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Relation between sexual dysfunctions and epilepsy, type of epilepsy, type of antiepileptic drugs: a prospective study

Abstract

Introduction

The aim of this study was to evaluate the incidence of sexual dysfunctions in males with epilepsy, the type of epilepsy, the frequency of seizures, the type of antiepileptic drugs (AEDs), the serum hormonal profile and the presence of psychiatric comorbidity.

Methods

Sixty-one patients focused on type of epilepsy, frequency of seizures, AEDs, hormonal profile and presence of mood disorders. We excluded all patients with severe neurologic and psychiatric impairment and patient who were not able to fill questionnaires. Mean age was 31.2 years (range 18-50 years); 31 patients (50.8%) had an idiopathic generalised epilepsy and 30 (49.2%) a focal epilepsy; among them, latter 18 (60%) had probably symptomatic type and 12 (40%) symptomatic type. Sexual functions were evaluated by “International Inventory of Erectile Function” questionnaire.

Results

Out of 61 enrolled patients, 22 (36.7%) showed sexual dysfunctions: erectile dysfunctions in 14 (23%), orgasmic dysfunctions in (11.5%) and sexual drive dysfunctions in 12 (19.7%). Out of 61 patients, 36 were subjected to blood measurement of sexual hormones and 21 (58.3%) showed hormonal modifications.

Conclusions

Sexual dysfunction are present in 36.7% of enrolled males with epilepsy; there is any association between sexual dysfunctions and various AEDs in the treatment, except for carbamazepine (CBZ); there is not any association between sexual dysfunctions and frequency of seizures; hormonal changes are associated with sexual dysfunction in males with epilepsy treated with AEDs but not with the orgasmic dysfunction; there is not any association between hormonal changes and type of AEDs, except for CBZ; depression is associated with sexual dysfunctions.

Urologia 2017; 84(2): 88 - 92

Article Type: ORIGINAL RESEARCH ARTICLE

DOI:10.5301/uro.5000222

Authors

Carlo Pavone, Ninfa Giacalone, Marco Vella, Lidia Urso, Leila Zummo, Brigida Fierro

Article History

Disclosures

Financial support: The authors received no financial support for the research.
Conflict of interest: The authors declare that there are no conflicts of interest.

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Introduction

Sexual dysfunctions (SDs) significantly reduce the quality of life in general population with a prevalence estimated between 20 and 22%. Most frequent reported SDs are erectile dysfunction, reduced libido, orgasmic and ejaculation dysfunctions. Aetiology of such disturbances is often related to various comorbidities such as cardiovascular disease, hyperglycaemia, hypertension and hypercholesterolemia. As far as patients with neurologic disease, epileptic patients are likely to have a greater risk for SDs if compared with general population (1). Epilepsy is a chronic neurological condition characterised by recurrent epileptic seizures. They happen because of sudden, abnormal electrical activity in the brain; there are many types of seizures and some have mild symptoms. Seizures are divided into two main groups: focal seizures that happen in just one part of the brain, and generalised that are a result of abnormal activity on both sides of the brain (2, 3). The epilepsy syndrome and localisation influence the presentation of SD. Studies report higher percentages of SD in persons with temporal lobe epilepsy (TLE) than primary generalised epilepsy (4, 5). Not only epilepsy but also antiepileptic drugs (AEDs) affect hormones and neuroendocrine systems. So, aetiology of such dysfunctions in patients with epilepsy is multifactorial, including disease by itself, epileptic seizures, drug therapy, lifestyle and psychological problems in addition to the physiologic effects of epileptic discharges in brain regions mediating sexual behaviour (6, 7). In patients with epilepsy, the prevalence of SDs varies between 38 and 71%; this variability is strictly related to the correct definition of “sexual dysfunction”. So, some authors indicate generic SDs with the term “hyposexuality”, but more recently, the growing interest in this topic allowed us to identify more exactly the type of SDs: reduced libido, orgasmic and erectile dysfunctions, satisfaction from sexual intercourse and sexual life of the patient (8-9-10). The epilepsy itself, type of seizures and their frequency are influencing and influence hypothalamic and pituitary structures and, consequently, the regular hormonal release, inducing an impairment of the correct sexual function (11). Studies in literature show that temporal lobectomy can reverse hormonal changes associated with TLE if complete seizure control is achieved (12, 13). Also, antiepileptic therapy, and mainly enzyme-inducing drugs, impaired not only hormonal release but also the protein-binding sexual hormones, modifying in turn share of active hormone in blood circulation. Furthermore, in people with epilepsy, anxiety, depression and social stigmate are to be kept in mind, as they strengthen the illness limiting the quality of life of these patients (14-15-16-17). The aim of the present prospective study is to evaluate the incidence of SDs in males with epilepsy, the type of epilepsy, the frequency of seizures, the type of AEDs in mono or poly-therapy, the serum hormonal profile and the presence of psychiatric comorbidity.

Materials and methods

We enrolled 61 patients, consecutively, focusing on type of epilepsy, frequency of seizures, AEDs, hormonal profile and presence of mood disorders. We excluded all patients with severe neurologic and psychiatric impairment and patients who were not able to fill questionnaires. Mean age was 31.2 years (range 18-50 years); 31 patients (50.8%) had an idiopathic generalised epilepsy and 30 (49.2%) a focal epilepsy; among them, latter 18 (60%) had probably symptomatic type and 12 (40%) symptomatic type (Tab. I).

Demographics

Demographics Cases n = 61 (%)
Mean age 31.2
Focal epilepsy 30/61 (49.2)
Generalised epilepsy 31/61 (50.8)
Idiopathic epilepsy 31/61 (50.8)
Probably symptomatic epilepsy 12/30 (40)
Symptomatic epilepsy 18/30 (60)
Frontal lobe epilepsy 6/30 (20)
Temporal lobe epilepsy 16/30 (53.3)
Occipital lobe epilepsy 3/30 (10)
Multifocal epilepsy 5/30 (16.7)

Patients with focal epilepsy included six (20%) with frontal lobe epilepsy, 16 (53.3%) with TLE, three (10%) with occipital lobe epilepsy and five (16.7%) with multifocal epilepsy. The seizures were frequent monthly or daily in 29 patients (47.5%). As far as type of therapy is concerned, 48 patients (78.7%) were on monotherapy and the remaining 13 (21.3%) on polytherapy. Valproate (VPA) was the most used drug (25 out of 61 patients; 41%), alone or associated with Carbamazepine (CBZ) (14), Levetiracetam (LEV) and Lamotrigine (LTG) (nine), Phenobarbital (PB) (eight), Topiramate (TPM) (seven) and oxcarbazepine (OXC) (six).

All patients enrolled were subjected to measurement of blood total testosterone levels, free testosterone, dehydroepiandrosterone sulphate (DHEAS) and delta-4-androstenedione. Sexual functions were evaluated by means of structural questionnaire “International Inventory of Erectile Function” IIEF which evaluates erectile function (IIEF I), orgasmic function (IIEF II), sexual drive (IIEF III), satisfaction intercourse (IIEF IV) and whole satisfaction of sexual life (IIEF V). To evaluate mood disorders, all patients performed Hamilton Rating Scale for Depression (HRSD). Statistical analysis was performed on the basis of Chi-square test to evaluate categorical variables and Student’s t test to analyse continuous variables. Statistical significance level was fixed as P<0.05. The protocol and procedures employed were reviewed and approved by the Local Research Ethics Committee for recruitment patients and the control group.

Results

Out of 61 enrolled patients, 22 (36.7%) showed SDs: erectile dysfunctions in 14 (23%), orgasmic dysfunctions in (11.5%) and sexual drive dysfunctions in 12 (19.7%).

Patients with SDs included 14 on monotherapy and eight on polytherapy (VPA in eight, six PB, five TPM, three LEV, three LTG, three OXC). Out of 61 patients, 36 were subjected to blood measurement of sexual hormones and 21 (58.3%) showed hormonal modifications: blood increased total testosterone was found in six patients (16.7%), reduced free testosterone was found in 12 (33.3%) and increased free testosterone in seven (19.4%). Reduced levels of DHEAS were found in nine patients (25%) and increased levels of DHEAS associated with reduced levels of Delta and rostenedione in only one.

In our study, as reported in the literature (Parazzini et al 2000), there is an increased prevalence in SD, and actually, mean age of epileptics with SD (39.36) is significantly greater if compared with that of patients without SD (29.54) with t = 4.544 and p<0.0001.

There is not any significant association between focal/generalised epilepsy and sexual changes (χ2 = 0.132, p = 0.7167) nor between focal frontal (χ2 = 0.091, p = 0.7635), temporal (χ2 = 0.196, p = 0.6583), occipital (χ2 = 0.515, p = 0.4730), multifocal epilepsy (χ2 = 1.297, p = 0.2547) and SDs. These latter are not associated with an increased frequency of seizures (χ2 = 0.309, p = 0.5783) (Tab. II).

Sexual dysfunctions and epilepsy

χ2 p
Sexual dysfunctions and types (focal or generalised) epilepsy 0.132 0.7167
Sexual dysfunctions and frontal lobe epilepsy 0.091 0.7635
Sexual dysfunctions and temporal lobe epilepsy 0.196 0.6583
Sexual dysfunctions and occipital lobe epilepsy 0.515 0.4730
Sexual dysfunctions and multifocal epilepsy 1.297 0.2547
Sexual dysfunctions and increased frequency of seizures 0.309 0.5783

Analysing data concerning the relationship between SD and AEDs, we did not find any significant association with mono or polytherapy (VPA, LEV, TPM, LTG, CBZ, OXC) (χ2 = 3.351, p = 0.0672), except for a weak significance between PB and SDs (χ2 = 4.266, p = 0.0389) (Tab. III).

Sexual dysfunctions and AEDs

χ2 p
Sexual dysfunctions and mono/polytherapy 3.351 0.0672
Sexual dysfunctions and VPA 0.078 0.7795
Sexual dysfunctions and LEV 0.036 0.8485
Sexual dysfunctions and TPM 2.731 0.0984
Sexual dysfunctions and LTG 0.036 0.8485
Sexual dysfunctions and CBZ 2.613 0.1060
Sexual dysfunctions and OXC 0.091 0.7635
Sexual dysfunctions and PB 4.266 0.0389

Our data do not indicate any association between hormonal changes and focal/generalised epilepsy as well as various types of focal epilepsy (frontal, temporal, occipital, multifocal) (Tab. IV).

Hormonal changes and epilepsy

χ2 p
Hormonal changes and types (focal or generalised) epilepsy 0.214 0.6439
Hormonal changes and frontal lobe epilepsy 0.842 0.3590
Hormonal changes and temporal lobe epilepsy 0.127 0.7219
Hormonal changes and occipital lobe epilepsy 0.968 0.3252
Hormonal changes and multifocal epilepsy 0.029 0.8639

A positive relationship was found between hormonal changes and the assumption of CBZ but not of other AEDs (VPA, LEV, TPM, LTG, OXC, PB) (χ2 = 5.581, p = 0.0182) (Tab. V).

Hormonal changes and AEDs

χ2 p
Hormonal changes and VPA 1.150 0.2836
Hormonal changes and LEV 0.166 0.6838
Hormonal changes and TPM 0.242 0.6228
Hormonal changes and LTG 0.823 0.3643
Hormonal changes and CBZ 5.581 0.0182
Hormonal changes and OXC 0.094 0.7598
Hormonal changes and PB 2.222 0.1360

We found, also, an association between hormonal changes and SDs in epileptic patients (χ2 = 10.414, p = 0.0013), mainly with erectile dysfunction (χ2 = 7.659, p = 0.0056) and changes of sexual drive (χ2 = 4.261, p = 0.0390), but not with orgasmic dysfunction (χ2 = 0.242, p = 0.6228) (Tab. VI).

Hormonal changes and sexual dysfunctions

χ2 p
Hormonal changes and sexual dysfunctions 10.414 0.0013
Hormonal changes and erectile dysfunctions 7.659 0.0056
Hormonal changes and sexual drive 4.261 0.0390
Hormonal changes and orgasmic dysfunctions 0.242 0.6228

Depression and SD are significantly related (χ2 = 9.883, p = 0.0017): mainly concerning sexual drive (χ2 = 37.773, p<0.0001), and erectile dysfunction (χ2 = 5.553, p = 0.0185), but not orgasmia dysfunction (χ2 = 0.062, p = 0.8038).

Discussion

SDs have been reported in literature in 38.7% of males with epilepsy. Hyposexuality is the predominant syndrome that is characterised by the loss of sexual desire, reduced sexual activity and sexual arousal (18, 19). On the contrary, organic sexual problems are also frequently seen (20). In our study, we used “International Inventory of Erectile Function” IIEF, a standardised questionnaire, to evaluate different SDs, and we found a prevalence of SD in 36.7% of patients (18, 19). Mean age of epileptics with SDs (31.2 years) is significantly greater if compared with that of patients without SDs (9). In nineties, Petra et al pointed out these data, relating them to an increase in levels of sexual hormone binding globuline (SHBG) in older epileptics (21). It was hypothesised that ictal discharges involving cortical regions, which mediate sexual behaviour, could play a role in genesis of various SDs, in particular limbic region: amygdala, and the corticomedial nucleus (both improving hypothalamic gonadotropin releasing hormone – GnRH – release) (22, 23). It is also possible that epileptic discharges could induce an abnormal bioavailability of serum hormonal concentrations, mainly of testosterone through an influence on hypothalamus, pituitary gland and eventually gonads (24, 25). Bauer et al showed that after surgical removal of epileptogenetic focus, an increase in serum level of total and free testosterone has been found (26). Actually, several studies showed that particularly men with TLE are affected. TLE is involved assuming an altered secretion of GnRH from the hypothalamus connected to temporal lobe. In our study, we did not find any significant relationship between a particular type of focal or generalised epilepsy and SDs, nor analysing seizure severity or seizure frequency as it has been described in literature (27). It could be explain considering our small sample. The reasons for developing SD are multi-factorial. Some of the symptoms are caused by the epilepsy itself, while others may be caused by the antiepileptic medication. Analysing the relationship between AEDs and SD, we did not find any significant associations with mono or polytherapy, and the presence of SDs, except for a weak significance between PB and SD. Even if we did not find a statistical significance, it is anyway interesting that we found SD in eight of 13 patients (62%) on polytherapy, while only 14 of 48 (29%) monotherapy patients were affected. So, we may speculate an association between chronic polytherapy and SDs in epileptic men. These data could be related to the activity of enzyme-inducing drugs on microsomial system that increase metabolism of sexual hormones, and production of proteins binding sexual hormones (SHBG) actually inducing a decrease of the amount of free, and biologically active, hormone. In a small sample of epileptics who assumed carbamazepine, Connel et al found a decrease of total testosterone and an increase of SHBG comparing them to a group of controls (27). Rattya confirmed these results in his study on 90 epileptics who assumed carbamazepine, oxcarbazepine and VPA; only patients who assumed CBZ and OXC showed hormonal variations related to SDs if compared with controls and those who assumed VPA (17, 28). However, the strong enzyme-inducing AEDs, which are metabolised in the liver, such as carbamazepine, phenytoin, phenobarbital or primidone, change the hormone balance of the male organism. These substances enhance the activity of the hepatic cytochrome-P450 enzyme system and increase the formation of sexual hormone binding globulin that, in return, reduces the free biologically active testosterone and increases the inactive bound form (29). Because sexual hormones are very important in supporting sexual drive and sexual function in man and in women, it is thought contributing to the SD observed in patients with epilepsy who are on chronic treatments. In our study, due to the small number of patients in each AED group, it would be worth a comparison between SD and AEDS pooling enzyme-inducing versus noninducing medications. But, because some patients are on polytherapy (including both enzyme-inducing and noninducing AEDs), it could not be possible analysing these data. Instead, we found a statistically significant association between the hormonal changes and SD (χ2 = 10.414, p = 0.0013). In particular, an association between blood increased total testosterone, free testosterone and increased levels of DHEAS with erectile dysfunction (χ2 = 7.659, p = 0.0056) and sexual drive (χ2 = 4.261, p = 0.0390), but not with orgasmic dysfunction (χ2 = 0.242, p = 0.6228). We did not find any significant relationship between a particular type of focal or generalised epilepsy and hormonal changes. Also, in our study, the presence of hormonal changes does not seem to be associated with any type of AEDs, including the new ones (LEV, TPM, LTG, OXC), except for CBZ (χ2 = 5.581, p = 0.0182), as reported by Rättyä et al (17) and Connell et al (27). Anyway in epileptic men, various mechanisms play a role in SD. Psychosocial factors that can impair sexuality, such as limitation of social contacts and poor self-esteem, affect a relatively large proportion of the population with epilepsy. In our study, we also hypothesised that depression could play a role in epileptic males. By mean of HRSD, we found a statistically relationship between depression and SDs, mainly concerning change in sexual drive, even though it is not so easy to rule out the possibility that depression is the consequence of SDs. On the contrary, Duncan (2005) also evaluated the association between SDs and hormonal variations indicating a marked decrease in serum values of serotonine as effect of the disease on limbic system within SD. Until now, studies relating troubles of mood and SDs are very few, as well as drug therapy. The initial important factor is acknowledgment of SD as a common problem associated with epilepsy. Patients are often too embarrassed to discuss these problems or may even lack subjective appreciation of their presence and extent. Physicians, too, are often uncomfortable about addressing them or may fail to recognise their frequency and importance. For the optimal care of patients with epilepsy, these barriers must be confronted and surmounted.

Conclusion

The results of the present study showed that

SDs are present in 36.7% of enrolled males with epilepsy,

mean age of males with epilepsy is significantly greater than of those without SDs

there is not any significant association between SDs (focal or generalised epilepsy), as well as with any type of focal epilepsy – there is any association between SDs various AEDs in the treatment, except for CBZ.

there is not any association between SDs and frequency of seizures.

hormonal changes are associated with SD in males with epilepsy treated with AEDs mainly the erectile dysfunction and change in sexual drive but not with the orgasmic dysfunction

there is not any association between hormonal changes and type of AEDs, except for CBZ.

depression is associated with SDs (change of sexual drive and the erectile dysfunction but not orgasmic dysfunction).

Disclosures

Financial support: The authors received no financial support for the research.
Conflict of interest: The authors declare that there are no conflicts of interest.
References
  • 1. Hellmis E Sexual problems in males with epilepsy--an interdisciplinary challenge! Seizure 2008 17 136 140 Google Scholar
  • 2. Proposal for revised classification of epilepsies and epileptic syndromes. Commission on Classification and Terminology of the International League Against Epilepsy. Epilepsia 1989 30 389 399 Google Scholar
  • 3. Engel J Jr International League Against Epilepsy (ILAE). A proposed diagnostic scheme for people with epileptic seizures and with epilepsy: report of the ILAE Task Force on Classification and Terminology. Epilepsia 2001 42 796 803 Google Scholar
  • 4. Morrell MJ Flynn KL Doñe S Flaster E Kalayjian L et al. Sexual dysfunction, sex steroid hormone abnormalities, and depression in women with epilepsy treated with antiepileptic drugs. Epilepsy Behav 2005 6 360 365 Google Scholar
  • 5. Harden CL Sexuality in women with epilepsy. Epilepsy Behav 2005 7 Suppl 2 S2 S6 Google Scholar
  • 6. Toone BK Wheeler M Nanjee M Fenwick P Grant R Sex hormones, sexual activity and plasma anticonvulsant levels in male epileptics. J Neurol Neurosurg Psychiatry 1983 46 824 826 Google Scholar
  • 7. Herzog AG A hypothesis to integrate partial seizures of temporal lobe origin and reproductive endocrine disorders. Epilepsy Res 1989 3 151 159 Google Scholar
  • 8. Pritchard PB Hyposexuality: a complication of complex partial epilepsy. Trans Am Neurol Assoc 1980 105 193 195 Google Scholar
  • 9. Parazzini F Menchini Fabris F Bortolotti A Calabrò A Chatenoud L et al. Frequency and determinants of erectile dysfunction in Italy. Eur Urol 2000 37 43 49 Google Scholar
  • 10. Nicolosi A Moreira ED Jr Shirai M Bin Mohd Tambi MI Glasser DB Epidemiology of erectile dysfunction in four countries: cross-national study of the prevalence and correlates of erectile dysfunction. Urology 2003 61 201 206 Google Scholar
  • 11. Murialdo G Galimberti CA Fonzi S Manni R Costelli P et al. Sex hormones and pituitary function in male epileptic patients with altered or normal sexuality. Epilepsia 1995 36 360 365 Google Scholar
  • 12. Taylor DC Sexual behavior and temporal lobe epilepsy. Arch Neurol 1969 21 510 516 Google Scholar
  • 13. Blumer D Walker AE Sexual behavior in temporal lobe epilepsy. A study of the effects of temporal lobectomy on sexual behavior. Arch Neurol 1967 16 37 43 Google Scholar
  • 14. Herzog AG Drislane FW Schomer DL Pennell PB Bromfield EB 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 45 764 768 Google Scholar
  • 15. Herzog AG Drislane FW Schomer DL Pennell PB Bromfield EB et al. Differential effects of antiepileptic drugs on sexual function and hormones in men with epilepsy. Neurology 2005 65 1016 1020 Google Scholar
  • 16. Brannon GE Rolland PD Anorgasmia in a patient with bipolar disorder type 1 treated with gabapentin. J Clin Psychopharmacol 2000 20 379 381 Google Scholar
  • 17. Rättyä J Turkka J Pakarinen AJ Knip M Kotila MA et al. Reproductive effects of valproate, carbamazepine, and oxycarbamazepine in men with epilepsy. Neurology 2001 56 31 36 Google Scholar
  • 18. Rosen RC Riley A Wagner G Osterloh IH Kirkpatrick J et al. The international index of erectile function (IIEF): a multidimensional scale for assessment of erectile dysfunction. Urology 1997 49 822 830 Google Scholar
  • 19. Rosen RC Cappelleri JC Gendrano N III. The International Index of Erectile Function (IIEF): a state-of-the-science review. Int J Impot Res 2002 14 226 244 Google Scholar
  • 20. Reynolds CF 3rd Frank E Thase ME Houck PR Jennings JR et al. Assessment of sexual function in depressed, impotent, and healthy men: factor analysis of a Brief Sexual Function Questionnaire for men. Psychiatry Res 1988 24 231 250 Google Scholar
  • 21. Montouris G Morris GL 3rd. Reproductive and sexual dysfunction in men with epilepsy. Epilepsy Behav 2005 7 Suppl 2 S7 S14 Google Scholar
  • 22. Hierons R Saunders M Impotence in patients with temporal-lobe lesions. Lancet 1966 2 7467 761 763 Google Scholar
  • 23. Kolárský A Freund K Machek J Polák O Male sexual deviation. Association with early temporal lobe damage. Arch Gen Psychiatry 1967 17 735 743 Google Scholar
  • 24. Stoffel-Wagner B Bauer J Flügel D Brennemann W Klingmüller D et al. Serum sex hormones are altered in patients with chronic temporal lobe epilepsy receiving anticonvulsant medication. Epilepsia 1998 39 1164 1173 Google Scholar
  • 25. Bauer J Stoffel-Wagner B Flügel D Kluge M Schramm J et al. Serum androgens return to normal after temporal lobe epilepsy surgery in men. Neurology 2000 55 820 824 Google Scholar
  • 26. Kuba R Pohanka M Zákopcan J Novotná I Rektor I Sexual dysfunctions and blood hormonal profile in men with focal epilepsy. Epilepsia 2006 47 2135 2140 Google Scholar
  • 27. Connell JM Rapeport WG Beastall GH Brodie MJ Changes in circulating androgens during short term carbamazepine therapy. Br J Clin Pharmacol 1984 17 347 351 Google Scholar
  • 28. Luef GJ Epilepsy and sexuality. Seizure 2008 17 127 130 Google Scholar
  • 29. Duncan S Talbot A Sheldrick R Caswell H Erectile function, sexual desire, and psychological well-being in men with epilepsy. Epilepsy Behav 2009 15 3 351 357 Google Scholar

Authors

Affiliations

  • Department of Emergency General Surgery and Organ Transplantation, University of Palermo, Palermo - Italy
  • Department of Neurology, Civic Hospital S. Antonio Abate, Trapani - Italy
  • Department of Experimental Biomedicine and Clinic Neuroscience, University of Palermo, Palermo - Italy

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