Maturitas 66 (2010) 327–328 Contents lists available at ScienceDirect Maturitas journal homepage: www.elsevier.com/locate/maturitas EMAS position statement: Managing the menopause in women with epilepsy C. Tamer Erel ∗ , Marc Brincat, Marco Gambacciani, Irene Lambrinoudaki, Mette H. Moen, Karin Schenck-Gustafsson, Florence Tremollieres, Svetlana Vujovic, Serge Rozenberg, Margaret Rees Istanbul University, Cerrahpasa School of Medicine, Department of Obstetrics and Gynecology, Istanbul 34301, Turkey article info Article history: Received 26 March 2010 Received in revised form 26 March 2010 Accepted 26 March 2010 Keywords: Epilepsy Menopause Osteoporosis Hormone therapy Antiepileptic drug abstract Introduction: Epilepsy is a major public health problem worldwide which is clinically characterized by recurrent seizures. Aim: The aim of this position statement is to provide evidence-based advice on management of the menopause in postmenopausal women derived from the limited data available. Materials and methods: Literature review and consensus of expert opinion. Results and conclusions: Women with epilepsy may undergo an earlier natural menopause, between 3 and 5 years depending on seizure frequency, but the data are limited. Data regarding the effects of the peri- menopause and menopause on epilepsy are conflicting: some studies show an increased risk of seizures but others do not. With regard to hormone therapy (HT) one study has shown an increase in seizures with oral therapy with conjugated equine estrogens and medroxyprogesterone acetate, but no data are available for other regimens. Women starting HT should be closely monitored as their antiepileptic drug (AED) needs may change. As vitamin D and calcium metabolism can be affected by AEDS, supplements should be considered. Herbal preparations should be avoided as their efficacy is uncertain and they may interact with AEDs. © 2010 Elsevier Ireland Ltd. All rights reserved. 1. Introduction Epilepsy is a chronic neurological disorder characterized by recurrent seizures, which may vary from a brief lapse of attention or muscle jerks, to severe and prolonged convulsions. Epilepsy is a major public health problem worldwide and fifty million people are thought to be affected [1]. The prevalence of epilepsy increases with age [2,3]. It increases from 90 per 100,000 people of age 65–70 years to 150 per 100,000 in those older than 80 years. In the elderly common causes of the first epileptic seizure include cere- brovascular disease, non-vascular dementias and neoplasms. The treatment goals are suppression and prevention of seizures. For these purposes, antiepileptic drugs (AEDs) are used. While most AEDs (carbamazepine, oxcarbazepine, phenobarbital, phenytoin, and topiramate) may induce the cytochrome P450 isoenzyme 3A4, some (lamotrigine, sulthiame) may not [4]. Therefore, certain AEDs may accelerate hepatic metabolism of hormonal preparations and decrease serum concentrations of bioactive sex steroids. Endogenous and exogenous sex steroids will affect seizure activ- ity and epilepsy in women [4–6]. Estrogen can be a very potent proconvulsant, whereas progesterone can be anticonvulsant. The latter effect seems to be medicated via allopregnanolone, a metabo- ∗ Corresponding author. E-mail address: tamererel@superonline.com (C.T. Erel). lite of progesterone. Women may therefore have changes in seizure threshold related to their menstrual cycle and at the menopause [5,6]. However, data regarding the effect of the perimenopause and menopause on epilepsy are scant and conflicting [7–11]. Some studies show an increased risk of seizures but others do not. It is important to note that women with epilepsy may undergo an earlier natural menopause, between 3 and 5 years depending on seizure frequency, but again the data are limited [12,13]. 2. Chronic conditions affecting postmenopausal women after the menopause The commonest cause of death in women is cardiovascular dis- ease and prevalence increases with age. Women with epilepsy may be at increased risk of cardiovascular disease due to AEDs such as valproate and the ketogenic diet which modify lipid metabolism [14]. Another major concern is bone health as epilepsy increases the risks of falls and fracture. Bone mineral density is significantly reduced in women using AEDs [15,16]. Furthermore taking AEDS doubles the risk of hip fracture [17]. Also a case–control study from the U.K. General Practice Research Database found that the risk of fractures increased with cumulative duration of exposure to AEDs (p for trend < 0.001), with the strongest association for greater than 12 years of use: adjusted OR 4.15 (95% CI 2.71–6.34). Risk esti- mates were higher in women than in men. There was no difference 0378-5122/$ – see front matter © 2010 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.maturitas.2010.03.026