多囊卵巢綜合征研究進(jìn)展

1、0153045607590Reproductive-age (4% to 12%) Primary generalized epilepsyCarbamazepine-treated epilepsy(10%)Untreated epilepsy10.5Valproate-treated epilepsy(11.1%)Idiopathic generalized epilepsyUnilateral temporolimbic epilepsyWith amenorrhea(37%)*With oligomenorrhea(90%)*Prevalence of PCOS, %*Franks s

2、. N 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. 既與雄激素程度有關(guān)，又決定于PSU雄激素受體對(duì)雄激素的敏感性A2和/或T的合成增多,腎上腺DHEA常無(wú)上升Ernst CL, et al. J Clin Psychiatry. 2002;63:(suppl 4):42-55.Genton P, et a

3、l. Epilepsia. 2001;42:295-304.卵巢組織上存在胰島素受體，胰島素刺激顆粒細(xì)胞分泌孕酮使黃素化并誘導(dǎo)LH受體合成，同時(shí)改變腎上腺細(xì)胞對(duì)ACTH的敏感性。胰島素基因5端有呈雙峰分布的可變數(shù)目串聯(lián)重復(fù)VNTR小衛(wèi)星，I類(lèi)等位基因縮短，III類(lèi)等位基因延長(zhǎng)。III類(lèi)等位基因純合子是導(dǎo)致無(wú)排卵型PCOS的遺傳素質(zhì).PCOS may be caused by interactions betweenGenetic factors (eg, autosomal dominant transmission)Endocrine factors (eg, increased LH/FS

4、H ratio, increased insulin and androgen concentrations)Metabolic factors (eg, increased 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

5、-65.Ernst CL, et al. J Clin Psychiatry. 2002;63(suppl 4):42-55.LH程度升高可能與少兒時(shí)期腎上腺皮質(zhì)功能亢進(jìn)生成弱雄激素過(guò)多，經(jīng)外周組織芳香化酶轉(zhuǎn)化成過(guò)多的雌激素(雌酮E1)持續(xù)干擾下丘腦垂體功能，引起LH與卵巢雄激素分泌過(guò)多。致無(wú)周期性高雌環(huán)境。高胰島素血癥和胰島素抵抗 胰島素可通過(guò)其垂體附近的受體促LH釋放，增強(qiáng)卵巢卵泡膜細(xì)胞17羥化酶作用，致使雄激素合成增多。 胰島素及IGF-1促進(jìn)LH刺激卵泡膜細(xì)胞雄激素的合成，同時(shí)抑制肝臟合成SHBG，使游離T升高。 胰島素通過(guò)胰島素受體直接作用于卵巢的卵泡膜細(xì)胞加速細(xì)胞內(nèi)孕酮轉(zhuǎn)化為17羥

6、孕酮及后者進(jìn)一步轉(zhuǎn)化為A2及T的過(guò)程。 INS/IGF系統(tǒng)可刺激P450c17mRNA在卵巢和腎上腺的表達(dá)和活性，促進(jìn)雄激素的合成。，PCOS正常體重組正常體重組(PCOS/NW)PCOS 肥胖組肥胖組(PCOS/OB)74例例158例例亞太地區(qū)肥胖標(biāo)準(zhǔn)亞太地區(qū)肥胖標(biāo)準(zhǔn) BMI25 kg/m2 正常體重正常體重對(duì)照組對(duì)照組(Control/NW)44例例注：與注：與Control/NW組比較，組比較， *P0.05，與，與PCOS/NW比較，比較， # P注：與注：與Control/NW組比較，組比較， *P0.05，與，與PCOS/NW比較，比較， # P1注：與注：與Control/NW組

7、比較，組比較， *P0.05，與，與PCOS/NW比較，比較， # P121 PCOS womenAge : 14-40 years WHO 1999 Arterioscler Thromb Vasc Biol 20:2414-2421; 2000Age-related changes in thePCOS phenotypeReproductive abnormalitiesClinical hyperandrogenismMetabolic abnormalitiesAdolescence Adult fertile age MenopausePostmenopause Metabolis

8、m, vol 43, no 5; 1994Insulin-sensitizersDiet, physical exercise-improve glucose tolerance-improve lipid abnormalities-reduce metabolic and other 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-induce