本文關(guān)鍵詞： 窗口 結(jié)合 雌激素 不同 激素 聯(lián)合 應(yīng)用 更年期 綜合征 治療 研究　出處：《北京協(xié)和醫(yī)學(xué)院》2017年博士論文　論文類型：學(xué)位論文

【摘要】：一、研究背景及目的絕經(jīng)是婦女生命發(fā)展過(guò)程中的自然生理現(xiàn)象,在絕經(jīng)前后的一段時(shí)間內(nèi),由于卵巢功能減退,雌、孕激素水平下降,婦女會(huì)出現(xiàn)以植物神經(jīng)功能紊亂為主,伴有器官功能減退,神經(jīng)心理等癥狀的癥候群,稱為更年期綜合征,多發(fā)生于45-55歲的婦女。絕經(jīng)激素治療(Menopausal Hormone Therapy,MHT)對(duì)緩解絕經(jīng)相關(guān)癥狀,預(yù)防骨質(zhì)疏松,減輕老年性泌尿生殖道萎縮,改善性功能,提高婦女的生活質(zhì)量的益處已被大量研究證據(jù)肯定。但是關(guān)于MHT對(duì)心血管疾病和乳腺癌的風(fēng)險(xiǎn)一直存在爭(zhēng)議。前沿的國(guó)際與國(guó)內(nèi)關(guān)于MHT的指南均推薦在絕經(jīng)10年內(nèi)或60歲之前開(kāi)始治療,選用最低有效劑量,對(duì)于雌孕激素的種類盡量選擇天然的。因此,我們希望研究標(biāo)準(zhǔn)劑量及低劑量的結(jié)合雌激素與天然孕酮或地屈孕酮聯(lián)用對(duì)于更年期管理的療效與安全性,從不同方案的MHT對(duì)癥狀緩解、血脂譜、血糖、骨密度、乳腺、子宮內(nèi)膜等的影響為觀察點(diǎn),試圖找到最適合中國(guó)女性的絕經(jīng)激素治療方案。二、研究方法研究采用單中心、隨機(jī)、開(kāi)放、平行對(duì)照設(shè)計(jì),選取40～60歲停經(jīng)6個(gè)月～≤5年的健康絕經(jīng)期婦女123例隨機(jī)分配到三個(gè)治療組:A組(CEE 0.3mg+P4100mg)、B 組(CEE 0.625mg+P4 100mg)、C 組(CEE 0.625mg+DHG1Omg),均為連續(xù)序貫方案,即28天為一個(gè)周期,每天口服雌激素,在周期最后12天加用孕激素,共用12個(gè)周期;采集病史及人口統(tǒng)計(jì)學(xué)資料,治療期間進(jìn)行常規(guī)體格檢查,進(jìn)行改良Kuppermann評(píng)分,抽血查血脂相關(guān)指標(biāo)如TC、TG、HDL-C、LDL-C、ApoA、ApoB以及血糖相關(guān)指標(biāo)如空腹血糖、糖化血紅蛋白、空腹胰島素,進(jìn)行性激素、乳腺鉬靶、骨密度等相關(guān)檢查,比較分析治療前后癥狀、心血管疾病及乳腺癌、骨質(zhì)疏松的危險(xiǎn)因素變化情況以及陰道流血的模式。三、研究結(jié)果完成試驗(yàn)者107例,占隨機(jī)入組受試者總數(shù)的87.0%,三組用藥前各指標(biāo)均無(wú)統(tǒng)計(jì)學(xué)差異。1、治療3個(gè)周期后改良Kupperman評(píng)分均明顯下降,其后的6個(gè)周期分值趨于平穩(wěn)。治療3個(gè)周期后,3組的完全緩解率、顯效率差異均無(wú)統(tǒng)計(jì)學(xué)意義,但 B 組有效率(89.2%)顯著高于 A 組(60%,P =0.024)和 C 組(61.9%,P =0.035),A組與C組比較,差異無(wú)統(tǒng)計(jì)學(xué)意義。治療結(jié)束后,3組的完全緩解率、顯效率、有效率差異均無(wú)統(tǒng)計(jì)學(xué)意義。2、標(biāo)準(zhǔn)劑量雌激素的兩組B組與C組在治療12個(gè)周期后HDL-C均顯著性升高,LDL-C水平、空腹血糖、糖化血紅蛋白均顯著性下降,A組與治療前比并無(wú)顯著性差異。三組的TC水平、HOMA-IR均無(wú)顯著性變化。C組的TG水平在治療后顯著升高了 33.1%(P = 0.026),且A、C兩組在治療后TG的變化水平有統(tǒng)計(jì)學(xué)差異(P0.001)。盡管B組的TG水平在治療后升高了 30.0%,但治療前后差異無(wú)統(tǒng)計(jì)學(xué)意義(P = 0.140),B、C兩組在治療后的變化也無(wú)統(tǒng)計(jì)學(xué)差異(P = 0.342)。3、對(duì)3組治療前后腰椎(L2-L4)、雙側(cè)股骨頸及雙側(cè)全股骨T值進(jìn)行前后比較,治療前3組各部位骨密度T值無(wú)顯著性差異,治療后3組組間T值均值亦無(wú)顯著性差異。4、A、B兩添加天然孕酮組,出血率明顯隨著雌激素劑量的增加而增加(B組44.09%;A組21.60%)。兩雌激素劑量相同組B、C組,添加地屈孕酮組者明顯高于添加天然孕酮組(C組80.21%;B組44.09%)。對(duì)標(biāo)準(zhǔn)劑量雌激素的B、C兩組,治療后內(nèi)膜厚度均顯著性增加。對(duì)標(biāo)準(zhǔn)劑量雌激素的兩組,加用天然孕酮組平均在加孕酮第8天開(kāi)始出血,加用地屈孕酮組平均在停地屈孕酮第3天開(kāi)始出血。出血時(shí)間中位數(shù)均為5天。5、A、B、C三個(gè)組發(fā)生乳脹的周期分別占30.2%,47.5%,87.9%,各組間差異均有顯著性。隨著時(shí)間的推移,每組乳脹的發(fā)生率也呈逐漸減少的趨勢(shì)。三組的乳腺密度在治療前后并無(wú)顯著性差異。四、研究結(jié)論:低劑量MHT與標(biāo)準(zhǔn)劑量MHT均能有效緩更年期癥狀,預(yù)防骨丟失。但標(biāo)準(zhǔn)劑量MHT對(duì)血脂和血糖的影響效果優(yōu)于低劑量MHT,低劑量MHT乳脹的發(fā)生率低。天然孕酮可能有拮抗雌激素升高甘油三酯的作用,在對(duì)代謝和乳脹方面,天然孕酮優(yōu)于地屈孕酮。天然孕酮100mg每天的劑量較地屈孕酮1Omg每天的劑量可能不足以支持內(nèi)膜。
[Abstract]:A research background and purpose, menopause is a natural physiological phenomenon during the development of women's life, in a period of time before and after menopause, because of ovarian function, estrogen, progesterone levels decline, women will appear to plant nerve function disorder, associated with organ dysfunction and neuropsychological symptoms of climacteric syndrome, called the syndrome occurred in a 45-55 year old woman. Postmenopausal hormone therapy (Menopausal Hormone, Therapy, MHT) to relieve menopausal symptoms, prevent osteoporosis, reduce senile urogenital atrophy, improve sexual function, improve the quality of life for the benefit of women has been a lot of research evidence certainly. But about MHT on cardiovascular diseases and the risk of breast cancer has been controversial. The forefront of domestic and international about MHT guidelines recommend starting treatment within 10 years after menopause before or at the age of 60, the lowest effective dose for Type of estrogen and progesterone to select natural. Therefore, we hope that the combination of standard dose and low dose of estrogen and progesterone or natural dydrogesterone combined with the efficacy and safety of menopause management, from different schemes of MHT remission of symptoms, blood lipids, blood glucose, bone density, breast, endometrial etc. for the observation point, trying to find the most appropriate treatment in postmenopausal hormone Chinese women. Two research methods using single center, randomized, open, parallel group design, select 40~60 years of menopause for 6 months to 5 years or less healthy menopause women 123 cases were randomly assigned to three treatment groups: group A (CEE 0.3mg+P4100mg), group B (CEE 0.625mg+P4 100mg), C group (CEE, 0.625mg+DHG1Omg) are continuous sequential scheme, that is for a period of 28 days, daily oral estrogen, in the last 12 days period with progesterone, used 12 cycles; and collecting history Demographic data, physical examination of the treatment period, the modified Kuppermann score, blood lipid related indicators such as TC, TG, HDL-C, LDL-C, ApoA, ApoB and blood glucose related indicators such as fasting blood glucose, glycosylated hemoglobin, fasting insulin, sex hormone, mammography, bone density examination, comparative analysis the symptoms before and after treatment, cardiovascular disease and breast cancer, the changes of risk factors of osteoporosis and vaginal bleeding. Three, 107 patients completed the trial results, the total subjects were randomized into 87% groups before treatment, three indexes had no significant difference in the.1, after 3 cycles of treatment improved Kupperman score 6 cycles were significantly decreased, followed by score stabilized. After 3 cycles of treatment, complete remission rate was 3, the effective rate had no significant difference, but the effective rate of group B (89.2%) was significantly higher than that of group A (60%, P =0.024)鍜，

本文編號(hào)：1469810