丙戊酸盐与拉莫三嗪所致高雄激素血症、排卵功能障碍及多囊卵巢综合征

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

作者信息

Morrell Martha J, Hayes Frances J, Sluss Patrick M, Adams Judith M, Bhatt Mohit, Ozkara Cigdem, Warnock Clay R, Isojärvi Jouko

机构信息

Stanford University, Stanford and Neuropace, Mountain View, CA 94043, USA.

出版信息

Ann Neurol. 2008 Aug;64(2):200-11. doi: 10.1002/ana.21411.

DOI:10.1002/ana.21411

PMID:18756476

Abstract

OBJECTIVE

To evaluate development of components of polycystic ovary syndrome (PCOS) and PCOS in women with epilepsy initiating valproate or lamotrigine therapy.

METHODS

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-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.

RESULTS

More 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).

INTERPRETATION

Development of HA occurred more frequently with valproate than lamotrigine, especially if medication was started at age younger than 26 years.

摘要

目的

评估癫痫女性患者在开始使用丙戊酸盐或拉莫三嗪治疗时多囊卵巢综合征（PCOS）各组分及PCOS的发生情况。

方法

有癫痫且月经周期规律的女性个体符合本前瞻性研究的条件。参与者被随机分为接受12个月丙戊酸盐治疗组（n = 225）或拉莫三嗪治疗组（n = 222）。每3个月测量血清雄激素水平。在两个3个月期间每周测量尿孕二醇葡萄糖醛酸水平。主要终点是PCOS组分的发生情况（即高雄激素血症或排卵功能障碍）。对初潮后超过2年的女性进行事后分析（拉莫三嗪组177例，丙戊酸盐组186例），以排除青春期的混杂效应。

结果

在前瞻性分析中，丙戊酸盐组发生（排卵功能障碍）的女性多于拉莫三嗪组（丙戊酸盐组54%，拉莫三嗪组38%；p = 0.010），在事后分析中也是如此（丙戊酸盐组36%，拉莫三嗪组23%；p = 0.007）。丙戊酸盐组发生PCOS的女性多于拉莫三嗪组（9%对2%；p = 0.007）。在年龄小于26岁开始治疗的患者中，丙戊酸盐组发生高雄激素血症比拉莫三嗪组更频繁（丙戊酸盐组44%，拉莫三嗪组23%；p = 0.002），但如果在26岁及以上开始治疗则相似（丙戊酸盐组24%，拉莫三嗪组22%）。