Sexual hormones and epilepsy: threat and opportunities

PURPOSE OF REVIEW: This article reviews recent developments in our knowledge of the reciprocal interactions between epilepsy and sex hormones and how these interactions may play a role in the pathophysiology and treatment of both. RECENT FINDINGS: Community studies confirm that menstrual disorders are overrepresented among women with epilepsy, especially among women with high seizure frequency and in those on valproate or polytherapy. Reproductive function is not affected in women with epilepsy who discontinued antiepileptic drug therapy during pubertal maturation. While valproate has been implicated as having particularly notable disruptive effects on reproductive function in women with epilepsy (polycystic ovaries and hyperandrogenemia), this was not evident in non-epileptic primates. The role of epilepsy itself is evident from a study that showed that the laterality of unilateral temporolimbic discharges is associated with predictable directional changes in hormonal secretion at all levels of the reproductive neuroendocrine axis. Epilepsy in men is associated with reduced levels of sexual function, bioactive testosterone and sperm. Various antiepileptic drugs may differ in this regard. SUMMARY: Epilepsy and antiepileptic drugs can alter sex hormone levels to promote the development of reproductive endocrine disorders in both women and men. Reproductive endocrine disorders may adversely affect both reproductive function and seizure control. Treatment of epilepsy and selection of antiepileptic drugs may be important to reproductive health in women and men with epilepsy. Sex steroids and their metabolites may also provide treatment for seizures.     

Valproate, hyperandrogenism, and polycystic ovaries: a report of 3 cases

BACKGROUND: Reproductive endocrine disorders characterized by menstrual disorders, polycystic ovaries, and hyperandrogenism seem to be common among women treated with sodium valproate for epilepsy. OBJECTIVE: To describe the development of valproate-related reproductive endocrine disorders in women with epilepsy. DESIGN: Case report. PATIENTS: Three patients developed a reproductive endocrine disorder during treatment with valproate. It was characterized by hyperandrogenism and polycystic ovaries in all cases, and it was associated with weight gain and menstrual disorders in 2 of the 3 women. RESULTS: Replacing valproate with lamotrigine resulted in a decrease in serum testosterone concentrations in all 3 women. The polycystic changes disappeared from the ovaries in 2 of the women after valproate therapy was discontinued, and the 2 women who had gained weight and developed amenorrhea while being treated with valproate lost weight and resumed menstruating after the change in medication. CONCLUSIONS: The 3 cases presented here illustrate the development of reproductive endocrine disorders after the initiation of valproate therapy in women with epilepsy. The disorders were characterized by hyperandrogenism and polycystic ovaries in all cases, and were associated with weight gain and menstrual disorders in 2 of the 3 women. An evaluation of ovarian structure and function should be considered in women of reproductive age being treated with valproate for epilepsy, especially if they develop menstrual cycle disturbances during treatment.     

Disorders of reproduction in patients with epilepsy: antiepileptic drug related mechanisms.

Epilepsy, antiepileptic drugs (AEDs), and the reproductive system have complex interactions. Fertility is lower in both men and women with epilepsy than in the general population. Moreover, reproductive endocrine disorders are more common among patients with epilepsy than among the population in general. These disorders have been attributed both to epilepsy itself and to AEDs. The use of the liver enzyme inducing AEDs phenobarbital, phenytoin and carbamazepine increases serum sex hormone binding globulin (SHBG) concentrations in both men and women with epilepsy. Over time the increase in serum SHBG levels leads to diminished bioactivity of testosterone and estradiol, which may result in diminished potency in men and menstrual disorders in some women, and, thus, to reduced fertility. Valproate (VPA) medication may have effects on serum androgen concentrations and it reduces serum follicle stimulating hormone levels in men with epilepsy. However, the clinical significance of the VPA related reproductive endocrine changes in men is unknown. On the other hand, in women the use of VPA is associated with a frequent occurrence of reproductive endocrine disorders characterized by polycystic changes in the ovaries, high serum testosterone concentrations (hyperandrogenism) and menstrual disorders. Young women with epilepsy seem to be especially vulnerable to the effects of VPA on serum androgen levels. The endocrine effects of the new AEDs have not been widely studied. However, it seems they may offer an alternative if reproductive endocrine problems emerge during treatment with the older antiepileptic drugs. On the other hand, it seems that in many cases the reproductive endocrine effects of the AEDs are reversible, if the medication is discontinued.     

Seizure type, antiepileptic drugs, and reproductive endocrine dysfunction in Indian women with epilepsy: a cross-sectional study

Background: There is paucity of data regarding occurrence of reproductive endocrine disorders in Asian women with epilepsy (WWE) on antiepileptic drug (AED) therapy. Purpose: To determine the occurrence of reproductive endocrine disorders in Indian WWE, by seizure type and the AED use. Methods: Consecutive 427 reproductive age WWE receiving various AEDs were screened for the occurrence of menstrual abnormalities, weight change, and hirsutism. Of these, 53 WWE with menstrual disturbances and/or hirsutism were further evaluated for ovarian morphology and reproductive hormonal profile. Results: Menstrual abnormalities and/or hirsutism were observed in 83 of 427 (19.4%) WWE irrespective of epileptic seizure type; of these, 50 (60.2%) received valproate, 21 (25.3%) received carbamazepine, 11 (13.3%) received phenytoin, and one (1.2%) received phenobarbitone as the primary AED. Almost half of valproate‐treated women had significant weight gain and obesity. Among 53 of 83 women evaluated further, 23.5% and 63.6% of valproate‐treated women, 25% and 58.3% of carbamazepine‐treated women, and none and 20% of phenytoin‐treated women had polycystic ovaries (PCO) and hyperandrogenemia (HA), respectively. Valproate‐treated women had significantly higher frequency of polycystic ovarian syndrome (PCOS) (11.8% vs. 2.5%, p < 0.0001) and mean serum testrosterone levels (1.78 vs. 1.36 ng/ml, p = 0.03), compared with women treated with other AEDs. Limitations: Limitations include small number of women in antiepileptic subgroups and a high drop out rate in women who underwent ultrasound and endocrinological investigations. Conclusion: Menstrual abnormalities, weight gain, obesity, and PCOS are frequent and significantly higher in WWE receiving valproate, independent of seizure type.     

Reproductive endocrine function in women with epilepsy: the role of epilepsy type and medication

The purpose of the analysis described here was to assess reproductive endocrine disorders in 148 women with epilepsy (WWE) by epilepsy type and antiepileptic drug use. Women with idiopathic generalized epilepsy had a higher prevalence of reproductive endocrine disorders than control subjects. In addition, hyperandrogenism, polycystic ovaries, and polycystic ovary syndrome were more prevalent in WWE on valproate than in WWE taking other drugs or control women. The use of VPA was a predictor of the development of polycystic ovaries and polycystic ovary syndrome, and the use of valproate and younger age predicted the development of hyperandrogenism. In conclusion, both idiopathic generalized epilepsy and valproate were associated with an increased risk of reproductive endocrine disorders in WWE in this post hoc reanalysis of data on a large number of WWE. This was especially evident if the epilepsy was active and required treatment early in life.     

Disorders of reproduction in patients with epilepsy: primary neurological mechanisms.

Reproductive disorders are unusually common among women and men with epilepsy. They are generally associated with and may be the consequence of reproductive endocrine disorders. Both epilepsy itself and antiepileptic drug use have been implicated in their pathophysiology. This review focuses on how temporolimbic dysfunction in epilepsy may disrupt normal neuroendocrine regulation and promote the development of reproductive endocrine disorders. The particular nature of the dysregulation may relate to the laterality and focality of the epilepsy and some hormonal changes may develop in close temporal relation to the occurrence of epileptiform discharges. In women, reproductive endocrine disorders include polycystic ovary syndrome, hypothalamic amenorrhea, functional hyperprolactinemia, and premature menopause. In men, hypogonadism may be hypogonadotropic, hypergonadotropic or related to hyperprolactinemia. The significance of these reproductive endocrine disorders is that they may contribute not only to sexual dysfunction and infertility but may also have an adverse impact on seizure control.     

Women and epilepsy: review and practical recommendations

Individuals with epilepsy experience a number of sex-specific problems. In women, pregnancy and delivery are obvious issues, fertility problems are more often encountered and they also seem to have a higher frequency of sexual problems. A large number of women with epilepsy experience seizure exacerbation in relation to the menstrual cycle and have higher frequencies of menstrual disturbances and polycystic ovaries. Cosmetic problems affecting skin, hair or weight may also be drug induced. The use of antiepileptic drugs may influence the effect of contraceptives leading to unplanned pregnancies and contraceptives may affect the serum levels of antiepileptic drugs. The care of pregnant women with epilepsy requires attention to a number of guidelines and close cooperation between neurologist and gynecologist is recommended. Although the majority of the women with epilepsy experience normal pregnancies and deliveries, their children have a higher risk of birth defects. At menopause, their seizure pattern may change and some antiepileptic drugs may increase the risk of osteoporosis. The optimal treatment of women with epilepsy should take into account these gender-specific issues in the different stages of life.     

Disorders of reproduction in epilepsy--what can we learn from animal studies?

Several animal studies have shown that both the epilepsy itself and many antiepileptic drugs (AEDs) affect reproductive endocrine function in both males and females. Epileptic activity may lead to arrested ovarian cyclicity, anovulatory cycles, polycystic ovaries, and endocrine changes in female animals. In males, seizures disturb normal reproductive physiology by inducing endocrine changes, alterations in gonadal size, and hyposexuality. Several AEDs also affect endocrine function, fertility, and gonadal morphology in both sexes. This paper reviews the literature regarding animal studies related to reproductive disorders in epilepsy. Although care should always be taken when applying data from animal experiments to the human situation, animal models provide a unique possibility for investigating the independent effects of the epilepsy itself and the effects of AEDs in isolation, without confounding factors. By constantly comparing results from clinical and animal studies, and by developing appropriate animal models, several mechanistic questions regarding the complex interplay between epilepsy, hormones, and AEDs can be explored. Animal experiments should play an integral part in the study of reproductive endocrine disorders in epilepsy.     

Reproductive Endocrine Considerations and Hormonal Therapy for Women with Epilepsy

Summary: Animal experimental and human clinical investigations show that estrogens lower and progestins raise many seizure thresholds. In women, seizure frequency varies with the serum estradiol to progesterone ratio. The fluctuation of this ratio during the menstrual cycle is a major factor in catamenial epilepsy. A decline in serum antiseizure medication levels premenstrually may be another factor. Estradiol to progesterone ratios are elevated in anovulatory or inadequate luteal phase cycles. This may explain a propensity for seizure onset at the time of menarche and the exacerbation of seizures during the months or years leading up to menopause. It may also be an important factor in the association between reproductive endocrine disorders and epilepsy. Specifically, polycystic ovarian syndrome and hypogonadotro-pic hypogonadism are significantly overrepresented among women with epilepsy. Epilepsy may promote the development of these disorders. These disorders, in turn, are characterized by inadequate luteal phase cycles that may promote the development or occurrence of seizures. In the setting of catamenial epilepsy or reproductive endocrine disorders, progestins, such as natural progesterone and parenteral medroxyprogesterone, or antiestrogenic agents, such as clomi-phene, constitute rational and effective adjuncts to therapy.     

Sexual and reproductive dysfunction associated with antiepileptic drug use in men with epilepsy

The association between epilepsy and sexual disorders has long been known. However, the etiology remains uncertain, although it is likely to be multifactorial in origin involving neurological, endocrine, iatrogenic, psychiatric and psychosocial factors. Sexual disorders associated with epilepsy can be directly related to seizures (ictal), or unrelated in time to seizure occurrence (interictal). The most common sexual dysfunction is hyposexuality, even if hypersexuality and different paraphilias have been reported in males with epilepsy. Epilepsy and antiepileptic drugs can also alter sex hormone levels to promote the development of reproductive endocrine disorders. This article aims to explore the prevalence and etiology of sexual and reproductive dysfunctions in men with epilepsy, highlighting the pivotal role of antiepileptic drugs in their pathogenesis.     

Higher androgens and weight gain with valproate compared with lamotrigine for epilepsy

BACKGROUND: Valproate is used widely for the treatment of epilepsy but has been associated with hyperandrogenism, hyperinsulinemia, and dyslipidemia. The mechanism for these associations is unknown, but they have been hypothesized to be secondary to valproate-associated weight gain. This study was conducted to test the hypothesis that the antiepileptic drug lamotrigine, which also has a broad spectrum of anti-seizure efficacy, would not be associated with endocrine abnormalities and would not cause weight gain. OBJECTIVE AND METHODS: This open-label, cross-sectional study compared (1) endocrine and lipid measures during the early follicular phase of the menstrual cycle; (2) prevalence of menstrual disorders (from patient diaries recorded over three cycles); and (3) body weight of women with epilepsy on lamotrigine monotherapy (n=119) with those on valproate monotherapy (n=103) for <5 years. RESULTS: Mean total serum testosterone and androstenedione levels were higher (P<0.02) in the valproate group compared with the lamotrigine group. More lamotrigine patients (87%) than valproate patients (77%) reported regular menstrual cycles at the Screening Visit. The prevalence of anovulation did not differ between lamotrigine and valproate. Mean HDL cholesterol levels were higher (P<0.01) with lamotrigine compared with valproate as were LDL and total cholesterol levels (P<0.05). Mean total insulin levels did not significantly differ between the groups. Whereas mean body weight in lamotrigine patients did not differ between the time lamotrigine treatment was initiated and the Study Visit, mean weight in valproate patients increased by 3.7 kg. CONCLUSIONS: Compared with lamotrigine monotherapy, valproate monotherapy was associated with weight gain and higher androgen levels in women with epilepsy. These data suggest that the hyperandrogenism observed in some women using valproate for epilepsy may be secondary to drug therapy. Lamotrigine monotherapy may be more appropriate than valproate for women in whom reproductive endocrine or metabolic abnormalities are potential concerns, i.e. women with concerns about weight gain, diabetes, hirsutism, polycystic ovary syndrome, menstrual dysfunction or infertility.     

Antiepileptic drugs, sex hormones, and PCOS

Reproductive endocrine dysfunction in women with epilepsy is an important issue, and in recent years there is growing evidence to support the effect on sex hormones of both epilepsy per se and various antiepileptic drugs (AEDs). Focal epileptic discharges from the temporal lobe may have a direct influence on the function of the hypothalamic-pituitary axis, thereby altering the release of sex steroid hormones. The role of laterality and severity of epilepsy is still conflicting. The use of the liver enzyme-inducing AEDs--such as phenobarbital, phenytoin, and carbamazepine--can increase serum sex hormone-binding globulin concentrations, leading to diminished bioactivity of testosterone (T) and estradiol. Valproic acid, an enzyme inhibitor, has been associated with the occurrence of reproductive endocrine disorders characterized by high serum T, free androgen index, androstenedione, dehydroepiandrosterone sulfate concentrations, and with polycystic changes in ovaries and menstrual disorders. A better understanding of the effects of AEDs on sex hormones is key to selecting the appropriate AEDs and is crucial for reproductive health in female patients.     

Epilepsy therapy: issues for women and men

It has been suggested that polycystic ovary syndrome is a common finding in women treated with valproate. However, in a recent study this suggestion could not be confirmed. There is currently no clear evidence that valproate contributes to the development of the polycystic ovary syndrome. Focal epileptic discharges may have an impact on the hypothalamic-pituitary-ovarian or -testicular axis. In the case of successful epilepsy surgery the impact of epilepsy on endocrine functioning may cease. This may lead to a normalization of disturbed menstrual cycles in women, and leads to a post-surgical increase of serum androgens in men. Both findings are supplemented by the results of animal experiments. Children exposed to antiepileptic drugs during pregnancy show a normal psychomotor and cognitive development. However, newly developed as well as traditional antiepileptic drugs increase the risk that a child exposed to these drugs during pregnancy will develop a malformation.     

Sodium valproate, hyperandrogenism and altered ovarian function in Indian women with epilepsy: a prospective study

PURPOSE: To assess the association of long-term sodium valproate therapy with reproductive endocrine disorders in Indian women with generalized epilepsy. METHODS: Clinical parameters, ovarian morphology, and serum reproductive hormone concentrations were evaluated in 30 clinically normal and eumenorrheic reproductive age women with generalized epilepsy who were newly initiated on valproate. Longitudinal evaluations were done in 25 of these women after 1 year, and in some of them after 2 and 3 years of therapy. RESULTS: Of the 25 women who completed 1 year follow-up, we observed clinically relevant weight gain in 40%, hirsutism in 20%, menstrual abnormalities in 24%, polycystic ovaries (PCO) in 16%, polycystic ovarian syndrome (PCOS) in 20%, and a significant increase in mean serum testosterone (p=0.046). A significant positive correlation existed between weight gain and the development of menstrual abnormalities (r=0.66, p<0.0001), hirsutism (r=0.53, p=0.006) and PCO (r=0.51, p=0.012). No correlation existed between weight change and serum reproductive hormonal changes. Yearly follow-up for next 2 years in some of these women revealed persistence of menstrual abnormalities, hirsutism and PCO, a significant linear increase in mean body weight, body mass index, and serum testosterone concentrations, and an increase in serum LH levels from second year onwards. LIMITATIONS: Limitations include small sample size and a high dropout rate on follow-up. CONCLUSIONS: Long-term valproate therapy in Indian women with generalized epilepsy is associated with development of hirsutism, significant weight gain, stable or progressive alterations in reproductive hormonal function, and ultimately a higher occurrence of PCOS.     

Premature ovarian failure in women with epilepsy

PURPOSE: Women with epilepsy (WWE) have an increased risk for several reproductive endocrine disorders that may affect their fertility. The incidence of premature ovarian failure (POF) in women with epilepsy has not been systematically studied. This study examined the incidence of POF in women with epilepsy. METHODS: Fifty consecutively evaluated cognitively normal women with epilepsy, aged 38-64 years, whose seizures began before age 41 years, were interviewed for symptoms of perimenopause and menopause. Endocrine studies, performed in women aged 45 years or younger at the time of evaluation, included serum follicle-stimulating hormone (FSH; done on menstrual cycle day 3 in menstruating women), inhibin A levels when FSH was normal, thyroid-stimulating hormone (TSH), prolactin, and, in menstruating women, menstrual cycle day 20 serum progesterone level. Nonsurgical premature menopause was defined as secondary amenorrhea of >12 months' duration with FSH levels of >14 International Units (IU) in women younger than 42 years. Premature perimenopause was defined by the presence of one or more of the following: somatic perimenopausal symptoms; change in previously regular menstrual cycles without evidence of other reproductive endocrine disturbance; and FSH level of >14 IU or inhibin A level of <7 pg/ml. Similarly aged neurologically normal women seen in the menopause and sleep clinics served as control subjects. Statistical analysis included Fisher's exact test, Kruskal-Wallis test, t test, and multivariate logistic regression analysis with significance set at p < 0.05. RESULTS: Seven (14%) of 50 women with epilepsy had nonsurgical premature perimenopause (six of seven) or menopause (one of seven), compared with three of 82 control (p=0.042). Five of 41 women with localization-related epilepsy (LRE) had POF compared with two of nine women with primary generalized epilepsy (PGE; p=0.595). Mean age of POF was 39.6 years (range, 37-42 years). Seizure duration, age at seizure onset, seizure severity and lateralization, smoking history, age of menarche, body mass index and incidence of depression was not statistically different between women with and without POF. There was no statistically significant association between POF and antiepileptic drugs (AEDs). Women with POF were more likely to have had catamenial exacerbation of their seizures than were women without POF (p=0.02). CONCLUSIONS: Women with epilepsy have an increased risk for developing POF. This finding should be considered in counseling women with epilepsy on family planning.     

Seizures, hormones and sexuality.

Sexual disorders (both hyposexuality and sexual dysfunction) are common in people with epilepsy, occurring in up to two-thirds of patients. However, characteristically, patients do not spontaneously report these problems. Nocturnal penile tumescence testing suggests that the erectile dysfunction has a neurophysiological component. The aetiology remains uncertain but is likely to be multifactorial, involving neurological, endocrine, iatrogenic, cognitive, psychiatric and psychosocial factors. Epilepsy-related factors include the age of onset/duration of epilepsy along with the seizure type and focus. In addition, seizure frequency might be relevant as successful epilepsy surgery can result in an improvement in sexual functioning despite remaining on anticonvulsant medication. Endocrine changes (raised sex hormone binding globulin and reduced free testosterone) have been reported in men with epilepsy, especially when treated with hepatic-enzyme inducing antiepileptic drugs. Studies have not been performed evaluating anticonvulsants that do not induce hepatic enzymes such as lamotrigine. The association between these endocrine changes and hyposexuality is not known. The relationship between seizures, hormones and anticonvulsant medication in women is explored, focusing on issues such as catamenial epilepsy, the menopause, hormone replacement therapy and the polycystic ovarian syndrome. Suggestions for future research and treatment issues are discussed.     

Hormones and Epilepsy Through the Lifetime

Summary: Hormones influence brain function from gestation throughout life and may affect the seizure threshold by altering neuronal excitability. Estrogen enhances and progesterone diminishes neuronal excitability experimentally, whereas testosterone and corticosteroids have less consistent effects. Hormonal effects in the CNS also depend on the region of brain in which the hormone acts. Sites of action for most steroid hormones include the hypothalamus and limbic cortex, providing a mechanism for modulating behavior and endocrine function. Seizure patterns may change at certain life stages, perhaps as a result of alterations in hormones. At puberty, epilepsy and benign rolandic epilepsy often remit, while juvenile myoclonic and photosensitive epilepsy may arise. Other types of epilepsy do not respond predictably to events in the reproductive life or to advancing age. In some women, fluctuations in hormones over the menstrual cycle appear to increase seizure vulnerability, probably reflecting changes in relative amounts of estrogen and progesterone. Seizure patterns can be altered, for better or worse, during pregnancy. Whether this reflects the effects of hormones or changes in levels of antiepileptic drugs is not resolved. More information is needed about changes in established epilepsy at menopause and in the elderly. Better understanding of endocrine effects on seizures over a lifetime should lead to more effective epilepsy therapies.     

Medical comorbidities in the treatment of epilepsy

The treatment of epilepsy extends far beyond seizure control. Many comorbidities have a significant impact on the medical management and quality of life of patients with epilepsy. In this review, we examine interactions between epilepsy and some common medical conditions. Psychiatric disorders with a high prevalence in epilepsy include mood disorders, anxiety disorders, and psychosis. Depression is common, psychosis occurs both in direct relation to seizures and interictally, and suicide rates are increased. Changes in sexual function and reduced fertility and marriage rates are described, including a discussion of polycystic ovary syndrome, which is increased in women with epilepsy. The effects of other chronic medical comorbid conditions are reviewed, including the effects of antiepileptic medications on bone health and the impact of renal insufficiency on pharmacological therapy of epilepsy.     

Diagnosis and Treatment of Epilepsy

Summary:  Purpose: The correct diagnosis of epilepsy leads to an appropriate treatment.
Methods: The first step is to distinguish epileptic seizures from nonepileptic attacks, and to make a precise seizure diagnosis and classification. The next step is to identify the etiology or basic disorders underlying the epilepsy by physical and neurologic examinations, laboratory tests, including EEGs and neuroradiologic examinations. Although the EEG is the most important laboratory examination for the diagnosis of epilepsy, limitations of EEG interpretations must be recognized.
Results: A syndromic classification of the patients, to determine whether they fit known syndromes, should be attempted. If patients do not match a described syndrome, a neurobiologic approach, utilizing genetic, neurophysiological, and neuropharmacologic knowledge, alternatively provides useful information to understand the neurobiologic background of epilepsy.
Conclusions: Both approaches have advantages and disadvantages for diagnosing and treating epilepsy. Both approaches can be used interchangeably with patients with seizure disorders, depending upon their condition. The epilepsy diagnosis, etiology, and seizure-type diagnosis should be reevaluated when seizure control is insufficient with first- and second-line antiepileptic drugs.     

癫痫妇女生殖内分泌状况调查及临床特征分析

目的 对育龄期癫痫妇女的生殖内分泌状况进行调查,并对生殖内分泌紊乱,尤其是多囊卵巢综合征(polycystic ovary syndrome,PCOS)患者的临床特征进行系统分析,便于发现问题,及时干预.方法 对139例育龄期女性癫痫患者进行人体测量学及体征评分、月经评估、性激素测定及盆腔超声检查,收集超重、中心性肥胖、月经稀发或闭经、黄体生成素(LH)/卵泡刺激素(FSH)、高雄激素血症、多囊卵巢(polycystic ovary,PCO)共6项指标,利用统计学方法 分析其生殖内分泌紊乱的特征.结果 139例育龄期女性癫痫患者年龄(22.5±7.0)岁,其中30岁以下的处于生殖能力高峰的育龄女性占84.89%;患者中PCOS患病率达12.75%,明显高于我国普通育龄女性PCOS患病率.诊断PCOS特异度高的指标分别为高雄激素血症(100%)、LH/FSH＞2(93%)、月经稀发或闭经(90%);诊断灵敏度高的指标分别为PCO(92%)、月经稀发或闭经(85%)、高雄激素血症(54%).LH[PCOS组(10.24±6.92)IU/L,非PCOS组(4.16±2.62)IU/L,t=-3.899]、LH/FSH值[PCOS组(2.20±1.16),非PCOS组(0.87±0.56),t=-4.240)和睾酮水平[PCOS组(1.07±0.35)ng/ml,非PCOS组(0.46±0.25)ng/ml,t=-4.918]在PCOS组和非PCOS组之间的差异具有统计学意义(P＜0.01).结论 性激素指标是诊断PCOS的客观指标;应重视对女性癫痫患者进行身高、体重、腹围、月经史、卵巢B超等指标的监测.当患者存在可疑生殖内分泌紊乱的临床特征时,必须检查性激素,以便及时发现异常,早期干预.

Abstract：

Objective To investigate the reproductive endocrine status of women with epilepsy at childbearing age and to systematically analyze the clinical features of reproductive endocrine disorders,especially polycystic ovarian syndrome (PCOS),to facilitate early detection and timely intervention.Methods In this study,scoring of anthropometry and physical signs,menstrul assessment,examination of sex hormone and pelvic ultrasound in women with epilepsy at childbearing age were performed,and the data such as overweight,central obesity,oligo/amenorrhea,luteinizing hormone (LH)/follicule-stimulating hormone (FSH),hyperandrogenism and polycystic ovary (PCO) were collected. The characteristics of their reproductive endocrine hormone disorders were analyzed statistically. Results The age of these patients was (22. 5 ± 7.0 ) years,and women younger than 30 years old and at their peak fertility accounted for 84. 89%. The prevalence rate of PCOS in women with epilepsy at childbearing age (12. 75% ) was significantly higher than that of ordinary women at childbearing age (7.2%) in China.Highly specific indicators for PCOS were hyperandrogenism (100%),LH/FSH ＞ 2 (93%) and oligo/amenorrhea (90%),whilst the highly sensitive indicators for PCOS were PCO (92%), oligo/amenorrhea (85%) and hyperandrogenism (54%). This study revealed statistically significant difference in LH,LH/FSH and testosterone (T) between PCOS group (LH: (10.24 ± 6.92) IU/L; LH/FSH;(2.20 ± 1.16);T: ( 1.07 ± 0. 35) ng/ml) and non-PCOS group ( LH: (4. 16 ± 2.62 ) IU/L; LH/FSH:( 0. 87 ± 0. 56 );T: (0. 46 ±0. 25) ng/ml,t = -3. 899,-4. 240 and -4. 918 respectively,all P ＜0. 01 ). Conclusions Hormone indices are objective indicators for the diagnosis of PCOS. In clinical practice,attention should be paid to height,weight,abodominal circumference,menstrul history and ultrasound examination of the ovary in women with epilepsy.When reproductive endocrine hormone disorders are suspected from clinical features,the sex hormones (T,LH,and FSH ) should be checked to allow timely detection and early interventions.