562
Views
43
CrossRef citations to date
0
Altmetric
Review

The effect of epilepsy and antiepileptic drugs on sexual, reproductive and gonadal health of adults with epilepsy

Pages 807-819 | Received 26 Jan 2016, Accepted 29 Feb 2016, Published online: 21 Mar 2016

References

  • Hauser WA. Incidence and prevalence. In: Engel J, Pedley TA, editors. Epilepsy: a comprehensive textbook. Philadelphia (PA): Lippincott-Raven; 1997. p. 47–57.
  • Kandil MR, Ahmed WA, Sayed AM, et al. Pattern of epilepsy in childhood and adolescence: a hospital-based study. African J Neurol Sci. 2007;26(1):33–45.
  • Wallace H, Shorvon S, Tallis R. 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. 1998;352(9145):1970–1973.
  • Isojärvi JI, Repro M, Pakarinen AJ, et al. Carbamazepine, phenytoin, sex hormones and sexual function in men with epilepsy. Epilepsia. 1995;36(4):366–370.
  • Rättyä J, Turkka J, Pakarinen AJ, et al. Reproductive effects of valproate, carbamazepine, and oxcarbazepine in men with epilepsy. Neurology. 2001;56(1):31–36.
  • Kuba R, Pohanka M, Zakopcan J, et al. Sexual dysfunctions and blood hormonal profile in men with focal epilepsy. Epilepsia. 2006;47(12):2135–2140.
  • Hamed SA, Mohamed KA, EL-taher A, et al. The sexual and reproductive health in men with generalized epilepsy: a multidisciplinary evaluation. Int J Impot Res. 2006;18(3):287–292.
  • Hamed SA. Neuroendocrine hormonal conditions in epilepsy: relationship to reproductive and sexual functions. Neurologist. 2008;14(3):157–169.
  • Hamed SA, Ahmad HK, Youssef AH, et al. Erectile function in men with epilepsy: relationship to demographic-, clinical-, endocrinal-, psychosocial- related variables. J Neurol Neurosci. 2013;4(2):5. doi:10.3823/336.
  • Hamed SA, Hermann BP, Moussa EMM, et al. Evaluation of penile vascular status in men with epilepsy with erectile dysfunction. Seizure. 2015;25:40–48.
  • Quinta Gomes AL, Nobre PJ. Prevalence of sexual problems in Portugal: results of a population-based study using a stratified sample of men aged 18 to 70 years. J Sex Res. 2014;51(1):13–21.
  • Morrell MJ, Guldner GT. Self-reported sexual function and sexual arousability in women with epilepsy. Epilepsia. 1996;37(12):1204–1210.
  • Schneck CD, Thomas MR, Gundersen D. Sexual side effects associated with valproate. J Clin Psychopharmacol. 2002;22(5):532–534.
  • Herzog AG, Coleman AE, Jacobs AR, et al. Relationship of sexual dysfunction to epilepsy laterality and reproductive hormone levels in women. Epilepsy Behav. 2003;4(4):407–413.
  • Zelená V, Kuba R, Pohanka M, et al. Sexual functions in women with focal epilepsy. A preliminary study. Epileptic Disord. 2007;9(Suppl 1):S83–S92.
  • Jaafarpour M, Khani A, Khajavikhan J, et al. Female sexual dysfunction: prevalence and risk factors. J Clin Diagn Res. 2013;7(12):2877–2880.
  • Laumann EO, Nicolosi A, Glasser DB, et al.; GSSAB Investigators’ Group. Sexual problems among women and men aged 40-80 y: prevalence and correlates identified in the Global Study of Sexual Attitudes and Behaviors. Int J Impot Res. 2005;17(1):39–57.
  • Calabrò RS, Marino S, Bramanti P. Sexual and reproductive dysfunction associated with antiepileptic drug use in men with epilepsy. Expert Rev Neurother. 2011;11(6):887–895.
  • Bergen D, Daugherty S, Eckenfels E. Reduction of sexual activities in females taking antiepileptic drugs. Psychopathology. 1992;25(1):1–4.
  • Connell JM, Rapeport WG, Beastall GH, et al. Changes in circulating androgens during short term carbamazepine therapy. Br J Clin Pharmacol. 1984;17(3):347–351.
  • Bauer J, Stefan H, Schrell U, et al. Serum prolactin concentrations and epilepsy: a study which compares healthy subjects with a group of patients in presurgical evaluation and circadian variations with those related to seizures. Eur Arch Psychiatry Clin Neurosci. 1992;241(6):365–371.
  • Perucca E, Hedges A, Makki KA, et al. A comparative study of the relative enzyme inducing properties of anticonvulsant drugs in epileptic patients. Br J Clin Pharmacol. 2004;58(7):S854–863.
  • Mölleken D, Richter-Appelt H, Stodieck S, et al. Sexual quality of life in epilepsy: correlations with sex hormone blood levels. Epilepsy Behav. 2009;14(1):226–231.
  • Elia J, Imbrogno N, Delfino M, et al. Retrograde ejaculation and abnormal hormonal profile in a subject under treatment with valproate and phenytoin. Arch Ital Urol Androl. 2010;82(4):193–194.
  • Najafi MR, Ansari B, Zare M, et al. Effects of antiepileptic drugs on sexual function and reproductive hormones of male epileptic patients. Iran J Neurol. 2012;11(2):37–41.
  • Herzog AG, Seibel MM, Schomer DL, et al. Reproductive endocrine disorders in women with partial seizures of temporal lobe origin. Arch Neurol. 1986;43(4):341–346.
  • Cummings LN, Giudice L, Morrell MJ. Ovulatory function in epilepsy. Epilepsia. 1995;36(4):355–359.
  • Klein P, Serje A, Pezzullo JC. Premature ovarian failure in women with epilepsy. Epilepsia. 2001;42(12):1582–1589.
  • Harden CL, Koppel BS, Herzog AG, et al. Seizure frequency is associated with age at menopause in women with epilepsy. Neurology. 2003;61(4):451–455.
  • Hamed SA, Hamed EA, Shokry M, et al. The reproductive conditions and lipid profile in females with epilepsy. Acta Neurol Scand. 2007;115(1):1–12.
  • Shechter-Amir D, Yavetz H, Homonnai TZ, et al. Semen parameters among epileptic males treated with carbamazepine. Isr J Med Sci. 1993;29(10):648–649.
  • Taneja N, Kucheria K, Jain S, et al. Effect of phenytoin on semen. Epilepsia. 1994;35(1):136–140.
  • Yerby MS, McCoy GB. Male infertility: possible association with valproate exposure. Epilepsia. 1999;40(4):520–521.
  • Røste LS, Taubøll E, Haugen TB, et al. Alterations in semen parameters in men with epilepsy treated with valproate or carbamazepine monotherapy. Eur J Neurol. 2003;10(5):501–506.
  • Hayashi T, Yoshinaga A, Ohno R, et al. Asthenozoospermia: possible association with long-term exposure to an anti-epileptic drug of carbamazepine. Int J Urol. 2005;12(1):113–114.
  • Hayashi T, Yoshida S, Yoshinaga A, et al. Improvement of oligoasthenozoospermia in epileptic patients on switching anti-epilepsy medication from sodium valproate to phenytoin. Scand J Urol Nephrol. 2005;39(5):431–432.
  • Xiaotian X, Hengzhong Z, Yao X, et al. Effects of antiepileptic drugs on reproductive endocrine function, sexual function and sperm parameters in Chinese Han men with epilepsy. J Clin Neurosci. 2013;20(11):1492–1497.
  • Hamed SA, Moussa EMM, Tohamy AM, et al. Seminal fluid analysis and testicular volume in adults with epilepsy receiving valproate. J Clin Neurosci. 2015;22(3):508–512.
  • Luef G, Abraham I, Trinka E, et al. Hyperandrogenism, postprandial hyperinsulinism and the risk of PCOS in a cross sectional study of women with epilepsy treated with valproate. Epilepsy Res. 2002;48(1–2):91–102.
  • Isojärvi JI, Laatikainen TJ, Pakarinen AJ, et al. Polycystic ovaries and hyperandrogenism in women taking valproate for epilepsy. N Engl J Med. 1993;329(19):1383–1388.
  • Ribacoba-Montero R, Martínez-Faedo C, Díaz-Díaz C, et al. Remission of polycystic ovary syndrome associated with valproic acid in an epileptic female. Rev Neurol. 2003;36(7):639–642.
  • Morrell MJ, Giudice L, Flynn KL, et al. Predictors of ovulatory failure in women with epilepsy. Ann Neurol. 2002;52(6):704–711.
  • Polson DW, Adams J, Wadsworth J, et al. Polycystic ovaries – a common finding in normal women. Lancet. 1988;1(8590):870–872.
  • Isojärvi JI, Taubøll E, Pakarinen AJ, et al. Altered ovarian function and cardiovascular risk factors in valproate-treated women. Am J Med. 2001;111(4):290–296.
  • Knochenhauer ES, Key TJ, Kahsar-Miller M, et al. 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(9):3078–3082.
  • Balen AH, Laven JSE, Tan S-L, et al. Ultrasound assessment of the polycystic ovary: international consensus definitions. Hum Reprod Update. 2003;9(6):505–514.
  • Cogen PH, Antunes JL, Correll JW. Reproductive function in temporal lobe epilepsy: the effect of temporal lobectomy. Surg Neurol. 1979;12(3):243–246.
  • Collins WCJ, Lanigan O, Callaghan N. Plasma prolactin concentrations following epileptic and pseudoseizures. J Neurol Neurosurg Psychiatry. 1983;46(6):505–508.
  • Sperling MR, Pritchard PB 3rd, Engel J Jr, et al. Prolactin in partial epilepsy: an indicator of limbic seizures. Ann Neurol. 1986;20(6):716–722.
  • Morrell MJ, Sperling MR, Stecker M, et al. Sexual dysfunction in partial epilepsy: a deficit in physiologic sexual arousal. Neurology. 1994;44(2):243–247.
  • Edwards HE, Burnham WM, MacLusky NJ. Partial and generalized seizures affect reproductive physiology differentially in the male rat. Epilepsia. 1999;40(11):1490–1498.
  • Edwards HE, Burnham WM, Ng MM, et al. Limbic seizures alter reproductive function in the female rat. Epilepsia. 1999;40(10):1370–1377.
  • Maes M, Calabrese JR. Mechanisms of action of valproate in affective disorders. In: Joffe RT, Calabrese JR, editors. Anticonvulsants in mood disorders. New York (NY): Marcel Dekker; 1994. p. 100–101.
  • Luine VN, Wu V, Hoffman CS, et al. GABAergic regulation of lordosis: influence of gonadal hormones on turnover of GABA and interaction of GABA with 5-HT. Neuroendocrinology. 1999;69(6):438–445.
  • Nelson-DeGrave VL, Wickenheisser JK, Cockrell JE, et al. Valproate potentiates androgen biosynthesis in human ovarian theca cells. Endocrinology. 2004;145(2):799–808.
  • Muuronen A, Kaste M, Nikkila EA, et al. Mortality from ischaemic heart disease among patients using anticonvulsive drugs: a case-control study. BMJ. 1985;291(6507):1481–1483.
  • Hamed SA, Nabeshima T. The high atherosclerotic risk among epileptics: the atheroprotective role of multivitamins. J Pharmacol Sci. 2005;98(4):340–353.
  • Hamed SA, Hamed EA, Kandil MR, et al. Serum thyroid hormone balance and lipid profile in patients with epilepsy. Epilepsy Res. 2005;66(1–3):173–183.
  • Voudris KA, Attilakos A, Katsarou E, et al. Early and persistent increase in serum lipoprotein (a) concentrations in epileptic children treated with carbamazepine and sodium valproate monotherapy. Epilepsy Res. 2006;70(2–3):211–217.
  • Hamed SA, Hamed EA, Hamdy R, et al. Vascular risk factors and oxidative stress as independent predictors of asymptomatic atherosclerosis in adult patients with epilepsy. Epilepsy Res. 2007;74(2–3):183–192.
  • Hamed SA. Leptin and insulin homeostasis in epilepsy: relation to weight adverse conditions. Epilepsy Res. 2007;75(1):1–9.
  • Hamed SA, Fida NM, Hamed EA. States of serum leptin and insulin in children with epilepsy: risk predictors of weight gain. Eur J Ped Neurol. 2009;13(3):261–268.
  • Chang CS, Liao CH, Lin CC, et al. Patients with epilepsy are at an increased risk of subsequent stroke: a population-based cohort study. Seizure. 2014;23(5):377–381.
  • Hamed SA. The effect of antiepileptic drugs on thyroid hormonal function: causes and implications. Expert Rev Clin Pharmacol. 2015;8(6):741–750.
  • Beyenburg S, Mitchell AJ, Schmidt D, et al. Anxiety in patients with epilepsy: systematic review and suggestions for clinical management. Epilepsy Behav. 2005;7:161–171.
  • Hamed SA, Elserogy YE, Abdou MA, et al. The risks of suicidality in adult patients with epilepsy. World J Psych. 2012;2(2):33–42.
  • Hamed SA, Metwaly NA, Hassan MM, et al. Depression in adults with epilepsy: relationship to psychobiological variables. World J Neurol. 2012;2:1.
  • Heath RG. Pleasure and brain activity in man. Deep and surface electroencephalograms during orgasm. J Nerv Ment Dis. 1972;154(1):3–18.
  • Rubinow DR, Schmidt PJ. Androgens, brain, and behavior. Am J Psychiatry. 1996;153(8):974–984.
  • Gerendai I, Halász B. Neuroendocrine asymmetry. Front Neuroendocrinol. 1997;18(3):354–381.
  • Martin JB, Reichlin S. Clinical neuroendocrinology. 2nd ed. Philadelphia (PA): Davis; 1987.
  • Mahesh VB, Brann DW. Regulation of the preovulatory gonadotropin surge by endogenous steroids. Steroids. 1998;63(12):616–629.
  • Davidson JM, Kwan M, Greenleaf WJ. Hormonal replacement and sexuality in men. Clin Endocrinol Metab. 1982;11(3):599–623.
  • Anderson DC. Sex-hormone-binding globulin. Clin Endocrinol (Oxf). 1974;3(1):69–96.
  • Davies DT, Massa R, James R. Role of testosterone and of its metabolites in regulating gonadotrophin secretion in the Japanese quail. J Endocrinol. 1980;84(2):211–222.
  • Herzog AG, Drislane FW, Schomer DL, et al. Differential 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(7):764–768.
  • Lardone MC, Piottante A, Valdevenito R, et al. Histological and hormonal testicular function in oligo/azoospermic infertile men. Andrologia. 2013;45(6):379–385.
  • Bauer J, Stoffel-Wagner B, Flügel D, et al. Serum androgens return to normal after temporal lobe epilepsy surgery in men. Neurology. 2000;55(6):820–824.
  • Löfgren E, Mikkonen K, Tolonen U, et al. Reproductive endocrine function in women with epilepsy: the role of epilepsy type and medication. Epilepsy Behav. 2007;10(1):77–83.
  • Dana-Haeri J, Trimble M, Oxley J. Prolactin and gonadotrophin changes following generalised and partial seizures. J Neurol Neurosurg Psychiatry. 1983;46(4):331–335.
  • Mellanby J, Dwyer J, Hawkins CA, et al. Effect of experimental limbic epilepsy on the estrus cycle and reproductive success in rats. Epilepsia. 1993;34(2):220–227.
  • Molaie M, Culebras A, Miller M. Nocturnal plasma prolactin rise in patients with complex partial seizures. Ann Neurol. 1985;18(6):719–722.
  • Yung WKA, Janys T. Primary neurological tumors. In: Goetz CG, Pappert EJ, editors. Textbook of clinical neurology. Philadelphia (PA): WB Saunders; 1999. p. 948–956.
  • Bilo L, Meo R, Nappi C, et al. Reproductive endocrine disorders in women with primary generalized epilepsy. Epilepsia. 1988;29(5):612–619.
  • Silveira DC, Klein P, Ransil BJ, et al. Lateral asymmetry in activation of hypothalamic neurons with unilateral amygdaloid seizures. Epilepsia. 2000;41(1):34–41.
  • Friedman MN, Geula C, Holmes GL, et al. GnRH-immunoreactive fiber changes with unilateral amygdala-kindled seizures. Epilepsy Res. 2002;52(2):73–77.
  • Baird AD, Wilson SJ, Bladin PF, et al. The amygdala and sexual drive: insights from temporal lobe epilepsy surgery. Ann Neurol. 2004;55(1):87–96.
  • Aull-Watschinger S, Pataraia E, Baumgartner C. Sexual auras: predominance of epileptic activity within the mesial temporal lobe. Epilepsy Behav. 2008;12(1):124–127.
  • Suffren S, Braun CMJ, Guimond A, et al. Opposed hemispheric specializations for human hypersexuality and orgasm? Epilepsy Behav. 2011;21(1):12–19.
  • O’Donovan C, Kusumakar V, Graves GR, et al. Menstrual abnormalities and polycystic ovary syndrome in women taking valproate for bipolar mood disorder. J Clin Psychiatry. 2002;63(4):322–330.
  • Røste LS, Taubøll E, Isojarvi JIT, et al. Gonadal morphology and sex hormones in male and female Wistar rats after long-term lamotrigine treatment. Seizure. 2003;12(8):621–667.
  • Sveberg Røste L, Taubøll E, Berner A, et al. Morphological changes in the testis after long-term valproate treatment in male Wistar rats. Seizure. 2001;10(8):559–565.
  • Grant AC, Oh H. Gabapentin-induced anorgasmia in women. [letter to the editor]. Psychiatry. 2002;159(7):1247.
  • Luef G, Krämer G, Stefan H. Oxcarbazepine treatment in male epilepsy patients improves pre-existing sexual dysfunction. Acta Neurol Scand. 2009;119(2):94–99.
  • Isojärvi JI, Pakarinen AJ, Rautio A, et al. Serum sex hormone levels after replacing carbamazepine with oxcarbazepine. Eur J Clin Pharmacol. 1995;47(5):461–464.
  • Perloff MD, Thaler DE, Otis JA. Anorgasmia with gabapentin may be common in older patients. Am J Geriatr Pharmacother. 2011;9(3):199–203.
  • Mattson RH, Cramer JA, Collins JF, et al. Comparison of carbamazepine, phenobarbital, phenytoin, and primidone in partial and secondarily generalized tonic–clonic seizures. N Engl J Med. 1985;313(3):145–151.
  • Macphee GJA, Larkin JG, Butler E, et al. Circulating hormones and pituitary responsiveness in young epileptic men receiving long-term antiepileptic medication. Epilepsia. 1988;29(4):468–475.
  • Bonuccelli U, Murialdo G, Martino E, et al. Effects of carbamazepine on prolactin secretion in normal subjects and in epileptic subjects. Clin Neuropharmacol. 1985;8(2):165–174.
  • Wasilewska-Dziubinska E, Gajewska A, Wolinska-Witort E, et al. Valproate inhibits GnRH-induced gonadotropin release from anterior pituitary cells of male rat in vitro. Neuro Endocrinol Lett. 2011;32(2):206–211.
  • Stephen LJ, Kwan P, Shapiro D, et al. Hormone profiles in young adults with epilepsy treated with sodium valproate or lamotrigine monotherapy. Epilepsia. 2001;42(8):1002–1006.
  • Balaguer Martinez JV, Lopez Garcia MJ, Andres Celma M, et al. Effects of valproate on sexual development. An Pediatr (Barc). 2003;58(5):443–448.
  • Vainionpää LK, Rättyä J, Knip M, et al. Valproate-induced hyperandrogenism during pubertal maturation in girls with epilepsy. Ann Neurol. 1999;45(4):444–450.
  • Svalheim S, Taubøll E, Bjørnenak T, et al. Do women with epilepsy have increased frequency of menstrual disturbances? Seizure. 2003;12(8):529–533.
  • El-Khayat HA, Abd El-Basset FZ, Tomoum HY, et al. Physical growth and endocrinal disorders during pubertal maturation in girls with epilepsy. Epilepsia. 2004;45(9):1106–1115.
  • Mikkonen K, Vainionpää LK, Pakarinen AJ, et al. Long-term reproductive endocrine health in young women with epilepsy during puberty. Neurology. 2004;62(3):445–450.
  • Schachter SC. Oxcarbazepine: current status and clinical applications. Expert Opin Investig Drugs. 1999;8(7):1103–1112.
  • Silva HC, Carvalho MJ, Jorge CL, et al. Sexual disorders in epilepsy. Results of a multidisciplinary evaluation. Arq Neuropsiquiatr. 1999;57(3B):798–807.
  • Husain AM, Carwile ST, Miller PP, et al. Improved sexual function in three men taking lamotrigine for epilepsy. South Med J. 2000;93(3):335–336.
  • Herzog AG, Fowler KM. Sexual hormones and epilepsy: threat and opportunities. Curr Opin Neurol. 2005;18(2):167–172.
  • Gil-Nagel A, López-Muñoz F, Serratosa JM, et al. Effect of lamotrigine on sexual function in patients with epilepsy. Seizure. 2006;15(3):142–149.
  • Goodwin GM, Bowden CL, Calabrese JR, et al. A pooled analysis of 2 placebo-controlled 18-month trials of lamotrigine and lithium maintenance in bipolar I disorder. J Clin Psychiatry. 2004;65(3):432–441.
  • Grabowska-Grzyb A, Nagańska E, Wolańczyk T. Hypersexuality in two patients with epilepsy treated with lamotrigine. Epilepsy Behav. 2006;8(3):663–665.
  • Svalheim S, Taubøll E, Luef G, et al. Differential effects of levetiracetam, carbamazepine, and lamotrigine on reproductive endocrine function in adults. Epilepsy Behav. 2009;16(2):281–287.
  • Rauchenzauner M, Bitsche G, Svalheim S, et al. Effects of levetiracetam and valproic acid monotherapy on sex-steroid hormones in prepubertal children–results from a pilot study. Epilepsy Res. 2010;88(2–3):264–268.
  • Harden CL, Nikolov BG, Kandula P, et al. Effect of levetiracetam on testosterone levels in male patients. Epilepsia. 2010;51(11):2348–2351.
  • Calabrò RS, Italiano D, Militi D, et al. Levetiracetam-associated loss of libido and anhedonia. Epilepsy Behav. 2012;24(2):283–284.
  • Civardi C, Collini A, Gontero P, et al. Vasogenic erectile dysfunction topiramate-induced. Clin Neurol Neurosurg. 2012;114(1):70–71.
  • Morrell MJ, Flynn KL, Doñe S, et al. Sexual dysfunction, sex steroid hormone abnormalities, and depression in women with epilepsy treated with antiepileptic drugs. Epilepsy Behav. 2005;6(3):360–365.
  • McCarthy MM, Malik KF, Feder HH. Increased GABAergic transmission in medial hypothalamus facilitates lordosis but has the opposite effect in preoptic area. Brain Res. 1990;507(1):40–44.
  • Drislane FW, Coleman AE, Schomer DL, et al. Altered pulsatile secretion of luteinizing hormone in women with epilepsy. Neurology. 1994;44(2):306–310.
  • Azadzoi KM, Park K, Andry C, et al. Relationship between cavernosal ischemia and corporal veno-occlusive dysfunction in an animal model. J Urol. 1997;157(3):1011–1017.
  • Hamed SA. Antiepileptic drugs influences on body weight in people with epilepsy. Expert Rev Clin Pharmacol. 2015;8(1):103–114.
  • Hamed SA, Radwan MEM, Abdellah MM. Fatty liver in adults with epilepsy receiving antiepileptic medications: relationship to the associated metabolic risks. Exp Rev Clin Pharmacol. 2016 Jan 8:1–8. [Epub ahead of print].
  • Isojärvi JI, Löfgren E, Juntunen KS, et al. Effect of epilepsy and antiepileptic drugs on male reproductive health. Neurology. 2004;62(2):247–253.
  • Falker G, Krause W. Oligoasthenoteratozoospermia in valproic acid therapy. Z Hautkr. 1988;63(2):142–143.
  • Chen SS, Shen MR, Chen TJ, et al. Effects of antiepileptic drugs on sperm motility of normal controls and epileptic patients with long-term therapy. Epilepsia. 1992;33(1):149–153.
  • Shetty AJ, Narayana K. The effects of carbamazepine on sperm morphology in wistar rats. Indian J Physiol Pharmacol. 2007;51(3):255–260.
  • Walker RM, Smith GS, Barsoum NJ, et al. Preclinical toxicology of the anticonvulsant calcium valproate. Toxicology. 1990;63(2):137–155.
  • Rajender S, Monica MG, Walter L, et al. Thyroid, spermatogenesis, and male infertility. Front Biosci (Elite Ed). 2011;3:843–855.
  • Hug G, McGraw CA, Bates SR, et al. Reduction of serum carnitine concentrations during anticonvulsant therapy with phenobarbital, valproic acid, phenytoin, and carbamazepine in children. J Pediatr. 1991;119(5):799–802.
  • Coppola G, Epifanio G, Auricchio G, et al. Plasma free carnitine in epilepsy children, adolescents and young adults treated with old and new antiepileptic drugs with or without ketogenic diet. Brain Dev. 2006;28(6):358–365.
  • Borum PR, Bennett SG. Carnitine as an essential nutrient. J Am Coll Nutr. 1986;5(2):185–186.
  • Gobello C, Castex G, Corrada Y. Serum and seminal markers in the diagnosis of disorders of the genital tract of the dog: a mini-review. Theriogenology. 2002;57(4):1285–1291.
  • Hamed SA, Abdella MM. The risk of asymptomatic hyperammonemia in children with idiopathic epilepsy treated with valproate: relationship to blood carnitine status. Epilepsy Res. 2009;86(1):32–41.
  • De Rosa M, Boggia B, Amalfi B, et al. Correlation between seminal carnitine and functional spermatozoal characteristics in men with semen dysfunction of various origins. Drugs RD. 2005;6(1):1–9.
  • Lenzi A, Lombardo F, Sgrò P, et al. Use of carnitine therapy in selected cases of male factor infertility: a double-blind crossover trial. Fertil Steril. 2003;79(2):292–300.
  • Jeulin C, Lewin LM. Role of free L-carnitine and acetyl-L-carnitine in post-gonadal maturation of mammalian spermatozoa. Hum Reprod Update. 1996;2(2):89–102.
  • Coude FX, Grimber G, Pelet A, et al. Action of the antiepileptic drug, valproic acid, on fatty acid oxidation in isolated rat hepatocytes. Biochem Biophys Res Commun. 1983;115(2):730–736.
  • Rogiers V, Vandenberghe Y, Vercruysse A. Inhibition of gluconeogenesis by sodium valproate and its metabolites in isolated rat hepatocytes. Xenobiotica. 1985;15(8–9):759–765.
  • Demerdash A, Shaalan M, Midani A, et al. Sexual behavior of a sample of females with epilepsy. Epilepsia. 1991;32(1):82–85.
  • Jensen P, Jensen SB, Sørensen PS, et al. Sexual dysfunction in male and female patients with epilepsy: a study of 86 outpatients. Arch Sex Behav. 1990;19(1):1–14.
  • Mtchedlishvili Z, Bertram EH, Kapur J. Diminished allopregnanolone enhancement of GABA (A) receptor currents in a rat model of chronic temporal lobe epilepsy. J Physiol. 2001;537(Pt 2):453–465.
  • Harden C, MacLusky NJ. Aromatase inhibitors as add-on treatment for men with epilepsy. Expert Rev Neurother. 2005;5(1):123–127.
  • Goldstein I, Lue TF, Padma-Nathan H, et al. Oral sildenafil in the treatment of erectile dysfunction. Sildenafil Study Group. N Engl J Med. 1998;338(20):1397–1404.
  • Mazer NA. Testosterone deficiency in women: etiologies, diagnosis, and emerging treatments. Int J Fertil Womens Med. 2002;47(2):77–86.
  • Moynihan R. FDA panel rejects testosterone patch for women on safety grounds. BMJ. 2004;329(7479):1363.
  • Basson R, McInnes R, Smith MD, et al. Efficacy and safety of sildenafil citrate in women with sexual dysfunction associated with female sexual arousal disorder. J Womens Health Gend Based Med. 2002;11(4):367–377.
  • Sánchez Longo LP, González Saldaña LE. Hormones and their influence in epilepsy. Acta Neurol Latinoam. 1966;12(1):29–47.
  • Jacobs AR, Edelheit PB, Coleman AE, et al. Late-onset congenital adrenal hyperplasia: a treatable cause of anxiety. Biol Psychiatry. 1999;46(6):856–859.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.