Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Of 50 consecutive women with partial seizures of temporal lobe origin (temporal lobe epilepsy [TLE]) evaluated for reproductive dysfunction, 28 had menstrual problems. Of those, 19 had reproductive endocrine disorders. Polycystic ovarian syndrome and hypogonadotropic hypogonadism occurred significantly more often in women with TLE than in the general female population. Polycystic ovarian syndrome was associated with predominantly left-sided lateralization of interictal epileptic discharges; hypogonadotropic hypogonadism was more commonly found with right-sided discharges. Hyposexuality occurred more often in women with predominantly right-sided interictal epileptic discharges and was associated with low serum luteinizing hormone levels. There are several possible interpretations: epileptic discharges in medial temporal limbic structures may disrupt hypothalamic regulation of pituitary gonadotropin secretion; anovulatory cycles of reproductive endocrine disorders may promote the development of epileptic discharges; and TLE and some associated reproductive endocrine disorders may represent the parallel effects of prenatal factors common to the development of the brain and the reproductive system.
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PMID:Reproductive endocrine disorders in women with partial seizures of temporal lobe origin. 293 94

A reduction of fertility in women with epilepsy has been reported since 1950 and is confirmed in recent epidemiological studies. This phenomenon has usually been attributed to the increase of medical and socioeconomic problems in these patients or to hyposexuality, which has been consistently observed in epileptic subjects. Recently, a higher occurrence of reproductive endocrine diseases has been reported in epileptic women and proposed as an important cause of reduced fertility. In particular, polycystic ovary syndrome and hypothalamic ovarian failure have been reported in epileptic women with increased frequency compared to the general population. Moreover, an abnormal pattern of luteinizing hormone (LH) pulsatility has been observed in normally cycling, drug-free epileptic women. We suggest that epilepsy may interfere with the functional activity of the gonadotropin releasing hormone (GnRH) pulse generator. It is possible that paroxysmal discharges spreading within the hypothalamus might affect the regularity of the GnRH pulse generator; alternatively, a neurotransmitter dysfunction might at the same time be responsible both for the lowering of the seizure threshold and for the dysfunction of GnRH secretion. The consequent alteration of LH pulsatility might in the long run, under the effect of additional factors, give rise to a clinical reproductive endocrine disorder.
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PMID:Reduced fertility and neuroendocrine dysfunction in women with epilepsy. 794 81

Impaired reproductive function is thought to frequently affect women with epilepsy, mainly when seizures originate in the temporal lobe. In this study, we evaluated menstrual cycle features and assessed ovulation by determining luteal progesterone (Pg) levels in 101 consecutive women with epilepsy (36 with idiopathic generalized epilepsy -IGE; 65 with partial epilepsy -PE), aged between 16 and 50 years, treated with various antiepileptic drugs (AED). PE originated in the temporal lobe (TLE) in 40 subjects, in the frontal lobe in 13, in the parietal lobe in 2, while the origin of focal seizures remained undetermined in 10 patients. In all patients, menstrual and reproductive history, body mass index, hair distribution and hormonal pattern were assessed. Suprapubic ovary ultrasound (US) examination was carried out in 83 patients (28 with IGE, 55 with PE). Three patients with IGE and one with PE were amenorrheic. Oligomenorrhea occurred in 16 patients, polymenorrhea in 2. Changes in menstrual cyclicity were independent from epilepsy type (19.4% in IGE; 23.1% in PE) and from origin of focal discharges (22.5% of patients with TLE; 20.0% with origin in other brain areas). Luteal Pg levels remained below 2 ng/ml in 30 patients independently of epilepsy type. Corpus luteum dysfunction was combined with hyperandrogenism in 15 of these patients. In the other cases different alterations of hypothalamus-pituitary-ovary axis were observed. Valproic acid blunted luteal Pg surge more frequently than other AED. Polycystic ovaries (PCO) were observed in 14 (16.9%) patients (21.0% with IGE: 14.5% with PE). These prevalences are not higher than those reported in the general population. Among PE patients, PCO was found in 1 case with undetermined focal origin and in 7 TLE cases, who also had ovary volume significantly larger than patients with seizures originating from the frontal or parietal lobe. Epileptic women exhibited an increased occurrence of multifollicular ovaries (MFO) found in 12 cases (14.4% vs 5% in the general population). However, no defined hormonal or clinical pictures were associated with this US alteration in most patients. These findings reappraise the impact of ovary alterations in women mainly affected by mild to moderate epilepsy, on differing AED regimens, with the exception of more frequent ovulatory dysfunction and PCO occurrence in patients taking VPA.
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PMID:Menstrual cycle and ovary alterations in women with epilepsy on antiepileptic therapy. 941 5

Valproate is effective for treatment of a variety of seizure types both in adults and in children with epilepsy, but it induces obesity and polycystic ovaries in a considerable proportion of adult women, particularly when the medication is started before the age of 20. In the present study we evaluated reproductive endocrine function in 41 girls, 8 to 18 years old, taking valproate for epilepsy and in 54 healthy control girls. Among the girls taking valproate, 16 were prepubertal, 11 were pubertal, and 14 were postpubertal, and the corresponding numbers were 20, 13, and 21 in the control group. The mean serum testosterone concentrations of prepubertal, pubertal, and postpubertal girls taking valproate were significantly higher than those of the control girls at the same pubertal stage. Hyperandrogenism, defined as serum testosterone levels higher than the mean + 2SD in the control girls at the same pubertal stage, was seen in 38% of prepubertal, 36% of pubertal, and 57% of postpubertal girls taking valproate. In addition, postpubertal girls taking valproate were more obese than the controls and the mean serum insulin-like growth factor binding protein-1 concentration of pubertal and postpubertal hyperandrogenic girls taking valproate was lower than in valproate-treated girls without hyperandrogenism. Valproate may induce hyperandrogenism in girls with epilepsy during the sensitive period of pubertal maturation, and the frequency of hyperandrogenism increases with pubertal development. This emphasizes the importance of careful endocrine observation of girls taking valproate for epilepsy.
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PMID:Valproate-induced hyperandrogenism during pubertal maturation in girls with epilepsy. 1076 74

Epilepsy is a common neurological disorder that may be affected by reproductive hormones and may complicate reproductive health. Many women with epilepsy experience changes in seizure frequency and severity with changes in reproductive cycles, including at puberty, over the menstrual cycle, with pregnancy and at menopause. Ovarian steroids alter neuronal excitability at the membrane and in the genome. Altered protein synthesis as a consequence of changes in RNA mediated gene transcription is one mechanism for steroid mediated effects on excitability. These genomic effects are delayed and sustained. In contrast, membrane effects are immediate and short duration. These effects are mediated at both the GABA-A and NMDA receptors. Estrogen also dynamically alters synaptic connectivity. Estrogen enhances excitability and lowers the seizure threshold, whereas progesterone enhances inhibition and increases the seizure threshold. In experimental models of epilepsy, estrogen is proconvulsant and progesterone is anticonvulsant. The net effect of these steroid actions is to alter neuronal excitability over physiological cycles. Some epilepsy syndromes are expressed or worsened at puberty. One third to one half of women with epilepsy have catamenial seizure patterns, with seizures most likely to occur in the perimenstrual period and at ovulation. More research is needed to understand the effects of menopause on epilepsy. Antiepileptic drugs may exacerbate the risk of reproductive endocrine disorders in women with epilepsy. Fertility rates are lower for women with epilepsy. Women with epilepsy are more likely to have anovulatory menstrual cycles, abnormal pituitary LH release and altered ovarian steroid concentrations. Polycystic ovaries are detected more often in women with epilepsy, particularly those on valproate. Treatment of hormone sensitive seizures relies on standard AEDs. Small trials suggest that adjunctive progesterone therapy is sometimes helpful. The newer AEDs, gabapentin and lamotrigine may have some advantages for women with epilepsy. These drugs do not alter levels of steroid hormones and do not interfere with effectiveness of hormonal contraception. Experience in pregnancy is limited. The dynamic effects of hormones on seizure expression and of seizures on reproductive health complicate the management of epilepsy in women. Newer AEDs may offer advantages for women with epilepsy in the reproductive years.
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PMID:Epilepsy in women: the science of why it is special. 1048 15

Long-term valproate treatment is associated with polycystic ovaries and endocrine disorders in women with epilepsy. The mechanisms responsible for these effects are unknown, but both the epilepsy itself and the drug per se may be of importance. The aim of this study was to investigate possible effects of the drug on gonadal structure and function in animals with no epileptic disorders. Three groups, each of 15 female Wistar rats, were fed perorally with a valproate mixture (50 mg / kg or 200 mg / kg) or control solution once daily for 90 days, giving mean valproate concentrations within the normal human range. A significant, 20% increase in ovary weight was found in both low- (P = 0.027) and high- (P < 0.001) dose animals together with a significantly increased number of ovarian follicular cysts. Mean serum testosterone concentration was significantly reduced in both low- and high-dose animals. There was a non-significant trend towards reduced estrogen levels, while progesterone levels were unchanged. Even if the hormonal changes are somewhat different from those in humans, the findings demonstrate that changes in gonadal structure and endocrine function also occur in intact animals indicating a drug-specific effect. Our findings encourages further studies using animal models to elucidate possible mechanisms involved in the endocrine side-effects of antiepileptic drugs.
Seizure 1999 Dec
PMID:Long-term valproate treatment induces changes in ovarian morphology and serum sex steroid hormone levels in female Wistar rats. 1062 13

Reproductive dysfunction and endocrine disorders are common among both women and men with epilepsy, and, in particular, with temporal lobe epilepsy. In clinical studies, it is hard to separate the effects of seizures from the effects of medication and life style. Studies in rodents, however, suggest that seizures per se can contribute to reproductive dysfunction. In female rats, generalized seizures disrupt normal ovarian cyclicity in adults, and repeated electroshock seizures delay the onset of puberty in juveniles. Right amygdala kindling in adult female rats causes acyclicity, the development of polycystic ovaries and premature aging of the hypothalamic-pituitary neuroendocrine axis, leading to chronic anovulation and continuous estrogen exposure. In adult male rats, repeated electroshock seizures result in transient hypogonadism, characterized by decreased serum testosterone levels and lowered gonadal tissue weight. In contrast, right amygdala kindling increases serum testosterone, estradiol levels and gonadal weight. These findings suggest that reproductive dysfunction in women and men with epilepsy may result from recurrent seizure activity, due to seizure-related interference with the normal functions of the hypothalamic-pituitary-gonadal axis.
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PMID:The effect of seizures and kindling on reproductive hormones in the rat. 1097 55

This review touches on the historical links between epilepsy, seizures and the uterus and ovaries which have fascinated and misled physicians since Greco-Roman times. It then examines present knowledge of ovarian function and its effect on epileptic activity and vice versa before exploring the modern controversy about polycystic ovaries and the polycystic ovary syndrome, epilepsy and anticonvulsant medication. Based on present evidence, women with epilepsy are more prone to develop polycystic (polyfollicular) ovaries than other women due to the epilepsy itself. But women with epilepsy related polycystic (polyfollicular) ovaries are vulnerable to the effects of sodium valproate (possibly particularly during adolescence) and may develop the polycystic ovary syndrome: this is reversible if the valproate is withdrawn. Lamotrigine and carbamazepine seem to prevent the development of the syndrome.
Seizure 2001 Apr
PMID:Epilepsy and the ovary (cutting out the hysteria). 1143 23

Some chronic diseases have a favourable course and are cured spontaneously. Allergic diseases such as eczema, hay fever and asthma have a good outcome in more than 75% of cases within 7 to 25 years, depending on the kind of allergy. Migraines have also a good evolution in children and after menopause. Many symptoms due to menstruation such as dysmenorrhea, premenstrual syndrome or anemia, disappear after menopause as well as diseases due to estrogens such as uterine leiomyoma, endometriosis and prolactinoma. The risk of epilepsy relapse after a first seizure is about 40% after 2 years. The risk is lower in children. Attention deficit disorder affects 3 to 5% of children but is present in only 30% of them in adult age. The prevalence of depression decreases in women between 30 and 60 years of age. Functional somatic syndromes such as fibromyalgia, irritable bowel syndrome or dyspepsia decrease in 2/3 of cases within 5 to 10 years if there is no history of anxio-depressive symptoms. However, prognosis is reserved when initial symptoms are severe or if they are connected to sexual abuse, domestic violence or depression. Other diseases have a spontaneous favourable course such as myopia, idiopathic infertility, polycystic ovary disease or ventricular arrhythmia. The knowledge of a good prognosis enables to avoid unnecessary treatments and to reassure many patients.
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PMID:[The benefits of aging. I. Patience and cure: spontaneous beneficial course of certain diseases]. 1172 11

This review touches on the historical links between epilepsy, seizures and the uterus and ovaries which have fascinated and misled physicians since Greco-Roman times. It then examines present knowledge of ovarian function and its effect on epileptic activity and vice versa before exploring the modern controversy about polycystic ovaries and the polycystic ovary syndrome, epilepsy and anticonvulsant medication. Based on present evidence, women with epilepsy are more prone to develop polycystic (polyfollicular) ovaries than other women due to the epilepsy itself. But women with epilepsy related polycystic (polyfollicular) ovaries are vulnerable to the effects of sodium valproate (possibly particularly during adolescence) and may develop the polycystic ovary syndrome: this is reversible if the valproate is withdrawn. Lamotrigine and carbamazepine seem to prevent the development of the syndrome.
Seizure 2002 Apr
PMID:Epilepsy and the ovary (cutting out the hysteria). 1218 60


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