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

The relationship between epilepsy and endocrine system has attracted the attention of investigators for a number of years. Epilepsy is a common neurological disorder; both seizures and antiepileptic drugs can compromise the physical and hormonal aspects of sexual development. Impairment of libido and sexual potency have been frequently reported in male epileptic patients. Women with epilepsy have a greater risk of infertility (anovulatory cycles and polycystic ovary syndrome). This review analyses the main data from the literature in order to clarify the role of epilepsy and antiepileptic drugs on sex hormones in epileptic patients. As gonad dysfunction is frequently observed in women and men with epilepsy, particularly when taking antiepileptic drugs, ovarian and testicular function must be carefully monitored.
 ...
PMID:Sex hormones in patients with epilepsy-hormonal changes in epileptic men and women taking antiepileptics. 1582 74

Antiepileptic drug (AED) treatment is associated with multiple short- and long-term side effects. Effects on endocrine function, including weight change, reproductive function, thyroid function, and bone health are examples of these side effects. Some AEDs affect weight, resulting in weight gain or loss. Levetiracetam and lamotrigine are weight-neutral agents, whereas valproate is associated with weight gain. Reproductive dysfunction is reported in women and men with epilepsy treated with AEDs. In women, the most common symptoms are hyperandrogenism, menstrual disorders with ovulatory failure, polycystic ovary-appearing ovaries or polycystic ovary syndrome, and hyperinsulinemia. These symptoms may be secondary to epilepsy or to AED treatment, particularly with valproate. In men, effects on sperm quality and motility, delayed sexual development, and small testicular size have been described in association with AED treatment. Carbamazepine reduces testosterone levels, whereas valproate increases androgen levels. Oxcarbazepine is not associated with changes in testosterone levels. Treatment with all of these agents can result in changes in sperm, including concentration, morphology, and motility. Enzyme-inducing AEDs are known to result in decreased thyroid hormones. Recent studies found reduced serum thyroid hormone concentrations in men and young girls treated with carbamazepine and oxcarbazepine. However, all patients were clinically euthyroid, and these changes were reversible after AED withdrawal. Persons with epilepsy treated with AEDs are at increased risk for fracture. Not only is this increased because of seizure activity, but also because of treatment with AEDs. AED treatment results in decreased bone mineral density, the most sensitive predictor of fracture and changes in biochemical indices of bone metabolism, including calcium, vitamin D, and markers of bone formation and resorption. Identifying each of these endocrine abnormalities is important because it may be necessary and beneficial to change AED treatment. In addition, multiple therapies exist for the treatment of polycystic ovary syndrome, infertility, and decreased bone mineral density.
 ...
PMID:Effects of Treatment on Endocrine Function in Patients with Epilepsy. 1596 90

The function of the hypothalamic-pituitary axis (HPA), including the production of luteinizing hormone, follicle-stimulating hormone, gonadotropin-releasing hormone, and prolactin, and the concentrations and metabolism of its end products, such as estrogen, testosterone, and dehydroepiandrosterone, appear to be modified in many people with epilepsy. Effects of the disorder itself and effects of antiepileptic drugs (AEDs) both appear to contribute to these hormonal alterations, which may be associated with sexual dysfunction. Focal epileptic discharges from the temporal lobe may affect HPA function, as is suggested by the normalization of androgen levels seen in men with temporal lobe epilepsy who become seizure-free after surgery. Hepatic enzyme-inducing AEDs such as carbamazepine and phenytoin may be most clearly linked to altered metabolism of sex steroid hormones, but valproic acid, an enzyme inhibitor, has also been implicated in the causation of reproductive endocrine abnormalities. Polycystic ovaries and polycystic ovarian syndrome (PCOS) are widely believed to be common in women with epilepsy, but the actual prevalence and the pathogenesis of PCOS in this population are disputed. Hormonal changes and sexual dysfunction need to be addressed in any comprehensive approach to epilepsy management, as well as any comprehensive epilepsy research program. Avoidance of enzyme-inducing AEDs and achievement of freedom from seizures as the goal of treatment are strongly recommended.
 ...
PMID:Human sexuality, sex hormones, and epilepsy. 1624 1

Valproate is commonly used for treatment of a variety of seizure types in both children and adults. However, if the medication is started before the age of 20 years, it may affect reproductive endocrine functions. In order to investigate the possible role of valproate treatment in the development of obesity, hyper-insulinism and polycystic ovaries, we studied metabolic parameters and ovarian morphology/size in prepubertal girls with epilepsy. Our study included 14 girls with epilepsy and 15 healthy age-matched controls. The age of the patients ranged from 7 years to 13 years. Mean body weight, fasting serum insulin and glucose levels and HOMA index of girls in the study group were significantly greater than those of the control girls (p < 0.05). Serum androstenedione, prolactin and free testosterone were significantly lower in the VPA-treated girls than in the controls, whereas SHBG level was higher (p < 0.05). There was no difference between the groups for ovarian morphology. In conclusion, our findings showed that valproate treatment may lead to hyperinsulinemia and hypoandrogenism during the prepubertal period. This emphasizes that a mature adult endocrine system may not be necessary for the development of VPA-related hyperinsulinemia.
 ...
PMID:Valproate-induced insulin resistance in prepubertal girls with epilepsy. 1635 11

Several reports in the literature describe an increased prevalence of polycystic ovary syndrome (PCOS) in women with epilepsy. The possible pathogenesis of the association between epilepsy and PCOS is not clear yet, and different hypotheses have been proposed: while some authors suggest that epilepsy may affect the hypothalamic control of reproductive function, others propose a pathogenic role of the antiepileptic drug valproate. In this article we review the literature on the subject, and propose a pathogenic theory in which both epilepsy and valproate play different and significant roles in inducing reproductive endocrine disturbances in women with seizures.
 ...
PMID:Epilepsy and polycystic ovary syndrome: where is the link? 1699 24

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.
 ...
PMID:Women and epilepsy: review and practical recommendations. 1734 Nov 77

The current study was carried out to determine the possible associations between side of focus, catameniality, reproductive dysfunction (RD), and chronology variables for epilepsy and concomitant RD in women. Eighty women of childbearing potential with temporal lobe epilepsy were included in the study. Catamenial epilepsy was observed mainly in women with left-sided foci, and a noncatamenial pattern in women with right-sided foci. Left-sided foci were associated with polycystic ovary syndrome, and right-sided foci with hypogonadotropic hypogonadism. Catamenial epilepsy with right-sided foci was associated with longer duration of epilepsy (P=0.021), trend toward earlier age at onset of epilepsy, and trend toward longer interval between onset of epilepsy and onset of RD compared with catamenial epilepsy with left-sided foci. On the other hand, noncatamenial epilepsy with right-sided foci was characterized by a shorter interval between onset of epilepsy and onset of RD in comparison with noncatamenial epilepsy with left-sided activity (P=0.03). In addition, comparison of patients with right-sided foci with catamenial and noncatamenial patterns of seizures revealed earlier age of epilepsy onset (P=0.049), longer duration of epilepsy (P=0.017) and of RD (P=0.036), and longer interval between onset of epilepsy and onset of RD (P=0.048) in patients with catamenial epilepsy. From an evolutionary point of view, catamenial epilepsy with right-sided focal activity seems to be the oldest subtype.
 ...
PMID:Chronology and evolution of temporal lobe epilepsy and endocrine reproductive dysfunction in women: relationships to side of focus and catameniality. 1757 42

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.
Seizure 2008 Mar
PMID:Disorders of reproduction in epilepsy--what can we learn from animal studies? 1815 32

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.
Seizure 2008 Mar
PMID:Disorders of reproduction in patients with epilepsy: primary neurological mechanisms. 1816 18

Nasal obstruction and consequent mouth breathing have been shown to change the acid-base balance, producing respiratory acidosis. Additionally, there exists a large body of evidence maintaining that acidosis affects the activity of ATP-sensitive potassium (K(ATP)) channels, which play a crucial role in the function of the central nervous system (CNS), for example, in modulating seizure threshold. Thus, in the study described here, we examined whether mouth breathing, induced by surgical ligation of nostrils, could affect the seizure threshold induced by pentylenetetrazole in male NMRI mice. Using the selective K(ATP) channel opener (diazoxide) and blocker (glibenclamide), we also evaluated the possible role of K(ATP) channels in this process. Our data revealed that seizure threshold was increased 6 to 72 hours after nasal obstruction, reaching a peak 48 hours afterward, compared with either control or sham-operated mice (P<0.01). There was a significant decrease in pH of arterial blood samples and increase in CO(2) partial pressure (PCO(2)) during this time. Systemic injection of glibenclamide (1 and 2mg/kg, ip, daily) significantly prevented the increase in seizure threshold in 48-hour bilaterally nasally obstructed mice, whereas it had no effect on seizure threshold in sham-operated mice. Systemic injection of diazoxide (25mg/kg, ip, daily) had no effect on seizure threshold in all groups, whereas higher doses (50 and 100mg/kg, ip, daily) significantly increased seizure threshold in both 48-hour-obstructed and sham-operated mice. The decrease in seizure threshold induced by glibenclamide (2mg/kg, ip, daily) was prevented by diazoxide (25mg/kg, ip, daily). These results demonstrate for the first time that mouth breathing, which could result in respiratory acidosis, increases seizure threshold in mice and K(ATP) channels may play a role in this effect.
 ...
PMID:Mouth breathing increases the pentylenetetrazole-induced seizure threshold in mice: a role for ATP-sensitive potassium channels. 1850 11


<< Previous 1 2 3 4 Next >>