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1.
OBJECTIVE: Evidence indicates that valproate (VPA) may have an adverse impact on reproductive endocrine and metabolic functions in women with epilepsy. This study explores whether the association of VPA with reproductive endocrine abnormalities is applicable to women with bipolar disorder (BD) or is unique to women with epilepsy. METHODS: Thirty female patients aged 18-40 years with a DSM-IV diagnosis of BD (15 on lithium monotherapy and 15 on VPA monotherapy or VPA in combination with lithium therapy) and 15 with idiopathic generalized epilepsy (IGE) on VPA monotherapy were evaluated for reproductive endocrine functioning and metabolic parameters. RESULTS: The menarche age, mean length of menstrual cycle and mean length of menses were not significantly different between groups. None of the bipolar patients on lithium, three (20%) of the bipolar patients on VPA and seven (47%) of the epileptic patients on VPA reported menstrual disturbances. Hirsutism scores of the epilepsy group were significantly higher than those bipolar women, regardless of treatment. Serum total testosterone levels were significantly higher in patients (both with BD and with IGE) treated with VPA than in those treated with lithium. Serum FSH levels were significantly lower and LH-to-FSH ratio was significantly higher in patients with epilepsy than in patients with BD, regardless of treatment. The weight parameters and lipid values investigated did not differ significantly between the groups. CONCLUSION: The study supports the conclusion that VPA may be associated with menstrual abnormalities and increased total testosterone levels in both bipolar and epileptic patients although women with BD did not show clinical features of hyperandrogenism (menstrual abnormalities, hirsutism and truncal obesity) as did frequently as women with epilepsy.  相似文献   

2.
Disturbances of reproductive endocrine hormones are more often found in men with epilepsy than in the general population. There is an ongoing debate whether this can be attributed to chronic use of antiepileptic drugs or to the epilepsy itself. The aim of the present study was to evaluate the degree of endocrine disturbances in men with epilepsy compared with healthy controls, and to investigate whether there was a drug-specific effect of valproate (VPA) or carbamazepine (CBZ). Men with epilepsy, 20-40 years old, having used either VPA (n = 16) or CBZ (n = 19) as monotherapy for >2 years were included and compared with age-matched controls. Men with epilepsy (VPA + CBZ) had significantly lower FSH values and higher C-peptide values compared with controls. Regarding possible drug-specific effects, the VPA treated patients had significantly higher dehydroepiandrosterone (DHEAS) levels and lower FSH and LH concentrations compared with the controls, whereas there were no differences in testosterone, testosterone/sexhormone-binding globulin (SHBG) ratio or androstenedione levels. Men on VPA also had significantly lower free carnitine/total carnitine, which may have implications for sperm motility, and also higher insulin and C-peptide concentrations. The CBZ treated patients had significantly lower testosterone/SHBG ratio than the controls. Compared with the CBZ treated patients, men on VPA had significantly higher DHEAS concentrations and lower levels of follicle stimulating hormone (FSH), luteinizing hormone (LH) as well as a lower free carnitine/total carnitine ratio. A marked age dependency was found in all three groups regarding several of the endocrine hormones. In conclusion, drug-specific endocrine effects of VPA and CBZ were found in men with epilepsy. Long-term VPA treatment leads to significant changes in DHEAS, FSH, LH, insulin, C-peptide and carnitine ratio. Long-term CBZ treatment leads to significant lower testosterone/SHBG ratio. A strict age matching were found to be of importance in the evaluation of endocrine function in men.  相似文献   

3.
BACKGROUND: Long-term treatment with valproate (VPA) or carbamazepine (CBZ) may induce reproductive endocrine disorders in patients with epilepsy. METHODS: Serum concentrations of reproductive hormones were studied in 17 women and 22 men with recently diagnosed epilepsy before they started either VPA or CBZ medication, and 1 and 3 months later. RESULTS: No weight gain or clinical signs of hormonal disorders were observed during the follow-up. The mean serum levels of testosterone, luteinizing hormone, follicle-stimulating hormone, and sex hormone-binding globulin (SHBG) increased, and dehydroepiandrosterone sulfate (DHEAS) decreased, in women starting VPA. Serum testosterone levels increased in half of the women on VPA. Serum concentrations of progesterone and dehydroepiandrosterone increased, and gonadotropins decreased, in men on VPA during the follow-up. Serum SHBG levels increased and DHEAS decreased during the first months of CBZ treatment in both sexes. In addition, the free-androgen index decreased in men after starting CBZ. CONCLUSIONS: Hormonal changes occur after only 1 month's use of VPA or CBZ. VPA-treatment seems to be associated with increased serum androgen levels, but the profile of hormonal changes appears to be different in women than in men. The use of CBZ, in turn, was associated with increased SHBG concentrations and thus with diminished sex steroid function in both sexes. The women with increased serum testosterone levels in the early phase of VPA medication may be at increased risk for VPA-related endocrine disorders later during treatment.  相似文献   

4.
Summary:  Purpose: To assess growth and the serum lipid profile in girls with epilepsy receiving monotherapy at a mean age of 12.6 years and approximately 6 years later.
Methods: A population-based cohort of 77 girls with epilepsy and 49 healthy controls participated in this follow-up study including two cross-sectional evaluations (age range, 8–18.5 years on the first evaluation, and 12.5–25.8 years on the second evaluation). Forty of the patients were initially taking valproate (VPA), 19, carbamazepine (CBZ), and 18, oxcarbazepine (OXC). Growth data were compiled, body mass index (BMI) was calculated, and serum total (TC), and high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C) cholesterol and triglyceride concentrations were analyzed.
Results: Linear growth and final height did not differ between the patients and the controls. At follow-up, the mean BMI of the patients who were off medication (61%) was similar to that of the controls, whereas the patients initially treated with VPA who were still taking any medication had a higher BMI. On the first evaluation, the patients taking VPA had low serum HDL-C, and those taking CBZ or OXC had high serum TC and LDL-C concentrations. At follow-up, serum lipid levels were similar in the patients off medication and the controls.
Conclusions: Neither epilepsy nor antiepileptic therapy affects linear growth or final height, but they may have unfavorable effects on body weight and serum lipid concentrations. Lipid-profile impairment seems to be transient if the medication is discontinued. Overweight is common in patients treated with VPA during puberty if epilepsy and medication continue into adulthood.  相似文献   

5.
Purpose : We aimed to define the morphologic effects of valproate (VPA) and oxcarbazepine (OXC) on ovarian folliculogenesis in rats.
Methods : Forty female wistar rats (21–24 days old and weighted between 46.4 and 55.3 g) were divided equally into 4 experimental groups, which were applied tap water (control group), 300 mg/kg/day VPA, 100 mg/kg/day OXC, and both VPA and OXC via gavage for 90 days. Ovaries of the rats on proestrous and diesterous phase of estrous cycle according to daily vaginal smear were taken out and placed in a fixation solution. Immunohistochemical and apoptosis (TUNEL) staining protocols were applied.
Results : The number of follicles decreased and that of corpora lutea increased significantly in OXC, VPA, and OXC+VPA treated groups compared with control group (p < 0.05). The number of TUNEL positive ovarian follicles was 1.40 ± 0.52 in control group, but it significantly increased to 3.50 ± 0.53, 3.50 ± 0.53, and 4.90 ± 0.88 in VPA, OXC, and VPA+OXC groups (p < 0.0001). The increase in the number of TUNEL positive granulosa cells was also significant for OXC and VPA+OXC groups (p < 0.0001). Immunohistochemical HSCORE decreased for TGFβ1 and IGF1 staining and increased for P53 staining in all drug groups compared with control group (p < 0.001). Intensity of P53 labeling increased, while intensity of TGFβ1, IGF-1, and GDF-9 immunoreactivity decreased significantly in all drug groups compared with control group (p < 0.001).
Conclusion : Long-term treatment with VPA or OXC from prepuberty to adulthood causes apoptosis and deterioration of folliculogenesis in rat ovarian follicles.  相似文献   

6.
Summary:  Purpose: A retrospective study was carried out on 53 cases with childhood epilepsy to evaluate the validity of the initial selection of antiepileptic drug (AED).
Methods: We investigated the AEDs selected at the beginning of the treatment from the medical records of 53 untreated cases. A follow-up study was undertaken to evaluate the effects of the AEDs. In the second study, we investigated the AEDs of 10 cases with atypical benign partial epilepsy (ABPE), to clarify whether the initial AEDs selected for rolandic epilepsy were related to the appearance of ABPE.
Results: The AEDs used at the initial stage consisted of carbamazepine (CBZ), valproic acid (VPA), phenobarbital (PB), and vitamin B6. The main AEDs were CBZ and VPA for localization-related epilepsy, and VPA for generalized epilepsy. The initial selection of AEDs in 41 (85.4%) of 48 cases treated with AEDs were considered to be correct from the results of follow-up. We could not specify any AEDs that related to the appearance of ABPE.
Conclusions: The selection of AED in this series was considered to be most appropriate. We proposed a criterion to determine whether to begin the AED treatment immediately at the initial seizure.  相似文献   

7.
Summary:  Purpose: To evaluate reproductive endocrine function in boys and young men with epilepsy taking an antiepileptic drug in a population-based, controlled study.
Methods: Seventy patients and 70 controls matched for age and pubertal stage participated in this study. Twenty-eight patients were taking carbamazepine (CBZ); five, lamotrigine (LTG); 12, oxcarbazepine (OXC); and 25, valproate (VPA) as monotherapy for epilepsy. All subjects were examined clinically, and their medical histories were obtained. Serum reproductive hormone and sex hormone–binding globulin concentrations were measured, and testicular ultrasonography was performed.
Results: Serum testosterone levels were within the normal range in young male patients with epilepsy. However, the patients taking VPA had high serum androstenedione levels at all pubertal stages. In prepuberty, their serum androstenedione values were already approximately fivefold compared with the values of the controls (8.7 n M ; SD, 4.0 vs. 1.8 n M , SD, 1.0; p < 0.0003), and they were elevated in 64% of the VPA-treated patients compared with none of the other patients, p = 0.0006. Serum sex hormone–binding globulin levels were increased, and serum dehydroepiandrosterone sulfate concentrations decreased in the pubertal patients taking CBZ. The mean testicular volumes did not differ between the patients and the controls.
Conclusions: CBZ and VPA, but not LTG and OXC, are associated with changes in serum sex-hormone levels in boys and young men with epilepsy. However, the long-term health consequences of these reproductive endocrine changes during pubertal development remain to be established.  相似文献   

8.
PURPOSE: This study investigated the effect of epilepsy and/or antiepileptic drugs (AEDs) on the physical growth, pubertal development, and androgenic status of girls with epilepsy between ages 8 and 18 years. METHODS: Sixty-six female patients with epilepsy, their mean ages 13.47 +/- 3.5 years, were included. Anthropometric measurements, staging of pubertal maturation, and clinical manifestations of hyperandrogenism were assessed, as well as measurement of serum levels of testosterone, dehydroepiandrosterone sulfate (DHEAS), sex hormone-binding globulin (SHBG), and free androgen index (FAI). Of the included patients, 44 had transabdominal ultrasonic examination of the ovaries and fasting serum insulin levels were measured. Forty healthy age-matched females served as a control group. RESULTS: Patients showed reduced mean height percentile compared with controls (z = 2.07; p = 0.04), which was negatively correlated with the duration of their epilepsy. Patients showed increased frequency of obesity, especially postpubertal girls taking valproate (VPA; 67%), who also showed higher insulin levels (t = 8.01; p = 0.0003). Patients showed increased frequency of clinical hyperandrogenemia in the different stages of puberty. High levels of testosterone and DHEAS were found in female patients with epilepsy, especially pubertal and postpubertal girls. Hyperandrogenism (clinical and/or laboratory) was most affected by the types of AEDs, with higher incidence in patients taking VPA compared with those taking enzyme-inducing AEDs (chi2= 9.16; p = 0.01). Eighteen percent of the patients were diagnosed as having polycystic ovary syndrome (PCOS). No difference was found in the types of seizures, degree of seizure control, type of AEDs, or insulin levels between patients with and those without PCOS. CONCLUSIONS: Longer duration of the disease has a negative impact on the stature of female patients with epilepsy. Postpubertal girls taking VPA are more liable to obesity, which is associated with increased incidence of hyperinsulinemia. Clinical and/or laboratory evidence of hyperandrogenism is seen at a high frequency in patients, especially with the use of VPA. Furthermore, female patients with epilepsy especially in the postpubertal stage of sexual maturation, have a high prevalence of PCOS, independent of the type of AED or the characteristics of the epilepsy disorder.  相似文献   

9.
Polycystic Ovarian Syndrome in Women with Epilepsy: A Review   总被引:4,自引:1,他引:3  
Susan Duncan 《Epilepsia》2001,42(S3):60-65
Summary: Polycystic ovarian syndrome (PCOS) remains a controversial issue in women with epilepsy. The syndrome is characterized by clinical signs of endocrine dysfunction, such as irregular menstruation, hirsutism, and infertility, but its pathogenesis and presentation are heterogeneous. There are few data on the relationship between epilepsy and PCOS. Studies by a Finnish group have raised the issue of an association between valproate (VPA) and PCOS in young women with epilepsy. These studies, however, were retrospective, laid emphasis on polycystic ovary morphology rather than on clinical endocrine dysfunction, and were undertaken in selected populations. Further studies, both in Italy and Germany, failed to replicate the findings of the Finnish group. Future research should ideally be prospective and include baseline data in untreated women. No compelling data lead to a specific contraindication of the use of VPA in young women, and the drug remains a first-line treatment option.  相似文献   

10.
PURPOSE: Long-term valproate (VPA) treatment has been associated with reproductive endocrine disorders characterized by hyperandrogenism and polycystic changes in the ovaries in women with epilepsy. Levetiracetam (LEV) is a promising, new antiepileptic drug that may represent an alternative to VPA for many patients. Here the effect of LEV and VPA on basal and gonadotropin-stimulated steroid secretion from prepubertal porcine ovarian follicular cells was compared and the conversion of testosterone to estradiol is measured. METHODS: Ovarian follicles were obtained from prepubertal pigs. Follicular theca and granulosa cells were cocultured and different concentrations of LEV or VPA added to the control or gonadotropin-stimulated cultures. RESULTS: VPA, but not LEV, caused a significant increase of LH-stimulated testosterone secretion and decreased FSH-stimulated estradiol secretion. VPA decreased conversion of testosterone to estradiol in both basal and FSH-stimulated cultures, while LEV only decreased testosterone to estradiol conversion after FSH stimulation and only at the highest, nontherapeutic drug concentration. Both drugs increased basal testosterone secretion at therapeutic drug levels. VPA also reduced basal estradiol secretion, while LEV decreased basal estradiol secretion only at nontherapeutic drug levels. CONCLUSION: Both LEV and VPA affect endocrine function in the prepubertal ovary. But while VPA alters both basal and gonadotropin-stimulated testosterone and estradiol secretion at therapeutic drug concentrations, LEV only affects basal hormone secretion at this concentration level. The possibility that LEV could be an alternative treatment to VPA if reproductive endocrine problems emerge in adult women, is discussed. However, extrapolation to the clinical situation is problematic and particular emphasis is placed on the need for further studies.  相似文献   

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