Download Research Article The Evaluation of Sexual Functions and Sex

J.Neurol.Sci.[Turk]
Journal of Neurological Sciences [Turkish] 30:(4)# 38; 693-701, 2013
http://www.jns.dergisi.org/text.php3?id=717
Research Article
The Evaluation of Sexual Functions and Sex Hormones in Male and Female Epilepsy
Patients Taking Valproic Acid and Carbamazepine Monotherapy
Abidin ERDAL, Gülnihal KUTLU, Yasemin Biçer GÖMCELI, Levent Ertuğrul İNAN
T.C.S.B. Ankara Eğitim ve Araştırma Hastanesi, Nöroloji Kliniği, Ankara, Türkiye
Summary
Objective: In patients with epilepsy, sexual dysfunction is seen at an higher incidence than in
patients with other chronic neurologic disorders. In this study, we examined sex hormone
levels and sexual dysfunction in patients with epilepsy who took carbamazepine (CBZ) and
valproic acid (VPA) monotheraphy.
Method: Female and male patients in reproductive period who had sexual partners within the
last three months referring to Neurology Department Epilepsy Clinic of Ankara Hospital
between December 2009 – November 2010 and who have been followed for at least one year
with CBZ or VPA monotherapy were included in the study. There were 35 patients in the
study; 18 patients who took VPA and 17 patients who took CBZ. These patients' medical
history, epilepsy history, sex hormone levels, drug blood levels, Hamilton Depression Rating
Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A) and Arizona Sexual Experience
Scale (ASEX) levels were examined.
Results: The rate of sexual dysfunction was found statistically significant to be higher in
women patients with epilepsy than men irrespective of drugs, anxiety and depression.
Dehydroepiandrostenedionesulphate (DHEAS) and progesterone (PG) levels were found
statistically significant to be higher in male patients who took VPA. The number of
pregnancies was statistically significant lower in female patients using VPA and it was
associated with VPA induced hyperandrogenism.
Conclusion: Sexual dysfunction and alterations in sex hormones may occur frequently in
epilepsy patients. The most significant finding of our study was high rates of sexual
dysfunction in women. Further studies are necessary to support our findings.
Key words: Sexual
Antiepileptic drugs
dysfunction,
Dehydroepiandrostenedionesulphate,
Progesterone,
Valproik Asit ve Karbamazepin Monoterapili Kadın ve Erkek Epilepsi Hastalarında
Cinsel Fonksiyonların ve Seks Hormonlarının Değerlendirilmesi
Özet
Amaç: Epilepsi hastalarında, diğer kronik nörolojik hastalığı olanlara göre daha yüksek bir
insidansta cinsel disfonksiyon görülmektedir. Bu çalışmada, karbamazepin (CBZ) ve valproik
asit (VPA) monoterapisi alan epilepsi hastalarında seks hormon seviyelerini ve seksüel
disfonksiyonu araştırdık.
Yöntem: Çalışmaya S. B. Ankara Eğitim ve Araştırma Hastane'si Nöroloji Kliniği epilepsi
polikliniğine Aralık 2009 – Kasım 2010 tarihleri arasında başvuran en az bir yıldır takip
edilmekte olan CBZ ve VPA monoterapisi alan reprodüktif çağdaki, son üç ay içinde cinsel
partneri olan kadın ve erkek hastalar alınmıştır. VPA kullanan 18 hasta, CBZ kullanan 17
hasta olmak üzere toplam 35 hasta çalışmamızda yer almıştır. Bu hastaların medikal
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J.Neurol.Sci.[Turk]
özgeçmişleri, epilepsi özgeçmişleri, seks hormon seviyeleri, ilaç kan düzeyleri, Hamilton
Depresyonu Derecelendirme Ölçeği (HAM-D), Hamilton Anksiye Değerlendirme Ölçeği
(HAM-A) ve Arizona Cinsel Yaşam Ölçeği (ASEX) değerleri incelenmiştir.
Bulgular: Epilepsili kadın hastalarda, epilepsili erkek hastalara göre seksüel disfonksiyon
oranı ilaçlar, anksiyete ve depresyondan bağımsız, istatistiksel olarak anlamlı yüksek
bulunmuştur.
Çalışmamızda
VPA
kullanan
erkek
hastalarda,
dihidroksiepiandrostenedionsülfat (DHEAS) ve progesteron (PG) seviyesi istatistiksel olarak
anlamlı yüksek tespit edilmiştir. VPA kullanan kadın hastalarda gebelik sayısı istatistiksel
olarak anlamlı düşük bulunmuştur ve bu da VPA' nın oluşturduğu hiperandrojenizmle ilişkili
olabilir.
Sonuç: Epilepsi hastalarında, seksüel disfonksiyon ve seks hormon seviyelerinde değişiklikler
sık oluşabilir. Çalışmamızın en önemli bulgusu kadınlarda cinsel disfonksiyon oranının
yüksek olmasıdır. Bizim bulgularımızı desteklemek için daha fazla çalışma gereklidir.
Anahtar Kelimeler: Seksüel disfonksiyon, dihidroepiandrostenedionsülfat, progesteron,
antiepileptik ilaçlar
with the ethical standards laid down in the
2008 revision of Declaration of Helsinki.
Female and male patients in reproductive
period who had sexual partners within the
last three months referring to Neurology
Department Epilepsy Clinic of Ankara
Hospital between December 2009 –
November 2010 and who have been
followed for at least one year with CBZ or
VPA monotherapy were included in the
study. Informed consent was obtained from
the patients. Pregnant patients and patients
with endocrinopathies were excluded from
the study.
INTRODUCTION
Sexual dysfunction occurs more commonly
in men and women with epilepsy
compared to normal individuals at the
same ages.(16,18) The etiology of sexual
dysfunction in epilepsy is multifactorial,
i.e.
endocrinological,
neurological,
psychological and social factors all play
role.(16) The impact of epilepsy on
reproductive system was related to
complex partial seizures, particularly
temporal lobe seizures. Complex partial
seizures are associated with hippocampus
and amygadala atrophy and it is known
that these structures are involved with
Sexual
reproductive
behavior.(20)
dysfunction in epilepsy may also be
iatrogenic.(4,10)
In
addition,
many
psychogenic factors (such as anxiety and
depression) may also affect sexuality.(6,25)
The aim of the present study was to
investigate and compare the prevalence of
anxiety, depression, sexual dysfunction
and sexuel hormone levels in male and
female epilepsy patients who took CBZ
and VPA.
Demographic data of all patients, medical
history, the age of the onset of epilepsy,
type and duration of epilepsy, type and
frequency of seizures, the age of onset of
epilepsy
treatment,
the
dose
of
antiepileptic drug (AED) used, its duration
and blood level, family history of epilepsy,
contraceptive methods used, the number of
pregnancies and history of menstruation
were recorded. In all patients, drug blood
level, thyroid stimulating hormone (TSH),
free T3, free T4, prolactin (PRL), total
testosterone (TT), free testosterone (FT),
estradiol
(E2),
progesterone
(PG),
luteinizing
hormone
(LH),
follicle
stimulating hormone (FSH), human
chorionic gonadotropin (HCG), serum
biochemistry and complete blood count
MATERIAL AND METHODS
This study received prior approval from
the ethics committee of the Ministry of
Health, Ankara Research and Training
Hospital and was performed in accordance
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J.Neurol.Sci.[Turk]
was examined. In addition, in male patients
DHEAS levels were also measured. In the
measurement of hormone levels in
patients, blood was drawn from male
patients in morning of any day of the
month while it was drawn within the first
three days of menstruation period in
female patients.
evaluation of data, descriptive statistical
methods (mean, standard deviation) and in
the comparison of qualitative data, T test
and chi-square test were used. Correlation
between parameters was evaluated with
Spearman correlation analysis. P value
under 0.05 was considered significant.
For psychological evaluation, Hamilton
Depression Rating Scale (HAM-D) and
Hamilton Anxiety Rating Scale (HAM-A)
were used.(1,8,23-24) In order to evaluate
sexual dysfunction, Arizona Sexual
Experience Scale (ASEX), which is a
Likert-type self rating scale with male and
female
forms
was
used.
Likert
distinguished between a scale proper,
which emerges from collective responses
to a set of items (usually eight or more),
and the format in which responses are
scored along a range.(3) ASEX evaluates
sex drive, arousal, vaginal lubrication,
penile erection, ability to reach orgasm,
and satisfaction from orgasm. Scores at or
over 11 are reported to indicate sexual
dysfunction in Turkish reliability and
validity study.(13,21)
Overall 42 patients were included in the
study and among them one woman using
CBZ became pregnant before hormone
analysis and another woman on VPA had
high beta-HCG values and they were
excluded from the study. Three patients on
VPA (one male, two female) withdrew
their consent and dropped out from the
study. In addition, two women on CBZ
were excluded as they could not undergo
blood analysis in the first three days of
menstruation.
RESULTS
Hence, overall 35 patients, 18 patients on
VPA, and 17 patients on CBZ were
included in evaluation. The distribution of
drug groups according to epilepsy type and
sex is shown in Table 1. Overall mean age
was 32.63, mean age in CBZ group 34.82,
and that in VPA group 30.56. Drug doses
of male and female patients, mean duration
of drug use and blood drug levels are
shown in Table 2 and 3.
Statistical methods
Findings of the study were evaluated by
SPSS (Statistical Package for Social
Sciences) for Windows 17.0. In the
Table 1. Distribution of drug groups according to type of epilepsy
Type of Epilepsy
CBZ
VPA
(mean age)
n / (%)
n / (%)
1 / (5,9)
9 / (50,0)
16 /( 94,1)
8 / (44.4)
-
1 / (5,6)
17 / (100)
18 / (100)
Primary
(28.20±2,19)
Partial
(34,33±1,97)
Unclassified
(36)
Overall
(32,63±1,55)
*percentages are given for lines
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Tablo 2. Mean drug dose and duration and blood drug levels in male and female patients taking CBZ and VPA.
CBZ taking♀and♂
(n=17)
CBZ taking ♀
(n=8)
CBZ taking ♂
(n=9)
VPA taking♀and♂
(n=18)
VPA taking ♀
(n=7)
VPA taking ♂
(n=11)
Blood drug level
Drug dose
Duration of use
(mg/day)
(month)
608,82±54,61
90,76±22,10
6,88±0,60
643,75±79,86
74,13±18,15
7,01±0,85
577,78±77,78
105,56±39,12
6,76±0,88
958,33±97,45
61,94±13,24
454,90±43,39
821,43±105,14
101,43±27,03
411,45±61,60
1045,45±142,30
36,82±6,84
482,56±59,95
(CBZ mg/L)
(VPA µmol/L)
Table 3. Mean hormone levels and sexual dysfunction according to drug groups in male and female patients.
CBZ
VPA
(n=17)
(n=18)
Male (n=9)
Female (n=8)
Male (n=11)
Female (n=7)
Sexual Dysfunction (+)
3
8
8
6
Sexual Dysfunction (-)
6
-
3
1
10,23±1,13
9,16±0,91
10,46±1,66
18,08±4,15
TT (ng/dl)
459,39±49,50
40,44±4,85
525,62±55,92
45,06±8,27
FT (pg/ml)
13,13±1,24
1,59±0,28
16,46±1,40
1,83±0,20
E2 (pg/ml)
32,15±6,77
56,58±7,81
31,52±4,84
81,96±31,31
PG (ng/ml)
0,46±0,10
0,65±0,07
1,11±0,21
2,18±1,23
LH (IU/ml)
6,24±0,64
4,65±0,89
5,14±0,64
4,33±0,40
FSH (IU/ml)
5,70±1,06
8,60±1,57
4,40±1,30
5,43±0,98
DHEAS (µg/dl)
83,59±8,16
-
251,85±48,76
-
PRL (ng/ml)
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(ASEX ≥ 11) and in 28.6% (n=10), it was
absent. Sexual dysfunction was found in
93.3% (n=14) of female patients, and in
55% of male patients (n=11), with a
statistically significant difference (p<0.05).
When comparison was made according to
drug group, sexual dysfunction was present
in 64.7% (n=11) of CBZ users and 77.8%
of (n=14) VPA users. In CBZ group, in
patients without sexual dysfunction, FT
levels were statistically significant higher
(p<0.05). Mean ASEX scores were
statistically significant higher in female
patients (p<0.05). Of male patients with
sexual dysfunction, 8 was in VPA and the
remaining 3 in CBZ group. Sexual
dysfunction was detected in 8 women in
CBZ and 6 women in VPA group with no
statistically significant difference (p>0.05).
In female patients mean HAM-D scale
scores were 5.33±1.10 and HAM-A scores
4.53±0.66 and mean ASEX score was
15.47±1.05. In male patients, the
corresponding scores were respectively
3.70±0.45; 2.90±0.40 and 10.70±0.76
(Figure 1). There was no statistically
significant difference between male and
female patients with regard to mean scores
obtained with HAM-D and HAM-A scales
(p>0.05). However, ASEX scores were
statistically significant higher in female
patients (p<0.05).
In CBZ using female patients; as the
duration of drug use was increased, FT
values increased (p<0.05). As the drug
dose increased, HAM-D scale values
increased and when PRL values increased,
ASEX scores decreased (p<0.05, p<0.05).
In CBZ using male patients, as drug dose
was increased FT values rose and as drug
blood level increased PG values rose and
as duration of drug use increased, TT
values decreased (p<0.05).
In VPA using female patients LH values
decreased as VPA blood levels increased
(p<0.05). In VPA using male patients, as
the drug dose increased, FT and TT values
rose and as duration of drug use was
prolonged, DHEAS values fell (p<0.05). In
addition, HAM-D scores increased in
parallel to ASEX scores (p<0.05).
Although there was no statistically
significant difference between drug groups
in terms of the number of living healthy
children (p>0.05), the number of
pregnancies was mean 3.75±0.6 in CBZ
group and 1.57±0.6 in VPA group, with a
statistically significant difference between
groups (p<0.05).
PRL, E2, PG levels were respectively 1.97,
1.44 and 3.35 fold higher in female
patients in VPA group than those in CBZ
group, but the difference was not
statistically significant (p>0.05). PG ve
DHEAS levels were statistically significant
higher in male patients in VPA group than
those in CBZ group (p<0.05). Although
testesterone
levels
were
within
physiological value, patients on CBZ have
slightly lower levels than those on VPA.
In female and male patients examined
separately; there was no statistically
significant difference between CBZ and
VPA groups in terms of five major global
aspects of sexual dysfunction in ASEX:
drive, arousal, penile erection/vaginal
lubrication, ability to reach orgasm, and
satisfaction from orgasm (p>0.05).
According to ASEX, in 71.4% of (n=25)
all patients sexual dysfunction was present
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J.Neurol.Sci.[Turk]
Figure 1: Mean HAM-D, HAM-A, ASEX scales' ratings comparison by gender
lower quality of sexual life.(17) However,
even though sexual dysfunction was found
to be higher in female patients using CBZ,
low number of cases makes interpretation
of data more difficult.
DISCUSSION
The cause of sexual dysfunction is quite
complex in both female and male epilepsy
patients. AEDs used, epileptic seizures,
underlying
brain
pathology,
and
psychiatric comorbidity may be considered
among these causes.(12) AED give rise to
sexual dysfunction by altering metabolism
and phramacokinetics of sexual hormones
as well as affecting GABAergic and
seratonergic neuromodulatory systems as
shown in animal studies.(12,22)
Herzog stressed that enzyme inducing
drugs induce aromatase enzyme, hence the
transformation of testesteron to estradiol in
the periphery via this enzyme is increased.
Estradiol, in turn, increases sex hormonebinding globulin (SHBG) levels and has a
negative feedback effect on LH. Herzog
also stated that this mechanisms should
also be borne in mind when evaluating
hormonal changes during CBZ treatment.(5)
As to women, enzyme inducing AED's
decreases bioactivity of E2, testesteron and
other sex steroids by increasing the
synthesis
SHBG
and
leads
to
hyperandrogenism in women with
epilepsy.(7) In women who receive long
term CBZ treatment, menstrual disorders
may occur due to the decrease in bioactive
E2.(7,15) In our study, when drug blood
level increased in CBZ using patients,
ASEX values increased as well. However,
low number of patients was a limiting
factor for statistical evaluation. In our
study, it was found that in male patients
using CBZ, FT values rose statistically
In our study, no statistically significant
difference was found between drug groups
with respect to ASEX scores. Nevertheless,
mean ASEX scores were found to be
statistically significant higher in women
than in men, which indicated that sexual
dysfunction was experienced at a higher
rate in female epilepsy patients than in
male epilepsy patients. The causes of this
difference may be that in Turkish society
male patients have difficulty in expressing
themselves
regarding
dysfunction.(2)
Similarly, in the Turkish reliability and
validity study of ASEX, higher ASEX
scores were obtained by female patients
than male patients.(21) In another study,
female sex was found to be associated with
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J.Neurol.Sci.[Turk]
In our study, DHEAS level was found to
be statistically significant higher in male
patients in VPA group than those in CBZ
group, which is compatible with the results
reported in the literature. And we observed
that DHEAS values decreased in male
patients using VPA with the duration of
use was prolonged. TT and FT levels are
normal range of all groups. All of these
findings suggest that there is no difference
in ASEX scores was found between drug
groups. Besides, PG level also was
significantly higher in male patients in
VPA group. Although PG level was found
to be 3.35 fold higher in women patients in
VPA group than those in CBZ group, this
difference was not found to be statistically
significant. In view of the literature, this
finding may be interpreted as follows:
epilepsy itself decreases pregnelolon and
17 hydroxypregnelolon levels or it
increases progesteron levels, being helped
by VPA in doing so.(11)
significant as drug dose and duration of
dose increased, which may be related to
adaptation mechanisms. In addition, in
male patients using CBZ, TT levels
decreased with the duration of drug use.
In males with epilepsy receiving VPA,
DHEAS
and
androstenedion
concentrations increase. DHEAS is the
precursor of androgen in males. This
results in increase in androgen load in
males, which in turn helps the
metabolization of DHEAS to GABAergic
steroids.(7,19-20) In our study, although the
difference between male and female
patients using VPA in terms of duration of
use was not statistically significant,
duration of VPA use was 2.8 fold higher in
women than that in men. However, we
observed that DHEAS values decreased in
male patients using VPA with the duration
of use was prolonged. All of these findings
suggest
that
various
adaptation
mechanisms may develop in the body as
the duration of VPA and CBZ use
increases. However, further studies on the
issue are required.
In patients using CBZ, HAM-D scores
increase statistically significant especially
with the increase in dose. However, when
patients are evaluated individually,
diagnosis of depression is not made
according to HAM-D scale. This
difference may be largely attributed to the
fact that majority of patients in CBZ group
has partial origin epilepsies. Patients who
took high doses of CBZ may generally be
considered to be more refractory. In
various studies, the rate of sexual
dysfunction was reported to vary between
30-60%.(12)
Women are more susceptible to
endocrinological effects of VPA. In young
girls using VPA, hyperandrogenism
including weight gain, hirsutism and
android obesity occur, while in mature
women, it leads to polycystic ovarian
syndrome and hyperinsulinism. Menstrual
disorders, particularly amenorrhea and
oligomenorrhea are common. In women
using VPA, sexual dysfunction is not
uncommon. Decrease in libido and
anorgasmia occur.(7) In our study, FSH and
LH levels decreased statistically significant
as VPA levels increased.
One of the most striking results of the
present study was that the rate of sexual
dysfunction in women is quite high
irrespective of depression and anxiety
scores. Since our sample size is small,
these findings need to be corroborated by
comparative studies including control
groups representing general population.
Bioactive testesterone correlates with
sexual function in men and women, and
patients with epilepsy have less bioactive
testesterone than others.(9-10,12,14) In our
study ASEX values decreased as FT values
rose, which emphasizes the importance of
FT levels in sexual function in both men
and women.
Acknowledgment
The authors thank Ministry of Health,
Ankara Research and Training Hospital' s
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J.Neurol.Sci.[Turk]
biochemistry clinic for their help in blood
hormone level analyses.
3.
Conflict of interest
None of the authors has any conflict of
interest to disclose. We confirm that we
have read the Journal's position on issues
involved in ethical publication and affirm
that this report is consistent with those
guidelines.
4.
5.
6.
Correspondence to:
Abidin Erdal
E-mail: [email protected]
7.
8.
9.
Received by: 21 April 2013
Revised by: 20 October 2013
Accepted: 27 November 2013
10.
The Online Journal of Neurological
Sciences (Turkish) 1984-2013
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Journal of Neurological Sciences (Turkish)
Abbr: J. Neurol. Sci.[Turk]
ISSNe 1302-1664
11.
12.
13.
14.
REFERENCES
15.
1.
2.
Akdemir A, Örsel SD, Dağ İ, Türkçapar HM,
İşcan N, Özbay H. Hamilton depresyon
derecelendirme
ölçeğinin
geçerliliği,
güvenilirliği ve klinikte kullanımı. Psikiyatri
Psikoloji Psikofarmakoloji Dergisi 1996; 4:
251-259.
Bayraktar Z, Atun A. Reasons of Turkish males
with erectile dysfunction for not presenting to
16.
700
urology clinics. Türkiye Klinikleri Journal of
Medical Sciences 2012; 32(1): 177-183.
Carifio J, Rocco J.P. Ten common
misunderstandings, misconceptions, persistent
myths and urban legends about likert scales
and likert response formats and their antidotes.
J Social Sciences 2007;3(3):106-116.
Devinsky O. Neurologist-induced sexual
dysfunction: enzyme-inducing antiepileptic
drugs. Neurology 2005; 65(7): 980-981.
Duncan S, Blacklaw J, Beastall GH, Brodie
MJ. Antiepileptic drug therapy and sexual
function in men with epilepsy.Epilepsia 1999;
40(2): 197-204.
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.
Hamed
SA.
Neuroendocrine
hormonal
conditions in epilepsy: relationship of
reproductive and sexual functions. The
Neurologist 2008; 14(8): 157-169.
Hamilton M. The assessment of anxiety states
by rating.Br J Med Psychol 1959; 32(1): 50-55.
Herzog AG, Coleman AE, Jacobs AR, Klein P,
Friedman MN, Drislane FW, Schomer DL.
Relationship of sexual dysfunction to epilepsy
laterality and reproductive hormone levels in
women. Epilepsy Behav 2003; 4: 407–413.
Herzog AG, Drislane FW, Schomer DL,
Pennell PB, Bromfield EB, Dworetzky BA,
Farina EL, Frye CA. Differential effects of
antiepileptic drugs on sexual function and
hormones in men with epilepsy. Neurology
2005; 65(7): 1016-1020.
Hill M, Zárubová J, Marusič P, Vrbíková J,
Velíková M, Kancheva R, Kancheva L,
Kubátová J, Dušková M, Zamrazilová,
Kazihnitková H, Šimůnková K, Stárka L. Effects
of valproate and carbamazepine monoterapy
on neuroactive steroids, their precursors and
metabolites in adult men with epilepsy. J
Steroid Biochem Mol Biol 2010; 122(4): 239252.
Kuba R, Pohanka M, Zákopcan J, Novotná I,
Rektor I.Sexual dysfunctions and blood
hormonal profile in men with focal epilepsy.
Epilepsia 2006; 47(12): 2135-2140.
McGahuey CA, Gelenberg AJ, Laukes CA,
Moreno FA, Delgado PL, McKnight KM,
Manber R. The arizona sexual experience scale
reliability and validity. J Sex Marital Ther
2000; 26(1): 25-40.
Morrell MJ, Flynn KL, Done S, Flaster E,
Kalayjian L, Pack AM. Sexual dysfunction, sex
steroid abnormalities, and depression in
women with epilepsy treated with antiepileptic
drugs. Epilepsy Behav 2005; 6: 360–365.
Morrell MJ, Flynn KL, Seale CG, Done S,
Paulson AJ, Flaster ER, Ferin M. Reproductive
dysfunction in women with epilepsy:
antiepileptic drug effects on sex-steroid
hormones. CNS Spectr 2001; 6(9): 771-772,
783-786.
Mölleken D, Richter-Appelt H, Stodieck S,
Bengner T. Sexual quality of life in epilepsy:
J.Neurol.Sci.[Turk]
17.
18.
19.
20.
21.
22.
23.
24.
25.
Correlations with sex hormone blood levels.
Epilepsy Behav2009; 14(1): 226-231.
Mölleken D, Richter-Appelt H, Stodieck S,
Bengner T. Influence of personality on sexual
quality of life in epilepsy. Epileptic Disord
2010; 12(2): 125-32.
Pack AM. Implications of hormonal and
neuroendocrine changes associated with
seizures and antiepileptic drugs: a clinical
perspective. Epilepsia 2010; 51 Suppl 3: 150153.
Rättyä J, Turkka J, Pakarinen AJ, Knip M,
Kotila MA, Lukkarinen O, Myllylä VV, Isojärvi
JI. Reproductive effects of valproate,
carbamazepine, and oxcarbazepine in men with
epilepsy.Neurology 2001; 56(1): 31-36.
Røste LS, Taubøll E, Mørkrid L, Bjørnenak T,
Saetre ER, Mørland T, Gjerstad L.
Antiepileptic
drugs
alter
reproductive
endocrine hormones in men with epilepsy. Eur
J Neurol 2005; 12(2): 118-124.
Soykan A. The reliability and validity of
Arizona sexual experiences scale in Turkish
ESRD patients undergoing hemodialysis. Int J
Import Res 2004; 16(6): 531-534.
Verrotti A, D\' Egidio C, Mohn A, Coppola G,
Parisi P, Chiarelli F. Antiepileptic drugs, sex
hormones, and PCOS. Epilepsia 2011; 52(2):
199-211.
Williams JB. A structured interview guide for
hamilton depression rating scale. Arch Gen
Psychiatry 1988; 45(8): 742-747.
Yazıcı MK, Demir B, Tanrıverdi N,
Karaağaoğlu E, Yolaç P. Hamilton Anksiyete
Değerlendirme Ölçeği, Değerlendiriciler Arası
Güvenilirlik ve Geçerlik Çalışması. Türk
Psikiyatri Dergisi 1998; 9(2): 114-120.
Zelená V, Kuba R, Soška V, Rektor I.
Depression as a prominent cause of sexual
dysfunction in women with epilepsy. Epilepsy
Behav 2011; 20(3): 539-544.
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