Isojärvi J I, Rättyä J, Myllylä V V, Knip M, Koivunen R, Pakarinen A J, Tekay A, Tapanainen J S
Department of Neurology, University of Oulu, Finland.
Ann Neurol. 1998 Apr;43(4):446-51. doi: 10.1002/ana.410430406.
We recently reported the frequent occurrence of polycystic ovaries and hyperandrogenism associated with weight gain and hyperinsulinemia in women taking valproate for epilepsy. The purpose of this study was to evaluate the risks related to valproate-induced hyperinsulinemia and their reversibility after discontinuing the medication. Sixteen women with valproate-related polycystic ovaries or hyperandrogenism participated in the study. Vaginal ultrasonography was performed, and endocrine and lipid parameters were measured. Thereafter, lamotrigine was substituted for valproate and the patients were observed for 12 months. Twenty-four healthy age-matched women served as control subjects. Twelve women completed the 12-month follow-up. While still on valproate they had centripetal obesity with associated hyperinsulinemia and unfavorable serum lipid profiles. The body-mass index and fasting serum insulin and testosterone concentrations decreased during the first year after replacing valproate with lamotrigine whereas the HDL-cholesterol/total cholesterol ratios increased from 0.17 +/- 0.06 to 0.26 +/- 0.05. The total number of polycystic ovaries in these women decreased from 20 during valproate medication to 11 one year after replacing valproate with lamotrigine. Valproate induces a metabolic syndrome with centripetal obesity, hyperinsulinemia, lipid abnormalities, and polycystic ovaries/hyperandrogenism in women with epilepsy. These valproate-related risks can be reduced by substituting lamotrigine for valproate.
我们最近报道，服用丙戊酸盐治疗癫痫的女性中，多囊卵巢和高雄激素血症频繁出现，并伴有体重增加和高胰岛素血症。本研究的目的是评估与丙戊酸盐诱导的高胰岛素血症相关的风险及其停药后的可逆性。16名患有丙戊酸盐相关多囊卵巢或高雄激素血症的女性参与了本研究。进行了阴道超声检查，并测量了内分泌和血脂参数。此后，用拉莫三嗪替代丙戊酸盐，并对患者进行了12个月的观察。24名年龄匹配的健康女性作为对照。12名女性完成了12个月的随访。在仍服用丙戊酸盐期间，她们出现向心性肥胖，并伴有高胰岛素血症和不良的血脂谱。在用拉莫三嗪替代丙戊酸盐后的第一年，体重指数、空腹血清胰岛素和睾酮浓度下降，而高密度脂蛋白胆固醇/总胆固醇比值从0.17±0.06增加到0.26±0.05。这些女性的多囊卵巢总数从服用丙戊酸盐期间的20个减少到用拉莫三嗪替代丙戊酸盐一年后的11个。丙戊酸盐在癫痫女性中诱发一种代谢综合征，包括向心性肥胖、高胰岛素血症、血脂异常以及多囊卵巢/高雄激素血症。用拉莫三嗪替代丙戊酸盐可降低这些与丙戊酸盐相关的风险。
