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)

The effect of chlormadinone acetate (24 mg/day) upon the plasma levels of pituitary gonadotropins and gonadal hormones on the number of generalized convulsions and spike EEG density was studied in a group of epileptic children with intractable seizures and with clinical signs suggestive of hyperandrogenism. In each case, the effect of chlormadino ne was evaluated in relation to hormone levels and seizures observed during a control period and under the effect of placebo, as follows: Control (PC); Chlormadinone acetate (PCL1); Placebo (PP); Chlormadinone acetate (PCL2). In a male child, the number of convulsive attacks observed in the control period (26/month) was reduced during PCL1 (2/month), increased during PP (12/month) and reduced again during PCL2 (0/month). Spike EEG density showed a parallel course to the clinical attacks. In this case, control testosterone levels were markedly high (40 ng/ml) and decreased during PCL1 to 4.0, increased again during PP to 34.0 and decreased again during PCL2 to 1.2 ng/ml. Plasma levels of pituitary gonadotropins were unchanged during the entire period of study. In other cases, neither the number of epileptic attacks nor spik e EEG density were apparently affected by this treatment and plasma levels of pituitary gonadotropins and gonadal hormones were also unchanged. These findings suggest that a latent state of hyperandrogenism may be detected in some epileptic patients with intractable seizures and that chlormadinone may reduce convulsive attacks in these patients, probably by decreasing plasma testosterone levels.
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PMID:[Effect of chlormandinone acetate upon seizures in epileptic children with latent signs of hyperandrogenism]. 5 36

A 10-year-old boy with idiopathic epilepsy refractory to treatment from age 4 and with clinical signs of hyperandrogenism was treated with chlormadinone acetate (24 mg/day) during two alternate periods of 3 months. The administration of chlormadinone was associated with a marked clinical and electroencephalographic improvement as well as a concomitant decrease in the levels of plasma testosterone and delta4 androstenedione. No changes in plasma gonadotropins were observed. Placebo had no effect neither in seizures nor in the concentration of hormones in the plasma. Since chlormadinone acetate is not a very potent gonadotropin inhibitor in males, it is suggested that the clinical and electroencephalographic improvement associated with the use of this compound, might be the consequence of a decrease in the plasma levels of androgens, mainly testosterone.
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PMID:Improvement of intractable idiopathic epilepsy with chlormadinone acetate. A case report. 6 43

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 neurologic disorder affecting women during the reproductive years. Seizures and some antiepileptic drugs (AEDs) can compromise reproductive health, and some AEDs can adversely affect carbohydrate and bone metabolism. Women with epilepsy have lower birth rates and more frequent anovulatory menstrual cycles. This appears to be related to seizure- and AED-associated reproductive endocrine disturbances. Carbamazepine (CBZ), phenytoin (PHT), and phenobarbital (PB) induce hepatic cytochrome P450 enzymes and lower endogenous estrogens, adrenal and ovarian androgens, and contraceptive steroids. Valproate (VPA) inhibits steroid hormone metabolism, elevates androgens, and predisposes to phenotypic signs of hyperandrogenism-hirsutism, obesity, acne, and frequent anovulatory cycles. VPA is associated with weight gain, probably by altering insulin metabolism. CBZ, PHT, and VPA, but not lamotrigine (LTG), are associated with lower levels of calcium. PHT, but not VPA or LTG, appears to accelerate bone turnover. AED effects on bone mineral metabolism may explain the elevated risk of fracture described in women with epilepsy. Prospective pregnancy registries are beginning to provide information about AED-associated teratogenesis. The North American Antiepileptic Drug Pregnancy Registry reports a 12% rate of major malformations after first trimester exposure to PB and an 8.6% rate after first trimester exposure to VPA. A prospective LTG-specific registry reports a 1.8% chance of major malformations after the first trimester. The registries will continue to release information as data become significant. In the meantime, practitioners can be alert to signs and symptoms of reproductive or metabolic health disturbances and participate in pregnancy registry efforts.
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PMID:Reproductive and metabolic disorders in women with epilepsy. 1282 65

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.
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PMID:Effects of Treatment on Endocrine Function in Patients with Epilepsy. 1596 90

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 2008 Mar
PMID:Disorders of reproduction in patients with epilepsy: antiepileptic drug related mechanisms. 1816 16

Epilepsy affects the menstrual cycle, aspects of contraception, fertility, pregnancy and bone health in women. It is common for seizure frequency to vary throughout the menstrual cycle. In ovulatory cycles, two peaks can be seen around the time of ovulation and in the few days before menstruation. In anovulatory cycles, there is an increase in seizures during the second half of the menstrual cycle. There is also an increase in polycystic ovaries and hyperandrogenism associated with valproate therapy. There are no contraindications to the use of non-hormonal methods of contraception in women with epilepsy. Non-enzyme-inducing antiepileptic drugs (AEDs) [valproate, benzodiazepines, ethosuximide, levetiracetam, tiagabine and zonisamide] do not show any interactions with the combined oral contraceptive (OC). There are interactions between the combined OC and hepatic microsomal-inducing AEDs (phenytoin, barbiturates, carbamazepine, topiramate [dosages>200 mg/day], oxcarbazepine) and lamotrigine. Pre-conception counselling should be available to all women with epilepsy who are considering pregnancy. Women with epilepsy should be informed about issues relating to the future pregnancy, including methods and consequences of prenatal screening, fertility, genetics of their seizure disorder, teratogenicity of AEDs, folic acid and vitamin K supplements, labour, breast feeding and care of a child. During pregnancy, the lowest effective dose of the most appropriate AED should be used, aiming for monotherapy where possible. Recent pregnancy databases have suggested that valproate is significantly more teratogenic than carbamazepine, and the combination of valproate and lamotrigine is particularly teratogenic. Most pregnancies in women with epilepsy are without complications, and the majority of infants are delivered healthy with no increased risk of obstetric complications in women. There is no medical reason why a woman with epilepsy cannot breastfeed her child. The AED concentration profiled in breast milk follows the plasma concentration curve. The total amount of drug transferred to infants via breast milk is usually much smaller than the amount transferred via the placenta during pregnancy. However, as drug elimination mechanisms are not fully developed in early infancy, repeated administration of a drug such as lamotrigine via breast milk may lead to accumulation in the infant. Studies have suggested that women with epilepsy are at increased risk of fractures, osteoporosis and osteomalacia. No studies have been undertaken looking at preventative therapies for these co-morbidities.
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PMID:Managing epilepsy in women of childbearing age. 1938 21

We report a male patient with hypothalamic hamartoma (HH) who manifested central precocious puberty (CPP) at 4 years of age. Gonadotropin-releasing hormone (GnRH) analogue treatment was started at 6 years of age and his pubertal signs were suppressed. At 9 years of age, the patient was emotionally unstable, aggressive, and antisocial. He had severe attention deficit hyperactivity disorder (ADHD)-like behavior and conduct disorder. No seizure activity was observed. GnRH analogue treatment was discontinued for 8 months from 9 years and 4 months of age due to his mother's illness. During this period sexual urges were observed. Treatment with daily methylphenidate markedly improved his behavioral problems. However, his sexual urges were not suppressed until 3 months after the GnRH analogue treatment was restarted. The present case is unique because the patient's behavioral problems were observed despite the parahypothalamic type of HH and absence of seizures. This case is also rare because behavioral problems were observed without seizures, and no ADHD cases with hamartoma have been reported previously. Recently, clinical studies have described an association between psychiatric morbidity, including ADHD, and hyperandrogenism disorders. Our patient's ADHD-like symptoms might be due to hyperandrogenism. In such cases, GnRH analogue with methylphenidate could be effective for improving ADHD-like symptoms.
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PMID:ADHD-like behavior in a patient with hypothalamic hamartoma. 2602 58

Epilepsy is a common chronic medical illness. Hyposexuality is the most frequent abnormality in men and women with epilepsy. In men with epilepsy, hypoandrogenimia, hypogonadism and sperm abnormalities are common. Testicular atrophy was also infrequently reported. In women with epilepsy, hyperandrogenism, polycystic ovaries (PCOs) and PCO syndrome are frequent. Decreased serum free testosterone, dehydroepiandrosterone levels, free androgen index and free testosterone/leutinizing hormone (LH) ratio and increased sex hormone binding globulin, estradiol, prolactin, LH, follicle stimulating hormone (FSH) levels and LH/FSH ratio are common with epilepsy. Disturbance of central and/or peripheral control of hypothalamic-pituitary-gonadal axis and alteration of central neurotrasmitters (GABA, glutamate and serotonin) by epileptic discharges or antiepileptic drugs (AEDs), direct gonadal toxicity by AEDs and pcyshicatric/psychosocial factors are all incriminated in sexual, reproductive and gonadal abnormalities associated with epilepsy. Patients may benefit from multidisplinary evaluation, tight seizure control, change the AED, androgen therapy, genital vasodilators, L-carnitine supplementation and psychotherapy.
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PMID:The effect of epilepsy and antiepileptic drugs on sexual, reproductive and gonadal health of adults with epilepsy. 2693 27


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