Evaluation of thyroid and parathyroid functions in children receiving long-term carbamazepine therapy

We studied serum calcium, phosphorus, alkaline phosphatase (ALP), thyroid hormones (total thyroxine [TT4], free thyroxine [FT4], thyroid-stimulating hormone [TSH]), parathyroid hormone (PH), and osteocalcine levels in children with epilepsy who had been receiving long-term carbamazepine (CBZ) therapy to determine whether there was any effect of CBZ therapy on these hormones. The study included 18 patients with epilepsy receiving CBZ and 16 healthy age-matched controls. The age ranged from 4-18 years (11.26 +/- 3.59 years) and 4.5-17 years (11.16 +/- 3.13 years) in the study and control group, respectively. The duration of CBZ use was between 10 months-5 years (3.12 +/- 1.09 years). When comparing the results we did not find any significant difference in serum calcium, phosphorus, ALP, osteocalcine and TSH and PH levels between the groups (p >.05). However, serum TT4 and FT4 levels were found to be significantly lower in the study group than those of control group (p <.05). However, we observed no clinical signs of hypothyroidism in all subjects. To these findings we suggest that serum thyroid hormone levels should be monitored in children receiving long-term CBZ therapy.     

Brief Communication: NO EFFECT OF LONG-TERM VALPROATE THERAPY ON THYROID AND PARATHYROID FUNCTIONS IN CHILDREN

In this study, we studied serum calcium, phosphorus, alkaline phosphatase, thyroid hormones (total thyroxine, free thyroxine, thyroid-stimulating hormone), parathyroid hormone, and osteocalcine levels in children with epilepsy who had been receiving long-term valproate (VPA) therapy in order to determine whether there was any effect of VPA therapy on these hormones. The study included 31 patients with epilepsy receiving VPA and 22 healthy age-matched controls. The age ranged from 15 months to 16 years and 18 months to 17 years in the study and control group, respectively. The duration of VPA use was between 12 months and 5 years (1.93 &#45 1.90 years). When comparing the results, we did not find any significant difference in any of the parameters, including serum calcium, phosphorus, alkaline phosphatase, osteocalcine, and thyroid and parathyroid hormone levels, between the study and control group. We suggest that VPA can safely be used with regard to thyroid and parathyroid dysfunction in childhood epilepsy.     

Long-term treatment of children with epilepsy with valproate or carbamazepine may cause subclinical hypothyroidism

PURPOSE: The aim of the study was to evaluate serum thyroid hormone balance in children receiving long-term therapy with carbamazepine (CBZ), valproate (VPA), and phenobarbital (PB). METHODS: We determined serum levels of triiodothyronine (T3), thyroxine (T4), free thyroxine (FT4), thyroxine-binding globulin (TBG), and thyroid-stimulating hormone (TSH) in 148 healthy children and 141 children with epilepsy who had been receiving CBZ (61 patients), VPA (51 patients), or PB (29 patients) for 12-161 months. In view of TSH values, three categories of subclinical hypothyroidism were considered: I, TSH greater than the control-group mean + 2 SD (4.37 mIU/L in our study) and <6 mIU/L; II, TSH between 6 and 12 mIU/L; and III, TSH >12 mIU/L. RESULTS: In all treated groups, mean T4 and FT4 levels were lower than in the control group, whereas the CBZ- and VPA-treated children additionally showed reduced mean T3 and TBG levels and increased mean TSH levels. In the group receiving CBZ, 8.2% had TSH values higher than the normal-range maximum, by comparison with only 3.6% of healthy children. The increase in TSH levels was particularly marked in VPA-treated children, accounting for 26% of patients with subclinical hypothyroidism. CONCLUSIONS: Our results, in contrast to previous reports, suggest that CBZ and particularly VPA may induce subclinical hypothyroidism. This suggests a need for careful monitoring of TSH levels in children receiving CBZ or VPA.     

No effect of long-term valproate therapy on thyroid and parathyroid functions in children

In this study, we studied serum calcium, phosphorus, alkaline phosphatase, thyroid hormones (total thyroxine, free thyroxine, thyroid-stimulating hormone), parathyroid hormone, and osteocalcine levels in children with epilepsy who had been receiving long-term valproate (VPA) therapy in order to determine whether there was any effect of VPA therapy on these hormones. The study included 31 patients with epilepsy receiving VPA and 22 healthy age-matched controls. The age ranged from 15 months to 16 years and 18 months to 17 years in the study and control group, respectively. The duration of VPA use was between 12 months and 5 years (1.93 +/- 1.90 years). When comparing the results, we did not find any significant difference in any of the parameters, including serum calcium, phosphorus, alkaline phosphatase, osteocalcine, and thyroid and parathyroid hormone levels, between the study and control group. We suggest that VPA can safely be used with regard to thyroid and parathyroid dysfunction in childhood epilepsy.     

Thyroid Function with Antiepileptic Drugs

Serum thyroid hormone balance was assessed in 108 patients receiving chronic antiepileptic drug (AED) therapy. Forty-five patients were receiving carbamazepine (CBZ), 26 phenytoin (PHT), 16 CBZ-PHT, 11 valproate (VPA), and 10 CBZ-VPA. Serum thyroxine (T4) and free thyroxine (FT4) concentrations were low in patient groups receiving CBZ and/or PHT. Serum T4 concentrations were below the normal range in 24 (53.3%) CBZ patients, 11 (42.3%) PHT patients, 12 (75%) CBZ-PHT patients, and in all 10 patients (100%) receiving CBZ-VPA. Furthermore, serum levels of FT4 were below the normal range in 13 (28.9%) CBZ patients, 6 PHT (23.1%) patients, 5 (31.3%) CBZ-PHT patients, and 5 (50%) CBZ-VPA patients. Despite the decreased serum T4 and FT4 levels in these patients, serum basal and stimulated thyrotropin (TSH) concentrations were normal, except for the slightly increased basal TSH in the CBZ-VPA group. In the VPA group, the findings were different from those in other patients: T4 serum levels were unchanged and FT4, T3, and basal TSH levels increased, but stimulated TSH levels did not differ from those of the control group. The decrease in serum thyroid hormone levels during CBZ and/or PHT medication probably is caused by an accelerated hepatic plasma clearance of these hormones due to induction of hepatic microsomal enzyme systems by these AEDs. VPA, an AED with no liver enzyme-inducing properties, does not cause similar changes. The feedback mechanism is not activated, possibly because of a hypothalamic interference by CBZ and PHT.(ABSTRACT TRUNCATED AT 250 WORDS)     

Carbamazepine and risk of hypothyroidism: a prospective study

OBJECTIVES - While carbamazepine (CBZ) decreases thyroid hormone concentrations it rarely causes hypothyroidism. We assessed prospectively the early effect of CBZ on thyroid status in thyroxine-supplemented hypothyroid patients, when compared with patients without a thyroid disorder. METHODS - In 29 patients, thyrotropin (TSH), total thyroxine (TT4) and free thyroxine (FT4) serum levels were assayed before starting CBZ, and then weekly for 7 weeks. Nineteen patients with no thyroid disorder (group A) were compared with 10 thyroxine-supplemented hypothyroid patients, stable before CBZ treatment (group B). RESULTS - In group A, TT4 decreased significantly by ca. 15-25%, starting from the first week (Friedman, P < 0.001). FT4 decline was smaller (ca. 10-15%) and delayed till the second week. FT4/TT4 ratio increased significantly (P < 0.001), while TSH only slightly (P = 0.073), never exceeding normal range. In group B, similar TT4 and FT4 decline was followed by significantly increasing TSH (P = 0.011), while the FT4/TT4 ratio was not significantly changed. In 3 of 10 patients TSH rose over 5 mIU/l, necessitating treatment adjustment. CONCLUSIONS - In patients with no thyroid disorder, CBZ causes hormonal changes of no clinical relevance, due to adaptive response. In T4-supplemented hypothyroid patients this adaptation is lacking, CBZ may precipitate subclinical or overt hypothyroidism, and early thyroid function monitoring seems advisable.     

抗癫痫药对男性癫痫患者性激素的影响

用放免法测定２０例服用苯妥英钠（ＤＰＨ），２０例服用卡马西平（ＣＢＺ）的男性癫痫患者的血清性激素水平，包括总睾酮（ＴＴ）、游离睾酮（ＦＴ）和雌二醇（Ｅ２），并与１０例性功能正常男性和２３例未服药的癫痫男性患者对比。结果发现：ＤＰＨ引起ＴＴ和Ｅ２升高，ＣＢＺ则引起下降。说明两种抗癫痫药对性激素的影响机理不同，因而处理也不完全相同。     

Effects of Carbamazepine Therapy on Serum Sex Hormone Levels in Male Patients with Epilepsy

The effects of carbamazepine (CBZ) therapy and epilepsy on sex hormone plasma levels in male patients with epilepsy were evaluated by measuring the levels of testosterone (T), free testosterone (FT), sex hormone binding globulin (SHBG), estradiol (E2), luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin (PRL), and dehydroepiandrosterone sulfate (DHEAS) and by calculating the free androgen index (FAI) in 23 male patients with epilepsy receiving CBZ medication, in 18 untreated male patients with epilepsy, and in 19 healthy age-matched control subjects. No significant differences in the mean T or FT levels were found between the three groups, but the CBZ-treated patients had significantly higher SHBG levels and their FAI values and DHEAS concentrations were lower. The LH, FSH, PRL, or E2 levels in CBZ-treated and untreated male patients with epilepsy did not differ from the controls. CBZ monotherapy does not significantly change the serum balance of sex hormones; however, CBZ clearly affects the serum levels of SHBG and DHEAS.     

Thyroid function in men taking carbamazepine, oxcarbazepine, or valproate for epilepsy

PURPOSE: Antiepileptic drugs (AEDs) may affect serum thyroid hormone concentrations. This study aimed to evaluate thyroid function in men taking carbamazepine (CBZ), oxcarbazepine (OCBZ), or valproate (VPA) for epilepsy. METHODS: Ninety men with epilepsy (40 taking CBZ, 29 taking OCBZ, and 21 taking VPA monotherapy) and 25 control subjects participated in the study. After clinical examination, a blood sample for hormone, gamma-glutamyl-transferase (GGT) and antibody (ab) assays was obtained. RESULTS: Serum thyroxine (T4) and free thyroxine (FT4) concentrations were low in men taking CBZ or OCBZ. Forty-five percent of men taking CBZ and 24% of men taking OCBZ had serum T4 and/or FT4 levels below the reference range. However, no correlations were found between T4 or FT4 and GGT concentrations in men taking CBZ or OCBZ. Thirteen percent of men taking CBZ, 17% of men taking OCBZ, and 6% of control men had increased levels of thyroid peroxidase (TPO)-ab and/or thyroglobulin (TG)-ab, but these were not associated with altered serum thyroid hormone concentrations. Serum triiodothyronine and thyrotropin levels in men taking CBZ or OCBZ were normal. In men taking VPA, the concentrations of thyroid hormones, thyrotropin, and antithyroid ab were normal. CONCLUSIONS: Serum thyroid hormone concentrations are low in CBZ- or OCBZ-treated men. However, these low levels do not seem to be due to liver enzyme induction or activation of immunologic mechanisms. Therefore, interference with hypothalamic regulation of thyroid function by CBZ and OCBZ seems possible. VPA does not have any significant effects on thyroid function.     

Thyroid and Myocardial Function After Replacement of Carbamazepine by Oxcarbazepine

Summary: We determined changes in serum concentrations of thyroid hormones during carbamazepine (CBZ) therapy during a 5-year prospective follow-up study of 20 patients with newly diagnosed epilepsy. In addition, we evaluated the effects of replacing CBZ with oxcarbazepine (OCBZ) in 12 male patients with epilepsy in a 6-month prospective follow-up study. Circulating thyroxine and free thyroxine levels decreased after 2-month CBZ treatment and remained at a low level during the 5-year follow-up. There were no associated changes in serum thyrotropin (TSH) concentrations. When CBZ was replaced by OCBZ, the function of the liver's P450 enzyme system normalized, as shown by an increase in antipyrine_T1/2, and a decrease in antipyrine_CL. Serum total and free thyroxine levels increased, and thereafter serum TSH levels decreased. Indexes of diastolic heart function improved concomitantly, which may reflect subclinical hypothyroidism at the cellular level during CBZ treatment. We conclude that normal thyroid function can be restored in patients with epilepsy by replacing CBZ with OCBZ.     

抗癫痫药物对癫痫患者甲状腺激素水平影响的研究

目的 研究癫痫患者甲状腺激素水平和抗癫痫药物对其影响以及与疗效之间的关系。方法 测定已确诊的45例未服用过抗癫痫药物的癫痫患者血清甲状腺激素水平并与30例健康对照组进行比较。再经卡马西平、苯妥英钠、丙戊酸钠三种抗癫痫药物分组单药治疗3个月、6个月、年后观察甲状腺激素水平的变化及与疗效之间的关系。结果 未服用抗癫痫药物的新诊断癫痫患者游离甲状腺素（FT4）水平显著低于健康对照组,经苯妥英钠、卡马西平分别治疗3个月、6个月、1年后T4、FT4、FT3显著低于治疗前水平,TSH无显著性变化。经丙戊酸钠治疗后的不同时间段各甲状腺激素水平与治疗前比较无显著性差异（P＞0．05）。甲状腺激素水平的变化与化疗效之间似无相关性。结论 癫痫的反复发作虽未经抗癫痫药物治疗已存在FT4水平的降低。苯妥英钠、卡马西平可明显造成癫痫患者的亚临床甲状腺功能降低（T4、FT4、FT3下降）,丙戊酸钠对患者甲状腺激素水平无显著影响。甲状腺激素水平的变化与疗效之间无相关性。     

非典型抗精神病药对精神分裂症患者血清甲状腺激素水平的影响

目的探讨非典型抗精神病药利培酮、奥氮平对精神分裂症患者甲状腺功能的影响。方法将符合《中国精神障碍分类与诊断标准(第3版)》(CCMD-3)的54例精神分裂症患者,采用随机数字表法分成服用利培酮和奥氮平两组,其中利培酮组29例,给药初始剂量为4 mg/d,2周内逐渐加至6 mg/d,观察至8周末;奥氮平组25例,给药初始剂量为10 mg/d,2周内逐渐加至15mg/d,观察至8周末。分别在治疗前、治疗第8周末测血清总三碘甲状腺原氨酸(TT3)、血清总甲状腺素(TT4)、游离三碘甲状腺原氨酸(FT3)、血清游离甲状腺素(FT4)及促甲状腺激素(TSH)水平。结果利培酮组治疗前后血清TT3、TT4、FT3、FT4、TSH水平差异均无统计学意义(P0.05),奥氮平组治疗前后血清TT3、TT4、TSH水平差异无统计学意义(P0.05),治疗前后FT3、FT4差异有统计学意义[(3.01±0.28)pg/mlvs.(2.81±0.26)pg/ml,(0.91±0.2)pg/mlvs.(0.77±0.14)pg/ml,P0.05]。利培酮组治疗后血清TT3、FT3水平升高,较奥氮平组差异有统计学意义(P0.05)。结论利培酮对精神分裂症患者甲状腺功能无实质影响,奥氮平能影响精神分裂症患者血清FT3、FT4的水平,在治疗中应注意监测服用奥氮平的精神分裂症患者的甲状腺激素水平。     

Influence of carbamazepine on serum thyroxine and triiodothyronine in patients with epilepsy

Hypothyroidism induced by anti-epileptic drug treatment gave rise to thyroid function test studies in patients treated with carbamazepine (CBZ) only. In 42 patients on long-term CBZ treatment thyroxine (T4), free T4-index (FT4I), and triiodothyronine (T3) concentrations in serum were significantly lower than in controls, while triiodothyronine uptake (T3U) and thyrotropin (TSH) concentrations did not differ between patients and controls. In 12 patients starting on CBZ, means T4, calculated FT4 and thyroxine binding globulin (TBG) were 1-5 months later reduced compared to the initial levels. Thus, CBZ reduced thyroid hormones, TBG and FT4I. A CBZ-induced increase in conversion and metabolism of the thyroid hormones could explain this effect. The normal T3U values and decreased concentrations of TBG make a competitive CBZ binding to TBG less probable. Although the thyroid hormones levels were found lowered in the patients, all remained clinically euthyroid during the study.     

颅脑损伤病人垂体前叶激素和甲状腺素变化的意义

目的：研究颅脑损伤病人垂体前叶激素，甲状腺激素与伤情严重程度及预后的关系。方法：采用时间分辨荧光免疫法检测97例急性颅脑损伤得血清泌乳素（PRL）、促卵泡生成素（FSH）、促甲状腺激素（TSH）、甲状腺素（TT3、TT4、FT3、FT4）水平，60例正常人作对照，伤情及预后分别采用GCS和GOS评分评估，对激素水平的变化与伤情严重程度及预后的关系进行分析。结果：颅脑损伤急性期PRL、FSH显增高，TT3、FT3显降低，损伤越严重，上述指标变化越明显，预后越差，上述指标变化亦越明显，结论：颅脑损伤病人PRL，FSH、TT3、FT3水平的变化可用来判断伤情的严重程度，观察预后。     

焦虑与抑郁障碍共病患者症状与血清甲状腺激素水平的相关分析

目的探讨焦虑与抑郁障碍共病患者症状与血清甲状腺激素及促甲状腺激素(TSH)水平的相关性,为焦虑与抑郁障碍共病的治疗提供理论依据。方法采用单纯随机抽样法,于2014年1月-2015年6月在四川省人民医院心身医学中心抽取50例符合《美国精神障碍诊断与统计手册(第4版)》(DSM-Ⅳ)中焦虑与抑郁障碍共病诊断标准的首次住院患者为研究对象。采用化学发光分析法检测患者血清总三碘甲状腺原氨酸(TT_3)、总甲状腺素(TT_4)、游离三碘甲状腺原氨酸(FT_3)、游离甲状腺素(FT_4)、促甲状腺激素(TSH)水平,并对患者进行焦虑自评量表(SAS)、抑郁自评量表(SDS)及症状自评量表(SCL-90)评定。结果焦虑抑郁障碍共病患者的甲状腺激素各项及TSH水平与SAS、SDS评分均无相关性(P均0.05);TT_4水平与SCL-90的躯体化因子评分呈负相关;FT_4水平与SCL-90中的其他因子评分呈负相关。结论焦虑与抑郁障碍共病患者的症状水平与血清甲状腺激素水平有一定的相关性。甲状腺激素水平的异常与焦虑抑郁障碍共病患者躯体化症状、睡眠及饮食问题的产生有一定的关系。     

Serum Steroid Hormones and Pituitary Function in Female Epileptic Patients During Carbamazepine Therapy

Ten regularly menstruating women with epilepsy were studied in a 12-month prospective follow-up study to evaluate the short-term effects of carbamazepine (CBZ) on serum sex hormone balance and pituitary function. Thirteen female epilepsy patients receiving long-term CBZ monotherapy (mean medication duration 5.3 years) were also studied. Controls were 17 regularly menstruating healthy volunteers. Untreated patients had higher free testosterone (FT) and luteinizing hormone (LH) serum concentrations than control subjects, whereas the other parameters did not differ between these two groups. However, serum sex hormone binding globulin (SHBG) levels increased and dehydroepiandrosterone sulfate (DHEAS) levels decreased during CBZ treatment. Although calculated free androgen index (FAI) decreased during CBZ therapy, the directly measured FT levels remained unaltered. These changes were found after 2 months and continued after 12 months of CBZ treatment. Moreover, patients with long-term CBZ also had high SHBG levels, low serum DHEAS levels, and low FAI values. Basal LH serum levels decreased during the first year of CBZ treatment and luteinizing hormone-releasing hormone (LH-RH)-stimulated LH concentrations were lower after 2 months of CBZ treatment. Although the serum basal follicle-stimulating hormone (FSH) and prolactin (PRL) levels were unaffected during the first year of CBZ therapy, the LH-RH-stimulated FSH concentrations and metoclopramide (MC)-stimulated PRL concentrations were lower after 12 months of CBZ treatment than before CBZ. Both basal and stimulated gonadotropin and PRL serum levels of long-term CBZ patients were unaffected. No changes were found in estradiol (E2), testosterone (T), or cortisol (C) serum concentrations during short or long-term CBZ treatment.(ABSTRACT TRUNCATED AT 250 WORDS)     

托吡酯与卡马西平对成年癫痫患者甲状腺激素的影响

目的探讨托吡酯（TPM）及卡马西平（CBZ）对成年癫痫患者甲状腺激素水平的影响。方法选择新确诊的100例成年癫痫患者（50例服用TPM、50例服用CBZ）为试验组,用化学发光法测定用药前甲状腺激素水平并与40例成年健康对照进行比较；再经TPM、CBZ单药治疗3、6个月及1年后检测血中甲状腺激素水平,并与治疗前比较。结果未经治疗的癫痫患者甲状腺激素水平与正常对照组比较无显著性差异（P＞0．05）；与治疗前相比,CBZ治疗3个月、6个月及1年后的游离T4（FT4）、三碘甲状腺原氨酸（TT3）及CBZ治疗6个月及1年后的甲状腺素（TT4）显著降低（P＜0．05）,而CBZ治疗3个月的TT4与服用CBZ后各时点的游离T3（FT3）、促甲状腺素（TSH）无显著性变化（P＞0．05）；经TPM治疗后的不同时段的甲状腺激素水平与治疗前比较均无显著性差异（P＞0．05）。结论CBZ治疗可造成成年癫痫患者甲状腺激素水平的降低。癫痫本身及TPM治疗并不引起成年患者甲状腺激素水平的改变,表明TPM治疗对成年癫痫患者的甲状腺功能更安全。     

Thyroid function in girls with epilepsy with carbamazepine, oxcarbazepine, or valproate monotherapy and after withdrawal of medication

Summary: Purpose: Antiepileptic drugs may affect the serum thyroid hormone concentrations. The aim of this study was to evaluate thyroid function in 78 girls taking carbamazepine (CBZ), oxcarbazepine (OXC), or valproate (VPA) monotherapy for epilepsy and after withdrawal of the treatment. Methods: Forty‐one girls taking VPA, 19 taking CBZ, and 18 taking OXC for epilepsy, as well as 54 healthy age‐matched controls, aged 8 to 18 years, participated in the study. All the girls were examined clinically, and their pubertal stage was assessed. Blood samples were obtained for thyroid hormone and antibody assays. These examinations were repeated after a mean follow‐up of 5.8 years to assess thyroid function, and 64 (82%) of 78 patients and 42 (78%) of 54 controls agreed to participate in the second evaluation. Results: In the first evaluation, the mean serum thyroid hormone concentrations were lower in the girls taking CBZ [thyroxine (T₄), 70.2; SD, 10.9 nM; and free thyroxine (FT₄), 11.5; SD, 1.8 pM] or OXC (T₄, 74.9; SD, 16.4 nM; and FT₄, 11.3; SD, 1.8 pM) than in the control girls (T₄, 96.6; SD, 15.1 nM, and FT₄, 14.4; SD, 1.5 pM; p < 0.001, all comparisons). However, thyrotropin (TSH) concentrations were normal in the girls taking CBZ or OXC. Sixty‐three% of the girls taking CBZ and 67% of the girls taking OXC had serum T₄ and/or FT₄ levels below the lower limit of the reference range. The VPA‐treated girls with epilepsy had normal serum T₄ and FT₄ concentrations, but slightly increased TSH levels (3.3; SD, 1.5 mU/L; p < 0.01) compared with the control girls (2.5; SD, 1.0 mU/L). Normal serum hormone concentrations were restored in the patients who discontinued the medication. Conclusions: Both CBZ and OXC reduce serum thyroid hormone concentrations in girls with epilepsy. Conversely, VPA is associated with normal serum thyroid hormone and increased thyrotropin levels. However, our results suggest that the changes in serum thyroid hormone and thyrotropin levels are reversible after withdrawal of the medication.     

Menstrual Disorders in Women with Epilepsy Receiving Carbamazepine

Summary: We measured concentrations of serum sex hormones and sex hormone binding globulin (SHBG) in relation to regularity of the menstrual cycles in 8 women before carbamazepine (CBZ) treatment was initiated and after 1 and 5 years of CBZ therapy. In addition, we evaluated menstrual cycle regularity and related endocrine changes in 56 women receiving CBZ treatment for >5 years. Serum SHBG levels increased, and serum concentrations of 17β-estradiol (estradiol) and estradiol/SHBG ratio decreased during CBZ treatment. Two of the 8 patients (25%) in the prospective study group developed menstrual irregularities during the first 5 years of therapy. In the cross-sectional study group of patients treated with CBZ for >5 years, the frequency of menstrual disturbances was also 25.0% (14 of 56 patients). Concentrations of serum sex hormones and SHBG were measured in 13 women with menstrual disorders and in 11 randomly selected women with regular cycles. In most cases, menstrual disorders were associated with increased serum SHBG and decreased serum estradiol levels and low estradiol/SHBG ratio. Long-term CBZ treatment results in increased serum SHBG levels and decreased estradiol effect, which correlate with the frequency of menstrual disorders in CBZ-treated women with epilepsy.     

Carbamazepine, Phenytoin, Sex Hormones, and Sexual Function in Men with Epilepsy

Summary We evaluated the effects of carbamazepine (CBZ) on serum androgen levels and sexual function prospectively for 5 years in 11 men with epilepsy and in 25 patients receiving either CBZ (14 patients) or phenytoin (PHT) (11) monotherapy for >5 years. Serum sex hormone binding globulin (SHBG) levels increased and free androgen index (FAI) decreased during CBZ treatment, and these changes correlated with duration of CBZ therapy. Similarly, serum SHBG levels increased and FA1 values decreased in patients receiving PHT for >5 years. CBZ and PHT increase serum SHBG levels, leading to decreased FAI. These drugrelated hormonal changes may be the primary cause of hyposexuality common in men with epilepsy.