本文選題：AMH + Inhibin�。� 參考：《華中科技大學(xué)》2016年博士論文

【摘要】：研究背景：抗苗勒氏管激素(antimullerian hormone, AMH)和抑制素B(inhibinB)在臨床上的應(yīng)用日益被重視,然而其在健康人群中的正常參考范圍卻一直未被建立；對(duì)中國(guó)健康育齡婦女來說,尤其缺乏可應(yīng)用于臨床的基于社區(qū)健康人群所建立的準(zhǔn)確的參考范圍,這種情況部分限制了抗苗勒氏管激素和抑制素在臨床實(shí)踐中的應(yīng)用。而且,在正常健康女性人群中,抗苗勒氏管激素、抑制素與其它臨床指標(biāo)如體質(zhì)指數(shù)BMI,竇狀卵泡數(shù)目AFC以及其他性別相關(guān)激素之間的相互關(guān)系至今未見文獻(xiàn)報(bào)道。研究目的：以建立正常女性的年齡特異性抗苗勒氏管激素和抑制素參考值范圍為目的,同時(shí)探索在健康女性人群中抗苗勒氏管激素、抑制素與其它臨床指標(biāo)的關(guān)系。研究設(shè)計(jì)：為建立準(zhǔn)確可靠的抗苗勒氏管激素、抑制素參考值范圍,我們開展了一項(xiàng)歷時(shí)3年(2011年10月-2014年12月),跨越不同地域的多中心、大樣本量的橫斷面研究。在沈陽(yáng)(華北),佛山(華南),成都(華西),鄭州、宜昌及武漢(華中)6個(gè)城市以廣告宣傳招募志愿者的形式招募了總計(jì)2055例20-55歲女性,年齡范圍跨越整個(gè)育齡期直至絕經(jīng)期。同時(shí),我們制定了嚴(yán)格的納入標(biāo)準(zhǔn)以確保納入的研究對(duì)象符合健康人群要求,經(jīng)過篩選,其中符合本實(shí)驗(yàn)納入標(biāo)準(zhǔn)者有1590例,占比77.37%,以納入的健康人群為研究對(duì)象制定AMH, inhibinB參考范圍。我們分別利用兩種試劑盒(Beckman Gen Ⅱ AMH assay及Ansh Labs AMH assay)檢測(cè)血清基礎(chǔ)AMH水平,用Beckman Gen Ⅱ AMH assay檢測(cè)了血清基礎(chǔ)inhibin B的水平。也檢測(cè)了卵泡期血清FSH,LH,E2,T,PRL和PRG的水平,同時(shí)通過經(jīng)陰道超聲檢查確定AFC的數(shù)目。主要結(jié)果：兩種AMH試劑盒檢測(cè)有很好的一致性,但同一樣本的AMH檢測(cè)數(shù)值有所不同,Beckman Gen Ⅱ AMH assay較Ansh Labs AMH assay的檢測(cè)數(shù)值偏高。兩種試劑盒都證實(shí)：血清抗苗勒氏管激素AMH水平隨年齡增長(zhǎng)呈逐漸下降的趨勢(shì),Beckman Gen Ⅱ AMH assay試劑盒的檢測(cè)結(jié)果顯示AMH下降趨勢(shì)可被該二次方程log(AMH)=(-1.970+0.296*Age-0.006*Age2)最好地?cái)M合。Ansh Labs AMH assay試劑盒的檢測(cè)結(jié)果卻顯示AMH與年齡Age的最佳擬合方程是log(AMH)=(-0.707+0.116*Age-0.002*Age2)。我們按年齡將研究人群劃分為6個(gè)亞組：20-25,25-30,30-33,33-37,37-40,40-55歲;Beckman Gen Ⅱ AMH assay試劑盒的檢測(cè)結(jié)果顯示各年齡組AMH中值水平為：6.23,5.65,4.55,3.74,2.78和1.09 ng/ml。各組5th-95th百分位數(shù)范圍(即本研究確定的參考值范圍)為：2.06-12.66,1.77-13.83,1.48-11.45,0.87-9.76,0.56-9.49,and 0.08-5.70 ng/ml。Ansh Labs AMH assay試劑盒的檢測(cè)結(jié)果顯示各年齡組AMH中值水平為：5.55,4.80,3.76,3.42,2.44和0.77ng/ml。各組5th-95th百分位數(shù)范圍為：1.43-13.14,1.31-13.55,1.06-10.97,0.69-9.52,0.38-8.03,0.04-4.79 ng/ml。AMH水平與AFCs,T,LH,PRL,PRG的水平呈正相關(guān)關(guān)系,與BMI和FSH水平呈負(fù)相關(guān),與E2沒有顯著的相關(guān)關(guān)系。在控制了混雜變量“年齡”與"BMI"之后,AMH與PRL的相關(guān)關(guān)系變得不顯著,而AMH與除PRL外的其它變量的相關(guān)關(guān)系未見改變。Inhibin B水平隨年齡的變化趨勢(shì)在40歲之前比較平穩(wěn),在40歲之后急劇下降,T檢驗(yàn)和Wilcoxon檢驗(yàn)均顯示20-40歲與40-55歲兩個(gè)年齡組之間的InhibinB水平有顯著性差異。我們按年齡將研究人群劃分為2個(gè)亞組：20-40,40-55歲；Beckman Inhibin B assay試劑盒的檢測(cè)結(jié)果顯示兩年齡組Inhibin B中值水平為：83.13和56.32 pg/ml:兩組5th-95th百分位數(shù)范圍為：34.38-143.75,2.6-142.33pg/ml.Inhibin B與AMH呈正相關(guān)(R=0.57,P0.001),與AFC呈正相關(guān)(R=0.34,P0.001),與T呈正相關(guān)(R=0.01,P=0.002)；Inhibin B與下列4個(gè)指標(biāo)負(fù)相關(guān)：FSH(R=-0.41,P0.001),LH(R=-0.20,P0.001),age(R=-0.30,P 0.001),BMI(R=-0.28,P0.001)；Inhibin B與PRG、PRL無顯著相關(guān)關(guān)系。結(jié)論：本研究建立了基于健康人群的中國(guó)女性血清AMH和Inhibin B的正常參考范圍,有利于臨床醫(yī)生更好的解讀和闡釋該指標(biāo)的臨床意義。研究背景：AFC和血清FSH,LH,E2,T等檢測(cè)是評(píng)價(jià)卵巢功能或診斷疾病的重要指標(biāo),在臨床上應(yīng)用廣泛。但現(xiàn)今,指導(dǎo)臨床診斷的各指標(biāo)參考范圍均是普通性參考范圍(universal ranges)而非年齡特異性參考范圍(age-specific ranges),而這些指標(biāo)比如AFC和生殖相關(guān)激素均是與年齡密切相關(guān)并隨著年齡增長(zhǎng)而變化的激素,故準(zhǔn)確的年齡特異性參考范圍要比普通性參考范圍更有臨床診斷價(jià)值。研究目的：我們以建立正常女性的年齡特異性AFC和血清FSH,LH,E2,T參考值范圍為目的,同時(shí)探索健康女性人群中各個(gè)臨床指標(biāo)的相互關(guān)系。研究設(shè)計(jì)：見上部分(與建立抗苗勒氏管激素、抑制素B參考范圍的設(shè)計(jì)類似)。研究結(jié)果：AFC隨年齡增長(zhǎng)而下降,其隨年齡的下降趨勢(shì)可被以下方程最佳擬合：AFC=9.0998+0.6128*Age-0.0159*Age2。FSH隨年齡增長(zhǎng)而升高,其隨年齡的升高趨勢(shì)可被以下方程擬合最佳：FSH=12.7885-0.5031*Age+0.0101*Age2。其他性別相關(guān)激素隨年齡變化的趨勢(shì)同樣可由最佳方程擬合：比如LH=11.5678-0.4101*Age+0.0059*Age2,E2=85.6229-3.002*Age+0.0546*Age2, T=33.1488+0.4427*Age-0.0176*Age2。我們按人群年齡分為3個(gè)亞組：20-30,30-40,40-55歲,分別制定了AFC,FSH,LH,E2和T在各個(gè)年齡組的參考范圍：各年齡組AFC中值水平為：14,11,5個(gè)；各年齡組FSH中值水平為：6.50,6.95,7.99 mIU/ml:各年齡組LH中值水平為：4.375,3.92,4.53 mIU/ml:各年齡組E2中值水平為：40.255,42.261,40.705pg/ml；各年齡組T中值水平為：31.54,26.56,18 pg/dl。我們還發(fā)現(xiàn)：AFC與年齡、BMI和FSH水平負(fù)相關(guān),與LH和T水平正相關(guān)。FSH與年齡、LH正相關(guān),與AFC、BMI, T負(fù)相關(guān)；LH與年齡、BMI負(fù)相關(guān),與AFC、FSH和E2正相關(guān)；E2與與年齡沒有顯著關(guān)系,與LH、T正相關(guān),與BMI負(fù)相關(guān)；結(jié)論：我們建立了正常女性的年齡特異性AFC和血清FSH,LH,E2,T參考值范圍,并在健康女性人群中確定了各指標(biāo)的相互關(guān)系。研究目的：明確與女性心血管疾病發(fā)病風(fēng)險(xiǎn)相關(guān)的卵巢衰老關(guān)鍵因子。研究方法：在同濟(jì)醫(yī)院的健康體檢中心進(jìn)行廣告招募,招募符合納入標(biāo)準(zhǔn)的女性志愿者共計(jì)536人參與該研究。所有受試者于月經(jīng)第1-5天早餐空腹采肘靜脈促凝血3-4m1,離心得到上層血清。檢測(cè)血清FSH, LH, E2,T,PRL等激素水平,酶聯(lián)免疫吸附技術(shù)(ELISA)檢測(cè)血清抗苗勒氏管激素AMH的水平,經(jīng)陰道超聲檢測(cè)其兩側(cè)卵巢內(nèi)2-10mm的卵泡數(shù)目AFC。同時(shí),檢測(cè)預(yù)示心血管疾病發(fā)病風(fēng)險(xiǎn)的指標(biāo),包括血脂四項(xiàng)(總膽固醇TC,總甘油三酯TG,高密度脂蛋白HDL-C,低密度脂蛋白LDL-C)以及超敏C反應(yīng)蛋白的水平。然后,分析代表卵巢功能的各種指標(biāo)與心血管疾病風(fēng)險(xiǎn)的指標(biāo)間的相關(guān)性。研究結(jié)果：通過雙變量Pearson線性相關(guān)分析可知,AMH與TC,TG,LDL-C負(fù)相關(guān)；FSH與TC,TG,LDL-C正相關(guān)；E2與TC,TG,LDL-C負(fù)相關(guān);LH與TC,TG,LDL-C正相關(guān);AFC與TC,TG,LDL-C負(fù)相關(guān)；T與LDL-C正相關(guān)；PRL與HDL-C正相關(guān),與h-CRP負(fù)相關(guān)。通過Logistic回歸分析可知,AMH與FSH可進(jìn)入以總的心血管疾病風(fēng)險(xiǎn)為Y值的回歸方程。結(jié)論：女性卵巢功能與心血管疾病發(fā)病風(fēng)險(xiǎn)密切相關(guān),其中卵巢衰老相關(guān)的各項(xiàng)指標(biāo)中,AMH與AFC比FSH,LH,E2等指標(biāo)在預(yù)警心血管疾病上可能更有優(yōu)勢(shì)；AMH可以作為預(yù)測(cè)心血管疾病風(fēng)險(xiǎn)的一個(gè)指標(biāo)。研究目的：驗(yàn)證抗苗勒氏管激素(AMH)及月經(jīng)情況與心血管疾病(包括冠心病和其它心血管疾病)的發(fā)病是否有相關(guān)性。研究方法：2013年10月至2015年12月,在同濟(jì)醫(yī)院心血管內(nèi)科收集到經(jīng)冠脈造影確診冠心病的年齡范圍在40-55歲之間的女性病人,共計(jì)128例,作為病例2組：同期收集因心慌心悸胸悶胸痛等癥狀入院治療,但經(jīng)冠脈造影不能確診冠心病者,共計(jì)101例,設(shè)為病例1組。同期在同濟(jì)醫(yī)院周邊的數(shù)個(gè)社區(qū)進(jìn)行廣告招募,按年齡分層匹配,募集到健康女性243例,作為正常對(duì)照(設(shè)為0組)。利用問卷調(diào)查包括月經(jīng)情況和孕產(chǎn)史等一般資料,并進(jìn)行血清激素AMH,血脂和超敏C反應(yīng)蛋白的檢測(cè)。利用方差分析比較病例2組、病例1組和對(duì)照0組在AMH水平、月經(jīng)情況上有無差異；另外比較3組之間的其它指標(biāo)包括：卵巢功能相關(guān)指標(biāo)(孕次,產(chǎn)次)和CVD相關(guān)風(fēng)險(xiǎn)因子(血脂、血壓、血糖)等有無差異。研究結(jié)果：年齡在各組間均無差異,即三組基線年齡相似,三組之間在研究指標(biāo)上具有可比性。方差分析發(fā)現(xiàn)三組間各指標(biāo)差異性：AMH水平、月經(jīng)情況(即絕經(jīng)與否)、孕次均表現(xiàn)為：在0組與1組,0組與2組有差異,但1組與2組之間無差異。產(chǎn)次在3組間均無差異；收縮壓：3組間均有差異：舒張壓：0組與2組有差異,但0組與1組,1組與2組之間無差異;TC和HDL-C和LDL-C:在3組間均無差異；TG：0組與1組有差異,但0與2組、1與2組無差異：血糖：0組與1組,0組與2組有差異,但1組與2組之間無差異;BMI在3組間均無差異;結(jié)論：AMH水平、月經(jīng)情況等卵巢功能指標(biāo)與冠心病密切相關(guān),而且AMH水平、月經(jīng)情況的差異性出現(xiàn)在TC、HDL-C和LDL-C指標(biāo)變化之前,可能具有更早期的預(yù)測(cè)價(jià)值。
[Abstract]:Background: the clinical application of antimullerian hormone (AMH) and inhibin B (inhibinB) is becoming more and more important in clinical practice. However, the normal reference range in healthy people has not been established. An accurate reference range, which partially restricts the application of anti Mullerian tube hormones and inhibin in clinical practice. Moreover, in normal healthy women, the relationship between the anti Mullerian tube hormone, inhibin and other clinical indicators such as the body mass index BMI, the number of sinus follicular numbers AFC and other sex related hormones The purpose of this study was to establish a reference range of age specific anti Mullerian tube hormone and inhibin for normal women, and to explore the relationship between anti Muller's hormone and inhibin and other clinical indicators in healthy women. Design: to establish a reliable and reliable anti Mullerian tube hormone and inhibin. In the range of reference values, we carried out a cross-sectional study of multi centers across different regions for 3 years (December October 2011 -2014). 6 cities in Shenyang (North China), Foshan (Southern China), Chengdu (Huaxi), Zhengzhou, Yichang, and Wuhan (Hua Zhong) recruited 2055 20-55 year old women in the form of advertising and recruitment of volunteers. Sex, the age range spanned the whole childbearing age and the menopause. At the same time, we made strict inclusion criteria to ensure that the subjects included in the study met the requirements of the healthy population. After screening, 1590 cases were included in the standard of the experiment, accounting for 77.37%, and the AMH, inhibinB reference range of the included healthy people was made for the study object. The level of serum base AMH was detected by two kits (Beckman Gen II AMH assay and Ansh Labs AMH assay). The level of serum base was detected by Beckman Gen II AMH. Two AMH kits have good consistency, but the AMH detection value of the same sample is different, and the detection value of Beckman Gen II AMH assay is higher than that of Ansh Labs AMH assay. The two kits have confirmed that the AMH level of serum anti Mullerian tube hormone is gradually decreasing with age. The detection results of the box show that the AMH descending trend can be best fitted to the detection results of the.Ansh Labs AMH assay kits by the two order equation log (AMH) = (-1.970+0.296*Age-0.006*Age2), but the best fitting equation of AMH and Age is log (AMH) =. We divide the study population into 6 subgroups according to age: 25,25-30,30-33,33-37,37-40,40-55 years old; the detection results of Beckman Gen II AMH assay kit showed that the median of AMH in each age group was the 5th-95th percentile range of 6.23,5.65,4.55,3.74,2.78 and 1.09 ng/ml. (that is, the range of reference values determined by this study) was 2.06-12.66,1.77-13.83,1.48-11.45,0.87-9.76,0.56-9.49, and 0.08. The detection results of -5.70 ng/ml.Ansh Labs AMH assay kit showed that the median of AMH in each age group was: the 5th-95th percentile range of 5.55,4.80,3.76,3.42,2.44 and 0.77ng/ml. groups was: 1.43-13.14,1.31-13.55,1.06-10.97,0.69-9.52,0.38-8.03,0.04-4.79 ng/ml.AMH level was positively related to the level of AFCs, MI and FSH were negatively correlated with E2, and the correlation between AMH and PRL became insignificant after controlling the mixed variables "age" and "BMI", while the correlation between AMH and other variables except PRL did not change the trend of.Inhibin B level with age and was more stable before 40 years of age, after 40 years of age. The decrease, T test and Wilcoxon test showed that there was a significant difference between 20-40 and 40-55 years old and two age groups. We divided the study group into 2 subgroups according to age, 20-40,40-55 years, and the Beckman Inhibin B assay kits showed that the median of Inhibin B in the two age group was 83.13 and 56.32 pg/ml:. The two 5th-95th percentile range is that 34.38-143.75,2.6-142.33pg/ml.Inhibin B is positively correlated with AMH (R=0.57, P0.001), and is positively correlated with AFC (R=0.34, P0.001), and is positively related to T (R=0.01, P=0.002). There is no significant correlation between Inhibin B and PRG and PRL. Conclusion: This study established a normal reference range of Chinese women's serum AMH and Inhibin B based on healthy people. It is beneficial for clinicians to better interpret and explain the clinical significance of this index. Background: AFC and serum FSH, LH, E2, T and other tests are the evaluation of ovarian function or diagnostic disease. The important index of disease is widely used in clinical practice. But today, the reference range for guiding clinical diagnosis is the common reference range (Universal ranges) rather than the age specific reference range (age-specific ranges). These indicators, such as AFC and reproductive related hormones, are closely related to age and vary with age. The accurate age specific reference range is more clinical diagnostic value than the common reference range. Objective: to establish the range of reference values of age specific AFC and serum FSH, LH, E2, T in normal women, and to explore the correlation of various clinical indicators in healthy women. Part (similar to the design of an anti Mullerian tube hormone, inhibin B reference range). Research results: AFC decreases with age, and its decrease with age can be best fitted to the following equation: AFC=9.0998+0.6128*Age-0.0159*Age2.FSH increases with age, and its age increases with the following equation to fit the best. FSH=12.7885-0.5031*Age+0.0101*Age2. other sex related hormones can also be fitted by the best equation for age. For example, LH=11.5678-0.4101*Age+0.0059*Age2, E2=85.6229-3.002*Age+0.0546*Age2, and T=33.1488+0.4427*Age-0.0176*Age2. are divided into 3 subgroups according to the age of the population: 20-30,30-40,40-55 years, respectively. The reference range of AFC, FSH, LH, E2 and T in all age groups: the median of AFC in each age group is 14,11,5, and the median of FSH in each age group is: 6.50,6.95,7.99 mIU/ml: in all age groups: the median level is: the median of each age group of 4.375,3.92,4.53, and the median of each age group. 31.54,26.56,18 pg/dl. we also found that AFC was negatively correlated with age, BMI and FSH levels, positive correlation with LH and T levels, LH positive, AFC, BMI, T. The range of age specific AFC and serum FSH, LH, E2, T reference values of normal women and the relationship between the indexes were determined in healthy women. Objective: to clarify the key factors of ovarian senescence related to the risk of cardiovascular disease in women. A total of 536 female volunteers were enrolled in the study. All the subjects were involved in the study. All the subjects received the elbow vein procoagulant 3-4m1 on the 1-5 day of the morning's breakfast and centrifugally obtained the upper serum. The serum levels of serum FSH, LH, E2, T and PRL were detected. The serum level of serum anti Mullerian tube hormone AMH was detected by enzyme linked immunosorbent assay (ELISA), and transvaginal ultrasound was used. At the same time, the number of 2-10mm follicles in the ovary on both sides of the ovary was detected at the same time, and the index of the risk of cardiovascular disease was detected, including four blood lipids (total cholesterol TC, total triglyceride TG, high density lipoprotein HDL-C, low density lipoprotein LDL-C) and the level of hypersensitive C reactive protein. Then, various indexes representing ovarian function and heart blood were analyzed. The correlation between the indicators of the risk of disease. Results: through the bivariate Pearson linear correlation analysis, AMH is negatively correlated with TC, TG, LDL-C; FSH is positively correlated with TC, TG, LDL-C; E2 and TC, TG are positively related; Through Logistic regression analysis, we can see that AMH and FSH can enter the regression equation with the total risk of cardiovascular disease as Y. Conclusion: female ovarian function is closely related to the risk of cardiovascular disease. Among the indexes related to ovarian senescence, AMH and AFC may be more advantageous in early warning of cardiovascular disease than FSH, LH, E2. AMH can be used as an indicator of the risk of cardiovascular disease. Purpose: to verify the correlation between anti Mullerian tube hormone (AMH) and menstruation and the incidence of cardiovascular diseases (including coronary heart disease and other cardiovascular diseases). Methods of study were collected from October 2013 to December 2015 in Tongji Hospital in cardiovascular medicine. The age range of coronary heart disease between 40-55 years old female patients, a total of 128 cases, as the 2 groups of cases: the same period collected for the symptoms of palpitation and chest pain, chest pain, chest pain and other symptoms hospitalized, but the coronary angiography can not be diagnosed with coronary heart disease, a total of 101 cases, set up as 1 groups in the same period of Tongji Hospital around a number of communities recruited, press recruitment, according to the hospital Age stratified matching, 243 healthy women were recruited as normal controls (set up as 0 groups). The questionnaire survey included general data on menstruation and pregnancy history, and the detection of serum hormone AMH, blood lipid and hypersensitivity C reactive protein. Use variance analysis to compare 2 groups of cases, cases 1 and control 0 at AMH levels, menstrual conditions The difference between the 3 groups included: ovarian function related indexes (gestation times, birth times) and CVD related risk factors (blood lipids, blood pressure, blood sugar) and other differences. The results of the study were that there were no differences in age between groups, that is, the baseline age of the three groups was similar and the three groups were comparable in the study index. Variance analysis found three The difference between groups: AMH level, menstrual condition (menopause or not), both in the 0 and 1 groups, the 0 group and the 2 groups, but there is no difference between the 1 and the 2 groups. There is no difference between the 3 groups. The systolic pressure is different between the 3 groups: the diastolic pressure is different from the 2 groups, but the 0 and 1 group, the 1 group and the 2 group, and the difference between the 0 group and the 2 group, and the difference between the 1 and the 2 groups; TC and HDL-C and LDL-C: were not different between the 3 groups, but there were differences between group TG:0 and group 1, but there was no difference between group 0 and 2, 1 and 2 groups, 0 group and 1 group, 0 group and 2 group, but there was no difference between group 1 and 2 group, and there was no difference between 0 groups. Conclusion: the ovarian function indexes such as AMH level, menstrual condition are closely related to coronary heart disease, and AMH level, menstruation The difference in situation appears before TC, HDL-C and LDL-C indicators change, and may have a more early predictive value.

【學(xué)位授予單位】：華中科技大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2016
【分類號(hào)】：R711.75

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