{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T02:25:02Z","timestamp":1778811902540,"version":"3.51.4"},"reference-count":32,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2008,8,28]],"date-time":"2008-08-28T00:00:00Z","timestamp":1219881600000},"content-version":"vor","delay-in-days":27,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2008,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To evaluate development of components of polycystic ovary syndrome (PCOS) and PCOS in women with epilepsy initiating valproate or lamotrigine therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Female 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\u2010month 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      More women in the valproate group than the lamotrigine group developed (OD) in the prospective (54% valproate, 38% lamotrigine;\n                      <jats:italic>p<\/jats:italic>\n                      = 0.010) and the post hoc (HA) analyses (36% valproate, 23% lamotrigine;\n                      <jats:italic>p<\/jats:italic>\n                      = 0.007). More women in the valproate group than the lamotrigine group developed PCOS (9 vs 2%;\n                      <jats:italic>p<\/jats:italic>\n                      = 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;\n                      <jats:italic>p<\/jats:italic>\n                      = 0.002) but was similar if treatment was started at age 26 years or older (24% valproate, 22% lamotrigine).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>Development 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\u2013211<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.21411","type":"journal-article","created":{"date-parts":[[2008,9,17]],"date-time":"2008-09-17T04:23:30Z","timestamp":1221625410000},"page":"200-211","source":"Crossref","is-referenced-by-count":75,"title":["Hyperandrogenism, ovulatory dysfunction, and polycystic ovary syndrome with valproate versus lamotrigine"],"prefix":"10.1002","volume":"64","author":[{"given":"Martha J.","family":"Morrell","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frances J.","family":"Hayes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick M.","family":"Sluss","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Judith M.","family":"Adams","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohit","family":"Bhatt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cigdem","family":"Ozkara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clay R.","family":"Warnock M.S.","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jouko","family":"Isoj\u00e4rvi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2008,8,28]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1157.1980.tb04072.x"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1986.00520040029014"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1157.1986.tb03605.x"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199311043291904"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.10391"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwh140"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0889-8529(05)70045-1"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0889-8529(05)70069-4"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF03348013"},{"key":"e_1_2_7_11_2","first-page":"52","article-title":"Effects of valproate, phenobarbital and carbamazepine on sex steroid setup in women with epilepsy","volume":"21","author":"Murialdo G","year":"1998","journal-title":"Clin Neuropharmacol"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/1531-8249(199904)45:4<444::AID-ANA5>3.0.CO;2-6"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1059-1311(03)00065-7"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9343(01)00806-3"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000106942.35533.62"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0920-1211(03)00085-8"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410430406"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/37.6.838"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajim.4700280611"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.293.6543.355"},{"key":"e_1_2_7_21_2","first-page":"377","volume-title":"Polycystic ovary syndrome","author":"Zawadski JK","year":"1992"},{"key":"e_1_2_7_22_2","first-page":"361","volume-title":"Estrogens and progestins. 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