Hyperandrogenism, ovulatory dysfunction, and polycystic ovary syndrome with valproate versus lamotrigine

• DOI: 10.1002/ana.21411
• Publication Date: 2008-09-17T08:23:30Z
• Authors: Martha J. Morrell; Frances J. Hayes; Patrick M. Sluss; Judith M. Adams; Mohit Bhatt; Cigdem Ozkara; Clay R. Warnock M.S.; Jouko Isojärvi
• Keywords: Adult; Ovulation; Epilepsy; Internationality; Adolescent; Triazines; Valproic Acid; Lamotrigine; 3. Good health; 03 medical and health sciences; 0302 clinical medicine; Humans; Female; Prospective Studies; Hyperandrogenism; Anovulation; Polycystic Ovary Syndrome

AbstractObjectiveTo evaluate development of components of polycystic ovary syndrome (PCOS) and PCOS in women with epilepsy initiating valproate or lamotrigine therapy.MethodsFemale individuals with epilepsy and regular menstrual cycles were eligible for this prospective study. Participants were randomized to 12 months of valproate (n = 225) or lamotrigine (n = 222) therapy. Serum androgen levels were measured every 3 months. Urinary pregnanediol glucuronide levels were measured weekly for two 3‐month periods. The primary end point was development of PCOS components (ie, hyperandrogenism or ovulatory dysfunction). A post hoc analysis was conducted in women more than 2 years after menarche (177 lamotrigine, (HA) 186 valproate) to exclude OD the confounding effect of puberty.ResultsMore women in the valproate group than the lamotrigine group developed (OD) in the prospective (54% valproate, 38% lamotrigine; p = 0.010) and the post hoc (HA) analyses (36% valproate, 23% lamotrigine; p = 0.007). More women in the valproate group than the lamotrigine group developed PCOS (9 vs 2%; p = 0.007). Development of HA was more frequent with OD valproate than lamotrigine among those initiating treatment at age younger than 26 years (44% valproate, 23% lamotrigine; p = 0.002) but was similar if treatment was started at age 26 years or older (24% valproate, 22% lamotrigine).InterpretationDevelopment of HA occurred more frequently with valproate than lamotrigine, especially if medication was started at age younger than 26 years. Ann Neurol 2008;64:200–211