殷冬梅 阮祥燕,* 趙 越 Alfred O. Mueck
(1.首都醫(yī)科大學(xué)附屬北京婦產(chǎn)醫(yī)院內(nèi)分泌科,北京 100026;2. 德國圖賓根大學(xué)婦產(chǎn)醫(yī)院內(nèi)分泌與絕經(jīng)中心,圖賓根 D-72076,德國)
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北京地區(qū)多囊卵巢綜合征病人內(nèi)分泌代謝特征分析
殷冬梅1阮祥燕1,2*趙 越1Alfred O. Mueck2
(1.首都醫(yī)科大學(xué)附屬北京婦產(chǎn)醫(yī)院內(nèi)分泌科,北京 100026;2. 德國圖賓根大學(xué)婦產(chǎn)醫(yī)院內(nèi)分泌與絕經(jīng)中心,圖賓根 D-72076,德國)
目的 分析北京地區(qū)不同亞型多囊卵巢綜合征(polycystic ovary syndrome,PCOS)病人臨床特征及性激素、糖脂代謝特征。方法 選擇190例來自北京地區(qū)的女性,其中142例未經(jīng)治療的PCOS病人作為研究組,48例年齡匹配的健康女性作為對(duì)照組;根據(jù)2003鹿特丹PCOS診斷標(biāo)準(zhǔn)及美國國立衛(wèi)生院(National Institute of Health,NIH)指南推薦將PCOS組病人分為4個(gè)亞型:亞型1,高雄激素+排卵異常(androgen excess +ovulatory dysfunction,AE+OD)40例;亞型2,高雄激素+卵巢多囊泡改變(androgen excess +polycystic ovarian morphology,AE+PCO)10例;亞型3,排卵異常+卵巢多囊泡改變(ovulatory dysfunction + polycystic ovarian morphology,OD+PCO)32例;亞型4,高雄激素+排卵異常+卵巢多囊泡改變(androgen excess+ ovulatory dysfunction + polycystic ovarian morphology,AE+OD+PCO)60例。測(cè)量所有受試者的臨床特征;測(cè)定血清性激素濃度及糖、脂代謝指標(biāo)。結(jié)果 PCOS組病人的體質(zhì)量指數(shù)(body mass index,BMI)、腰臀比(waist and hip ratio,WHR)、血清總睪酮(total testosterone,T)、黃體生成素(luteinizing hormone,LH)、LH/卵泡刺激素(follicle stimulating hormone,F(xiàn)SH)比值均高于對(duì)照組,差異有統(tǒng)計(jì)學(xué)意義(P<0.05);血清總膽固醇(total cholesterol,TC)、低密度脂蛋白膽固醇(low density lipoprotein-cholesterol, LDL-C)、三酰甘油(triglycerides,TG)及載脂蛋白B(apolipoprotein B,ApoB)濃度、ApoB/ApoA比值及空腹胰島素(fasting insulin,INS)、胰島素抵抗指數(shù)(homeostatic model assessment of insulin resistance,HOMA-IR)高于對(duì)照組,高密度脂蛋白膽固醇(high density lipoprotein-cholesterol,HDL-C)和載脂蛋白 A(apolipoprotein A,ApoA)濃度低于對(duì)照組,差異有統(tǒng)計(jì)學(xué)意義(P<0.05)。亞型1的BMI、WHR、T及LDL均高于亞型3,TC及LDL較亞型2增高;亞型4的BMI、T及LDL高于亞型3,T、LH及LH/FSH較亞型2增高,差異有統(tǒng)計(jì)學(xué)意義(P<0.05);亞型2和亞型3之間各個(gè)臨床特征及糖脂代謝參數(shù)的差異無統(tǒng)計(jì)學(xué)意義(P>0.05)。結(jié)論 北京地區(qū)PCOS病人中向心性肥胖、脂代謝紊亂及胰島素抵抗和高胰島素血癥的發(fā)病率較健康女性明顯升高;同時(shí)具備排卵異常和高雄的亞型1和亞型4這2個(gè)亞型的脂代謝紊亂及胰島素抵抗可能比較嚴(yán)重, 而月經(jīng)正常的亞型2和無高雄的亞型3其代謝變化相對(duì)比較溫和,臨床應(yīng)加以區(qū)分并強(qiáng)調(diào)個(gè)體化治療。
多囊卵巢綜合征;亞型;脂代謝;腹型肥胖;胰島素抵抗
多囊卵巢綜合征(polycystic ovary syndrome,PCOS)是育齡期女性常見的婦科內(nèi)分泌紊亂疾病。流行病學(xué)調(diào)查顯示,我國PCOS的患病率約為5.6%[1]。雖然有著悠久的研究歷史,但病因至今尚不十分清楚,發(fā)病機(jī)制非常復(fù)雜,是一種涉及內(nèi)分泌、代謝和遺傳等許多因素的內(nèi)分泌與代謝紊亂的疾病。臨床表現(xiàn)以排卵障礙、高雄激素表現(xiàn)或高雄激素血癥、卵巢多囊泡改變?yōu)橹饕卣?,且具有多種疾病的發(fā)病風(fēng)險(xiǎn),包括肥胖、胰島素抵抗、心血管疾病、子宮內(nèi)膜癌、甲狀腺疾病以及心理疾患等[2]。由于復(fù)雜的病因及潛在的病理機(jī)制導(dǎo)致PCOS的另一個(gè)重要特點(diǎn)是其臨床表現(xiàn)呈高度異質(zhì)性,不同地域和種族,不同表型的病人在生殖損害及代謝障礙方面表現(xiàn)出個(gè)體差異[3]。
因表型多樣,國內(nèi)外相關(guān)領(lǐng)域?qū)<也粩嗵剿鞑⒅贫≒COS診斷及分型標(biāo)準(zhǔn),目前國內(nèi)外在PCOS的診斷上多采用2003年歐洲人類生殖和胚胎學(xué)會(huì)與美國生殖醫(yī)學(xué)學(xué)會(huì)的(European Society for Human Reproduction and Embryology/American Society for Reproductive Medicine,ESHRE/ASRM)鹿特丹專家會(huì)議[4]制定的PCOS診斷標(biāo)準(zhǔn)。在鹿特丹標(biāo)準(zhǔn)的基礎(chǔ)上,2012年美國國立衛(wèi)生研究院(National Institute of Health,NIH)提出了分型指南[5],根據(jù)PCOS的幾個(gè)主要臨床表現(xiàn):排卵異常、高雄激素的臨床表現(xiàn)或高雄激素血癥、卵巢多囊泡,將其分為4個(gè)亞型,即:高雄+排卵異常(androgen excess +ovulatory dysfunction,AE+OD);高雄繳素+卵巢多囊泡改變(androgen excess +polycystic ovarian morphology,AE+PCO);排卵異常+卵巢多囊泡改變(ovulatory dysfunction + polycystic ovarian morphology,OD+PCO);高雄繳素+排卵異常+卵巢多囊泡改變(androgen excess+ ovulatory dysfunction + polycystic ovarian morphology,AE+OD+PCO)。
本研究據(jù)此將PCOS病人分為以上所述的4個(gè)亞型,旨在分析北京地區(qū)不同亞型PCOS病人的臨床特征及內(nèi)分泌和糖脂代謝特點(diǎn),為指導(dǎo)臨床的個(gè)體化治療提供循證依據(jù)。
1.1 研究對(duì)象
選擇2014年11月至2016年3月期間,在首都醫(yī)科大學(xué)附屬北京婦產(chǎn)醫(yī)院婦科內(nèi)分泌門診就診的190例長(zhǎng)期生活在北京地區(qū)的漢族女性,其中首次就診并未經(jīng)任何治療的PCOS病人142例,年齡24~40歲,平均年齡(28.56±3.28)歲。選取同期門診體檢,月經(jīng)規(guī)律的健康女性48例作為對(duì)照組,年齡23~36歲,平均年齡(29.60±3.55)歲。多囊卵巢綜合征的診斷根據(jù)2003鹿特丹標(biāo)準(zhǔn)[4]:①稀發(fā)排卵或無排卵;②高雄激素的臨床表現(xiàn)和(或)高雄激素血癥(高雄激素的臨床表現(xiàn):痤瘡、多毛、脫發(fā)(頭頂至前發(fā)際毛發(fā)稀疏);高雄激素血癥實(shí)驗(yàn)室標(biāo)準(zhǔn):1.90 nmol/L(依據(jù)北京婦產(chǎn)醫(yī)院實(shí)驗(yàn)室標(biāo)準(zhǔn));③卵巢多囊性改變(一側(cè)或雙側(cè)卵巢內(nèi)直徑2~9 mm的卵泡數(shù)≥12個(gè))。符合上述3項(xiàng)中任何2項(xiàng),即可診斷PCOS。排除標(biāo)準(zhǔn):①其他原因引起的雄激素過多如:先天性腎上腺皮質(zhì)增生、皮質(zhì)醇增多癥、卵巢分泌雄激素腫瘤以及甲狀腺功能異常等其他內(nèi)分泌疾病。②近3個(gè)月使用任何可能影響觀察指標(biāo)的藥物包括口服避孕藥、激素類藥、降糖藥、影響脂代謝藥等。③合并急慢性心血管及肝腎疾病。根據(jù)2012年NIH推薦指南[5]將PCOS組病人分為4個(gè)亞型:亞型1 40例(AE+OD:高雄激素+排卵異常);亞型2 10例(AE+PCO:高雄+卵巢多囊泡改變);亞型3 32例(OD+PCO:排卵異常+卵巢多囊泡改變);亞型4 60例(AE+OD+PCO:高雄+排卵異常+卵巢多囊泡改變)。
本研究獲得首都醫(yī)科大學(xué)附屬北京婦產(chǎn)醫(yī)院倫理委員會(huì)批準(zhǔn),受試者充分了解研究?jī)?nèi)容并簽署知情同意書。
1.2 研究方法
1.2.1 基本臨床特征的測(cè)量方法
所有病人均測(cè)量基本參數(shù)和進(jìn)行一般情況調(diào)查,包括:年齡、身高、體質(zhì)量、腰圍、臀圍;身高及體質(zhì)量的測(cè)量:赤腳、脫帽,穿單衣褲,雙手自然下垂,測(cè)量身高及體質(zhì)量;腰圍的測(cè)量:取站位,雙腳分開至25~30 cm,平穩(wěn)呼吸狀態(tài)下,在髂前上棘和第12肋下緣連線中點(diǎn)水平測(cè)量周徑。臀圍的測(cè)量:臀部最突出部位測(cè)量周徑;計(jì)算體質(zhì)量指數(shù)(body mass index,BMI)=體質(zhì)量(kg)/身高2(m2),腰臀比(waist and hip ratio,WHR)=腰圍(cm)/臀圍(cm)。
1.2.2 性激素及代謝指標(biāo)的標(biāo)本采集方法及內(nèi)容
月經(jīng)規(guī)律者于月經(jīng)周期的第2~4天或PCOS病人閉經(jīng)超過3個(gè)月未使用孕激素撤血情況下,空腹采血檢測(cè)卵泡刺激素(follicle stimulating hormone,F(xiàn)SH)、黃體生成素(luteinizing hormone,LH)、總睪酮(total testosterone,T);所有病人于清晨空腹?fàn)顟B(tài)下抽取靜脈血檢測(cè)空腹胰島素(fasting insulin,INS)、總膽固醇(total cholesterol,TC)、三酰甘油(triglycerides,TG)、低密度脂蛋白膽固醇(low density lipoprotein-cholesterol, LDL-C)、高密度脂蛋白膽固醇(high density lipoprotein-cholesterol,HDL-C)、載脂蛋白A(apolipoprotein A,ApoA)、載脂蛋白B(apolipoprotein B,ApoB)、脂蛋白a[lipoprotein(a),Lp(a)];采用穩(wěn)態(tài)模型評(píng)估胰島素抵抗指數(shù)(homeostatic model assessment of insulin resistance,HOMA-IR)=[空腹血糖(fasting blood glucose, FBG)×INS]/22.5。
1.2.3 檢測(cè)方法
性激素及空腹胰島素的測(cè)定采用西門子公司(德國)生產(chǎn)的電化學(xué)發(fā)光免疫分析儀(型號(hào):CENTAUR XP);血脂及脂蛋白指標(biāo)由Beckman公司(美國)生產(chǎn)的全自動(dòng)生物化學(xué)分析儀(型號(hào):DXC 800)檢測(cè)。
1.3 統(tǒng)計(jì)學(xué)方法
2.1 2組研究對(duì)象臨床特征及性激素與糖脂代謝比較
142例PCOS病人與48例對(duì)照組間的BMI、WHR、INS、HOMA-IR、LH、LH/FSH、T組間比較差異有統(tǒng)計(jì)學(xué)意義(P<0.01),且提示均高于健康對(duì)照組;TC、LDL、TG及ApoB濃度及ApoB/ApoA比值均高于健康對(duì)照組,差異有統(tǒng)計(jì)學(xué)意義(P<0.05),HDL及ApoA濃度低于健康對(duì)照組,差異有統(tǒng)計(jì)學(xué)意義(P<0.01); 4組亞型的INS濃度均高于對(duì)照組,差異有統(tǒng)計(jì)學(xué)意義(P<0.01);除亞型2的HOMA-IR與對(duì)照組的差異無統(tǒng)計(jì)學(xué)意義外,其余3個(gè)亞型均高于對(duì)照組,差異均有統(tǒng)計(jì)學(xué)意義(P<0.01)。同時(shí)具備排卵異常和高雄的1和亞型4的所有脂代謝指標(biāo)與對(duì)照組相比差異均有統(tǒng)計(jì)學(xué)意義(P<0.05); 亞型2的血脂參數(shù)與對(duì)照組相比差異無統(tǒng)計(jì)學(xué)意義(P<0.05)。亞型3除TG高于對(duì)照組(P<0.05)外,其余脂代謝指標(biāo)對(duì)照組相比差異也無統(tǒng)計(jì)學(xué)意義。
PCOS組的年齡和脂蛋白(a)濃度與對(duì)照組之間相比,差異無統(tǒng)計(jì)學(xué)意義(P=0.240,P=0.971)(表1、表2)。
2.2 各組亞型間臨床特征、性激素比較
不同亞型間,BMI、WHR及性激素濃度相比較,差異有統(tǒng)計(jì)學(xué)意義(P<0.01),亞型1(AE+OD)和亞型4(AE+OD+PCO)的BMI、WHR和T值高于亞型2(AE+PCO)和亞型3(OD+PCO),差異有統(tǒng)計(jì)學(xué)意義(P<0.05);同時(shí)具備排卵異常和卵巢多囊泡改變的亞型3和亞型4的LH濃度及LH/FSH比值高于無卵巢多囊泡改變的亞型1(P<0.05)。詳見表1。
2.3 各組亞型間糖脂代謝參數(shù)比較
組間TC和LDL-C值相比差異有統(tǒng)計(jì)學(xué)意義(P<0.05),有高雄的亞型1和亞型4的LDL-C濃度高于無高雄的亞型3,亞型1的TC和LDL-C高于亞型2,差異均有統(tǒng)計(jì)學(xué)意義(P<0.05),4組亞型間HOMA-IR值及INS和脂蛋白(a)水平相比,差異無統(tǒng)計(jì)學(xué)意義(P=0.971)(表1、2)。
表1 各組亞型間臨床特征、性激素比較
*P<0.05vscontrol group,#P<0.05vsphenotype 3,△P<0.05vsphenotype 4; AE:androgen excess; OD:ovulatory dysfunction;PCO:polycystic ovarian morphology;BMI:body mass index;WHR:waist and hip ratio;LH:luteinizing hormone;T:total testosterone.
表2 各組亞型間糖脂代謝參數(shù)比較
*P<0.05vscontrol group;#P<0.05vsphenotype 1;△P<0.05vsphenotype 4; AE:androgen excess; OD:ovulatory dysfunction;PCO:polycystic ovarian morphology; TC:total cholesterol;LDL-C:low-density lipoprotein-cholesterol;HDL-C:high density lipoprotein-cholesterol;TG:triglycerides;ApoA:apolipoprotein A;ApoB:apolipoprotein B;Lp(a):lipoprotein(a);INS:fasting insulin;HOMA-IR: homeostasis model assessment for insulin resistance.
PCOS是涉及多系統(tǒng)、多臟器的代謝性疾病,如卵巢、垂體、腎上腺、脂肪細(xì)胞及胰腺內(nèi)分泌等,幾乎影響女性一生的生殖生理狀態(tài)。其中主要的一個(gè)臨床特征是高雄激素表現(xiàn)和/或高雄激素血癥,本研究數(shù)據(jù)分析顯示:PCOS組病人的T、LH濃度及LH/FSH值均高于健康對(duì)照組,差異有統(tǒng)計(jì)學(xué)意義(P<0.01),PCOS的這些性激素特點(diǎn)已經(jīng)被許多研究所證實(shí)[6]。
本研究結(jié)果還顯示北京地區(qū)PCOS病人普遍存在向心性肥胖,與中國臺(tái)灣地區(qū)PCOS病人相似[7]。此外,胰島素抵抗及脂代謝異常的發(fā)生也較健康對(duì)照組明顯升高。Kumar等[8]針對(duì)印度女性的研究結(jié)果也顯示PCOS病人胰島素抵抗的發(fā)生及TC、LDL-C、TG濃度高于健康女性。
進(jìn)一步將142例PCOS病人分型后顯示:4種亞型的性激素及糖脂代謝呈現(xiàn)的特點(diǎn)不盡相同:亞型1的BMI、WHR、T及LDL-C均高于亞型3, TC及LDL-C較亞型2增高;亞型4的BMI、T及LDL-C高于亞型3,T、LH及LH/FSH較亞型2增高,差異有統(tǒng)計(jì)學(xué)意義(P<0.05)。Ganie等[9]將北印度PCOS女性分型研究后也發(fā)現(xiàn),盡管來自同一地區(qū),不同表型的PCOS病人其臨床特征、生物化學(xué)指標(biāo)及激素濃度也顯示出明顯差異。本研究發(fā)現(xiàn):同時(shí)具備高雄和月經(jīng)失調(diào)的亞型1和亞型4的腹型肥胖、胰島素抵抗及脂代謝紊亂最重,排卵正常而只有高雄+卵巢多囊泡改變的亞型2和無高雄的亞型3較輕。與另兩項(xiàng)研究[9-10]結(jié)果相一致, Dilbaz等[10]采用同樣的分型標(biāo)準(zhǔn)研究PCOS病人的臨床特征和代謝變化,認(rèn)為與其他亞型相比,月經(jīng)正常的PCOS病人其BMI及血LDL-C和總膽固醇濃度低于其他3種亞型,因此冠心病發(fā)病風(fēng)險(xiǎn)顯著降低;非高雄亞型的代謝改變比較溫和。
趙越等[11]對(duì)北京地區(qū)647例PCOS病人做的一項(xiàng)分型研究中顯示了與本研究結(jié)果相似的結(jié)果:AE+OD+PCO組血液總睪酮值最高,高雄激素表現(xiàn)最嚴(yán)重;OD+PCO組臨床體征最輕,表型溫和。但也研究者[11-12]持不同意見,Li等[12]將2 436名來自中國南方廣州地區(qū)的≥18歲PCOS病人進(jìn)行同樣的分型研究后認(rèn)為:4種PCOS表型之間代謝異常的發(fā)生或代謝異常的分布特征之間差異無統(tǒng)計(jì)學(xué)意義(P>0.05),不應(yīng)用于區(qū)分各種臨床PCOS表型。這是否是由于地域、民族的差異及飲食和生活習(xí)慣不同所導(dǎo)致不同的結(jié)果還需要進(jìn)一步的研究去證實(shí)。在Bozdag等[13]針對(duì)PCOS表型特征及流行病學(xué)的一項(xiàng)Meta分析研究后,認(rèn)為PCOS的診斷和治療應(yīng)考慮全球地域差異,在區(qū)域性診斷和精確治療策略的制定和實(shí)施過程中,必須考慮到代謝綜合征發(fā)生的地理差異,需要進(jìn)一步的努力探索和資源整合,增加全球PCOS的標(biāo)準(zhǔn)化診斷及表型研究的可比性。
2011年,我國生殖醫(yī)學(xué)及婦科內(nèi)分泌專家[14]首次基于漢族人群特點(diǎn),提出中國PCOS診斷標(biāo)準(zhǔn)及分型,強(qiáng)調(diào)了月經(jīng)異常是PCOS診斷的必要條件,并可按有無肥胖和中心性肥胖;有無糖耐量受損、糖尿病和代謝謝綜合征將其分型,建議分為經(jīng)典型(月經(jīng)異常和高雄激素血癥,有或無PCO),和無高雄激素血癥型(只有月經(jīng)異常和PCO),并認(rèn)為經(jīng)典PCOS代謝障礙表現(xiàn)較重,無高雄激素血癥的PCOS則較輕。本研究結(jié)果進(jìn)一步證實(shí)了我國PCOS診斷及分型標(biāo)準(zhǔn)的合理性,北京地區(qū)PCOS病人的糖脂代謝特征與之也是相吻合的。
Rizzo等[15]在比較了PCOS正常排卵亞型與異常排卵亞型在致動(dòng)脈粥樣硬化的脂代謝后認(rèn)為,前者致動(dòng)脈粥樣硬化的血脂異常程度輕于排卵異常病人且與胰島素抵抗程度相關(guān)。Mario等[16]在最新的一項(xiàng)研究中發(fā)現(xiàn):HOMA-IR可以作為一種表型特異性標(biāo)志物,當(dāng)其≥3.8時(shí)預(yù)示著PCOS病人早期代謝異常的發(fā)生及冠狀動(dòng)脈粥樣硬化性心臟病(以下簡(jiǎn)稱冠心病)發(fā)病率增加。本研究中,亞型3的HOMA-IR值最低,與健康對(duì)照組的差異雖無統(tǒng)計(jì)學(xué)意義(P>0.05),但均值也達(dá)到3.89±2.81,說明北京地區(qū)PCOS病人要普遍重視心血管疾病的預(yù)防。
Tziomalos[17]認(rèn)為,同時(shí)具備無排卵+高雄激素的病人比那些卵巢多囊泡改變+無排卵或+雄激素血癥病人有更顯著的胰島素抵抗和更高水平的促炎性反應(yīng)因子和血栓形成趨勢(shì)。Pinola等[18]發(fā)現(xiàn):無論是否高雄,PCOS病人肥胖尤其是腹型肥胖的發(fā)生率更高,但是雄激素增高的表型代謝綜合征的發(fā)病率較對(duì)照組高2~5倍,PCOS病人發(fā)生代謝綜合征的風(fēng)險(xiǎn)增加且與雄激素水平及腹型肥胖相關(guān)。?elik等[19]的研究結(jié)果也支持這一觀點(diǎn),他們將PCOS病人分為高雄激素和非高雄激素2組,比較多種代謝指標(biāo)及冠心病發(fā)病因素后認(rèn)為:代謝綜合征和心血管疾病的發(fā)病風(fēng)險(xiǎn)因PCOS的表型而異,與非高雄PCOS相比, PCOS高雄亞型的高密度脂蛋白降低,代謝綜合征的發(fā)病風(fēng)險(xiǎn)明顯增高。
導(dǎo)致PCOS表型及表現(xiàn)差異的原因尚無定論,Pau等[20]根據(jù)PCOS風(fēng)險(xiǎn)基因庫的基因型數(shù)據(jù)進(jìn)行分析,認(rèn)為不同基因表型的表達(dá)差異以及通過不同途徑和機(jī)制參與PCOS的代謝過程,可能與PCOS亞型形成存在潛在關(guān)系。
PCOS表型異質(zhì)性特點(diǎn),不同亞型的PCOS病人具備不同的內(nèi)分泌和糖脂代謝特征,其近期和遠(yuǎn)期合并癥發(fā)生的風(fēng)險(xiǎn)也存在差異。臨床醫(yī)生應(yīng)予以充分認(rèn)知,對(duì)于代謝異常型的PCOS,重視糾正代謝紊亂,預(yù)防心血管疾病等合并癥的發(fā)生顯得尤為重要,臨床上應(yīng)該根據(jù)PCOS的不同分型特點(diǎn),有針對(duì)性地進(jìn)行干預(yù)和預(yù)防篩選,做到個(gè)體化治療和指導(dǎo)預(yù)防。
[1] Li R, Zhang Q, Yang D, et al.Prevalence of polycystic ovary syndrome in women in China: a large community-based study [J]. Hum Reprod,2013, 28 (9):2562-2569.
[2] Palomba S, Santagni S, Falbo A, et al. Complications and challenges associated with polycystic ovary syndrome: current perspectives [J]. Int J Womens Health,2015, 31 (7):745-763.
[3] Chan J L, Kar S, Vanky E, et al. Racial and ethnic differences in the prevalence of metabolic syndrome and its components of metabolic syndrome in women with polycystic ovary syndrome (PCOS): a regional cross-sectional study [J]. Am J Obstet Gynecol, 2017, Epub of print.
[4] Rotterdam ESHRE/ASRM-sponsored. PCOS consensus on diagnostic criteria and long term health risks related to polycystic ovary syndrome [J].Hum Reprod,2004,19:41-47.
[5] National Institute of Health. Evidence-based methodology workshop on polycystic ovary syndrome[EB/OL]. [2017-06-05]. https://prevention.nih.gov/docs/programs/pcos/finelreport.pdf.
[6] Kumar A N, Naidu J N, Satyanarayana U, et al. Metabolic and endocrine characteristics of Indian women with polycystic ovary syndrome [J].Int J Fertil Steril, 2016,10 (1):22-28.
[7] Hsu M I. Clinical characteristics in Taiwanese women with polycystic ovary syndrome [J].Clin Exp Reprod Med,2015,42(3):86-93.
[8] Kumar A N, Naidu J N, Satyanarayana U,et al. Metabolic and endocrine characteristics of indian women with polycystic ovary syndrome [J].Int J Fertil Steril,2016,10(1):22-28.
[9] Ganie M A, Marwaha R K, Dhingra A, et al. Observation of phenotypic variation among Indian women with polycystic ovary syndrome (PCOS) from Delhi and Srinagar [J]. Gynecol Endocrinol,2016,15:1-5.
[10] Dilbaz B, Ozkaya E, Cinar M, et al.Cardiovascular disease risk characteristics of the main polycystic ovary syndrome phenotypes[J].Endocrine,2011,39(3):272-277.
[11]趙越, 阮祥燕, 崔亞美,等. 不同亞型的多囊卵巢綜合征病人臨床及實(shí)驗(yàn)室指標(biāo)特征的研究 [J].首都醫(yī)科大學(xué)學(xué)報(bào),2015,36(4):567-572.
[12] Li H, Li L, Gu J, et al. Should all women with Polycystic ovary syndrome Be screened for metabolic parameters? A hospital-based observational study[J].PLoS One,2016,30,11(11):e0167036.
[13] Bozdag G, Mumusoglu S, Zengin D, et al. The prevalence and phenotypic features of polycystic ovary syndrome: a systematic review and meta-analysis [J]. Hum Reprod,2016,31(12):2841-2855.
[14]陳子江,張以文,劉嘉茵,等.多囊卵巢綜合征診斷-中華人民共和國衛(wèi)生行業(yè)標(biāo)準(zhǔn)[J]. 中華婦產(chǎn)科雜志, 2012, 47(1): 74-75.
[15] Rizzo M, Berneis K, Hersberger M, et al. Milder forms of atherogenic dyslipidemia in ovulatory versus anovulatory polycystic ovary syndromephenotype [J].Hum Reprod, 2009,24(9):2286-2292.
[16] Mario F M, Graff S K, Spritzer P M. Adiposity indexesas phenotype-specific Markers of preclinical metabolic alterations and cardiovascular risk in polycystic ovary syndrome: a cross-sectional study [J].Exp Clin Endocrinol Diabetes, 2017, 125(5):307-315.
[17] Tziomalos K. Cardiovascular risk in the different phenotypes of polycystic ovary syndrome [J].Curr Pharm Des 2016,22(36):5547-5553.
[18] Pinola P, Puukka K, Piltonen T T, et al. Normo-and hyperandrogenic women with polycystic ovary syndrome exhibit an adverse metabolic profile through life[J].Fertil Steril, 2017,107(3):788-795.
[20] Pau C T, Mosbruger T, Saxena R,et al. Phenotype and tissue expression as a function of genetic risk in polycystic ovary syndrome[J]. PLoS One,2017,12(1):e0168870.
編輯 慕 萌
Analysis of endocrine and metabolic characteristics in patients with polycystic ovary syndrome in Beijing
Yin Dongmei1, Ruan Xiangyan1,2*,Zhao Yue1, Alfred O. Mueck2
(1.DepartmentofEndocrinology,BeijingObstetricsandGynecologyHospital,CapitalMedicalUniversity,Beijing100026,China; 2.SectionofEndocrinologyandMenopause,DepartmentofWomen’sHealth,UniversityofTubingen,TubingenD-72076,Germany)
Objective To analyze the clinical characteristics, sex hormones and lipid metabolism in patients with polycystic ovary syndrome (PCOS) in Beijing. Methods Totally 142 untreated PCOS patients were enrolled, and 48 age-matched healthy women were included as control group. Patients were diagnosed and grouped using the Rotterdam 2003 criteria. Based on the National Institutes of Health (NIH) guidelines, patients with PCOS were classified as: subtype-1, androgen excess+ ovulatory dysfunction (AE+OD)(n=40); subtype-2, androgen excess + polycystic ovarian morphology (AE+PCO)(n=10); subtype-3, ovulatory dysfunction + polycystic ovarian morphology (OD+PCO) (n=32); subtype-4, androgen excess + ovulatory dysfunction + polycystic ovarian morphology (AE+OD+PCO)(n=60). The screening panel consisted of a physical examination, weight and height measurement, ultrasonography of the ovaries, and measurements of hormone, glucose, lipid, and insulin resistance. Besides, endocrine and metabolic parameters were measured in all patients. Results In the PCOS group, body mass index (BMI), waist and hip ratio (WHR), total testosterone (T), luteinizing hormone (LH), LH / follicle stimulating hormone(FSH) ratio were higher than that of the control group with statistically significant difference (P<0.05). Total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), triglycerides (TG), apolipoprotein B (ApoB) levels, fasting insulin (INS), homeostatic model assessment of insulin resistance (HOMA-IR) and the ratio of ApoB to ApoA were significantly higher than those in the control group (P<0.05). Meanwhile, high density lipoprotein-cholesterol (HDL-C) and apolipoprotein A (ApoA) level were lower than the control group with statistically significant difference (P<0.05). The BMI, WHR, T and LDL-C of subtype-1 were higher compared to subtype-3, and TC and LDL-C were higher than subtype-2; the BMI, T and LDL-C of 4 subtypes were higher than the three other subtypes and T, LH and LH/FSH were higher than subtype-2 with statistically significant difference (P<0.05). There was no significant difference between subtype-2 and subtype-3 (P>0.05). Conclusion The incidence of central obesity, lipid metabolism disorders, insulin resistance and hyperinsulinemia in PCOS patients in Beijing was significantly higher than that in healthy women. Among the four subtypes of PCOS patients, this phenomenon maybe is most significant in subtypes 1 and 4 subgroups with both ovulation abnormality and hyperandrogenism, while subtypes with normal menstrual cycle or non-hyperandrogenic have more moderate metabolic changes, Distinction of the four subtypes should be made during clinical treatment and targeted therapy should be applied correspondingly.
polycystic ovary syndrome; subtype;lipid metabolic;abdominal obesity;insulin resistance
首都臨床特色應(yīng)用研究與成果推廣(Z161100000516143),首都衛(wèi)生發(fā)展科研專項(xiàng)項(xiàng)目(2016-2-2113),北京市醫(yī)院管理局臨床技術(shù)創(chuàng)新項(xiàng)目(XMLX201710),北京市衛(wèi)生系統(tǒng)高層次衛(wèi)生技術(shù)人才(學(xué)科帶頭人)(2014-2-016),國家外國專家局2017年度北京市引進(jìn)國外技術(shù)、管理人才項(xiàng)目(20171100004)。This study was supported by Capital Characteristic Clinic Project of China(Z161100000516143); Beijing Capital Foundation for Medical Science Development and Research(2016-2-2113); Clinical Technique Innovation Project of Beijing Municipal Administration of Hospitals(XMLX201710); Beijing Municipality Health Technology High-level Talent(2014-2-016);Foreign Technical and Administrative Talent Introduction Project in 2017,State Administration of Foreign Experts Affairs of China(20171100004).
時(shí)間:2017-07-16 17∶24 網(wǎng)絡(luò)出版地址:http://kns.cnki.net/kcms/detail/11.3662.r.20170716.1724.030.html
10.3969/j.issn.1006-7795.2017.04.003]
R711.75
2017-06-05)
*Corresponding author, E-mail:ruanxiangyan@163.com