title: Reproductive endocrine health in pubertal females with epilepsy on antiepileptic drugs: time to screen?
abstract: OBJECTIVE
  Although previous studies suggest that valproate (VPA) may induce reproductive endocrine disorders, the effects of newer antiepileptic drugs (AEDs) on reproductive endocrine health have not been widely investigated and compared with those of older AEDs. Therefore, this multicenter cross-sectional study aimed to evaluate the prevalence of reproductive endocrine dysfunctions in pubertal females with epilepsy receiving VPA, lamotrigine (LTG), or levetiracetam (LEV) monotherapy.
  
  
  METHODS
  Pubertal girls on VPA (n = 11), LTG (n = 8), or LEV (n = 13) monotherapy for at least 6 months were recruited. Healthy sex-matched and age-matched subjects were enrolled as controls (n = 32). Each participant underwent a comprehensive physical examination concerning signs of hyperandrogenism. The Ferriman-Gallwey score of hirsutism was assessed. In addition, all patients completed a standardized questionnaire regarding epilepsy, menstrual cycle, and hirsutism features. Adiposity indices were measured and weight gain was documented for each subject.
  
  
  RESULTS
  Hirsutism score, occurrence of hyperandrogenism features, and adiposity indices were significantly higher in the VPA group when compared with LEV and control groups. VPA therapy was more frequently associated with weight gain when compared with LTG and controls, whereas no significant differences with regard to signs of hyperandrogenism were found between VPA and LTG groups. Furthermore, no differences in menstrual disorders were observed between groups.
  
  
  CONCLUSIONS
  Pubertal girls with epilepsy receiving VPA monotherapy were more likely to develop signs of hyperandrogenism, that is, hirsutism and acanthosis, than those on LEV or controls. However, no differences in occurrence of menstrual disorders and other reproductive dysfunctions were found between VPA, LTG, LEV, and control groups. These findings do not allow us to clearly determine whether or not VPA, LEV, and LTG monotherapies considerably affect reproductive endocrine health in pubertal girls with epilepsy. Therefore, further prospective studies of larger sample sizes are needed to establish if screening tests should be recommended.
authors.affiliation: Department of Paediatrics, Saint Vincent Hospital Zams, Zams, Austria.
authors.forename: Markus
authors.initials: M
authors.lastname: Rauchenzauner
authors.affiliation: Department of Neurology, Epilepsy Unit, Medical University Innsbruck, Innsbruck, Austria.
authors.forename: Sarah
authors.initials: S
authors.lastname: Roscia
authors.affiliation: Department of Neurology, Epilepsy Unit, Medical University Innsbruck, Innsbruck, Austria.
authors.forename: Manuela
authors.initials: M
authors.lastname: Prieschl
authors.affiliation: Department of Gynaecological Endocrinology and Reproductive Medicine, Medical University Innsbruck, Innsbruck, Austria.
authors.forename: Ludwig
authors.initials: L
authors.lastname: Wildt
authors.affiliation: Department of Paediatrics I, Division of Pediatric Neurology, Medical University Innsbruck, Innsbruck, Austria.
authors.forename: Edda
authors.initials: E
authors.lastname: Haberlandt
authors.affiliation: Department of Paediatrics I, Division of Pediatric Neurology, Medical University Innsbruck, Innsbruck, Austria.
authors.forename: Matthias
authors.initials: M
authors.lastname: Baumann
authors.affiliation: Department of Paediatrics I, Division of Pediatric Neurology, Medical University Innsbruck, Innsbruck, Austria.
authors.forename: Kevin
authors.initials: K
authors.lastname: Rostasy
authors.affiliation: Department of Paediatrics, University of Chieti, Chieti, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Agostinelli
authors.affiliation: Department of Paediatrics, University of Chieti, Chieti, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Pizzolorusso
authors.affiliation: Department of Neurology, Epilepsy Unit, Medical University Innsbruck, Innsbruck, Austria.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Luef
authors.affiliation: Department of Paediatrics, University of Chieti, Chieti, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Verrotti
mesh_terms: D050154:Adiposity / Q000187:drug effects; D000293:Adolescent; D000927:Anticonvulsants / Q000009:adverse effects*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D004353:Drug Evaluation, Preclinical; D052244:Endocrine Disruptors / Q000009:adverse effects*; D004827:Epilepsy / Q000188:drug therapy; D005260:Female; D006628:Hirsutism / Q000453:epidemiology / Q000209:etiology*; D006801:Humans; D017588:Hyperandrogenism / Q000453:epidemiology / Q000209:etiology*; D000077213:Lamotrigine; D000077287:Levetiracetam; D010889:Piracetam / Q000009:adverse effects / Q000031:analogs & derivatives; D060728:Reproductive Health; D014227:Triazines / Q000009:adverse effects; D014635:Valproic Acid / Q000009:adverse effects
chemical_list: D000927:Anticonvulsants; D052244:Endocrine Disruptors; D014227:Triazines; D000077287:Levetiracetam; D014635:Valproic Acid; D000077213:Lamotrigine; D010889:Piracetam