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Study of Sexual Dysfunction in People Living with Epilepsy at a Tertiary Care Center of South India
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.293437
Keywords: Antiepileptic drugs, anxiety, depression, sexual dysfunction
One-eighth (about 55,00,000) of the People living with epilepsy (PWE) in the world reside in India. Sexual dysfunction is more common among PWE as compared to the general population. It has significant psychological, biological, and social ramifications and often leads to poor quality of life. Sexual dysfunction is an important yet under-diagnosed comorbidity among PWE. Sexual dysfunction is difficult to diagnose because of the taboo attached to it. The PWE is often not forthcoming with these complaints and at times think them to be unrelated to epilepsy.[1],[2],[3],[4],[5] The chronic antiepileptic drug (AED) use adds to the sexual and reproductive dysfunctions.[6],[7] The AEDs modulate the hypothalamo-pituitary-adrenal axis and may have direct inhibitory effects on sexual behavior.[5],[7] The PWE receiving enzyme-inducing drugs like carbamazepine and phenytoin have a higher incidence of sexual dysfunction.[5],[8] Hence, it is important to inquire about sexual history from every PWE as it may help in choosing the appropriate AED. PWE has a high prevalence of psychiatric co-morbidities (12%–41%), of which the depression (11%–60%) is the most common. The prevalence of anxiety is not well studied. These lead to poor quality of life and higher suicide rates among PWE.[1],[9] The association of these co-morbidities with sexual dysfunction has not been studied.[10],[11] We found only a single study[2] from the Indian subcontinent that has attempted to address sexual dysfunction and factors affecting it among PWE. This study was restricted to female subjects. The high number of PWE in India and the lack of research from this region on this aspect inspired us to conduct the present analysis. The primary objective of this study was to estimate the proportion of PWE with sexual dysfunction. We also determined various clinical factors associated with sexual dysfunction, including depression and anxiety.
Study setting This was a single-center, cross-sectional study conducted over a period of 3 months from March to May 2017 at an Epilepsy clinic of Department of Neurology of a tertiary care hospital in Puducherry, South India. PWE were selected from the weekly epilepsy clinic with an average patient input of 2500 per month. Free treatment is provided to most of these PWE, who come from Puducherry and the adjoining districts of Tamil Nadu, India. All the selected PWE underwent a two-step evaluation process. They were first diagnosed with epilepsy by a physician undergoing neurology training. The physician then initiated the PWE on the appropriate antiepileptic drugs (AED) in consultation with a senior neurologist. Diagnoses of epilepsy were made as per the definitions and classification of the International League Against Epilepsy (ILAE), 1981 and its modification 2010.[12],[13] PWE aged 18 to 45 years, literate in the local language, Tamil, with a history of seizures for at least one-year duration and regular sexual activity during past one year were included in the study. We excluded the PWE who was pregnant, reported substance abuse, diagnosed with intellectual impairment, encephalopathy, diabetes mellitus, hypertension, and thyroid disorders. Data collection Using a structured proforma, we extracted the relevant demographic and clinical details including the educational status, occupation, age of onset and duration of epilepsy, type and frequency of seizures, and the details of AEDs used from the PWE medical records. For assessing the sexual dysfunction, we used Tamil validated Changes in Sexual Functioning Questionnaire (CSFQ).[14] It has 14 questions (separate for male and female) and is designed to understand the sexual function of both men and women. The questionnaire assessed five domains of sexual functioning namely: sexual desire (frequency), sexual interest, sexual pleasure, sexual excitement, and sexual completion. PWE with scores below 47 (for male) and 41 (for female) were considered having sexual dysfunction.[14] Assessment of anxiety and depression was done using Tamil validated Patient Health Questionnaire 9 (PHQ-9)[15] and Generalized anxiety disorder 7 questionnaire (GAD-7).[16] A score of less than 5 was cut-off for depression and anxiety in both scoring systems. Scores of 0–5, 6–10, 11–15, and 16–20 represent mild, moderate, moderately severe, and severe levels of depression on the PHQ-915, whereas scores of 0–5, 6–10, and 11–15 represent mild, moderate, and severe anxiety on the GAD-7 questionnaire.[16] The participants filled the questionnaires privately in a separate room. A trained social worker provided assistance in case of difficulty in filling the questionnaires. The study was conducted after obtaining approval from the Institute's Ethics Committee (JIP/IEC/201710085) and in accordance with the Code of Ethics of the World Medical Association (Declaration of Helsinki). We took written informed consent from all the study participants. Statistical analysis Data are presented as the mean and standard deviation (SD) or median and interquartile range (IQR), as appropriate, for continuous variables and frequency and proportions for categorical variables. For comparison of continuous data, Student's t-test (means) or median test, and for categorical data, Chi-square or Fisher's exact test were used. P value <0.05 was considered as statistically significant. The analysis was done using SPSS Statistics for Windows, Version 19.0 (Chicago: SPSS Inc.).
We screened 3225 PWE. A total of 108 PWE were included in the study, of which 58 (53.7%) were females. The details of recruitment are shown in [Figure 1]. The majority (76, (70.3%)) had either primary or secondary generalized tonic-clonic seizures. Sixty-three PWE (58.3%) were on more than one antiepileptic drugs. Only nine PWE (8.3%) had seizures frequency of <1 seizure per year. PWE characteristics are shown in [Table 1].
Sixty-five (60.2%) of 108 PWE had sexual dysfunction based on CSFQ score. Twenty-six (52%, n = 50) males and 39 (67.2%, n = 58) PWE had sexual dysfunction. Sixty-four (59.3%) PWE had depression and sixty-three (58.3%) had anxiety. Most PWE had mild (27, 25.0%) to moderate (26, 24.1%) depression [Table 2]. We also analyzed various factors associated with sexual dysfunction among PWE. PWE not receiving valproate (P = 0.007), having depression (P = 0.01) and anxiety (P = 0.04) were significantly higher among those with sexual dysfunction. Depression and anxiety had a significant association with sexual dysfunction while occurring in isolation or when they occurred together (P = 0.03). The severity of depression and anxiety also showed a significant association with sexual dysfunction. These details are given in [Table 3] and [Table 4].
Nearly 60% of PWE in our setting screened positive for sexual dysfunction, depression, and anxiety. PWE not receiving valproate, and having depression and anxiety were more common among those with sexual dysfunction. The severity of depression and anxiety also showed a significant association with sexual dysfunction. Other factors analyzed did not show a significant association with sexual dysfunction. Sixty percent of our PWE had sexual dysfunction. A recent meta-analysis of nine studies (3 cross-sectional, 5 case-control, and 1 cohort) for a total of 599 PWE found the overall prevalence of sexual dysfunction to be 58%.[17] On reviewing the literature, we found only one study[2] from Indian subcontinent addressing this subject. It studied only female subjects (n = 60) and found sexual dysfunction in 70% of their subjects. Sixty-seven percent of our female PWE had sexual dysfunction which corroborates with this previous study. Another study of sexual dysfunction in Chinese Han women with epilepsy also found a higher prevalence of 70%.[18] Worldwide, sexual dysfunction affects 30% to 66% of male PWE and 14% to 50% of female PWE.[6] Various pathophysiological factors have been suggested to explain this phenomenon in the PWE. The disturbances of GnRH pulse generator, the spread of epileptiform activity to the limbic system, ictal or interictal activity interfering with hypothalamus-hypophysis-adrenal axis, temporal lobe epilepsy, and the AEDs altering the sex hormone levels are few hypotheses that try to explain this phenomenon. These pathophysiological mechanisms and multiple other factors like the higher prevalence of depression, low self-esteem, and social stigma might explain this conundrum of sexual dysfunction in PWE.[3] We did not find any association between the prescription of enzyme-inducing drugs and sexual dysfunction. On analysis, we found that it is inappropriate to comment on this result because most (87.0%) of our PWE were on one or the other hepatic-inducing drugs. The previous studies have postulated that hepatic inducers like phenytoin and carbamazepine induce cytochrome p450 and alter the sexual hormone levels leading to sexual dysfunction. Phenobarbitone, phenytoin, and carbamazepine affect sexual hormone metabolism and increase the hormone-binding globulins, thus reducing their levels. In addition, phenytoin has been shown to reduce the motility of sperm.[19] Valproate, on the other hand, does not induce the hepatic enzymes and is usually considered to be safe from the endocrine point of view. We also found that PWE who were given valproate either as monotherapy or poly-therapy were significantly fewer among those with sexual dysfunction. The polytherapy per se was not associated (P = 0.07) with sexual dysfunction. Lamotrigine is another drug that has been indicated to possess this safety effect.[3] Few studies discuss the problem of sexual dysfunction caused by the newer AEDs. The mechanism of sexual dysfunction caused by the newer AEDs is complex and poorly understood. Levetiracetam has been considered safe and apparently does not cause sexual dysfunction but three out of four of our PWE who were on levetiracetam developed sexual dysfunction. Our PWE did not receive other newer AEDs; however, newer AEDs like lamotrigine, gabapentin, pregabalin, oxcarbazepine, zonisamide, and topiramate can also cause sexual dysfunction. The evidence is clearly lacking and further studies are needed to clarify this issue.[19],[20],[21],[22],[23],[24] We used the CSFQ questionnaire to study our PWE. It was rightly pointed out by Nagel et al. that this score has been predominantly used in the psychiatry field and this score has not been used in the field of epilepsy. We found it to be a useful scale. Our study had a cross-sectional design but Nagel's study used it to monitor lamotrigine effect longitudinally (pre and posttherapy) over a period of 8 months.[3],[14] Epilepsy is known to be associated with psychiatric comorbidities. Depression and anxiety are known to be common among PWE. The prevalence of depression ranges from 11%–60% but that of anxiety is not known.[1],[9] Nearly two-thirds of our cases had depression and anxiety. These psychiatric comorbidities were also significantly associated with sexual dysfunction. This association has not been studied previously. A study that was done by Souza et al. also points to an association between sexual dysfunction, and depression and anxiety.[11] Hence, although ours is a purely cross-sectional study, it provides a basis for planning better designed larger studies. We also propose a basic algorithm that could help physicians to assess the sexual dysfunction in PWE [Figure 2].
Our study had a few limitations. Ours was a cross-sectional study; hence, the cause-effect relationship cannot be established between sexual dysfunction and the factors found to be associated with it. We did not have a control arm of the people living without epilepsy and, hence, could not compare the proportion of sexual dysfunction with that of the general population. The majority of PWE reporting to our epilepsy clinic are poor and illiterate but our study included only the literate PWE because we wanted the PWE to fill their forms in private owing to the intimate nature of the questionnaire. Subsequently, in-spite of screening 3225 PWE, we could recruit only 108 PWE. Our study still has a precision of 9.5%, which means that even after taking into account this sample size, at least 50% of our PWE have sexual dysfunction. In fact, our estimate of sexual dysfunction could be an underestimate as we excluded a large number of illiterate PWE. Most of the PWE were on the enzyme-inducing drugs as these are provided free of cost to the PWE. As enzyme-inducing drugs are known to be a risk factor for sexual dysfunction, this might have led to the high proportion of sexual dysfunction in our PWE.
A high proportion of PWE is affected by sexual dysfunction in our setting. It is a common yet under-diagnosed condition in the PWE. It has a significant association with other co-morbidities like depression and anxiety. The use of valproate and possibly other nonenzyme-inducing drugs leads to a lower incidence of sexual dysfunction in the PWE. There is a dearth of studies examining the association of sexual dysfunction with depression, anxiety, and newer nonenzyme-inducing drugs. In addition, it is our observation that the CSFQ might be a good tool to assess the sexual dysfunction in both males and females. It may also be helpful in monitoring the effect of drugs on sexual dysfunction. The high proportion of cases found to be having sexual dysfunction in our group of PWE warrants an urgent need for the physicians to be aware of this aspect of epilepsy. PWE often do not self-report this problem due to the stigma attached to it. Hence, the physicians and neurologists must keep a high index of suspicion for this problem. We suggest that the screening and monitoring for sexual dysfunction should be added to the usual epilepsy work-up. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patients have given their consent for their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4]
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