title: Higher androgens and weight gain with valproate compared with lamotrigine for epilepsy.
abstract: BACKGROUND
  Valproate is used widely for the treatment of epilepsy but has been associated with hyperandrogenism, hyperinsulinemia, and dyslipidemia. The mechanism for these associations is unknown, but they have been hypothesized to be secondary to valproate-associated weight gain. This study was conducted to test the hypothesis that the antiepileptic drug lamotrigine, which also has a broad spectrum of anti-seizure efficacy, would not be associated with endocrine abnormalities and would not cause weight gain.
  
  
  OBJECTIVE
  This open-label, cross-sectional study compared (1) endocrine and lipid measures during the early follicular phase of the menstrual cycle; (2) prevalence of menstrual disorders (from patient diaries recorded over three cycles); and (3) body weight of women with epilepsy on lamotrigine monotherapy (n=119) with those on valproate monotherapy (n=103) for <5 years.
  
  
  RESULTS
  Mean total serum testosterone and androstenedione levels were higher (P<0.02) in the valproate group compared with the lamotrigine group. More lamotrigine patients (87%) than valproate patients (77%) reported regular menstrual cycles at the Screening Visit. The prevalence of anovulation did not differ between lamotrigine and valproate. Mean HDL cholesterol levels were higher (P<0.01) with lamotrigine compared with valproate as were LDL and total cholesterol levels (P<0.05). Mean total insulin levels did not significantly differ between the groups. Whereas mean body weight in lamotrigine patients did not differ between the time lamotrigine treatment was initiated and the Study Visit, mean weight in valproate patients increased by 3.7 kg.
  
  
  CONCLUSIONS
  Compared with lamotrigine monotherapy, valproate monotherapy was associated with weight gain and higher androgen levels in women with epilepsy. These data suggest that the hyperandrogenism observed in some women using valproate for epilepsy may be secondary to drug therapy. Lamotrigine monotherapy may be more appropriate than valproate for women in whom reproductive endocrine or metabolic abnormalities are potential concerns, i.e. women with concerns about weight gain, diabetes, hirsutism, polycystic ovary syndrome, menstrual dysfunction or infertility.
authors.affiliation: Columbia University, New York, NY, USA.
authors.forename: Martha J
authors.initials: MJ
authors.lastname: Morrell
authors.forename: Jouko
authors.initials: J
authors.lastname: Isojärvi
authors.forename: Ann E
authors.initials: AE
authors.lastname: Taylor
authors.forename: Mogens
authors.initials: M
authors.lastname: Dam
authors.forename: Ricardo
authors.initials: R
authors.lastname: Ayala
authors.forename: Gema
authors.initials: G
authors.lastname: Gomez
authors.forename: Fiona
authors.initials: F
authors.lastname: O'Neill
authors.forename: Pat
authors.initials: P
authors.lastname: Tennis
authors.forename: John
authors.initials: J
authors.lastname: Messenheimer
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D000728:Androgens / Q000097:blood*; D016001:Confidence Intervals; D003430:Cross-Sectional Studies; D004827:Epilepsy / Q000097:blood* / Q000188:drug therapy / Q000378:metabolism; D005260:Female; D006801:Humans; D000077213:Lamotrigine; D014227:Triazines / Q000009:adverse effects* / Q000627:therapeutic use; D014635:Valproic Acid / Q000009:adverse effects* / Q000627:therapeutic use; D015430:Weight Gain / Q000187:drug effects* / Q000502:physiology
chemical_list: D000728:Androgens; D014227:Triazines; D014635:Valproic Acid; D000077213:Lamotrigine