long-term treatment of bipolar disorder – a review? Bipolar Disord. 2008;10:231–7.PubMedGoogle Scholar
  22. 22.
    McKnight RF, Adida M, Budge K, Stockton S, Goodwin GM, Geddes JR. Lithium toxicity profile: a systematic review and meta-analysis. Lancet. 2012;379:721–8.PubMedGoogle Scholar
  23. 23.
    Malhi GS, Tanious M. Optimal frequency of lithium administration in the treatment of bipolar disorder: clinical and dosing considerations. CNS Drugs. 2011;25(4):289–98.PubMedGoogle Scholar
  24. 24.
    Paton C, Adroer R, Barnes TR. Monitoring lithium therapy: the impact of a quality improvement programme in the UK. Bipolar Disord. 2013;15(8):865–75.PubMedGoogle Scholar
  25. 25.
    Schou M, Juel-Nielsen N, Ströngren E, Voldby H. The treatment of manic psychoses by the administration of lithium salts. J Neurol Psychiatr. 1954;17:250–60.Google Scholar
  26. 26.
    Mármol F. Estudio del mecanismo de acción neurofarmacológica del litio en el modelo experimental de plexo mientérico de cobayo. Barcelona: Universitad de Barcelona; 1989.Google Scholar
  27. 27.
    Belmaker RH. Bipolar disorder. N Engl J Med. 2004;351(5):476–86.PubMedGoogle Scholar
  28. 28.
    Gershon S, Chengappa KN, Malhi GS. Lithium specificity in bipolar illness: a classic agent for the classic disorder. Bipolar Disord. 2009;11(Suppl 2):34–44.PubMedGoogle Scholar
  29. 29.
    Thies-Flechner K, Müller-Oerlinghausen B, Seibert W, Walther A, Greil W. Effect of prophylactic treatment on suicide risk in patients with major affective disorders: data from a randomized prospective trial. Pharmacopsychiatry. 1996;29:103–7.Google Scholar
  30. 30.
    Tondo L, Jamison KR, Baldessarini RJ. Effect of lithium maintenance on suicidal behavior in major mood disorders. Ann N Y Acad Sci. 1997;836:339–51.PubMedGoogle Scholar
  31. 31.
    Goodwin FK, Fireman B, Simon GE, Hunkeler EM, Lee J, Revicki D. Suicide risk in bipolar disorder during treatment with lithium and divalproex. JAMA. 2003;290:1467–73.PubMedGoogle Scholar
  32. 32.
    Manji HK, Moore GJ, Chen G. Clinical and preclinical evidence for the neurotrophic effects of mood stabilizers: implications for pathophysiology and treatment of manic-depressive illness. Biol Psychiatry. 2000;48:740–54.PubMedGoogle Scholar
  33. 33.
    Alvano SA. Posibles mecanismos y acciones farmacológicas involucradas en el efecto antimaníaco y estabilizador del humor (Primera parte). Psicofarmacología. 2005;5(30):11–8.Google Scholar
  34. 34.
    Alda M. Lithium in the treatment of bipolar disorder: pharmacology and pharmacogenetics. Mol Psychiatry. 2015;20(6):661–70.PubMedPubMedCentralGoogle Scholar
  35. 35.
    Chiu CT, Chuang DM. Molecular actions and therapeutic potential of lithium in preclinical and clinical studies of CNS disorders. Pharmacol Ther. 2010;128(2):281–304.PubMedPubMedCentralGoogle Scholar
  36. 36.
    Coppen A. The biochemistry of affective disorders. Br J Psychiatry. 1967;113:1237–64.PubMedGoogle Scholar
  37. 37.
    El-Mallakh RS, Jefferson JW. Prethymoleptic use of lithium. Am J Psychiatry. 1999;156:1.Google Scholar
  38. 38.
    Kirshenbaum GS, Clapcote SJ, Duffy S, Burgess CR, Petersen J, Jarowek KJ, Yücel YH, Cortez MA, Snead OC 3rd, Vilsen B, Peever JH, Ralph MR, Roder JC. Mania-like behavior induced by genetic dysfunction of the neuron-specific Na+,K+-ATPase alpha3 sodium pump. Proc Natl Acad Sci U S A. 2011;108:18144–9.PubMedPubMedCentralGoogle Scholar
  39. 39.
    Reddy PL, Khanna S, Subhash MN, Channabasavanna SM, Rao BS. Erythrocyte membrane sodium-potassium adenosine triphosphatase activity in affective disorders. J Neural Transm Gen Sect. 1992;89:209–18.PubMedGoogle Scholar
  40. 40.
    Huang X, Lei Z, El-Mallakh RS. Lithium normalizes elevated intracellular sodium. Bipolar Disord. 2007;9:298–300.PubMedGoogle Scholar
  41. 41.
    Aperia A. New roles for an old enzyme: Na,K-ATPase emerges as an interesting drug target. J Intern Med. 2007;261:44–52.PubMedGoogle Scholar
  42. 42.
    Banerjee U, Dasgupta A, Rout JK, Singh OP. Effects of lithium therapy on Na+-K+-ATPase activity and lipid peroxidation in bipolar disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2012;37:56–61.PubMedGoogle Scholar
  43. 43.
    Zhang L, Zhang Z, Guo H, Wang Y. Na+/K+-ATPase-mediated signal transduction and Na+/K+-ATPase regulation. Fundam Clin Pharmacol. 2008;22:615–21.PubMedGoogle Scholar
  44. 44.
    Jope R. Effects of lithium treatment in vitro and in vivo on acetylcholine metabolism in rat brain. J Neurochem. 1979;33:487–95.PubMedGoogle Scholar
  45. 45.
    Price LH, Heninger GR. Lithium in the treatment of mood disorders. N Engl J Med. 1994;331:591–8.PubMedGoogle Scholar
  46. 46.
    Grof P, Grof E. Varieties of lithium benefit. Prog Neuropsychopharmacol Biol Psychiatry. 1990;14:689–96.PubMedGoogle Scholar
  47. 47.
    Manji HK, Hsiao JK, Risby ED, Oliver J, Rudorfer MV, Potter WJ. The mechanisms of action of lithium: I: effects on serotoninergic and noradrenergic systems in normal subjects. Arch Gen Psychiatry. 1991;48:505–12.PubMedGoogle Scholar
  48. 48.
    Akiskal HS, Downs J, Jordan P, Watson S, Daugherty D, Pruitt DB. Affective disorders in referred children and younger siblings of manic-depressives. Arch Gen Psychiatry. 1985;42:996–1003.PubMedGoogle Scholar
  49. 49.
    Borden C, Valproate, Schatzberg AF, Nemeroff CB. Textbook of psychopharmacology. 3rd ed. Washington, DC: American Psychiatric Publishing; 2004. p. 567–79.Google Scholar
  50. 50.
    Freeman MP, Wiegand C, Gelenberg AJ. Lithium. In: Schatzberg AF, Nemeroff CB, editors. Textbook of psychopharmacology. 3rd ed. Washington, DC: Amaerican Psychiatric Publishing; 2004. p. 547–65.Google Scholar
  51. 51.
    Manji HK, Lenox RH. Signaling: cellular insights into the pathophysiology of bipolar disorder. Biol Psychiatry. 2000;48:518–30.PubMedGoogle Scholar
  52. 52.
    Jope RS. Anti-bipolar therapy: mechanism of action of lithium. Mol Psychiatry. 1999;4:117–28.PubMedGoogle Scholar
  53. 53.
    Lenox RH, Frazer A. Mechanism of action of antidepressants and mood stabilizers. In: Davis KL, Charney D, Coyle JT, Nemeroff CB, editors. Neuropsychopharmacology, the fifth generation of progress. Philadelphia: Lippincott Williams & Wilkins; 2002. p. 1139–63.Google Scholar
  54. 54.
    Embi N, Rylatt DB, Cohen P. Glycogen synthase kinase-3 from rabbit skeletal muscle separation from cyclic-AMP-dependent protein kinase and phosphorylase kinase. Eur J Biochem. 1980;107:519–27.PubMedGoogle Scholar
  55. 55.
    Frame S, Cohen P. GSK3 takes centre stage more than 20 years after its discovery. Biochem J. 2001;359:1–16.PubMedPubMedCentralGoogle Scholar
  56. 56.
    Stambolic V, Ruel L, Woodgett JR. Lithium inhibits glycogen synthase kinase-3 activity and mimics wingless signalling in intact cells. Curr Biol. 1996;6:1664–8.PubMedGoogle Scholar
  57. 57.
    O’Brien WT, Klein PS. Validating GSK3 as an in vivo target of lithium action. Biochem Soc Trans. 2009;37:1133–8.PubMedPubMedCentralGoogle Scholar
  58. 58.
    Grimes CA, Jope RS. CREB DNA binding activity is inhibited by glycogen synthase kinase-3 beta and facilitated by lithium. J Neurochem. 2001;78:1219–32.PubMedPubMedCentralGoogle Scholar
  59. 59.
    Gould TD. Targeting glycogen synthase kinase-3 as an approach to develop novel mood-stabilising medications. Expert Opin Ther Targets. 2006;10:377–92.PubMedGoogle Scholar
  60. 60.
    Jope RS. Lithium and GSK-3: one inhibitor, two inhibitory actions, multiple outcomes. Trends Pharmacol Sci. 2003;24:441–3.PubMedGoogle Scholar
  61. 61.
    Zou Y. Wnt signaling in axon guidance. Trends Neurosci. 2004;27:528–32.PubMedGoogle Scholar
  62. 62.
    Meffre D, Grenier J, Bernard S, Courtin F, Dudev T, Shackleford G, Jafarian-Tehrani M, Massaad C. Wnt and lithium: a common destiny in the therapy of nervous system pathologies? Cell Mol Life Sci. 2014;71:1123–48.PubMedGoogle Scholar
  63. 63.
    Gould TD, Chen G, Manji HK. In vivo evidence in the brain for lithium inhibition of glycogen synthase kinase-3. Neuropsychopharmacology. 2004;29:32–8.PubMedGoogle Scholar
  64. 64.
    Ahn SW, Kim JE, Park KS, Choi WJ, Hong YH, Kim SM, Kim SH, Lee KW, Sung JJ. The neuroprotective effect of the GSK-3beta inhibitor and influence on the extrinsic apoptosis in the ALS transgenic mice. J Neurol Sci. 2012;320:1–5.PubMedPubMedCentralGoogle Scholar
  65. 65.
    Beaulieu JM, Caron MG. Looking at lithium: molecular moods and complex behaviour. Mol Interv. 2008;8:230–41.PubMedGoogle Scholar
  66. 66.
    Sit D. Women and bipolar disorder across the life span. J Am Med Wom Assoc. 2004;59:91–100.PubMedGoogle Scholar
  67. 67.
    Elenitza IM. Endocrinologic adverse effects of psychotropic drugs. Vertex. 2005;16(59):43–8.PubMedGoogle Scholar
  68. 68.
    Kraszewska A, Chlopocka-Wozniak M, Abramowicz M, Sowinski J, Rybakowski JK. A cross-sectional study of thyroid function in 66 patients with bipolar disorder receiving lithium for 10–44 years. Bipolar Disord. 2015;17(4):375–80.PubMedGoogle Scholar
  69. 69.
    Lazarus JH. Lithium and thyroid. Best Pract Res Clin Endocrinol Metab. 2009;23:723–33.PubMedGoogle Scholar
  70. 70.
    Constantiou C, Bolaris S, Valcana T, et al. Acute LiCl-treatment affects the cytoplasmic T4 availability and the expression pattern of thyroid hormone receptors in adult rat cerebral hemispheres. Neurosci Res. 2004;51:235–41.Google Scholar
  71. 71.
    Extein I, Pottash AL, Gold MS, et al. The thyroid-stimulating hormone response to thyrotropin-releasing hormone in mania and bipolar depression. Psychiatry Res. 1980;2:199–204.PubMedGoogle Scholar
  72. 72.
    Lazarus JH, John R, Bennie EH, Chalmers RJ, Crockett G. Lithium therapy and thyroid function a long-term study. Psychol Med. 1981;11:85–92.PubMedGoogle Scholar
  73. 73.
    Özerdem A, Tunca Z, Çımrın D, Hıdıroğlu C, Ergör G. Female vulnerability for thyroid function abnormality in bipolar disorder: role of lithium treatment. Bipolar Disord. 2014;16(1):72–82.PubMedGoogle Scholar
  74. 74.
    McKnight RF, Adida M, Budge K, Stockton S, Goodwin GM, Geddes JR. Lithium toxicity profile: a systematic review and meta-analysis. Lancet. 2012;379(9817):721–8.PubMedGoogle Scholar
  75. 75.
    Watanabe K, Kikuchi T. Adverse events of psychotropic drugs. Seishin Shinkeigaku Zasshi. 2014;116(4):323–31.PubMedGoogle Scholar
  76. 76.
    Kishore BK, Ecelbarger CM. Lithium: a versatile tool for understanding renal physiology. Am J Physiol Ren Physiol. 2013;304(9):F1139–49.Google Scholar
  77. 77.
    Grünfeld JP, Rossier BC. Lithium nephrotoxicity revisited. Nat Rev Nephrol. 2009;5:270–6.PubMedGoogle Scholar
  78. 78.
    Trepiccione F, Capasso G, Nielsen S, Christensen BM. Evaluation of cellular plasticity in the collecting duct during recovery from lithium-induced nephrogenic diabetes insipidus. Am J Physiol Ren Physiol. 2013;305(6):F919–29.Google Scholar
  79. 79.
    Raja M. Lithium and kidney, 60 years later. Curr Drug Saf. 2011;6:291–303.PubMedGoogle Scholar
  80. 80.
    Blount MA, Sim JH, Zhou R, Martin CF, Lu W, Sands JM, Klein JD. Expression of transporters involved in urine concentration recovers differently after cessation of lithium treatment. Am J Physiol Ren Physiol. 2010;298(3):F601–8.Google Scholar
  81. 81.
    Lydiard RB, Gelenberg AJ. Hazards and adverse effects of lithium. Annu Rev Med. 1982;33:327–44.PubMedGoogle Scholar
  82. 82.
    Gupta MD, Girish, Goyal M, Subhendu M, Tyagi S. Unusual case of syncope in a patient with ischemic heart disease. Ann Noninvasive Electrocardiol. 2014;19(4):395–7.PubMedGoogle Scholar
  83. 83.
    Altinbas K, Guloksuz S, Caglar IM, Caglar FN, Kurt E, Oral ET. Electrocardiography changes in bipolar patients during long-term lithium monotherapy. Gen Hosp Psychiatry. 2014;36(6):694–7.PubMedGoogle Scholar
  84. 84.
    Yeung CK, Chan HH. Cutaneous adverse effects of lithium: epidemiology and management. Am J Clin Dermatol. 2004;5:3–8.PubMedGoogle Scholar
  85. 85.
    Jafferany M. Lithium and psoriasis: what primary care and family physicians should know. Prim Care Companion J Clin Psychiatry. 2008;10(6):435–9.PubMedPubMedCentralGoogle Scholar
  86. 86.
    López-Jaramillo C, et al. Lithium treatment effects on the neuropsychological functioning of patients with bipolar I disorder. J Clin Psychiatry. 2010;71:1055–60.PubMedGoogle Scholar
  87. 87.
    McElroy SL. Obesity in patients with severe mental illness: overview and management. J Clin Psychiatry. 2009;70(Suppl 3):12–21.PubMedGoogle Scholar
  88. 88.
    Jacobson L. Hypothalamic-pituitary-adrenocortical axis: neuropsychiatric aspects. Compr Physiol. 2014;4(2):715–38.PubMedGoogle Scholar
  89. 89.
    Aichhorn W, Whitworth AB, Weiss EM, Marksteiner J. Second generation antipsychotics: is there evidence for sex differences in pharmacokinetic and adverse effect profiles? Drug Saf. 2006;29:587–98.PubMedGoogle Scholar
  90. 90.
    Young W. Review of lithium effects on brain and blood. Cell Transplant. 2009;18(9):951–75.PubMedGoogle Scholar
  91. 91.
    Serretti A, Chiesa A. A meta-analysis of sexual dysfunction in psychiatric patients taking antipsychotics. Int Clin Psychopharmacol. 2011;26(3):130–40.PubMedGoogle Scholar
  92. 92.
    Griffiths JJ, Zarate CA Jr, Rasimas JJ. Existing and novel biological therapeutics in suicide prevention. Am J Prev Med. 2014;47:195–203.Google Scholar
  93. 93.
    Perez Romera E, Muñoz E, Mohamed F, Dominguez S, Scardapane L, Villegas O, García Aseff S, Guzmán JA. Lithium effect on testicular tissue and spermatozoa of viscacha (Lagostomus maximus maximus). A comparative study with rats. J Trace Elem Med Biol. 2000;14(2):81–3.PubMedGoogle Scholar
  94. 94.
    Allagui MS, Hfaiedh N, Croute F, Guermazi F, Vincent C, Soleilhavoup JP, ElFeki A. Side effects of low serum lithium concentrations on renal, thyroid, and sexual functions in male and female rats. C R Biol. 2005;328(10–11):900–11.PubMedGoogle Scholar
  95. 95.
    Sadeghipour H, Dehghani M, Ghasemi M, Riazi K, Asadi S, Ebrahimi F, Honar H, Hajrasouliha AR, Tavakoli S, Sianati S, Dehpour AR. The nonadrenergic noncholinergic-mediated relaxation of corpus cavernosum was impaired in chronic lithium-treated rats: improvement with L-arginine. Eur J Pharmacol. 2008;586(1–3):300–5.PubMedGoogle Scholar
  96. 96.
    Saad AB, Rjeibi I, Alimi H, Ncib S, Smida A, Zouari N, Zourgui L. Lithium induced, oxidative stress and related damages in testes and heart in male rats: the protective effects of Malva sylvestris extract. Biomed Pharmacother. 2017;86:127–35.PubMedGoogle Scholar
  97. 97.
    Sheikha SH, LeGate LS, Banerji TK. Lithium suppresses ovariectomy-induced surges in plasma gonadotropins in rats. Life Sci. 1989;44(19):1363–9.PubMedGoogle Scholar
  98. 98.
    Khodadadi M, Pirsaraei ZA. Disrupting effects of lithium chloride in the rat ovary: involves impaired formation and function of corpus luteum. Middle East Fertil Soc J. 2013;18(1):18–23.Google Scholar
  99. 99.
    Jana D, Nandi D, Maiti RK, Ghosh D. Effect of human chorionic gonadotrophin coadministration on the activities of ovarian Delta5-3beta-hydroxysteroid dehydrogenase, and 17beta-hydroxysteroid dehydrogenase, and ovarian and uterine histology in lithium chloride-treated albino rats. Reprod Toxicol. 2001;15(2):215–9.PubMedGoogle Scholar
  100. 100.
    Mirakhori F, Zeynali B, Tafreshi AP, Shirmohammadian A. Lithium induces follicular atresia in rat ovary through a GSK-3β/β-catenin dependent mechanism. Mol Reprod Dev. 2013;80(4):286–96.PubMedGoogle Scholar
  101. 101.
    Thakur SC, Thakur SS, Chaube SK, Singh SP. Subchronic supplementation of lithium carbonate induces reproductive system toxicity in male rat. Reprod Toxicol. 2003;17(6):683–90.PubMedGoogle Scholar
  102. 102.
    Strauss B, Gross J. Effect of psychopharmacologic therapy on sexual functioning. Fortschr Neurol Psychiatr. 1984;52:293–301.PubMedGoogle Scholar
  103. 103.
    Kristensen E. Sexual side effects induced by psychotropic drugs. Dan Med Bull. 2002;49(4):349–52.PubMedGoogle Scholar
  104. 104.
    Grover S, Ghosh A, Sarkar S, Chakrabarti S, Avasthi A. Sexual dysfunction in clinically stable patients with bipolar disorder receiving lithium. J Clin Psychopharmacol. 2014;34(4):475–82.PubMedGoogle Scholar
  105. 105.
    Elnazer HY, Sampson A, Baldwin D. Lithium and sexual dysfunction: an under researched area. Hum Psychopharmacol. 2015;  https://doi.org/10.1002/hup.2457. Published online in Wiley Online Library (wileyonlinelibrary.com).Google Scholar
  106. 106.
    Pfeifer WD, Davis LC, Van der Velde CD. Lithium accumulation in some endocrine tissues. Acta Biol Med Ger. 1976;35:1519–23.PubMedGoogle Scholar
  107. 107.
    Denef C. Paracrinicity: the story of 30 years of cellular pituitary crosstalk. J Neuroendocrinol. 2008;20(1):1–70.PubMedPubMedCentralGoogle Scholar
  108. 108.
    Baştürk M, Karaaslan F, Esel E, Sofuoğlu S, Tutuş A, Yabanoğlu I. Effects of short and long-term lithium treatment on serum prolactin levels in patients with bipolar affective disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2001;25:315–22.PubMedGoogle Scholar
  109. 109.
    El Khoury A, Tham A, Mathé AA, Aberg-Wistedt A, StainMalmgren R. Decreased plasma prolactin release in euthymic lithium-treated women with bipolar disorder. Neuropsychobiology. 2003;48:14–8.PubMedGoogle Scholar
  110. 110.
    Pacchiarotti I, Murru A, Kotzalidis GD, Mar Bonnin C, Mazzarini L, Colom F, Vieta E. Hyperprolactinemia and medications for bipolar disorder: systematic review of a neglected issue in clinical practice. Eur Neuropsychopharmacol. 2015;25:1045–59.PubMedGoogle Scholar
  111. 111.
    Rasgon N, Altshuler L, Gudeman D, et al. Medication status and polycystic ovary syndrome in women with bipolar disorder: a preliminary report. J Clin Psychiatry. 2000;61:173–8.PubMedGoogle Scholar
  112. 112.
    Joffe H, Cohen LS, Suppes T, McLaughlin WL, Lavori P, Adams JM, Hwang CH, Hall JE, Sachs GS. Valproate is associated with new-onset oligoamenorrhea with hyperandrogenism in women with bipolar disorder. Biol Psychiatry. 2006;59(11):1078–86.PubMedGoogle Scholar
  113. 113.
    Polotsky AJ, Zhu L, Santoro N, Pollard JW. Lithium chloride treatment induces epithelial cell proliferation in xenografted human endometrium. Hum Reprod. 2009;24(8):1960–7.PubMedPubMedCentralGoogle Scholar
  114. 114.
    Freeman MP, Gelenberg AJ. Bipolar disorder in women: reproductive events and treatment considerations. Acta Psychiatr Scand. 2005;112:88–96.PubMedGoogle Scholar
  115. 115.
    Jacobson SJ, Jones K, Johnson K, Ceolin L, Kaur P, Sahn D, Donnenfeld AE, Rieder M, Santelli R, Smythe J, Pastuszak A, Einarson T, Koren G. Prospective multicentre study of pregnancy outcome after lithium exposure during first trimester. Lancet. 1992;339(8792):530–3.PubMedGoogle Scholar
  116. 116.
    Newport DJ, Viguera AC, Beach AJ, Ritchie JC, Cohen LS, Stowe ZN. Lithium placental passage and obstetrical outcome: implications for clinical management during late pregnancy. Am J Psychiatr. 2005;162(11):2162–70.PubMedGoogle Scholar
  117. 117.
    FDA. FDA Drug Safety Communication: antipsychotic drug labels updated on use during pregnancy and risk of abnormal muscle movements and withdrawal symptoms in newborns. 2011. Available from: http://www.fda.gov/Drugs/DrugSafety/ucm243903.htm.
  118. 118.
    Llewellyn A, Stowe ZN, Strader JR Jr. The use of lithium and management of women with bipolar disorder during pregnancy and lactation. J Clin Psychiatry. 1998;59(Suppl 6):57–64; discussion 65.PubMedGoogle Scholar
  119. 119.
    Frassetto F, Tourneur Martel F, Barjhoux CE, Villier C, Bot BL, Vincent F. Goiter in a newborn exposed to lithium in utero. Ann Pharmacother. 2002;36(11):1745–8.PubMedGoogle Scholar
  120. 120.
    Pinelli JM, Symington AJ, Cunningham KA, Paes BA. Case report and review of the perinatal implications of maternal lithium use. Am J Obstet Gynecol. 2002;187(1):245–9.PubMedGoogle Scholar
  121. 121.
    Yonkers KA, Wisner KL, Stowe Z, Leibenluft E, Cohen L, Miller L, Manber R, Viguera A, Suppes T, Altshuler L. Management of bipolar disorder during pregnancy and the postpartum period. Am J Psychiatry. 2004;161(4):608–20.PubMedGoogle Scholar
  122. 122.
    Diav-Citrin O, Shechtman S, Tahover E, Finkel-Pekarsky V, Arnon J, Kennedy D, Erebara A, Einarson A, Ornoy A. Pregnancy outcome following in utero exposure to lithium: a prospective, comparative, observational study. Am J Psychiatry. 2014;171(7):785–94.PubMedGoogle Scholar
  123. 123.
    Khan SJ, Fersh ME, Ernst C, Klipstein K, Albertini ES, Lusskin SI. Bipolar disorder in pregnancy and postpartum: principles of management. Curr Psychiatry Rep. 2016;18(2):13.PubMedGoogle Scholar
  124. 124.
    van der Lugt NM, van de Maat JS, van Kamp IL, Knoppert-van der Klein EA, Hovens JG, Walther FJ. Fetal, neonatal and developmental outcomes of lithium-exposed pregnancies. Early Hum Dev. 2012;88(6):375–8.PubMedGoogle Scholar
  125. 125.
    Deligiannidis KM, Byatt N, Freeman MP. Pharmacotherapy for mood disorders in pregnancy: a review of pharmacokinetic changes and clinical recommendations for therapeutic drug monitoring. J Clin Psychopharmacol. 2014;34(2):244–55.PubMedPubMedCentralGoogle Scholar
  126. 126.
    Licht RW, Vestergaard P, Kessing LV, Larsen JK, Thomsen PH. Psychopharmacological treatment with lithium and antiepileptic drugs: suggested guidelines from the Danish Psychiatric Association and the Child and Adolescent Psychiatric Association in Denmark. Acta Psychiatr Scand Suppl. 2003;108(s419):1–22.Google Scholar
  127. 127.
    Dodd S, Berk M. The pharmacology of bipolar disorder during pregnancy and breastfeeding. Expert Opin Drug Saf. 2004;3(3):221–9.PubMedGoogle Scholar
  128. 128.
    Abrial E, Bétourné A, Etiévant A, Lucas G, Scarna H, Lambás-Señas L, Haddjeri N. Protein kinase C inhibition rescues manic-like behaviors and hippocampal cell proliferation deficits in the sleep deprivation model of mania. Int J Neuropsychopharmacol. 2014;18(2). pii: pyu031.  https://doi.org/10.1093/ijnp/pyu031.
  129. 129.
    Chiu CT, Chuang DM. Molecular actions and therapeutic potential of lithium in preclinical and clinical studies of CNS disorders. Pharmacol Ther. 2010;128(2):281–304.PubMedPubMedCentralGoogle Scholar
  130. 130.
    Rowe MK, Chuang DM. Lithium neuroprotection: molecular mechanisms and clinical implications. Expert Rev Mol Med. 2004;18:1–18.Google Scholar
  131. 131.
    Wada A, Yokoo H, Yanagita T, Kobayashi H. Lithium: potential therapeutics against acute brain injuries and chronic neurodegenerative diseases. J Pharmacol Sci. 2005;99:307–21.PubMedGoogle Scholar
  132. 132.
    Quiroz JA, Machado-Viera R, Zarate CA Jr. Novel insights into lithium’s mechanism of action: neurotrophic and neuroprotective effects. Neuropsychobiology. 2010;62:50–60.PubMedPubMedCentralGoogle Scholar
  133. 133.
    Su H, Zhang W, Guo J, Guo A, Yuan Q, Wu W. Lithium enhances the neuronal differentiation of neural progenitor cells in vitro and after transplantation into the avulsed ventral horn of adult rats through the secretion of brain-derived neurotrophic factor. J Neurochem. 2009;108:1385–98.PubMedGoogle Scholar
  134. 134.
    Cabrera O, Dougherty J, Singh S, Swiney BS, Farber NB, Noguchi KK. Lithium protects against glucocorticoid induced neural progenitor cell apoptosis in the developing cerebellum. Brain Res. 2014;1545:54–63.PubMedGoogle Scholar
  135. 135.
    Fan M, Song C, Wang T, Li L, Dong Y, Jin W, Lu P. Protective effects of lithium chloride treatment on repeated cerebral ischemia-reperfusion injury in mice. Neurol Sci. 2015;36:315–21.PubMedGoogle Scholar
  136. 136.
    Dong BT, Guan-Jun Tu GY, Han YX, Chen Y. Lithium enhanced cell proliferation and differentiation of mesenchymal stem cells to neural cells in rat spinal cord. Int J Clin Exp Pathol. 2015;8(3):2473–83.PubMedPubMedCentralGoogle Scholar
  137. 137.
    Nciri R, Boujbiha MA, Jbahi S, Allagui MS, Elfeki A, Vincent C, Croute F. Cytoskeleton involvement in lithium-induced SH-SY5Y neuritogenesis and the role of glycogen synthase kinase 3β. Aging Clin Exp Res. 2015;27(3):255–63.PubMedGoogle Scholar
  138. 138.
    Rouhani M, Goliaei B, Khodagholi F, Nikoofar A. Antimanic drug sensitizes breast cancer cell line to ionizing radiation. Gen Physiol Biophys. 2014;33:235–42.PubMedGoogle Scholar
  139. 139.
    Lubner SJ, Kunnimalaiyaan M, Holen KD, Ning L, Ndiaye M, Loconte NK, Mulkerin DL, Schelman WR, Chen H. A preclinical and clinical study of lithium in low-grade neuroendocrine tumors. Oncologist. 2011;16(4):452–7.PubMedPubMedCentralGoogle Scholar
  140. 140.
    Li L, Song H, Zhong L, Yang R, Yang XQ, Jiang KL, Liu BZ. Lithium chloride promotes apoptosis in human leukemia NB4 cells by inhibiting glycogen synthase kinase-3 beta. Int J Med Sci. 2015;12(10):805–10.PubMedPubMedCentralGoogle Scholar
  141. 141.
    Novetsky AP, Thompson DM, Zighelboim I, Thaker PH, Powell MA, Mutch DG, Goodfellow PJ. Lithium chloride and inhibition of glycogen synthase kinase 3β as a potential therapy for serous ovarian cancer. Int J Gynecol Cancer. 2013;23(2):361–6.PubMedPubMedCentralGoogle Scholar
  142. 142.
    Maeng YS, Lee R, Lee B, Choi SI, Kim EK. Lithium inhibits tumor lymphangiogenesis and metastasis through the inhibition of TGFBIp expression in cancer cells. Sci Rep. 2016;6:20739.  https://doi.org/10.1038/srep20739.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Verónica Palmira Filippa
    • 1
  • Fabián Heber Mohamed
    • 1
    Email author
  1. 1.Faculty of Chemistry, Biochemistry and PharmacyNational University of San LuisSan LuisArgentina

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