31 With lamotrigine (LTG) no negative influence on the sexual hormone metabolism was found,32 which may also be hypothesized for other new AEDs without a clinically relevant interaction profile.33 In particular, the potential role of VPA for the risk of obesity, impaired insulin balance, and or PCO and PCOS has been actively discussed. This crucial question of the treatment with AEDs and fertility will be addressed in the following section. Obesity, PCO, PCOS, and antiepileptic drugs Obesity is

one of the most, common adverse effects seen with long-term AED treatment, and has been reported for almost every AED.33 Among the first-line Inhibitors,research,lifescience,medical AEDs, VPA is the main risk Inhibitors,research,lifescience,medical substance for obesity.34,35,36 According to the literature, the incidence of obesity on VPA varies widely, and ranges between 8% and 59%. 37 Female patients who suffered from weight gain while on VPA had increased insulin levels and insulin resistance,38 which was confirmed by the comparison with patients receiving CBZ or LTG39 Others reported normal insulin levels with VPA, CBZ, and oxcarbazepine (OXC) but. still confirmed the almost

specific weight gain on VPA.40 Inhibitors,research,lifescience,medical This weight gain was completely reversible 12 months after replacing VPA by LTG, as were hyperinsulinism, increased serum testosterone, and abnormally high body mass index.41 Obesity due to metabolic effects of VPA has become a major subject of recent research, since it was hypothesized Inhibitors,research,lifescience,medical that this metabolic development may induce PCOS,41 which is defined by the coincidence of oligo- or amenorrhea, hyperandrogenism, and the ultrasound

detection of polycystic ovaries.16 Inhibitors,research,lifescience,medical The most relevant findings in PCOS are shown in Table I. Whether or not this is correct, and specific for VPA is still a matter of controversy.33 Other groups did not. find relevant differences between PCOS and VPA, CBZ, PB, the total population, or untreated epilepsy patients.30,42 It has to be considered that the epilepsy itself may facilitate the development of PCOS by the metabolic changes mentioned above. A pilot study addressing this aspect reported that 25% of the Trichostatin A (TSA) investigated female patients with epilepsy suffered from PCOS, 80% of whom had not received AED therapy.43 In another study, one third of GSK-3 the patients with PCOS were not on medication.44 Oral hormonal contraception Impact of AEDs on oral hormonal contraception The oral application of sexual hormones is the major method of contraception. Liver sellckchem enzyme-inducing AEDs reduce the efficacy of oral contraceptives.24,45 It was estimated that the rate of unintentional pregnancies in spite of hormonal contraception was five to 25 times higher if enzyme-inducing AEDs were used.