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Harvard Review of Psychiatry Volume 11, 2003 - Issue 2
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Research Article

A Putative Relationship between Valproic Acid and Polycystic Ovarian Syndrome: Implications for Treatment of Women with Seizure and Bipolar Disorders

Hadine Joffe
,
Janet E. Hall
,
Lee S. Cohen
,
Ann E. Taylor
&
Ross J. Baldessarini
Pages 99-108 | Published online: 03 Jul 2009

  • Denicoff KD, Smith-Jackson EE, Bryan AL, All SO, Post RM. Valproate prophylaxis in a prospective clinical trial of refractory bipolar disorder. Am J Psychiatry 1997;154:1456-8.
  • Bowden CL, Swarm AC, Calabrese JR, McElroy SL, Morris D, Petty F, et al. Maintenance clinical trials in bipolar disorder: design implications of the divalproex-lithium-placebo study. Psychopharmacol Bull 1997;33:693-9.
  • Pope HG Jr, McElroy SL, Keck PE Jr, Hudson JI. Valproate in the treatment of acute mania. A placebo-controlled study. Arch Gen Psychiatry 1991;48:62-8.
  • Isojarvi JI, Laatikainen TJ, Pakarinen AJ, Juntunen KT, Myllyla W. Polycystic ovaries and hyperandrogenism in women taking valproate for epilepsy. N Engl J Med 1993;329: 1383-8.
  • BiIo L, Meo R, Valentine R, Di Carlo C, Striano S, Nappi C. Characterization of the reproductive endocrine disorders in women with epilepsy. J Clin Endo Metab 2001;86:2950-6.
  • Bauer J, Jarre A, Klingmuller D, Elger CE. Polycystic ovary syndrome in patients with focal epilepsy: a study in 93 women. Epilepsy Res 2000;41:163-7.
  • Herzog AG, Seibel MM, Schomer DL, Vaitukaitis JL, Geschwind N. Reproductive endocrine disorders in women with partial seizures of temporal lobe origin. Arch Neurol 1986;43: 341-6.
  • O'Donovan C, Kusumakar V, Graves GR, Bird DC. Menstrual abnormalities and polycystic ovary syndrome in women taking valproate for bipolar mood disorder. J Clin Psychiatry 2002;63:322-30.
  • Rasgon NL, Altshuler LL, Gudeman D, Burt VK, Tanavoli S, Hendrick V, et al. Medication status and polycystic ovary syndrome in women with bipolar disorder: a preliminary report. J Clin Psychiatry 2000;61:173-8.
  • Eberle AJ. Valproate and polycystic ovaries. J Am Acad Child Adolesc Psychiatry 1998;37:1009.
  • Garland EJ, Behr R. Hormonal effects of valproic acid? J Am Acad Child Adolesc Psychiatry 1996;35:1424-5.
  • Geller B, Luby J. Child and adolescent bipolar disorder: a review of the past 10 years. J Am Acad Child Adolesc Psychiatry 1997;36:1168-76.
  • Irwin M, Masand P. Valproate and polycystic ovaries. J Am Acad Child Adolesc Psychiatry 1998;37:9-10.
  • Johnston HF. More on valproate and polycystic ovaries. J Am Acad Child Adolesc Psychiatry 1999;38:354.
  • Taylor AE, Dunaif AE. Polycystic ovary syndrome andhyperandrogenism. In: Ryan KJ, Berkowitz RS, Barbieri RL, Dunaif AE, eds. Kistner's gynecology and women's health. 7th ed. Boston: Mosby, 1999:373-95.
  • Zawadzki JK, Dunaif A. Diagnostic criteria for polycystic ovary syndrome: towards a rational approach. In: Dunaif A, Givens JR, Haseltine FP, Merriam GR, eds. Current issues in endocrinology and metabolism: polycystic ovarian syndrome. Boston: Blackwell, 1992:377-84.
  • Franks S. Polycystic ovary syndrome. N Engl J Med 1995;333:853-61.
  • Carmina E, Koyama T, Chang L, Stanczyk FZ, Lobo RA. Does ethnicity influence the prevalence of adrenal hyperandrogenism and insulin resistance in polycystic ovary syndrome? Am J Obstet Gynecol 1992;167:1807-12.
  • Conway GS, Honour JW, Jacobs HS. Heterogeneity of the polycystic ovary syndrome: clinical, endocrine and ultrasound features in 556 patients. Clin Endocrinol (Oxford) 1989;30:459-70.
  • Asuncion M, Calvo RM, San Millan JL, Sancho J, Avila S, Escobar-Morreale HF. A prospective study of the prevalence of the polycystic ovary syndrome in unselected Caucasian women from Spain. J Clin Endo Metab 2000;85:2434-8.
  • Diamanti-Kaundarakis E, Kouli CR, Bergiele AT, Filandra FA, Tsianateli TC, Spina GG, et al. A survey of the polycystic ovary syndrome in the Greek island of Lesbos: hormonal and metabolic profile. J Clin Endocrinol Metab 1999;84:4006-11.
  • Knochenhauer ES, Key TJ, Kahsar-Miller M, Waggoner W, Boots LR, Azziz R. Prevalence of the polycystic ovary syndrome in unselected black and white women of the southeastern United States: a prospective study. J Clin Endocrinol Metab 1998;83:3078-82.
  • Pasquali R, Casimirri F. The impact of obesity on hyperandrogenism and polycystic ovary syndrome in premenopausal women. Clin Endocrinol (Oxford) 1993;39:1-16.
  • PasquaU R, Antenucri D, Casimirri F, Venturoli S, Paradisi R, Fabbri R, et al. Clinical and hormonal characteristics of obese amenorrheic hyperandrogenic women before and after weight loss. J Clin Endocrinol Metab 1989;68:173-9.
  • Taylor AE. Polycystic ovary syndrome. Endocrinol Metab Clin North Am 1998;27:877-902.
  • Hall JE. Polycystic ovarian disease as a neuroendocrine disorder of the female reproductive axis. Endocrinol Metab Clin North Am 1993;22:75-92.
  • Morales AJ, Laughlin GA, Butzow T, Maheshwari H, Baumann G, Yen SS. Insulin, somatotropic, and luteinizing hormone axes in lean and obese women with polycystic ovary syndrome: common and distinct features. J Clin Endocrinol Metab 1996;81:2854-64.
  • Dunaif A, Segal KR, Futterweit W, Dobrjansky A. Profound peripheral insulin resistance, independent of obesity, in polycystic ovary syndrome. Diabetes 1989;38:1165-74.
  • Stein IF, Leventhal ML. Amenorrhea associated with bilateral polycystic ovaries. Am J Obstet Gynecol 1935;29:181-91.
  • Adams J, Poison DW, Franks S. Prevalence of polycystic ovaries in women with anovulation and idiopathic hirsutism. Br Med J (Clin Res Ed) 1986;293:356-9.
  • Poison DW, Adams J, Wadsworth J, Franks S. Polycystic ovaries-a common finding in normal women. Lancet 1988;1: 870-2.
  • Brook CG, Jacobs HS, Stanhope R. Polycystic ovaries in childhood. Br Med J (Clin Res Ed) 1988;296:878.
  • Dramusic V, Rajan U, Chan P, Ratnam SS, Wong YC. Adolescent polycystic ovary syndrome. Ann N Y Acad Sci 1997;816:194-208.
  • Venturoli S, Porcu E, Fabbri R, Paradisi R, Ruggeri S, Bolelli G, et al. Menstrual irregularities in adolescents: hormonal pattern and ovarian morphology. Hormone Res 1986;24:269-79.
  • Caprio S. Insulin: the other anabolic hormone of puberty. Acta Paediatr Suppl 1999;88:84-7.
  • Ehrmann DA, Barnes RB, Rosenfield RL, Cavaghan MK, Imperial J. Prevalence of impaired glucose tolerance and diabetes in women with polycystic ovary syndrome. Diabetes Care 1999;22:141-6.
  • Legro RS, Kunselman AR, Dodson WC, Dunaif A. Prevalence and predictors of risk for type 2 diabetes mellitus and impaired glucose tolerance in polycystic ovary syndrome: a prospective, controlled study in 254 affected women. J Clin Endocrinol Metab 1999;84:165-9.
  • Hull MG. Epidemiology of infertility and polycystic ovarian disease: endocrinological and demographic studies. Gynecol Endocrinol 1987;1:235-45.
  • Sherman AI, Brown S. The precursors of endometrial carcinoma. Am J Obstet Gynecol 1979;135:947-56.
  • Dahlgren E, Johansson S, Lindstedt G, Knutsson F, Oden A, Janson PO, et al. Women with polycystic ovary syndrome wedge resected in 1956 to 1965: a long-term follow-up focusing on natural history and circulating hormones. Fertil Steril 1992;57:505-13.
  • Pierpoint T, McKeigue PM, Isaacs AJ, Wild SH, Jacobs HS. Mortality of women with polycystic ovary syndrome at long-term follow-up. J Clin Epidemiol 1998;51:581-6.
  • Hague WM, Adams J, Reeders ST, Peto TE, Jacobs HS. Familial polycystic ovaries: a genetic disease? Clin Endocrinol (Oxford) 1988;29:593-605.
  • Legro RS, Spielman R, Urbanek M, Driscoll D, Strauss JF 3rd, Dunaif A. Phenotype and genotype in polycystic ovary syndrome. Recent Progr Hormone Res 1998;53:217-56.
  • BiIo L, Meo R, Nappi C, Annunziato L, Striano S, Colao AM, et al. Reproductive endocrine disorders in women with primary generalized epilepsy. Epilepsia 1988;29:612-9.
  • Murialdo G, Galimberti CA, Magri F, Sampaolo P, Copello F, Gianelli MV, et al. Menstrual cycle and ovary alterations in women with epilepsy on antiepileptic therapy. J Endocrinol Invest 1997;20:519-26.
  • Vainionpaa LK, Rattya J, Knip M, Tapanainen JS, Pakarinen AJ, Lanning P, et al. Valproate-induced hyperandrogenism during pubertal maturation in girls with epilepsy. Ann Neurol 1999;46:444-60.
  • Rattya J, Vainionpaa L, Knip M, Lanning P, Isojarvi JI. The effects of valproate, carbamazepine, and oxcarbazepine on growth and sexual maturation in girls with epilepsy. Pediatrics 1999;103:688-93.
  • Lundberg B, Nergardh A, Ritzen EM, Samuelsson K. Influence of valproic acid on the gonadotropin-releasing hormone test in puberty. Acta Paediatr Scand 1986;76:787-92.
  • Matsunaga H, Sarai M. Elevated serum LH and androgens in affective disorder related to the menstrual cycle: with reference to polycystic ovary syndrome. Jpn J Psychiatry Neurol 1993;47:826-42.
  • Chadwick D. Standard approach to antiepileptic drug treatment in the United Kingdom. Epilepsia 1994;36(suppl 4): S3-10.
  • Pellock JM. Standard approach to antiepileptic drug treatment in the United States. Epilepsia 1994;36(suppl 4):S11-8.
  • Joffe H, Taylor AE, Hall JE. Polycystic ovarian syndrome--relationship to epilepsy and antiepileptic drug therapy. J Clin Endocrinol Metab 2001;867:2946-9.
  • Herzog AG. Polycystic ovarian syndrome in women with epilepsy: epileptic or iatrogenic? Ann Neurol 1996;39:669-90.
  • Nelson VL, Wickenheisser JK, Cockrell JE, Legro RS, Strauss JF, McAllister JM. The antiepileptic valproate is a potent regulator of androgen biosynthesis in human ovarian theca cells [abstract]. Endocrine Society Annual Meeting, San Franciso, CA, June 2002 [Report no. P2-609].
  • Dodge JC, Illig AM, Snyder PJ, Badura LL. GABA levels within the medial preoptic area: effects of chronic administration of sodium valproic acid. Psychoneuroendocrinology 2000;26:619-34.
  • niig AM, Melia K, Snyder PJ, Badura LL. Sodium valproate alters GnRH-GABA interactions during development in seizureprone mice. Brain Res 2000;886:192-200.
  • Snyder PJ, Badura LL. A potential mechanism of slowed pubertal maturation after chronic administration of sodium valproic acid. Neurology 1998;60:922-6.
  • Loscher W. Valproate: a reappraisal of its pharmacodynamic properties and mechanisms of action. Prog Neurobiol 1999;68:31-69.
  • Moshe SL. Mechanisms of action of anticonvulsant agents. Neurology 2000;55:S32-40, S64-8 (discussion).
  • Isojarvi JI, Laatikainen TJ, Knip M, Pakarinen AJ, Juntunen KT, Myllyla W. Obesity and endocrine disorders in women taking valproate for epilepsy. Ann Neurol 1996;39:679-84.
  • Isojarvi JI, Rattya J, Myllyla W, Knip M, Koivunen R, Pakarinen AJ, et al. Valproate, lamotrigine, and insulin-mediated risks in women with epilepsy. Ann Neurol 1998;43:446-61.
  • Caro JF, Dohm LG, Furies WJ, Sinha MK. Cellular alterations in liver, skeletal muscle, and adipose tissue responsible for insulin resistance in obesity and type II diabetes. Diabetes Metab Rev 1989;5:665-89.
  • Mattson RH, Cramer JA, Colline JF. A comparison of valproate with carbamazepine for the treatment of complex partial seizures and secondarily generalized tonic-clonic seizures in adults. N Engl J Med 1992;327:765-71.
  • Dinesen H, Gram L, Andersen T, Dam M. Weight gain during treatment with valproate. Acta Neurol Scand 1984;70:65-9.
  • Rasgon N, Altshuler LL, Elman S, Frye MA, Gitlin M. Increased insulin resistance in women with bipolar disorder. Paper presented at American Psychiatric Association Annual Meeting, Philadelphia, PA, May 2002.
  • Vestergaard P, Poulstrup I, Schou M. Prospective studies on a lithium cohort. 3. Tremor, weight gain, diarrhea, psychological complaints. Acta Psychiatr Scand 1988;78:434-41.
  • Feldman D, Goldberg JF. A preliminary study of the relationship between clozapine-induced weight gain and menstrual irregularities in schizophrenic, schizoaffective, and bipolar women. Ann Clin Psychiatry 2002;14:17-21.
  • Lader M. Some adverse effects of antipsychotics: prevention and treatment. J Clin Psychiatry 1999;60(suppl 12):18-21.
  • Wirshing DA, Wirshing WC, Kysar L, Berisford MA, Goldstein D, Pashdag J, et al. Novel antipsychotics: comparison of weight gain liabilities. J Clin Psychiatry 1999;60:358-63.
  • McElroy SL, Keck, PE, Friedman, LM. Minimizing and managing antidepreesant side effects. J Clin Psychiatry 1995;56(suppl 2):49-55.
  • Hagg S, Joelsson L, Mjomdal T, Spigset O, Qja G, Dahlqyist R. Prevalence of diabetes and impaired glucose tolerance in patients treated with clozapine compared with patients treated with conventional depot neuroleptic medications. J Clin Psychiatry 1998;59:294-9.
  • Andersen GD. A mechanistic approach to antiepileptic drug interactions. Ann Pharmacother 1998;32:554-63.
  • Isojarvi JI, Pakarinen AJ, Ylipalosaari PJ, MyllyIa W. Serum hormones in male epileptic patients receiving anticonvulsant medication. Arch Neurol 1990;47:670-6.
  • Morrell MJ. Epilepsy in women: the science of why it is special. Neurology 1999;53(4 suppl 1):S28-42.
  • Kalra SP. Mandatory neuropeptide-steroid signaling for the preovulatory luteinizing hormone-releasing hormone discharge. Endocr Rev 1993;14:507-38.
  • Meldrum BS, Akbar MT, Chapman AG. Glutamate receptors and transporters in genetic and acquired models of epilepsy. Epilepsy Res 1999;36:189-204.
  • Mahesh VB, Braun DW. Neuroendocrine mechanisms underlying the control of gonadotropin secretion by steroids. Steroids 1998;63:252-6.
  • Dhandapani KM, Brann DW. The role of glutamate and nitric oxide in the reproductive neuroendocrine system. Biochem Cell Biol 2000;78:165-79.
  • Wood C, Larsen L, Williams R. Menstrual characteristics of 2,343 women attending the Shepherd Foundation. Aust NZJ Obstet Gynaecol 1979;19:107-10.
  • McKinlay SM, Brambilla DJ, Posner JG. The normal menopause transition. Maturitas 1992;14:103-15.
  • Hamner MB, Arvanitis LA, Miller BG, Link CG, Hong WW. Plasma prolactin in schizophrenia subjects treated wtih Seroquel. Psychopharmacol Bull 1996;32:107-10.
  • David SR, Taylor CC, Kinon BJ, Breier A. The effects of olanzapine, risperidone, and haloperidol on plasma prolactin levels in patients with schizophrenia. Clin Ther 2000;22:1085-96.
  • Kleinberg DL, Davis JM, de Coster R, Van Baelen B, Brecher M. Prolactin levels and adverse events in patiente treated with risperidone. J Clin Psychopharmacol 1999;19:57-61.
  • Wudarsky M, Nicolson R, Hamburger SD, Spechler L, Gochman P, Bedwell H, et al. Elevated prolactin in pediatric patiente on typical and atypical antipsychotics. J Child Adolesc Psychopharmacol 1999;9:239-45.

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