1、0153045607590Reproductive-age(4%to 12%)Primary generalized epilepsyCarbamazepine-treated epilepsy(10%)Untreated epilepsy（10.5）Valproate-treated epilepsy(11.1%)Idiopathic generalized epilepsyUnilateral temporolimbic epilepsyWith amenorrhea(37%)*With oligomenorrhea(90%)*Prevalence of PCOS,%*Franks s.N
2、 Engl J Med.1995;333:853-861.Herzog AG,et al.Epilepsia.2001;42:311-315.Duncan S.Epilepsia.2001;42(suppl 3):60-65.Dunaif A,et al.Annu Rev Med.2001;52:401-419.Ernst CL,et al.J Clin Psychiatry.2002;63:(suppl 4):42-55.Genton P,et al.Epilepsia.2001;42:295-304.卵巢组织上存在胰岛素受体，胰岛素刺激颗粒细胞分泌孕酮使黄素化并诱导LH受体合成，同时改变肾
3、上腺细胞对ACTH的敏感性。胰岛素基因5端有呈双峰分布的可变数目串联重复（VNTR）小卫星，I类等位基因缩短，III类等位基因延长。III类等位基因纯合子是导致无排卵型PCOS的遗传素质.PCOS may be caused by interactions betweenGenetic factors(eg,autosomal dominant transmission)Endocrine factors(eg,increased LH/FSH ratio,increased insulin and androgen concentrations)Metabolic factors(eg,in
4、creased insulin resistance,decreased SHBG)Neurologic factors(eg,epileptic discharges)Environmental factors(eg,anabolic steroids)Herzog AG,et al.Epilepsia.2001;42:311-315.Duncan S.Epilepsia.2001;42(suppl 3):60-65.Ernst CL,et al.J Clin Psychiatry.2002;63(suppl 4):42-55.高胰岛素血症和胰岛素抵抗 胰岛素可通过其垂体附近的受体促LH释放
5、，增强卵巢卵泡膜细胞17羟化酶作用，致使雄激素合成增多。胰岛素及IGF-1促进LH刺激卵泡膜细胞雄激素的合成，同时抑制肝脏合成SHBG，使游离T升高。胰岛素通过胰岛素受体直接作用于卵巢的卵泡膜细胞加速细胞内孕酮转化为17羟孕酮及后者进一步转化为A2及T的过程。INS/IGF系统可刺激P450c17mRNA在卵巢和肾上腺的表达和活性，促进雄激素的合成。PCOS正常体重组正常体重组(PCOS/NW)PCOS 肥胖组肥胖组(PCOS/OB)74例例158例例亚太地区肥胖标准亚太地区肥胖标准 BMI25 kg/m2 正常体重正常体重对照组对照组(Control/NW)44例例注：与注：与Control
6、/NW组比较，组比较，*P0.05，与，与PCOS/NW比较，比较，#P0.05注：与注：与Control/NW组比较，组比较，*P0.05，与，与PCOS/NW比较，比较，#P0.05注：与注：与Control/NW组比较，组比较，*P0.05，与，与PCOS/NW比较，比较，#P0.05注：与注：与Control/NW组比较，组比较，*P0.05，与，与PCOS/NW比较，比较，#P0.05121 PCOS womenAge:14-40 years WHO 1999 Arterioscler Thromb Vasc Biol 20:2414-2421;2000Age-related cha
7、nges in thePCOS phenotypeReproductive abnormalitiesClinical hyperandrogenismMetabolic abnormalitiesAdolescence Adult fertile ageMenopausePostmenopause Metabolism,vol 43,no 5;1994Insulin-sensitizersDiet,physical exercise-improve glucose tolerance-improve lipid abnormalities-reduce metabolic and other
8、 CVD risk factorsPrevention of long-term outcomes?-diabetes-hypertension-CDV(?)-etcShort term effects:-reduce body weight-improve fat distribution-improve insulin-resistance-reduce hyperinsulinemiaImproved hyperandrogenism and related disorders(hirsutism,menstrual alterations,etc)Increase ovulation rate(spontaneous and drug-induced)and fertility rateImprove quality of life and self-esteem+Flutamide氟化酰胺氟化酰胺 氟化酰胺仅为雄素受体拮抗剂，而不影响血清雄激素浓度剂量250mg每日23次应配伍OC，以免引起意外妊娠男胎女化。
