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Epilepsy and sexuality

Open ArchivePublished:January 04, 2008DOI:https://doi.org/10.1016/j.seizure.2007.11.009

      Summary

      Sexual dysfunction is frequently reported by patients with epilepsy. Despite its fundamental role in human life, there has been surprisingly little research into the neurological control of human sexual behaviour. Multiple causes may lead to sexual dysfunction. The basis for hyposexuality has been attributed to both epilepsy and antiepileptic drug (AED) use, making it difficult to distinguish between the illness-specific and pharmacological impacts on sexual functioning. Low levels of androgens are associated with sexual arousal insufficiency and sexual dysfunction. When examining sexual dysfunction in men and women with epilepsy, the Arizona Sexual Experience Scale (ASEX) may be helpful in evaluating sexual function. Laboratory tests for oestrogen, free and total testosterone, and serum SHBG (sexhormone binding globuline) may also be useful in evaluating sexual health.
      Sporadic case studies suggest that hypersexuality is a rare but dramatic outcome of unilateral temporal lobectomy. Sexual seizure manifestations are also rare clinical phenomena during or after complex partial seizures that have received attention in the recent literature.

      Keywords

      Introduction

      Sexuality is an important and private aspect of life and sexuality and epilepsy have been intimately linked since ancient time. In the modern medical era of epilepsy Gastaut and Collomb published that many patients with complex partial seizures have an apparent lack of interest in sexual activity.
      • Gastaut H.
      • Collomb H
      Sexual behavior in psychomotor epileptics.
      Data from animal studies support the hypothesis that hyposexuality occurs as a result of epileptiform activity in the temporal lobe, but not in the motor cortex.
      • Feeny D.M.
      • Gullota F.P.
      • Gilmore W.
      Hyposexuality produced by temporal lobe Epilepsy in the cat.
      In patients with epilepsy, alterations in interictal sexual behaviour have been frequently reported, particularly in temporal lobe epilepsy (TLE). The most common interictal sexual dysfunction associated with TLE is hyposexuality.
      • Kolarsky A.
      • Freund K.
      • Machek J.
      • Polak O.
      Male sexual deviation: association with early temporal lobe damage.
      Enzyme-inducing antiepileptic drugs (EIAED) are metabolized in the hepatic P450 system (e.g. 3A4, 2C9, 2C19), induce hepatic enzymes, increase the hepatic synthesis of sexhormone binding globuline (SHBG), and increase the metabolism of sex hormones
      • Stoffel-Wagner B.
      • Bauer J.
      • Flügel D.
      • Brennemann W.
      • Klingmüller D.
      • Elger C.E.
      Serum sex hormones are altered in patients with chronic temporal lobe epilepsy receiving anticonvulsant medication.
      that might have an additional influence on sexuality in patients with epilepsy.
      Both, men and women with epilepsy appear to have altered gonadal function. It is still unclear whether AEDs or epilepsy cause the abnormality involving prolactin, luteinizing hormone (LH), estradiol, SHBG, and dehydroepiandrosterone (DHEA) in women and also follicle stimulating hormone (FSH), free testosterone (FT), inhibin, DHEA, and 17ά-OH progesterone in men with epilepsy.
      • Bauer J.
      • Blumenthal S.
      • Reuber M.
      • Stoffel-Wagner B.
      Epilepsy syndrome, focus location, and treatment choice affect testicular function in men with epilepsy.

      Methodological aspects and definitions

      Hyposexuality

      Hyposexuality is defined as diminished sexual drive or libido, or typically as sexual activity less than once per month, and may or may not be accompanied by erectile or orgasmic dysfunction.
      • Blumer D.
      Hypersexual episodes in temporal lobe epilepsy.
      Early studies describing a relationship between hyposexuality and TLE have received methodological criticisms.
      • Toone B.
      Epilepsy and sexual life.
      Control groups and female patients were rarely included, and diagnostic criteria for epilepsy were often poorly defined. Many studies included heterogeneous or biased samples without consideration of comorbid conditions. Nevertheless, the majority of studies have supported an association between TLE and hyposexuality.
      • Shukla G.D.
      • Srivastava O.N.
      • Katiyar B.C.
      Sexual disturbances in temporal lobe epilepsy: a controlled study.
      Hyposexuality may be the result of altered neuroendocrine regulation caused by epilepsy itself
      • Herzog A.G.
      • Coleman A.E.
      • Jacobs A.R.
      • Klein P.
      • Friedmann M.N.
      • Drislane F.W.
      • et al.
      Interictal EEG discharges, reproductive hormones, and menstrual disorders in epilepsy.
      • Herzog A.G.
      A relationship between particular reproductive endocrine disorders and the laterality of epileptiform discharges in women with epilepsy.
      or AED exposure,
      • Isojärvi J.I.T.
      • Taubøll E.
      • Herzog A.G.
      Effects of antiepileptic drugs on reproductive endocrine function in individuals with epilepsy—a review.
      gonadal toxicity of some AEDs,
      • Taubøll E.
      • Isojärvi J.I.T.
      • Flinstad Harbo H.
      • Pakarinen A.J.
      • Gjerstad L.
      Effects of long-term valproate treatment on serum sex steroid hormone levels and ovarian morphology in female wistar rats.
      altered peripheral steroid and binding protein synthesis and metabolism,
      • Isojärvi J.I.T.
      • Taubøll E.
      • Herzog A.G.
      Effects of antiepileptic drugs on reproductive endocrine function in individuals with epilepsy—a review.
      and possibly altered neurotrophic effects of the limbic system, hypothalamus, and autonomic nuclei on the growth and maintenance of the ovaries, mediated via direct autonomic innervation of the gonads.
      • Gerendai I.
      • Csaba Z.
      • Voko Z.
      • Csernus V.
      Involvement of a direct neural mechanism in the control of gonadal functions.
      The relationship of pulse frequency to the nature and laterality of paroxysmal discharges makes it unlikely that endocrine abnormalities and hyposexuality can be attributed to AEDs alone and strengthens the notion that temporal lobe epileptiform discharges may disrupt hypothalamic regulation of pituitary secretion.
      • Herzog A.G.
      • Drislane F.W.
      • Schomer D.L.
      • Lavesque L.A.
      • Ives J.
      • Blume H.W.
      • et al.
      Abnormal pulsatile secretion of luteinizing hormone in men with epilepsy: Relationship to laterality and nature of paroxysmal discharges.
      Hormonal changes also can show close temporal relationship to the occurrence of interictal epileptiform discharges and may vary in relation to the laterality of the discharges.
      • Herzog A.G.
      • Coleman A.E.
      • Jacobs A.R.
      • Klein P.
      • Friedmann M.N.
      • Drislane F.W.
      • et al.
      Interictal EEG discharges, reproductive hormones, and menstrual disorders in epilepsy.
      Although sexual dysfunction is common in epileptic patients, quantification of sexual dysfunction is limited by the paucity of validated, user-friendly scales. To evaluate sexual interest and function in people with epilepsy standardized questionnaire are needed. Sexual interest and potency are equally weighted in the S-score questionnaire, i.e., two questions for each category with a maximum total score of 10.
      • Herzog A.G.
      • Drislane F.W.
      • Schomer D.L.
      • Pennell P.B.
      • Bromfield E.B.
      • Dworetzky B.A.
      • et al.
      Differential effects of antiepileptic drugs on sexual function and hormones in men with epilepsy.
      Sexual functioning measured by using the Arizona Sexual Experience Scale (ASEX), a brief five-item scale designed to assess the core elements of sexual functioning: drive, arousal, penile erection/vaginal lubrication, ability to reach orgasm, and satisfaction with orgasm is often used in studies for both, men and women. Possible total scores range from 5 to 30, with the higher scores indicating more sexual dysfunction. Each item is rated with a six-point Likert system, with higher scores reflecting impaired sexual functioning. A total ASEX score ≥19, any one item with a score of ≥5, or any three items with a score of 4 have all been found to be correlated with sexual dysfunction.
      • McGahuey C.A.
      • Gelenberg A.J.
      • Laukes C.A.
      • Moreno F.A.
      • Delgado P.L.
      • McKnight K.M.
      • et al.
      The Arizona Sexual Experience Scale (ASEX): reliability and validity.

      Hypersexuality

      Hypersexuality, or a dramatic increase in sexual drive, has been reported in some patients after unilateral temporal lobectomy.
      • Blumer D.
      Hypersexual episodes in temporal lobe epilepsy.
      • Baird A.D.
      • Wilson S.J.
      • Bladin P.B.
      • Saling M.M.
      • Reutens D.C.
      Hypersexuality after temporal lobe resection.
      It is defined as “sexual arousal and response that is clearly abnormal in frequency and intensity for a given individual”.
      • Blumer D.
      Hypersexual episodes in temporal lobe epilepsy.
      Blumer
      • Blumer D.
      Hypersexual episodes in temporal lobe epilepsy.
      identified common traits in three patients, including the manifestation of hypersexuality after a “postoperative silent period” of 3–6 weeks, persistent sexual arousal, homosexual behaviour, accompanying dietary changes and loss of anger or “tameness”. Cogen et al. suggested that hypersexuality after unilateral temporal lobectomy represented a partial Klüver Bucy Syndrom because of the underlying pathology in the contralateral temporal lobe.
      • Cogen P.H.
      • Antunes J.L.
      • Correll J.W.
      Reproductive function in temporal lobe epilepsy: the effect of temporal lobectomy.
      Overall, the sporadic case studies suggest that hypersexuality is a rare but dramatic outcome of unilateral temporal lobectomy.

      Ictal and postictal sexual behaviour

      Sexual seizure manifestations are rare clinical phenomena during or after complex partial seizures. They can be subdivided into distinct symptoms: Auras with sexual content, which have been related to seizure activity originating within the temporal lobes, somatosensory sensations in the genitals, reported in patients with parietal lobe epilepsy, and sexual automatisms consisting of fondling and grabbing of the genitals as well as hypermotoric pelvic and truncal movements.
      • Leutmezer F.
      • Serles W.
      • Bacher J.
      • Gröppel G.
      • Pataraia E.
      • Aull S.
      • et al.
      Genital a.utomatisms in complex partial seizures.
      Genital automatisms (GAs), defined as repeated fondling, grabbing, or scratching of the genitals, are a rare symptom during or after epileptic seizures. They must be separated from other genital or sexual seizure manifestations. GAs occur in seizures originating from the temporal lobe, frontal lobe, as well as in generalized seizures. In a recently published study of 23 patients with epilepsy, men exhibited GAs significantly more often than did women. GAs were associated with unilateral hand automatisms in 70% and with periictal urinary urge in 22%.
      • Dobesberger J.
      • Walser G.
      • Unterberger I.
      • Embacher N.
      • Luef G.
      • Bauer G.
      • et al.
      Genital automatisms: a video-EEG study in patients with medically refractory seizures.
      The mechanisms for GAs are far from clear. The authors of the later study support the hypothesis of transient bitemporal dysfunction leading to GAs.

      Conclusions

      The quality of human life is a summation of many factors. Male and female sexuality, relationships and successful reproduction are paramount in the accomplishment of a meaningful life for most individuals.
      • Penovich P.E.
      The effects of epilepsy and its treatment on sexual and reproductive function.
      Despite its fundamental role in human life, there has been surprisingly little research into the neurological control of human sexual behaviour. Blumer and Walker
      • Blumer D.
      • Walker A.E.
      The neural basis of sexual behaviour.
      proposed two reasons for this neglect. Firstly, physicians are not routinely trained to explore the sex life of their patients, and secondly, “there has been a stifling trend in research to investigate only what can be measured by objective methods”. In a review of the literature examining the effects of neurological insult on human sexual behaviour, Baird et al. provide a synthesis of the findings to date, and identified key brain regions associated with specific aspects of human sexual behaviour. These include subcortical and cortical regions, with the mesial temporal lobe and the amygdala in particular being a crucial structure in the mediation of human sexual drive.
      • Baird A.D.
      • Wilson S.J.
      • Bladin P.F.
      • Saling M.M.
      • Reutens D.C.
      Neurological control of human sexual behaviour: insights from lesion studies.
      Men and women with epilepsy frequently complain, if asked, of sexual dysfunction and appear to have a higher incidence of sexual dysfunction than persons with other chronic neurologic illnesses. However the causes of sexual dysfunction in people with epilepsy are multifactorial. Poor self-esteem or limited social opportunities may interfere with the development of normal sexual interactions.
      In patients with epilepsy, several studies have demonstrated impaired sexual arousal, sexual functioning, and fertility. At the hormonal level, focal temporal lobe epilepsy was studied in a paradigm involving erotic audiovisual stimulation and measures of genital blood flow.
      • Morrell M.J.
      • Sperling M.R.
      • Stecker M.
      • Dichter M.A.
      Sexual dysfunction in partial epilepsy: a deficit in physiologic sexual arousal.
      Blood flow was impaired compared with control subjects despite similar subjective arousal. In 5/6 men with focal epilepsy who had erectile complaints, one study revealed impaired nocturnal erectile function. Many women with epilepsy experience vaginismus, lack of lubrication, and dyspareunia despite normal libido. Epileptic discharges in those brain regions that are related to sexuality (temporal and frontal lobes) may disrupt sexual function. Specific underlying mechanisms are currently unknown, but probably involve changes in neurotransmitters, and altered levels of pituitary and gonadal hormones. Many seizures result in transient elevation of serum prolactin, which has been associated with reduced libido and impotence. Improved seizure control may alleviate much sexual dysfunction. Sex hormones are actively metabolized in the liver by the cytochrome P450 family of oxidase enzymes, which is also involved in the metabolism of many AEDs. AEDs may variably inhibit or stimulate hepatic metabolism and thus modulate endogenous sex levels. Antiepileptic drugs affect sexual behaviour in several ways: alterations in hormone metabolism and binding, and direct effects on cortical function.
      Therapeutic intervention should begin with an explanation that sexual dysfunction can be a unique symptom of epilepsy. An effort should be made to improve seizure control with current AEDs. If this is not successful, an alternative antiepileptic drug should be considered. If other medical or psychological causes of sexual dysfunction are excluded and adjustment of antiepileptic drugs is not helpful or possible, specific sex therapy techniques may prove useful. Individual and couple psychotherapy may be helpful if there are problems in the relationship.

      References

        • Gastaut H.
        • Collomb H
        Sexual behavior in psychomotor epileptics.
        Ann Med Psychol. 1954; 112: 657-696
        • Feeny D.M.
        • Gullota F.P.
        • Gilmore W.
        Hyposexuality produced by temporal lobe Epilepsy in the cat.
        Epilepsia. 1998; 39: 140-149
        • Kolarsky A.
        • Freund K.
        • Machek J.
        • Polak O.
        Male sexual deviation: association with early temporal lobe damage.
        Arch Gen Psychiatry. 1967; 17: 735-743
        • Stoffel-Wagner B.
        • Bauer J.
        • Flügel D.
        • Brennemann W.
        • Klingmüller D.
        • Elger C.E.
        Serum sex hormones are altered in patients with chronic temporal lobe epilepsy receiving anticonvulsant medication.
        Epilepsia. 1998; 39: 1164-1173
        • Bauer J.
        • Blumenthal S.
        • Reuber M.
        • Stoffel-Wagner B.
        Epilepsy syndrome, focus location, and treatment choice affect testicular function in men with epilepsy.
        Neurology. 2004; 62: 243-246
        • Blumer D.
        Hypersexual episodes in temporal lobe epilepsy.
        Am J Psychiatry. 1970; 126: 1099-1106
        • Toone B.
        Epilepsy and sexual life.
        in: Hopkins A. Shorvon S. Cascino G. Epilepsy. 2nd ed. Chapman & Hall, London1995: 557-564
        • Shukla G.D.
        • Srivastava O.N.
        • Katiyar B.C.
        Sexual disturbances in temporal lobe epilepsy: a controlled study.
        Br J Psychiatry. 1979; 134: 288-292
        • Herzog A.G.
        • Coleman A.E.
        • Jacobs A.R.
        • Klein P.
        • Friedmann M.N.
        • Drislane F.W.
        • et al.
        Interictal EEG discharges, reproductive hormones, and menstrual disorders in epilepsy.
        Ann Neurol. 2003; 54: 625-637
        • Herzog A.G.
        A relationship between particular reproductive endocrine disorders and the laterality of epileptiform discharges in women with epilepsy.
        Neurology. 1993; 43: 1907-1910
        • Isojärvi J.I.T.
        • Taubøll E.
        • Herzog A.G.
        Effects of antiepileptic drugs on reproductive endocrine function in individuals with epilepsy—a review.
        CNS Drugs. 2005; 19: 207-223
        • Taubøll E.
        • Isojärvi J.I.T.
        • Flinstad Harbo H.
        • Pakarinen A.J.
        • Gjerstad L.
        Effects of long-term valproate treatment on serum sex steroid hormone levels and ovarian morphology in female wistar rats.
        Seizure. 1999; 8: 490-493
        • Gerendai I.
        • Csaba Z.
        • Voko Z.
        • Csernus V.
        Involvement of a direct neural mechanism in the control of gonadal functions.
        J Steroid Biochem Mol Biol. 1995; 53: 299-305
        • Herzog A.G.
        • Drislane F.W.
        • Schomer D.L.
        • Lavesque L.A.
        • Ives J.
        • Blume H.W.
        • et al.
        Abnormal pulsatile secretion of luteinizing hormone in men with epilepsy: Relationship to laterality and nature of paroxysmal discharges.
        Neurology. 1990; 40: 1557-1561
        • Herzog A.G.
        • Drislane F.W.
        • Schomer D.L.
        • Pennell P.B.
        • Bromfield E.B.
        • Dworetzky B.A.
        • et al.
        Differential effects of antiepileptic drugs on sexual function and hormones in men with epilepsy.
        Neurology. 2005; 65: 1016-1020
        • McGahuey C.A.
        • Gelenberg A.J.
        • Laukes C.A.
        • Moreno F.A.
        • Delgado P.L.
        • McKnight K.M.
        • et al.
        The Arizona Sexual Experience Scale (ASEX): reliability and validity.
        J Sex Marital Ther. 2000; 26: 25
        • Baird A.D.
        • Wilson S.J.
        • Bladin P.B.
        • Saling M.M.
        • Reutens D.C.
        Hypersexuality after temporal lobe resection.
        Epilepsy Behav. 2002; 3: 173-181
        • Cogen P.H.
        • Antunes J.L.
        • Correll J.W.
        Reproductive function in temporal lobe epilepsy: the effect of temporal lobectomy.
        Surg Neurol. 1979; 12: 243-246
        • Leutmezer F.
        • Serles W.
        • Bacher J.
        • Gröppel G.
        • Pataraia E.
        • Aull S.
        • et al.
        Genital a.utomatisms in complex partial seizures.
        Neurology. 1999; 52: 1188-1191
        • Dobesberger J.
        • Walser G.
        • Unterberger I.
        • Embacher N.
        • Luef G.
        • Bauer G.
        • et al.
        Genital automatisms: a video-EEG study in patients with medically refractory seizures.
        Epilepsia. 2004; 45: 777-780
        • Penovich P.E.
        The effects of epilepsy and its treatment on sexual and reproductive function.
        Epilepsia. 2000; 41: 53-61
        • Blumer D.
        • Walker A.E.
        The neural basis of sexual behaviour.
        in: Benson D.F. Blumer D. Psychiatric aspects of neurological disease. Grune & Stratton, New York1975: 199-217
        • Baird A.D.
        • Wilson S.J.
        • Bladin P.F.
        • Saling M.M.
        • Reutens D.C.
        Neurological control of human sexual behaviour: insights from lesion studies.
        JNNP. 2007; 78: 1042-1049
        • Morrell M.J.
        • Sperling M.R.
        • Stecker M.
        • Dichter M.A.
        Sexual dysfunction in partial epilepsy: a deficit in physiologic sexual arousal.
        Neurology. 1994; 44: 243-247