丙戊酸镁对女性癫痫患者生殖内分泌的影响

Effects of magnesium valproate on endocrine system and reproductive functions of female epileptics

目的了解丙戊酸对女性癫痫患者生殖内分泌的影响。方法选择2009年7月至2010年3月在河南省人民医院和郑州大学第一附属医院癫痫中心确诊为癫痫，并单独服用丙戊酸镁缓释片治疗的青春和育龄期女性癫痫患者30例。分别检测服药前、服药后3、6、12个月时卵泡刺激激素（FSH）、黄体生成素（LH）、催乳素（PRL）、雌二醇（E2）、孕酮（P）、睾酮（T）水平，观察月经及卵巢功能变化。结果30例服用丙戊酸镁的女性癫痫患者治疗3、6、12个月的黄体生成素、卵泡刺激素水平与治疗前相比差异无统计学意义；服药3、6个月催乳素水平较服药前显著下降（P值分别为0．010，0．014）；服药3、6,12个月的雌二醇水平与服药前相比持续性降低（P值分别为0．005，0．037，0．035）；服药3个月的孕酮水平较服药前显著下降（P值为0．009）；服药3、6、12个月睾酮水平与服药前相比持续性升高（P值分别为0．036，0．002，0．006）。6例患者有（6／30，20％）月经异常；3例（3／30，10％）有多囊卵巢。结论服用丙戊酸镁可引起女性癫痫患者生殖内分泌激素变化并引起月经改变、多囊卵巢等内分泌紊乱，随着服药时间延长，可能发生多囊卵巢综合征（PCOS）。

Objective To explore the effects of valproate （VPA） on endocrine system in adolescent and reproductive female patients with epilepsy. Methods A total of 30 adolescent and reproductive female patients with a diagnosis of epilepsy at our hospital during July 2009 to March 2010 were recruited. All eases with magnesium VPA alone were included. The levels of follicle-stimulating hormone （ FSH ）, luteinizing hormone （LH）, prolaetin （ PRL）, estradiol （ E2 ）, progesterone （P） and tesosterone （T） were detected respectively at pre-therapy and 3, 6 and 12 months post-therapy. And the changes of menstruation and ovaries were recorded. Results The serum concentration of PRL was lower at 3 and 6 months post-therapy than that at pre-therapy. There was significant difference （P = 0.010 and 0.014） . The serum concentration of E2 significantly decreased after a 3-month therapy of valproate （ P 〈 0. 05 ）. While comparing the parameter＇s level between the initial test and at a 3, 6 and 12-month follow-up, the level of P significantly decreased in the later groups than that of the former one while the level of T showed a marked increase. The levels of FSH and LH were not significantly different at pre- and post-therapy. And 6 （ 20% ） of them presented with menstrual dysfunctions and 3 （ 10% ） polyeystie ovary. Conclusion The valproate therapy can not only cause the changes of endocrine system and hormonal levels, but also induce such endocrine dysfunction syndromes as menstrual suspension and polyeystie ovary. It eventually causes polyeystic ovary syndrome.