Relation between sexual dysfunctions and epilepsy, type of epilepsy, type of antiepileptic drugs: a prospective study
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Article Type: ORIGINAL RESEARCH ARTICLE
AuthorsCarlo Pavone, Ninfa Giacalone, Marco Vella, Lidia Urso, Leila Zummo, Brigida Fierro
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.
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.
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.
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.
- • Accepted on 08/02/2017
- • Available online on 18/03/2017
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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 (
|Demographics||Cases n = 61 (%)|
|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
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
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) (
Sexual dysfunctions and epilepsy
|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) (
Sexual dysfunctions and AEDs
|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) (
Hormonal changes and epilepsy
|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) (
Hormonal changes and AEDs
|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) (
Hormonal changes and sexual dysfunctions
|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).
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.
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).
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- Pavone, Carlo [PubMed] [Google Scholar] 1
- Giacalone, Ninfa [PubMed] [Google Scholar] 1, * Corresponding Author (firstname.lastname@example.org)
- Vella, Marco [PubMed] [Google Scholar] 1
- Urso, Lidia [PubMed] [Google Scholar] 2
- Zummo, Leila [PubMed] [Google Scholar] 3
- Fierro, Brigida [PubMed] [Google Scholar] 3
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