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Antiepileptic Drugs and Becoming Pregnant

  • MJ Eadie
  • FJE Vajda

Abstract

There is published evidence that intake of antiepileptic drugs may affect the possibility of a woman becoming pregnant. Use of the drugs in her male partner may tend to decrease his libido and sexual activity, thus diminishing the chances of pregnancy occurring. A similar effect on libido may occur in the woman being treated with antiepileptic drugs, and the treatment may be responsible for circulating sex hormone concentration alterations that result in menstrual disturbances, this combination of effects tending to lessen fertility. Taking antiepileptic drugs in the non-pregnant state, particularly the older agents that induce formation of enzymes that catalyse the metabolism of steroidal sex hormones, also tends to decrease the circulating concentrations of steroidal hormones used for contraceptive purposes. This effect may increase the chances of undesired pregnancies occurring.

Keywords

Antiepileptic Drug Polycystic Ovary Premature Ovarian Failure Ethinyl Oestradiol Male Control Subject 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. Artama M, Isojärvi JI, Auvinen A (2006) Antiepileptic drug use and birth rate in patients with epilepsy – a population-based cohort study in Finland. Hum Reprod 21:2290–2295CrossRefPubMedGoogle Scholar
  2. Bartoli A, Gatti G, Cipolla G et al (1997) A double-blind, placebo-controlled study on the effect of vigabatrin on in vivo parameters of hepatic microsomal enzyme induction and on the kinetics of steroid oral contraceptives in healthy female volunteers. Epilepsia 38:702–707CrossRefPubMedGoogle Scholar
  3. Bilo L, Meo R, Valentino R, Di Carlo C, Striano S, Nappi C (2001) Characterization of reproductive endocrine disorders in women with epilepsy. J Clin Endocrinol Metab 86:2950–2956CrossRefPubMedGoogle Scholar
  4. Cawello W, Rosenkranz B, Schmid B, Wierich W (2013) Pharmacodynamic and pharmacokinetic evaluation of coadministration of lacosamide and an oral contraceptive (levonorgestrel plus ethinylestradiol) in healthy female volunteers. Epilepsia 54:530–536CrossRefPubMedGoogle Scholar
  5. Coulam CB, Annegers JF (1979) Do anticonvulsants reduce the efficacy of oral contraceptives? Epilepsia 20:519–525CrossRefPubMedGoogle Scholar
  6. Crawford PM (2009) Managing epilepsy in women of childbearing age. Drug Saf 32:293–307CrossRefPubMedGoogle Scholar
  7. Crawford P, Chadwick D, Cleland P, Tjia J, Cowie A, Back DJ, Orme ML (1986) The lack of effect of sodium valproate on the pharmacokinetics of oral contraceptive steroids. Contraception 33:23–29CrossRefPubMedGoogle Scholar
  8. Crawford P, Chadwick DJ, Martin C, Tjia J, Back DJ, Orme M (1990) The interaction of phenytoin and carbamazepine with combined oral contraceptive steroids. Br J Clin Pharmacol 30:892–896PubMedCentralCrossRefPubMedGoogle Scholar
  9. Davis AR, Westhoff CL, Stanczyk FZ (2011) Carbamazepine coadministration with an oral contraceptive: effects on steroid pharmacokinetics, ovulation, and bleeding. Epilepsia 52:243–247PubMedCentralPubMedGoogle Scholar
  10. Doose DR, Wang SS, Padmanabhan M, Schwabe S, Jacobs D, Bialer M (2003) Effect of topiramate or carbamazepine on the pharmacokinetics of an oral contraceptive containing norethindrone and ethinyl estradiol in healthy obese and nonobese female subjects. Epilepsia 44:540–549CrossRefPubMedGoogle Scholar
  11. Eldon MA, Underwood BA, Randinitis EJ, Sedman AJ (1998) Gabapentin does not interact with a contraceptive regimen of norethindrone acetate and ethinyl estradiol. Neurology 50:1146–1148CrossRefPubMedGoogle Scholar
  12. Falcão A, Vaz-da-Silva M, Gama H, Nunes T, Almeida L, Soares-da-Silva P (2013) Effect of eslicarbazepine acetate on the pharmacokinetics of a combined ethinylestradiol/ oral contraceptive in healthy women. Epilepsy Res 105:368–376CrossRefPubMedGoogle Scholar
  13. Fattore C, Cipolla G, Gatti G, Limido GL, Sturm Y, Bernasconi C, Perucca E (1999) Induction of ethinylestradiol and levonorgestrel metabolism by oxcarbazepine in healthy women. Epilepsia 40:783–787CrossRefPubMedGoogle Scholar
  14. Gaffield ME, Culwell KR, Lee CR (2011) The use of hormonal contraception among women taking anticonvulsant therapy. Contraception 83:16–29CrossRefPubMedGoogle Scholar
  15. Grabowska-Grzyb A, Nagańska E, Wolańczyk T (2006) Hypersexuality in two patients with epilepsy treated with lamotrigine. Epilepsy Behav 8:663–665CrossRefPubMedGoogle Scholar
  16. Griffith SG, Dai Y (2004) Effect of zonisamide on the pharmacokinetics and pharmacodynamics of a combination ethinyl estradiol-norethindrone oral contraceptive in healthy women. Clin Ther 26:2056–2065CrossRefPubMedGoogle Scholar
  17. Hamed SA (2008) Neuroendocrine hormonal conditions in epilepsy: relationship to reproductive and sexual functions. Neurologist 14:157–169CrossRefPubMedGoogle Scholar
  18. Harden CL (2006) Sexuality in men and women with epilepsy. CNS Spectr 11(8 Suppl 9):13–18PubMedGoogle Scholar
  19. Isojärvi J (2008) Disorders of reproduction in patients with epilepsy: antiepileptic drug related mechanisms. Seizure 17:111–119CrossRefPubMedGoogle Scholar
  20. Isojarvi JI, Tapanainen JS (2000) Valproate, hyperandrogenism, and polycystic ovaries: a report of 3 cases. Arch Neurol 57:1064–1068CrossRefPubMedGoogle Scholar
  21. Isojärvi JI, Löfgren E, Juntunen KS, Pakarinen AJ, Päivänsalo M, Rautakorpi I, Tuomivaara L (2004) Effect of epilepsy and antiepileptic drugs on male reproductive health. Neurology 62:247–253CrossRefPubMedGoogle Scholar
  22. Jalava M, Sillanpää M (1997) Reproductive activity and offspring health of young adults with childhood-onset epilepsy: a controlled study. Epilepsia 38:532–540CrossRefPubMedGoogle Scholar
  23. Jankovic SM, Jankovic SV, Kostic J, Kostic I, Jakovljevic M (2006) Inhibitory effects of selected antiepileptics on spontaneous motility of isolated human oviducts. Eur J Clin Pharmacol 62:707–712CrossRefPubMedGoogle Scholar
  24. Kariuki JG, Joshi MD, Adam AM, Kwasa TO, Machoki M (2008) Fertility rate of epileptic women at Kenyatta National Hospital. East Afr Med J 85:341–346CrossRefPubMedGoogle Scholar
  25. Klein P, Serje A, Pezzullo JC (2001) Premature ovarian failure in women with epilepsy. Epilepsia 42:1584–1589CrossRefPubMedGoogle Scholar
  26. Livingstone S (1972) Comprehensive management of epilepsy in infancy, childhood and adolescence. Charles C Thomas, SpringfieldGoogle Scholar
  27. Luef G, Krämer G, Stefan H (2009) Oxcarbazepine treatment in male epilepsy patients improves pre-existing sexual dysfunction. Acta Neurol Scand 119:94–99CrossRefPubMedGoogle Scholar
  28. Mattson RH, Cramer JA, Collins JF et al (1985) Comparison of carbamazepine, phenobarbital, phenytoin and primidone in partial and secondarily generalized tonic-clonic seizures. N Engl J Med 313:145–151CrossRefPubMedGoogle Scholar
  29. Najafi MR, Ansari B, Zare M, Fatehi F, Sonbolestan A (2012) Effects of antiepileptic drugs on sexual function and reproductive hormones of male epileptic patients. Iran J Neurol 11:37–41PubMedCentralPubMedGoogle Scholar
  30. Pennell PB (2009) Hormonal aspects of epilepsy. Neurol Clin 27:941–965PubMedCentralCrossRefPubMedGoogle Scholar
  31. Ragueneau-Majlessi I, Levy RH, Janik F (2002) Levetiracetam does not alter the pharmacokinetics of an oral contraceptive in healthy women. Epilepsia 43:697–702CrossRefPubMedGoogle Scholar
  32. Reis RM, de Angelo AG, Sakamoto AC, Ferriani RA, Lara LA (2013) Altered sexual and reproductive functions in epileptic men taking carbamazepine. J Sex Med 10:493–499CrossRefPubMedGoogle Scholar
  33. Rosenfeld WE, Doose DR, Walker SA, Nayak RK (1997) Effect of topiramate on the pharmacokinetics of an oral contraceptive containing norethindrone and ethinyl estradiol in patients with epilepsy. Epilepsia 38:317–323CrossRefPubMedGoogle Scholar
  34. Røste LS, Taubøll E, Haugen TB, Bjørnenak T, Saetre ER, Gjerstad L (2003) Alterations in semen parameters in men with epilepsy treated with valproate or carbamazepine monotherapy. Eur J Neurol 10:501–506CrossRefPubMedGoogle Scholar
  35. Saano V, Glue P, Banfield CR et al (1995) Effects of felbamate on the pharmacokinetics of a low-dose combination oral contraceptive. Clin Pharmacol Ther 58:523–531CrossRefPubMedGoogle Scholar
  36. Schindlbeck C, Janni W, Friese K (2006) Failure of Implanon contraception in a patient taking carbamazepin for epilepsia. Arch Gynecol Obstet 273:255–256CrossRefPubMedGoogle Scholar
  37. Sidhu J, Job S, Singh S, Philipson R (2006) The pharmacokinetic and pharmacodynamic consequences of the co-administration of lamotrigine and a combined oral contraceptive in healthy female subjects. Br J Clin Pharmacol 61:191–199PubMedCentralCrossRefPubMedGoogle Scholar
  38. Sivaraaman K, Mintzer S (2011) Hormonal consequences of epilepsy and its treatment in men. Curr Opin Endocrinol Diabetes Obes 18:204–209CrossRefPubMedGoogle Scholar
  39. Verrotti A, Loiacono G, Laus M, Coppola G, Chiarelli F, Tiboni GM (2011) Hormonal and reproductive disturbances in epileptic male patients: emerging issues. Reprod Toxicol 31:519–527CrossRefPubMedGoogle Scholar
  40. Wallace H, Shorvon S, Tallis R (1998) Age-specific incidence and prevalence rates of treated epilepsy in an unselected population of 2,052,922 and age-specific fertility rates of women with epilepsy. Lancet 352:1970–1973CrossRefPubMedGoogle Scholar
  41. Wang H, Bos JH, de Jong-van den Berg LT (2012) Co-prescription of antiepileptic drugs and contraceptives. Contraception 85:28–31CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • MJ Eadie
    • 1
  • FJE Vajda
    • 2
  1. 1.Clinical Neurology and NeuropharmacologyUniversity of Queensland, and Honorary Consultant Neurologist, Royal Brisbane and Women’s HospitalBrisbaneAustralia
  2. 2.Department of Medicine and Neurology Director of the Australian Epilepsy and Pregnancy RegisterUniversity of Melbourne and Royal Melbourne HospitalMelbourneAustralia

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