Skip to main content
SpringerLink
Log in

Effects of treatment on endocrine function in patients with epilepsy

  • Published:
Current Treatment Options in Neurology Aims and scope Submit manuscript

Opinion statement

Antiepileptic drug (AED) treatment is associated with multiple short- and long-term side effects. Effects on endocrine function, including weight change, reproductive function, thyroid function, and bone health are examples of these side effects. Some AEDs affect weight, resulting in weight gain or loss. Levetiracetam and lamotrigine are weight-neu-tral agents, whereas valproate is associated with weight gain. Reproductive dysfunction is reported in women and men with epilepsy treated with AEDs. In women, the most common symptoms are hyperandrogenism, menstrual disorders with ovulatory failure, polycystic ovary-appearing ovaries or polycystic ovary syndrome, and hyperinsulinemia. These symptoms may be secondary to epilepsy or to AED treatment, particularly with valproate. In men, effects on sperm quality and motility, delayed sexual development, and small testicular size have been described in association with AED treatment. Car-bamazepine reduces testosterone levels, whereas valproate increases androgen levels. Oxcarbazepine is not associated with changes in testosterone levels. Treatment with all of these agents can result in changes in sperm, including concentration, morphology, and motility. Enzyme-inducing AEDs are known to result in decreased thyroid hormones. Recent studies found reduced serum thyroid hormone concentrations in men and young girls treated with carbamazepine and oxcarbazepine. However, all patients were clini-cally euthyroid, and these changes were reversible after AED withdrawal. Persons with epilepsy treated with AEDs are at increased risk for fracture. Not only is this increased because of seizure activity, but also because of treatment with AEDs. AED treatment results in decreased bone mineral density, the most sensitive predictor of fracture and changes in biochemical indices of bone metabolism, including calcium, vitamin D, and markers of bone formation and resorption. Identifying each of these endocrine abnor-malities is important because it may be necessary and beneficial to change AED treat-ment. In addition, multiple therapies exist for the treatment of polycystic ovary syndrome, infertility, and decreased bone mineral density.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. Gidal BE, Sheth RD, Magnus L, Herbeuval AF: Levetirace-tam does not alter body weight: analysis of randomized, controlled clinical trials. Epilepsy Res 2003, 56:121–126.

    Article  PubMed  CAS  Google Scholar 

  2. Biton V, Mirza W, Montouris G, et al.: Weight change asso-ciated with valproate and lamotrigine monotherapy in patients with epilepsy. Neurology 2001, 56:172–177.

    Article  PubMed  CAS  Google Scholar 

  3. Morrell MJ, Isojarvi J, Taylor AE, et al.: Higher androgens and weight gain with valproate compared with lamotrig-ine for epilepsy. Epilepsy Res 2003, 54:189–199.

    Article  PubMed  CAS  Google Scholar 

  4. Morrell MJ, Flynn KL, Seale CG, et al.: Reproductive dysfunction in women with epilepsy: antiepileptic drug effects on sex-steroid hormones. CNS Spectr 2001, 6:771–786.

    PubMed  CAS  Google Scholar 

  5. Herzog AG, Coleman AE, Jacobs AR: Interictal EEG dis-charges, reproductive hormones, and menstrual disor-ders in epilepsy. Ann Neurol 2003, 54:625–637. Reproductive endocrine function was evaluated in women with unilateral temperolimbic epilepsy and normal control subjects to assess effects of epilepsy, epilepsy laterality, and AED treatment. Significant differences were found at all levels of the reproductive neuroendocrine axis. These effects were found to be secondary to epilepsy and AED treatment.

    Article  PubMed  Google Scholar 

  6. Rattya J, Pakarinen AJ, Knip M, et al.: Early hormonal changes during valproate or carbamazepine treat-ment: a 3-month study. Neurology 2001, 57:440–444. Serum concentrations of reproductive hormones were studied in men and women with recently diagnosed epilepsy. Hor-monal changes occurred after 1 month of treatment with val-proate or carbamazepine. Carbamazepine treatment resulted in increased sex hormone binding globulin concentration. Valproate treatment was associated with increased serum androgen levels.

    PubMed  CAS  Google Scholar 

  7. Vainionpaa LK, Rattya J, Knip M, et al.: Valproate-induced hyperandrogenism during pubertal maturation in girls with epilepsy. Ann Neurol 1999, 45:444–450.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

  9. Mikkonen K, Vainionpaa LK, Pakarinen AJ, et al.: Long-term reproductive endocrine health in young women with epilepsy during puberty. Neurology 2004, 62:445–450.

    PubMed  CAS  Google Scholar 

  10. Herzog AG, Drislane FW, Schomer DL, et al.: Differen-tial effects of antiepileptic drugs on sexual function and reproductive hormones in men with epilepsy: interim analysis of a comparison between lamotrigine and enzyme-inducing antiepileptic drugs. Epilepsia 2004, 45:764–768.

    Article  PubMed  CAS  Google Scholar 

  11. Rattya J, Turkka J, Pakarinen AJ, et al.: Reproductive effects of valproate, carbamazepine, and oxcarba-zepine in men with epilepsy. Neurology 2001, 56:31–36.

    PubMed  CAS  Google Scholar 

  12. Roste LS, Tauboll E, Morkrid L, et al.: Antiepileptic drugs alter reproductive endocrine hormones in men with epilepsy. Eur J Neurol 2005, 12:118–124.

    Article  PubMed  CAS  Google Scholar 

  13. Bauer J, Blumenthal S, Reuber M, Stoffel-Wagner B: Epi-lepsy syndrome, focus location, and treatment choice affect testicular function in men with epilepsy. Neurol-ogy 2004, 62:243–246.

    Google Scholar 

  14. Isojarvi JI, Lofgren E, Juntunen KS, et al.: Effect of epi-lepsy and antiepileptic drugs on male reproductive health. Neurology 2004, 62:247–253. Reproductive health was assessed in 60 men with epilepsy and compared with 41 controls subjects Men with epilepsy were treated with carbamazepine, oxcarbazepine, and valproate. Men treated with carbamazepine had reduced levels of dehydroepi-androsterone and men treated with valproate had high concentrations of androstenedione. Carbamazepine, oxcarbazepine, and valproate treatment were associated with sperm abnormalities.

    PubMed  CAS  Google Scholar 

  15. Mikkonen K, Tapanainen P, Pakarinen AJ: Serum andro-gen levels and testicular structure during pubertal maturation in male subjects with epilepsy. Epilepsia 2004, 45:769–776.

    Article  PubMed  CAS  Google Scholar 

  16. Isojarvi JI, Turkka J, Pakarinen AJ, et al.: Thyroid func-tion in men taking carbamazepine, oxcarbazepine, or valproate for epilepsy. Epilepsia 2001, 42:930–934.

    Article  PubMed  CAS  Google Scholar 

  17. Vainionpaa LK, Mikkonen K, Rattya J, et al.: Thyroid function in girls with epilepsy with carbamazepine, oxcarbazepine, or valproate monotherapy and after withdrawal of medication. Epilepsia 2004, 45:197–203. Thyroid function was assessed in 78 girls taking carbam-azepine, oxcarbazepine, or valproate and compared with con-trol subjects. Carbamazepine and oxcarbazepine reduced serum thyroid hormone concentrations in girls with epilepsy. There were no thyroid hormone changes in valproate-treated girls. The changes found were reversible after withdrawal of the medication.

    Article  PubMed  CAS  Google Scholar 

  18. Souverein PC, Webb DJ, Petri H, et al.: Incidence of fractures among epilepsy patients: a population-based retrospective cohort study in the General Practice Research Database. Epilepsia 2005, 46:304–310.

    Article  PubMed  Google Scholar 

  19. Vestergaard P, Rejnmark L, Mosekilde L: Fracture risk associated with use of antiepileptic drugs. Epilepsia 2004, 45:1330–1337.

    Article  PubMed  CAS  Google Scholar 

  20. Farhat G, Yamout B, Mikati MA, et al.: Effect of antiepi-leptic drugs on bone density in ambulatory patients. Neurology 2002, 58:1348–1353.

    PubMed  CAS  Google Scholar 

  21. Andress DL, Ozuna J, Tirschwell D, et al.: Antiepileptic drug-induced bone loss in young male patients who have seizures. Arch Neurol 2002, 59:781–786.

    Article  PubMed  Google Scholar 

  22. Ensrud KE, Walczak TS, Blackwell T, et al.: Antiepileptic drug use increases rates of bone loss in older women: a prospective study. Neurology 2004, 62:2051–2057.

    PubMed  CAS  Google Scholar 

  23. Pack AM, Olarte LS, Morrell MJ, et al.: Bone mineral density in an outpatient population receiving enzyme-inducing antiepileptic drugs. Epilepsy Behav 2003, 4:169–174.

    Article  PubMed  Google Scholar 

  24. Sato Y, Kondo I, Ishida S, et al.: Decreased bone mass and increased bone turnover with valproate therapy in adults with epilepsy. Neurology 2001, 57:445–449.

    PubMed  CAS  Google Scholar 

  25. Pack AM, Morrell MJ, Marcus R, et al.: Bone mass and turnover in women with epilepsy on antiepileptic drug monotherapy. Ann Neurol 2005, 57:252–257. Premenopausal women with epilepsy treated with AED monotherapy had analysis markers of bone and mineral metabolism analyzed. Phenytoin use was associated changes in bone metabolism and turnover. Subjects receiving lamot-rigine had no significant reductions in calcium or increases in markers of bone turnover.

    Article  PubMed  CAS  Google Scholar 

  26. Verrotti A, Greco R, Morgese G, et al.: Increased bone turnover in epileptic patients treated with carbam-azepine. Ann Neurol 2000, 47:385–388. Adolescents had analysis of markers of bone turnover before treatment with carbamazepine and 1 year later. Results were compared to with a control group. Those adolescents treated with carbamazepine had significantly elevated markers of bone formation and resorption independent of changes in vitamin D.

    Article  PubMed  CAS  Google Scholar 

  27. Verotti A, Greco R, Latini G, et al.: Increased bone turn-over in prepubertal, pubertal, and postpubertal patients receiving carbamazepine. Epilepsia 2002, 43:1488–1492.

    Article  Google Scholar 

  28. Lord J, Wilkin T: Metformin in polycystic ovary syn-drome. Curr Opin Obstet Gynecol 2004, 16:481–486.

    Article  PubMed  Google Scholar 

  29. Drezner MK: Treatment of anticonvulsant drug-induced bone disease. Epilepsy Behav 2004, 5(Suppl 2):S41–47.

    Article  PubMed  Google Scholar 

  30. Delmas PD: Treatment of postmenopausal osteoporosis. Lancet 2002, 359:2018–2026.

    Article  PubMed  CAS  Google Scholar 

  31. Chestnut III CH: Calcitonin in the prevention and treatment of osteoporosis. Osteoporos Int 1993, 3(Suppl 1):206–207.

    Article  PubMed  Google Scholar 

  32. Rossouw JE, Anderson GL, Prentice RL, et al.: Risks and benefits of estrogen plus progesterone in healthy postmenopausal women: principal results from the Women’s Health Initiative randomized controlled trial. JAMA 2002, 288:366–368.

    Article  Google Scholar 

  33. Harden CL, Pulver MC, Ravdin L, Javobs AR: The effect of menopause and perimenopause on the course of epilepsy. Epilepsia 1999, 40:1402–1407.

    Article  PubMed  CAS  Google Scholar 

  34. Ettinger B, Black DM, Mitlak, et al.: Reduction of vertebral fracture risk in postmenopausal women with osteoporo-sis treated with raloxifene: results from a 3-year random-ized clinical trial. JAMA 1999, 282:637–645.

    Article  PubMed  CAS  Google Scholar 

  35. Quattrocchi E, Kourlas H: Teriparatide: a review. Clin Ther 2004, 26:841–854.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Neurological Institute, Columbia University, 710 West 168th Street, 2nd Floor, Rt. 201, 10032, New York, NY, USA

    Alison Pack MD

Authors
  1. Alison Pack MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pack, A. Effects of treatment on endocrine function in patients with epilepsy. Curr Treat Options Neurol 7, 273–280 (2005). https://doi.org/10.1007/s11940-005-0037-8

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11940-005-0037-8

Keywords

Search

Navigation