Nonenzyme-inducing Antiepileptic Drugs Research Articles

Cost–benefit analysis, cost-effectiveness analysis, and impact of antiepileptic drugs on the risk of fracture in patients with epilepsy: A nationwide cohort study

PurposeAlthough nonenzyme-inducing antiepileptic drugs (nEIAEDs) are accepted for the treatment of epilepsy, few studies have examined the costs, benefits, and cost-effectiveness of nEIAEDs in relation to the incidence of fracture among patients with epilepsy. In the present study, we performed cost–benefit and cost-effectiveness analyses comparing the influence of enzyme-inducing AEDs (EIAEDs) and nEIAEDs on the risk of fracture in this population. MethodsA total of 4864 patients with epilepsy were classified into EIAED and nEIAED groups. Propensity score matching was applied to reduce the influence of selection bias. Clinical outcomes were measured in relation to AED fee, medical expenses associated with epilepsy and fracture, and the total number of fractures. Cost–benefit and cost-effectiveness analyses were performed for all patients. ResultsPatients in the unmatched EIAED cohort (n = 3686) were older and had more comorbidities. After matching, the cohorts exhibited similar features (n = 2432 each). Fracture risk was lower in the nEIAED group than in the EIAED group (HR = 0.70). The additional medical expense of nEIAEDs in fractures and epilepsy for 2 years per person was 107,731 New Taiwan dollars (NT$). The additional cost for nEIAEDs to reduce one event of fracture was $14,789,421 NT$. ConclusionsPatients with epilepsy using nEIAEDs had a lower risk of fracture than those using EIAEDs. However, the cost–benefit ratio and cost-effectiveness of such treatment were lower in the nEIAED group than in the EIAED group.

Efficacy and tolerability of perampanel in children and adolescents with pharmacoresistant epilepsy: The first real-world evaluation in Asian pediatric neurology clinics

AimThis study investigated the efficacy and safety of perampanel (PER) adjunctive therapy in pediatric patients with epilepsy whose seizures are pharmacoresistant to existing antiepileptic drugs. MethodsA clinical retrospective study was conducted from 2016 to 2017 in the pediatric neurology clinic at a tertiary children's hospital. We reviewed the data obtained from 66 children whose seizures were pharmacoresistant to more than two antiepileptic drugs, and could be followed up for a minimum of 3 months after PER adjunctive therapy initiation. The efficacy was estimated by the PER response rate at 3-, 6-, and 12-month follow-up evaluations, and adverse events were also recorded. ResultsThe rate of seizure reduction of >50% was 30.3%, 37.5%, and 34.7% for all seizure types at 3, 6, and 12 months, in which 7.6%, 8.9%, and 14.3% of the patients became seizure-free at these time points, respectively. No significant differences were found between enzyme-inducing and nonenzyme-inducing antiepileptic drugs in combination with PER with regard to the responder rate. Five patients with Dravet syndrome were included in the study. Four of them (80%) exhibited 50% seizure reduction at the last visit, at which point, two patients (40.0%) were seizure-free. The retention rate was 51% at 12 months. Adverse events were documented in 25 patients (35.7%) and led to PER discontinuation in eight patients (12.1%). The most common adverse events comprised irritability, skin rash, dizziness, and somnolence; however, all were transient and successfully managed after PER dose reduction or discontinuation. ConclusionThe current data support the value of adjunctive PER in child and adolescent patients with pharmacoresistant epilepsy in daily clinical practice. Perampanel was efficacious and generally well-tolerated as an add-on treatment for epilepsy.

Influence of Comedication on Levetiracetam Pharmacokinetics.

To evaluate the effect of concomitant antiepileptic therapy on levetiracetam (LEV) pharmacokinetics. A 6-year retrospective observational study. Patients were grouped according to the antiepileptic drug used as concomitant medication: group A, LEV in monotherapy; group B, LEV + enzyme-inducing antiepileptic drugs (EIAEDs); and group C, LEV + non-enzyme-inducing antiepileptic drugs (NEIAEDs). Apparent oral levetiracetam clearance (LEV CL/F) and basal serum levetiracetam concentrations (LEV C0) were compared among the different groups by analysis of variance. A total of 330 LEV C0 corresponding to 205 patients (56% men) were identified. The mean (±SD) of LEV CL/F in group A (n = 180), B (n = 92), and C (n = 58) was 4.41 ± 2.06 L/h, 7.23 ± 3.72 L/h, and 4.87 ± 1.65 L/h, respectively. EIAEDs increased LEV CL/F (L/h) by 64% compared with the monotherapy group and by 48% compared with the NEIAEDs group. The greatest induction in LEV CL/F, compared with the LEV monotherapy group, was observed with carbamazepine, followed by oxcarbazepine and phenobarbital, and was increased by 81%, 64%, and 44%, respectively. LEV C0 values were significantly lower in the EIAEDs group than in the monotherapy group (17.30 ± 7.77 versus 20.08 ± 9.69 mcg/mL; P = 0.038) or indeed the NEIAEDs group (17.30 ± 7.77 versus 20.49 ± 9.46 mcg/mL; P = 0.027). Comedication with EIAEDs increased LEV CL/F by more than 40%, whereas carbamazepine had the greatest inducing potency with LEV CL/F being 81% higher than that of the monotherapy group. These data suggest that monitoring LEV serum concentration during polytherapy with EIAEDs is indicated.

White Matter Hyperintensities on Brain Magnetic Resonance Imaging in People with Epilepsy: A Hospital-Based Study.

We aim to explore whether people with epilepsy have increased white matter hyperintensities (WMHs). Eligible patients were categorized into newly diagnosed epilepsy (NE) and chronic epilepsy (CE); the latter were subdivided to those treated with enzyme-inducing antiepileptic drugs (EIAEDs) with or without non-enzyme-inducing antiepileptic drugs (NEIAEDs) and those with NEIAEDs only. WMHs were measured using age-related white matter changes (ARWMC) scale and compared between patients and healthy control group. Higher scores indicate greater WMH changes. The strengths of associations were estimated as incidence rate ratios (IRRs) with 95% confidence interval (CI). A total of 217 patients were included in the analysis, of whom 67 had NE, 45 had CE treated with NEIAEDs, and 105 had CE treated with EIAEDs. Age was positively associated with ARWMC score (IRR per year, 1.03; 95%CI, 1.03-1.04, P < 0.001). Compared with the healthy control group (n = 23), all patient groups had higher ARWMC score (P < 0.05). The difference was greatest in patients receiving EIAEDs (IRR, 2.13; 95%CI, 1.22-3.70, P = 0.007). WMHs tended to be observed in people with epilepsy, especially in those treated with EIAEDs. People with epilepsy with white matter changes should be evaluated for stroke risk, particularly if they are receiving EIAEDs.

Longitudinal Change of Vitamin D Status in Children With Epilepsy on Antiepileptic Drugs: Prevalence and Risk Factors

BackgroundOur aim was to evaluate the prevalence and risk factors of vitamin D deficiency and the changes of vitamin D level among children with epilepsy on antiepileptic drugs. MethodsThe levels of serum 25-hydroxy vitamin D were measured at the start of antiepileptic drugs and at 6- to 12-month intervals in children with epilepsy taking antiepileptic drugs in Pusan National University Children's Hospital. Vitamin D deficiency was defined as 25-hydroxy vitamin D levels <20 ng/mL and insufficiency between 21 and 29 ng/mL. ResultsA total of 143 children (103 boys and 40 girls) with the mean age of 7.4 ± 5.4 years were included. The mean follow-up duration was 1.8 ± 0.8 years. At the start of antiepileptic drugs and the last follow-up, vitamin D deficiency or insufficiency was recognized in 56.6% (81 of 143) and 79.0% (113 of 143), respectively (P < 0.01). The mean value of initial 25-hydroxy vitamin D was 31.1 ± 14.7 ng/mL, which was significantly decreased to 20.2 ± 14.9 ng/mL (P < 0.01) in the last follow-up. Polytherapy (−16.0 ± 13.6 ng/mL), longer duration of ≥2 years (−23.5 ± 9.1 ng/mL), tube feeding (−18.2 ± 14.5 ng/mL), and overweight with body mass index of eighty-fifth percentile or greater (−17.0 ± 12.1 ng/mL) had a significant negative effect for the longitudinal change of 25-hydroxy vitamin D. Age, etiologies, seizure outcomes, and type of antiepileptic drugs (enzyme-inducing versus nonenzyme-inducing antiepileptic drugs) did not affect the longitudinal decrease of 25-hydroxy vitamin D. ConclusionsA high proportion of these children on antiepileptic drugs had hypovitaminosis D and a significant decrease between the initial and the last follow-up. Polytherapy and longer duration of antiepileptic drugs, tube feeding, and overweight were independently associated with longitudinally significant decrease of 25-hydroxy vitamin D.

Osteoporosis is associated with antiepileptic drugs: a population-based study.

Controversy remains regarding the risk of bone abnormalities due to enzyme-inducing antiepileptic drugs (EIAEDs) and non-enzyme-inducing antiepileptic drugs (NEIAEDs). This case-control study aimed to investigate the possible association between osteoporosis and epilepsy disease and AEDs therapy using a population-based dataset in Taiwan. We first identified 48,102 cases, ≥ 18 years of age, who received a first-time diagnosis of osteoporosis, and then randomly selected 144,306 controls. We used conditional logistic regression analyses to compute the odds ratio (OR) and corresponding 95% confidence interval (CI) to compare a previous diagnosis of epilepsy between cases and controls. We found that of the 192,408 sampled subjects, epilepsy was found in 117 (0.24%) cases and 240 (0.17%) controls (p<0.001). Cases were found to be more likely to have previously been diagnosed with epilepsy than controls (OR: 1.41, 95% CI: 1.11 ≈ 1.78, p<0.01), after taking confounders into consideration. Furthermore, we found that, compared to controls, the adjusted OR of cases in which enzyme-inducing AEDs had been prescribed was 2.06 (95% CI: 1.43 ≈ 2.95). A higher proportion of cases with prescribed NEIAED was also found (OR: 2.09, 95% CI: 1.49 ≈ 2.92) compared to controls. This study demonstrates that patients with osteoporosis were more likely to have epilepsy and receive EIAED or NEIAED treatment. For patients with epilepsy who take AEDs, attention should be paid to the adverse effects of osteoporosis.

P450 enzyme-inducing and non-enzyme-inducing antiepileptic drugs for seizure prophylaxis after glioma resection surgery: A meta-analysis

PurposeThe prognoses of seizure treatment with P450 enzyme-inducing and non-enzyme-inducing antiepileptic drugs after glioma resection surgery were investigated across several clinical studies. However, the results of these studies are inconsistent. We examined the relevant studies and conducted a meta-analysis of these two types of anti-epileptic drugs. MethodsA bibliography search using the EMBASE, MEDLINE, ClinicalTrials.gov, and Cochrane Central Register of Controlled Trials databases was performed to identify potentially relevant articles and conference abstracts that investigated the effects of non-enzyme-inducing antiepileptic drugs (NEIAEDs) and enzyme-inducing antiepileptic drugs (EIAEDs) on the seizure prognoses of glioma patients. ResultsOne RCT study and five observational studies were included. Pooled estimates of the relative risks (OR) and 95% confidence intervals (CI) were calculated. The pooled odds ratio for NEIAEDs vs. EIAEDs for patients with glioma was 1.12 (95% CI=0.70–2.10). The pooled odds ratio for NEIAEDs vs. EIAEDs for low-grade gliomas was 1.77 (95% CI=0.71–4.40). The pooled odds ratio for LEV vs. PHY was 1.459 (95% CI=0.731–2.910). ConclusionsNo significant difference between the efficacies of P450 enzyme-inducing and non-enzyme-inducing antiepileptic drugs for prophylactic late seizure treatment was observed. However, few RCTs were available, and the acquisition of further evidence through high-quality RCTs is highly recommended.

Chemotherapy and immunotherapy of brain tumors: What the epileptologist must know

I present an overview of therapy for the most common brain tumors encountered in clinical practice if adult patients. Current therapy paradigms and evolving therapies are reviewed. The introduction of non-enzyme-inducing antiepileptic drugs (NEIADs) has simplified the approach to combined medical treatment of epilepsy and brain tumors, but the major interactions between enzyme-inducing antiepileptic drugs (EIAEDs) are included, to serve as guidance in selecting these medications if they are required.

THU0383 Osteoporosis in Epilepsy and Multiple Sclerosis Patients.

BackgroundOsteoporosis is the most common type of bone disease. There is recent mounting evidence indicating that patients with multiple sclerosis (MS) and epilepsy (EP) have decreasing bone mineral density (BMD)...

Statin medication in patients treated with antiepileptic drugs in Norway

The lipid-lowering response of statins metabolized by cytochrome P450 3A4 (CYP3A4) has previously been shown to be diminished by concurrent use of enzyme-inducing antiepileptic drugs (EIAEDs). The aim of this study was to compare statin prescription in patients receiving EIAEDs versus non-enzyme-inducing antiepileptic drugs (NEIAEDs), before and after introduction of prescribing restrictions for statins in Norway. The Norwegian Prescription Database was used to extract data on patients using antiepileptic drugs and statins during 2004 and 2008. Statin type and dose used were compared between patients treated with at least one EIAED (i.e., carbamazepine, phenobarbital, phenytoin, primidone) and those receiving NEIAEDs only (i.e., all other antiepileptic drugs). The number of included patients co-medicated with statins and AEDs was 4855 in 2004 and 9880 in 2008. Among these patients, 2827 and 3160, respectively, were treated with EIAEDs. The CYP3A4 statins (i.e., simvastatin, atorvastatin and lovastatin) accounted for 85% of all statins in 2004, increasing to 93% in 2008. There was no significant difference in the likelihood of being prescribed a CYP3A4 statin versus a non-CYP3A4 statin among patients receiving EIAEDs and NEIAEDs. The average daily dose of individual CYP3A4 statins was not different between the AED groups. The present study shows that the interaction risk between CYP3A4-metabolized statins and EIAEDs is largely overlooked in Norwegian clinical practice. To avoid therapeutic failure of statin treatment in patients using AEDs, implementation of strategies for systematic management of drug interactions is warranted.

Placebo‐corrected efficacy of modern nonenzyme‐inducing AEDs for refractory focal epilepsy: Systematic review and meta‐analysis

Given serious concerns over the adverse effects of enzyme induction, modern nonenzyme-inducing antiepileptic drugs (AEDs) may be preferable, provided they have similar efficacy as enzyme-inducing AEDs. This is currently unclear. Therefore, we performed a meta-analysis of the evidence to determine the placebo-corrected efficacy of adjunctive treatment with modern nonenzyme-inducing AEDs versus modern enzyme-inducing AEDs that are on the market for refractory focal epilepsy. Of 322 potentially eligible articles reviewed in full text, 129 (40%) fulfilled eligibility criteria. After excluding 92 publications, 37 studies dealing with a total of 9,860 patients with refractory focal epilepsy form the basis for the evidence. The overall weighted pooled-risk ratio (RR) in favor of enzyme-inducing AEDs over placebo was 2.37 (95% confidence interval [CI] 1.77-3.18, p < 0.001) for at least 50% seizure reduction and 4.45 (2.26-8.76, p < 0.001) for seizure freedom. The corresponding weighted pooled RR in favor of nonenzyme-inducing AEDs over placebo was 2.28 (95% CI 2.03-2.57, p < 0.001) for at least 50% seizure reduction and 3.23 (95% CI 2.23-4.67, p < 0.001) for seizure freedom. In a meta-regression analysis in the same sample with at least 50% seizure reduction as outcome, the ratio of RRs for enzyme-inducing AEDs (eight studies) versus nonenzyme-inducing AEDs (29 studies) was 1.01 (95% CI 0.77-1.34, p = 0.92)). Similarly, the ratio of RRs for a seizure-free outcome for enzyme-inducing AEDs (six studies) versus nonenzyme-inducing AEDs (19 studies) was 1.38 (95% CI 0.60-3.16, p = 0.43). Although the presence of moderate heterogeneity may reduce the validity of the results and limit generalizations from the findings, we conclude that the efficacy of adjunctive treatment with modern nonenzyme-inducing AEDs is similar to that of enzyme-inducing AEDs. Given the negative consequences of enzyme induction, our data suggest that nonenzyme-inducing AEDs may be useful alternatives to enzyme-inducing AEDs for treatment of refractory focal epilepsy.

Disease- and treatment-related effects on the pituitary–gonadal functional axis: a study in men with epilepsy

The consideration of the patient's gender has become an established practice in the choice of antiepileptic drugs (AEDs) for the treatment of epilepsy. This study was undertaken to confirm that temporal lobe epilepsy and the use of hepatic enzyme-inducing AEDs, have a negative effect on sex hormones in men. We calculated the testosterone (T)/luteinizing hormone (LH) ratio to reflect the effects of epilepsy or its treatment on the most important androgen and its pituitary control hormone. Of 324 men with focal epilepsy identified (untreated or on AED monotherapy), 201 were eligible for inclusion (mean age 37.5 years, mean duration of epilepsy 14.7 years). A total of 105 men served as healthy controls (mean age 33.9 years). Patients with temporal lobe epilepsy were more likely to show abnormal T/LH ratios than patients with extratemporal epilepsy (p < 0.01). Patients receiving AEDs with marked hepatic enzyme-inducing effects were more likely to have low T/LH ratios than patients taking nonenzyme-inducing AEDs or healthy controls (p < 0.01). Focus localization and AED choice affect male sex hormones. Findings raise some concerns about the effect of enzyme-inducing AEDs on sexual endocrine functions.

The association between antiepileptic drug and HMG-CoA reductase inhibitor co-medication and cholesterol management in patients with epilepsy

Pharmacokinetic interactions have been demonstrated in enzyme-inducing antiepileptic drugs (EIAEDs) and statins; however, their clinical significance is not well established. The purpose of this study was to evaluate the association of EIAEDs and non-enzyme-inducing antiepileptic drugs (NEIAEDs) on statin dose adjustments and low-density lipoprotein (LDL) cholesterol levels in patients with epilepsy. Retrospective insurance claims from 2000 to 2006 from the Ingenix Impact (formerly Integrated Health Care Information Services) database were analyzed. Two cohorts were compared, EIAEDs+statin and NEIAEDs+statin: 1118 patients were analyzed (58% men; 66% aged >55 years); 506 (45%) initiated with an EIAED. Outcomes assessed included statin dose adjustments and, for a subset of subjects, risk of mean LDL >100mg/dL during the 12-month follow-up period. Descriptive statistics were calculated and regression models estimated. Among the EIAED group, 72% initiated with phenytoin; among the NEIAED group, 57% initiated with gabapentin. For the EIAED group, the risk of upward statin dose adjustments was significantly greater (odds ratio=1.36; P=0.04) compared with the NEIAED group; similarly, the risk of having mean LDL >100mg/dL was significantly greater (odds ratio=41.22; P=0.005) and increased during the follow-up period (+26.6mg/dL; P=0.001) for the EIAED group. This study suggests that concomitant use of EIAEDs and statins may be associated with reduced clinical effectiveness of statins. Patients with epilepsy who use EIAEDs and statins concomitantly may require greater vigilance for optimal cholesterol management.

Changes in sex steroid levels in women with epilepsy on treatment: Relationship with antiepileptic therapies and seizure frequency

Reproductive dysfunction in epilepsy is attributed to the seizures themselves and also to antiepileptic drugs (AEDs), which affect steroid production, binding, and metabolism. In turn, neuroactive steroids may influence neuronal excitability. A previous study in this cohort of consecutive women with epilepsy showed that patients with more frequent seizures had higher cortisol and lower dehydroepiandrosterone sulfate levels than those with rare or absent seizures. The present study was aimed at evaluating, in these same women, the possible relationship between some clinical parameters, seizure frequency, AED therapies, and sex hormone levels. Estradiol (E2), progesterone (Pg), sex hormone-binding globulin (SHBG), and free estrogen index (FEI) were measured during the luteal phase in 113 consecutive females, 16-47 years old, with different epilepsy syndromes on enzyme-inducing AED (EIAED) and/or non-enzyme-inducing AED (NEIAED) treatments, and in 30 age-matched healthy women. Hormonal data were correlated with clinical parameters (age, epilepsy syndrome, disease onset, and duration), seizure frequency assessed on the basis of a seizure frequency score (SFS), and AED therapies. E2, Pg, and FEI were lower, whereas SHBG levels were higher in the epilepsy patients than in the controls. However, sex steroid and SHBG levels were not different between groups of patients categorized according to SFS. Therapies with EIAEDs accounted for changes in E2 levels and FEI. Despite globally decreased sex steroid levels in serum, actual hormone titers were not significantly correlated with SFS in consecutive epilepsy women; rather, these hormonal changes were explained by AED treatments, mainly when EIAED polytherapies were given.

Antiepileptic drug use and rates of hip bone loss in older men

To test the hypotheses that older community dwelling men taking non-enzyme-inducing antiepileptic drugs (NEIAEDs) and those taking enzyme-inducing antiepileptic drugs (EIAEDs) have increased rates of hip bone loss. We ascertained antiepileptic drug (AED) use (interviewer-administered questionnaire with verification of use by containers) and measured hip bone mineral density (BMD) (using dual energy x-ray absorptiometry) at baseline and an average of 4.6 years later in a cohort of 4,222 older community-dwelling men enrolled in the Osteoporotic Fractures in Men study. Men were categorized as nonusers (no AED use at either examination, n = 4060), NEIAED user (use of NEIAED only at either examination, n = 100), or EIAED user (use of EIAED only at either examination, n = 62). After adjustment for multiple potential confounders (age, race, clinic site, health status, pain interfering with work or activity, physical activity, smoking status, alcohol use, total calcium intake, diabetes, chronic kidney disease, vitamin D supplement use, bisphosphonate use, selective serotonin reuptake inhibitor use, inability to rise from a chair, body mass index, and baseline BMD), the average rate of decline in total hip BMD was -0.35%/year among nonusers compared with -0.53%/year among NEIAED users (p = 0.04) and -0.46%/year among EIAED users (p = 0.31). Multivariable adjusted rate of loss was -0.60%/year among men taking NEIAED at both examinations, -0.51%/year among men taking NEIAED at one examination only, and -0.35%/year among nonusers (p for trend = 0.03). Findings were similar at hip subregions. Use of non-enzyme-inducing antiepileptic drugs was independently associated with increased rates of hip bone loss in this cohort of older community-dwelling men.

Best Practice Guidelines for the Management of Women with Epilepsy

Being a woman with epilepsy is not the same as being a man with epilepsy. Epilepsy affects sexual development, menstrual cycle, aspects of contraception, fertility, and reproduction. MENSTRUAL CYCLE, EPILEPSY, AND FERTILITY: The diagnosis of epilepsy and the use of antiepileptic drugs (AEDs) present women of childbearing age with many problems; both the disease and its treatment can alter the menstrual cycle and fertility. CONTRACEPTION IN EPILEPSY: There are no contraindications to the use of nonhormonal methods of contraception in women with epilepsy (see Table 3). Nonenzyme-inducing AEDs (valproate sodium, benzodiazepines, ethosuximide, and levetiracetam) do not show any interactions with the combined oral contraceptive pill. There are interactions between the COCP and hepatic microsomal-inducing AEDs (phenytoin, barbiturates, carbamazepine, topiramate [doses above 200 mg/day], and oxcarbazepine) and also lamotrigine. SEXUALITY: The majority of women with epilepsy appear to have normal sex lives, although in some women with epilepsy, both the desire and arousal phases may be inhibited. PRECONCEPTION COUNSELING: Preconception counseling should be available to all women with epilepsy who are considering pregnancy. Women with epilepsy should be aware of a number of issues relating to future pregnancy, including methods and consequences of prenatal screening, genetics of their seizure disorder, teratogenicity of AEDs, folic acid and vitamin K supplements, labor, breast feeding, and childcare. 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 sodium and lamotrigine is particularly teratogenic. Most pregnancies are uneventful in women with epilepsy, and most babies are delivered healthy with no increased risk of obstetric complications in women. BREAST FEEDING: All women with epilepsy should be encouraged to breastfeed their babies. 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. THE CARE OF CHILDREN OF MOTHERS WITH EPILEPSY: Although there is much anxiety about the possible risks to a child from the mother's epilepsy, there is little published evidence. The risk of the child being harmed depends on the type of seizure and its severity and frequency, and this risk is probably small if time is taken to train mothers and caregivers in safety precautions. MENOPAUSE: During menopause, about 40% of women report worsening of their seizure disorder, 27% improve, and a third had no change. Hormone replacement therapy is significantly associated with an increase in seizure frequency during menopause, and this is more likely in women with a history of catamenial epilepsy. BONE HEALTH: Women with epilepsy are at increased risk of fractures, osteoporosis, and osteomalacia.