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Disorders of reproduction in patients with epilepsy

Reproduktionsstörungen bei Patienten mit Epilepsie

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Abstract

Disorders of reproduction are unusually common among people with epilepsy. They are generally associated with and may be the consequence of reproductive endocrine disorders. Epilepsy itself and epileptic seizures have been implicated in their pathophysiology.

This review focuses on how temporolimbic dysfunction in epilepsy might disrupt normal neuroendocrine regulation and promote the development of reproductive endocrine disorders. The particular nature of the dysregulation may relate to the laterality and focality of the epilepsy and some hormonal changes may develop in close temporal relation to the occurrence of epileptiform discharges. In women, reproductive endocrine disorders include polycystic ovary syndrome, hypothalamic amenorrhea, functional hyperprolactinemia, and premature menopause. In men, hypogonadism may be hypogonadotropic, hypergonadotropic or related to hyperprolactinemia. The significance of these reproductive endocrine disorders is that they may contribute not only to sexual dysfunction and infertility, but may also have an adverse impact on seizure control.

This review also includes sections on special considerations in the treatment of reproductive endocrine disorders for women and men with epilepsy.

Zusammenfassung

Reproduktionsstörungen sind unter Menschen mit Epilepsie ungewöhnlich weit verbreitet. Sie sind allgemein mit reproduktiven endokrinen Störungen verbunden und können auch deren Resultat sein. In ihrer Pathophysiologie spielen die Epilepsie selbst sowie epileptische Anfälle eine Rolle.

Dieser Überblick befasst sich mit der Frage, wie temporolimbische Dysfunktion bei Epilepsie die normale neuroendokrine Regulation stören und die Entwicklung von reproduktiven endokrinen Störungen fördern kann. Die besondere Natur der Dysregulation mag mit der Lateralität und Fokalität der Epilepsie zusammenhängen und manche hormonelle Veränderungen können sich im engen zeitlichen Zusammenhang zum Auftreten von epileptiformen Entladungen entwickeln. Bei Frauen umfassen reproduktive endokrine Störungen das polyzystische Ovar-Syndrom, die hypothalamische Amenorrhoe, die funktionelle Hyperprolaktinämie und die vorzeitige Menopause. Bei Männern kann der Hypogonadismus hypogonadotrop, hypergonadotrop oder durch Hyperprolaktinämie verursacht sein. Die Bedeutung dieser reproduktiven Erkrankungen ist, dass sie nicht nur zu sexueller Dysfunktion und Unfruchtbarkeit führen, sondern auch ungünstige Auswirkungen auf die Anfallsbehandlung haben können.

Der Überblick enthält auch Abschnitte zu speziellen Überlegungen in der Behandlung von reproduktiven endokrinen Störungen bei Frauen und Männern mit Epilepsie.

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References

  1. Herzog AG (1989) A hypothesis to integrate partial seizures of temporal lobe origin and reproductive disorders. Epilepsy Res 3:151–159

    Article  CAS  PubMed  Google Scholar 

  2. Herzog AG, Seibel MM, Schomer DL et al (1986) Reproductive endocrine disorders in women with partial seizures of temporal lobe origin. Arch Neurol 43:341–346

    Article  CAS  PubMed  Google Scholar 

  3. Herzog AG, Seibel MM, Schomer DL et al (1986) Reproductive endocrine disorders in men with partial seizures of temporal lobe origin. Arch Neurol 43:347–350

    Article  CAS  PubMed  Google Scholar 

  4. Herzog AG, Drislane FW, Schomer DL et al (2005) Differential effects of antiepileptic drugs on sexual function and reproductive hormones in men with epilepsy. Neurology 65:1016–1020

    Article  CAS  PubMed  Google Scholar 

  5. Isojarvi JI, Laatkainen TJ, Pakarinen AJ et al (1993) Polycystic ovaries and hyperandrogenism in women taking valproate for epilepsy. N Engl J Med 329:1383–1388

    Article  CAS  PubMed  Google Scholar 

  6. Herzog AG (2002) Reproductive endocrine regulation in men with epilepsy: effects on reproductive function and neuronal excitability. Ann Neurol 51:539–542

    Article  CAS  PubMed  Google Scholar 

  7. Herzog AG, Coleman AE, Jacobs AR et al (2003) Interictal EEG discharges, reproductive hormones and menstrual disorders in epilepsy. Ann Neurol 54:625–637

    Article  PubMed  Google Scholar 

  8. Hamed SA, Hamed EA, Shokry M, Omar H, Abdellah MM (2007) The reproductive conditions and lipid profile in females with epilepsy. Acta Neurol Scand 115:12–22

    Article  CAS  PubMed  Google Scholar 

  9. Svalheim S, Taubøll E, Bjørnenak T et al (2003) Do women with epilepsy have increased frequency of menstrual disturbances? Seizure 12:529–533

    Article  PubMed  Google Scholar 

  10. Herzog AG, Friedman MN (2002) Menstrual cycle interval and ovulation in women with localization-related epilepsy. Neurology 57:2133–2135

    Article  Google Scholar 

  11. Backstrom T (1976) Epileptic seizures in women related to plasma estrogen and progesterone during the menstrual cycle. Acta Neurol Scandinav 54:321–347

    Article  CAS  Google Scholar 

  12. Herzog AG, Klein P, Ransil BJ (1997) Three patterns of catamenial epilepsy. Epilepsia 38:1082–1088

    Article  CAS  PubMed  Google Scholar 

  13. Herzog AG, Fowler KM, Sperling MR, Liporace J, Kalayjian LA, Heck C, Krauss GL, Dworetzky BA, Pennell PB (2011) and the Progesterone Trial Study Group. Variation of Seizure Frequency with Ovulatory Status of Menstrual Cycles. Epilepsia 52:1843–1848

    Article  PubMed Central  PubMed  Google Scholar 

  14. Morrell MJ, Giudice L, Flynn KL et al (2002) Predictors of ovulatory failure in women with epilepsy. Ann Neurol 52:704–711

    Article  PubMed  Google Scholar 

  15. Lofgren E, Mikkonen K, Tolonen U, Pakarinen A, Koivunen R, Myllyla VV, Tapanainen JS, Isojarvi JI (2007) Reproductive endocrine function in women with epilepsy: The role of epilepsy type and medication. In Epilepsy Behav 10:77–83

    Article  Google Scholar 

  16. Schupf N, Ottman R (1994) Likelihood of pregnancy in individuals with idiopathic/cryptogenic epilepsy: social and biologic influences. Epilepsia 35:750–756

    Article  CAS  PubMed  Google Scholar 

  17. Dansky LV, Andermann E, Andermann F (1980) Marriage and fertility in epileptic patients. Epilepsia 21:261–271

    Article  CAS  PubMed  Google Scholar 

  18. Webber MP, Hauser WA, Ottman R, Annegers JF (1986) Fertility in persons with epilepsy: 1935–1974. Epilepsia 27:746–752

    Article  CAS  PubMed  Google Scholar 

  19. Bilo L, Meo R, Nappi C et al (1988) Reproductive endocrine disorders in women with primary generalized epilepsy. Epilepsia 29:612–619

    Article  CAS  PubMed  Google Scholar 

  20. Herzog AG, Schachter SC (2001) On the association between valproate and polycystic ovary syndrome. Epilepsia 42:311–315

    Article  CAS  PubMed  Google Scholar 

  21. Eagleson CA, Gingrich MB, Pastor CL, Arora TK, Burt CM, Evans WS, Marshall JC (2000) Polycystic ovarian syndrome: evidence that flutamide restores sensitivity of the gonadotropin-releasing hormone pulse generator to inhibition by estradiol and progesterone. J Clin Endocrinol Metab 85:4047–4052

    CAS  PubMed  Google Scholar 

  22. Lobo RA (1995) A disorder without identity: “HCA,” “PCO,” “PCOD,” “PCOS,” “SLS,” What are we to call it? Fertil Steril 63:1158–1160

    CAS  PubMed  Google Scholar 

  23. Klein P, Serje A, Pezzullo JC (2001) Premature ovarian failure in women with epilepsy. Epilepsia 42:1584–1589

    Article  CAS  PubMed  Google Scholar 

  24. Harden CL, Koppel BS, Herzog AG et al (2003) Seizure frequency is associated with age of menopause in women with epilepsy. Neurology 61:451–455

    Article  CAS  PubMed  Google Scholar 

  25. Herzog AG (1993) A relationship between particular reproductive endocrine disorders and the laterality of epileptiform discharges in women with epilepsy. Neurology 43:1907–1910

    Article  CAS  PubMed  Google Scholar 

  26. Kalinin VV, Zheleznova EV (2007) Chronology and evolution of temporal lobe epilepsy and endocrine reproductive function in females. Relationships with foci laterality and catameniality. Epilepsy and Behavior 11:185–191

    Article  PubMed  Google Scholar 

  27. Bilo L, Meo R, Valentino R, Buscaino GA, Striano S, Nappi C (1991) Abnormal patterns of luteinizing hormone pulsatility in women with epilepsy. Fertil Steril 55:705–711

    CAS  PubMed  Google Scholar 

  28. Knobil E (1980) The neuroendocrine control of the menstrual cycle. Recent Prog Horm Res 36:53–80

    CAS  PubMed  Google Scholar 

  29. Spratt DI, Finkelstein JS, Butler JP et al (1987) Effects of increasing the frequency of low doses of gonadotropin releasing hormone (GnRH) on gonadotropin secretion in GnRH-deficient men. J Clin Endocrinol Metab 64:1179

    Article  CAS  PubMed  Google Scholar 

  30. Zolovick AJ (1972) Effects of lesions and electrical stimulation of the amygdala on hypothalamic-hypophyseal regulation. In: Eleftheriou BE (Hrsg) The Neurobiology of the Amygdala. Plenum Press, New York, NY

    Google Scholar 

  31. Kaada B (1972) Stimulation and regional ablation of the amygdaloid complex with reference to functional representations. In: Eleftheriou BE (Hrsg) The Neurobiology of the Amygdala. Plenum Press, New York, NY

    Google Scholar 

  32. Dreifuss JJ, Murphy JT, Gloor P (1968) Contrasting effects of two identified amygdaloid efferent pathways on single hypothalamic neurons. J Neurophysiol 31:237–248

    CAS  PubMed  Google Scholar 

  33. Silveira DC, Klein P, Ransil BJ et al (2000) Lateralized asymmetry in activation of hypothalamic neurons with unilateral amygdaloid seizures. Epilepsia 41:34–41

    Article  CAS  PubMed  Google Scholar 

  34. Amado D, Cavalheiro EA, Bentivoglio M (1993) Epilepsy and hormonal regulation: the patterns of GnRH and galanin immunoreactivity in the hypothalamus of epileptic female rats. Epilepsy Res 14:149–159

    Article  CAS  PubMed  Google Scholar 

  35. Friedman MN, Geula C, Holmes GL, Herzog AG (2002) GnRH-immunoreactive fiber changes with unilateral amygdala-kindled seizures. Epilepsy Res 52:73–77

    Article  CAS  PubMed  Google Scholar 

  36. Sanchez MA, Dominguez R (1995) Differential effects of unilateral lesions in the medial amygdala on spontaneous and induced ovulation. Brain Res Bull 38:313–317

    Article  CAS  PubMed  Google Scholar 

  37. Gerendai I, Csaba Z, Voko Z, Csernus V (1995) Involvement of a direct neural mechanism in the control of gonadal functions. J Steroid Biochem Molec Biol 53:299–305

    Article  CAS  PubMed  Google Scholar 

  38. Gerendai I, Halasz B (1997) Neuroendocrine asymmetry. Front Neuroendocrinol 18:354–381

    Article  CAS  PubMed  Google Scholar 

  39. Edwards HE, Burnham WM, Ng MM, Asa S, MacLusky NJ (1999) Limbic seizures alter reproductive function in the female rat. Epilepsia 40:1370–1377

    Article  CAS  PubMed  Google Scholar 

  40. Herzog AG (2007) Is there a lateralized asymmetry in the sensitivity of the brain to hormones in epilepsy? Epilepsy &amp Behavior 11:157–159

    Article  Google Scholar 

  41. Isojärvi JI, Taubøll E, Herzog AG (2005) Effects of antiepileptic drugs on reproductive endocrine function in individuals with epilepsy – a review. CNS 19:207–223

  42. Herzog AG (1996) Polycystic ovarian syndrome in women with epilepsy: epileptogenic or iatrogenic? Ann Neurol 39:559–560

    Article  CAS  PubMed  Google Scholar 

  43. Herzog AG (2015) Differential impact of antiepileptic drugs on the effects of contraceptive methods on seizures: interim findings of the epilepsy birth control registry. Seizure: Eur J Epilepsy. http://dx.doi.org/10.1016/j.seizure.2015.02.011

    Google Scholar 

  44. Taneja N, Kucheria K, Jain S, Maheshwari MC (1994) Effect of phenytoin on semen. Epilepsia 35:136–140

    Article  CAS  PubMed  Google Scholar 

  45. Stoffel-Wagner B, Bauer J, Flugel D et al (1998) Serum sex hormones are altered in patients with chronic temporal lobe epilepsy receiving anticonvulsant medication. Epilepsia 39:1164–1173

    Article  CAS  PubMed  Google Scholar 

  46. Christiansen P, Deigaard J, Lund M (1975) Potens, fertilitet of konshormonudskillelse hos yngre manglige epilepsilidend. Ugeskr Laeger 137:2402–2405

    CAS  PubMed  Google Scholar 

  47. Fenwick PBC, Mercer C, Grant R et al (1986) Nocturnal penile tumescence and serum testosterone levels. Arch Sex Behav 15:13–21

    Article  CAS  PubMed  Google Scholar 

  48. MacPhee JA, Larkin JG, Butler E, Graham HB, Brodie MJ (1988) Circulating hormones and pituitary responsiveness in young epileptic men receiving long-term antiepileptic medication. Epilepsia 29:468–475

    Article  CAS  PubMed  Google Scholar 

  49. Toone BK, Wheeler M, Nanjee M et al (1983) Sex hormones, sexual activity and plasma anticonvulsant levels in male epileptics. J Neurol, Neurosurg Psychiat 46:824–826

    Article  CAS  Google Scholar 

  50. Duncan S, Blacklaw J, Beastall GH, Brodie MJ (1999) Antiepileptic drug therapy and sexual function in men with epilepsy. Epilepsia 40:197–204

    Article  CAS  PubMed  Google Scholar 

  51. Taylor DC (1969) Sexual behavior and temporal lobe epilepsy. Arch Neurol 21:510–516

    Article  CAS  PubMed  Google Scholar 

  52. Sapolsky RM (1985) Stress-induced suppression of testicular function in the wild baboon: role of glucocorticoids. Endocrinol 116:2273–2278

    Article  CAS  Google Scholar 

  53. Gallagher BB, Murvin A, Flanigin HF et al (1984) Pituitary and adrenal function in epileptic patients. Epilepsia 25:683–689

    Article  CAS  PubMed  Google Scholar 

  54. Clarke D, Fearon U, Cunningham SK, McKenna TJ (1996) The steroidogenic effects of b-endorphin and joining peptide: a potential role in the modulation of adrenal androgen production. J Endocrinol 151:301–307

    Article  CAS  PubMed  Google Scholar 

  55. van Goozen SHM, van den Ban E, Matthys W et al (2000) Increased adrenal androgen functioning in children with oppositional defiant disorder: a comparison with psychiatric and normal controls. J Am Acad Child Adolesc Psychiatry 39:1446–1451

    Article  PubMed  Google Scholar 

  56. Sapolsky RM, Krey LC (1988) Stress-induced suppression of luteinizing hormone concentrations in wild baboons: role of opiates. J Clin Endocrinol Metab 66:722–726

    Article  CAS  PubMed  Google Scholar 

  57. Jacobs AR, Edelheit PB, Coleman AE, Herzog AG (1999) Late onset congenital adrenal hyperplasia: a treatable cause of anxiety. Biol Psychiat 46:856–859

    Article  CAS  PubMed  Google Scholar 

  58. Murialdo G, Galimberti CA, Fonzi S et al (1995) Sex hormones and pituitary function in male epileptic patients with altered or normal sexuality. Epilepsia 36:358–363

    Article  Google Scholar 

  59. Feeney DM, Gullotta FP, Gilmore W (1998) Hyposexuality produced by temporal lobe epilepsy in the cat. Epilepsia 39:140–149

    Article  CAS  PubMed  Google Scholar 

  60. Edwards HE, McIntyre Burnham W, MacLusky NJ (1999) Partial and generalized seizures affect reproductive physiology differentially in the male rat. Epilepsia 40(11):1490–1498

    Article  CAS  PubMed  Google Scholar 

  61. Herzog AG, Russell V, Vaitukaitis JL, Geschwind N (1982) Neuroendocrine dysfunction in temporal lobe epilepsy. Arch Neurol 39:133–135

    Article  CAS  PubMed  Google Scholar 

  62. Herzog AG, Drislane FW, Schomer DL et al (1990) Abnormal pulsatile secretion of luteinizing hormone in men with epilepsy: Relationship to lateralization of epileptiform discharges. Neurol 40:1557–1561

    Article  CAS  Google Scholar 

  63. Quigg M, Kiely JM, Shneker B et al (2002) Interictal and postictal alterations of pulsatile secretion of luteinizing hormone in temporal lobe epilepsy in men. Ann Neurol 51:559–566

    Article  PubMed  Google Scholar 

  64. Sperling MR, Pritchard PB, Engel J, Daniel C, Sagel J (1986) Prolactin in partial epilepsy: an indicator of limbic seizures. Ann Neurol 20:716–722

    Article  CAS  PubMed  Google Scholar 

  65. Bear DM, Fedio P (1977) Quantitative analysis of interictal behavior in temporal lobe epilepsy. Arch Neurol 34:454–467

    Article  CAS  PubMed  Google Scholar 

  66. Daniele A, Azzoni A, Bizzi A et al (1997) Sexual behavior and hemispheric laterality of the focus in patients with temporal lobe epilepsy. Biol Psychiatry 42:617–624

    Article  CAS  PubMed  Google Scholar 

  67. Nordeen EJ, Yahr P (1982) Hemispheric asymmetries in the behavioral and hormonal effects of sexually differentiating mammalian brain. Science 218:391–393

    Article  CAS  PubMed  Google Scholar 

  68. Bauer J, Blumenthal S, Reuber M, Stoffel-Wagner B (2004) Epilepsy syndrome, focus location, and treatment choice affect testicular function in men with epilepsy. Neurology 62:243–246

    Article  PubMed  Google Scholar 

  69. Bauer J, Stoffel-Wagner B, Flugel D, Kluge M, Schramm J, Bidlingmaier F, Elger CE (2000) Serum androgens return to normal after temporal lobe epilepsy surgery in men. Neurology 55:820–824

    Article  CAS  PubMed  Google Scholar 

  70. Blumer D, Walker AE (1967) Sexual behavior in temporal lobe epilepsy. A study of the effects of temporal lobectomy on sexual behavior. Arch Neurol 16:37–43.70 2

  71. Hamed S, Mohamed K, El-Taher A, Hamed E, Omar H (2006) The sexual and reproductive health in men with generalized epilepsy: a multidisciplinary evaluation. Int J Impot Res 18:287–295

  72. Wong M, Moss R (1992) Long-term and short-term electrophysiological effects of estrogen on the synaptic properties of hippocampal CA1 neurons. J Neurosci 12:3217–3225

    CAS  PubMed  Google Scholar 

  73. Frye CA, Rhodes ME, Walf AA, Harney JP (2001) Testosterone reduces pentylenetetrazole-induced ictal activity of wild type mice but not those deficient in type I 5a-reductase. Brain Res 918:182–186

    Article  CAS  PubMed  Google Scholar 

  74. Sachedo R, Sathyan RR (2005) Amelioration of erectile dysfunction following a switch from carbamazepine to oxcarbazepine: recent clinical experience. Curr Med Res Opin 21(7):1065–1068

    Article  Google Scholar 

  75. Herzog AG, Klein P, Jacobs AR (1998) Testosterone versus testosterone and testolactone in treating reproductive and sexual dysfunction in men with epilepsy and hypogonadism. Neurol 50:782–784

    Article  CAS  Google Scholar 

  76. Herzog AG, Farina EL, Drislane FW, Schomer DL, Smithson SD, Fowler KM, Dworetzky BA, Bromfield EB (2010) A comparison of anastrozole and testosterone versus placebo and testosterone treatment of sexual dysfunction in men with epilepsy and hypogonadism. Epilepsy &amp Behavior 17:264–271

    Article  Google Scholar 

  77. Nieoczym D, Soca K, Rundfeldt C, Wlaz P (2010) Pharmacological Reports 62:383–391

    Article  CAS  PubMed  Google Scholar 

  78. Riazi K, Roshanpour M, Rafiei-Tabatabaei N, Homayoun H, Ebrahimi F, Dehpour AR (2006) The proconvulsant effect of sildenafil in mice: role of nitric oxide-cGMP pathway. Br J Pharmacol 147:935–943

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  79. Gilad R, Lampl Y, Eshel Y, Sadeh M (2002) Tonic-clonic seizures in patients taking sildenafil. BMJ 325:869–869

    Article  PubMed Central  PubMed  Google Scholar 

  80. Koussa S, Hage CS, Tohmé A, Riachi M (2006) Epileptic seizures and vardenafil. Rev Neurol 162:651–652

    Article  CAS  PubMed  Google Scholar 

  81. Prostin VR (1991) Pediatric Package insert, Upjohn (U.S.), rev 2/90, rec 9/91

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  1. Harvard Neuroendocrine Unit, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, 02215, Boston, MA, USA

    A. G. Herzog M.D.

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Herzog, A.G. Disorders of reproduction in patients with epilepsy. Z. Epileptol. 28, 254–263 (2015). https://doi.org/10.1007/s10309-015-0012-7

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