窗口期结合雌激素与不同孕激素联合应用对更年期综合征的治疗研究

发布时间：2018-01-28 04:48

  本文关键词： 窗口 结合 雌激素 不同 激素 联合 应用 更年期 综合征 治疗 研究　出处：《北京协和医学院》2017年博士论文　论文类型：学位论文

【摘要】：一、研究背景及目的绝经是妇女生命发展过程中的自然生理现象,在绝经前后的一段时间内,由于卵巢功能减退,雌、孕激素水平下降,妇女会出现以植物神经功能紊乱为主,伴有器官功能减退,神经心理等症状的症候群,称为更年期综合征,多发生于45-55岁的妇女。绝经激素治疗(Menopausal Hormone Therapy,MHT)对缓解绝经相关症状,预防骨质疏松,减轻老年性泌尿生殖道萎缩,改善性功能,提高妇女的生活质量的益处已被大量研究证据肯定。但是关于MHT对心血管疾病和乳腺癌的风险一直存在争议。前沿的国际与国内关于MHT的指南均推荐在绝经10年内或60岁之前开始治疗,选用最低有效剂量,对于雌孕激素的种类尽量选择天然的。因此,我们希望研究标准剂量及低剂量的结合雌激素与天然孕酮或地屈孕酮联用对于更年期管理的疗效与安全性,从不同方案的MHT对症状缓解、血脂谱、血糖、骨密度、乳腺、子宫内膜等的影响为观察点,试图找到最适合中国女性的绝经激素治疗方案。二、研究方法研究采用单中心、随机、开放、平行对照设计,选取40～60岁停经6个月～≤5年的健康绝经期妇女123例随机分配到三个治疗组:A组(CEE 0.3mg+P4100mg)、B 组(CEE 0.625mg+P4 100mg)、C 组(CEE 0.625mg+DHG1Omg),均为连续序贯方案,即28天为一个周期,每天口服雌激素,在周期最后12天加用孕激素,共用12个周期;采集病史及人口统计学资料,治疗期间进行常规体格检查,进行改良Kuppermann评分,抽血查血脂相关指标如TC、TG、HDL-C、LDL-C、ApoA、ApoB以及血糖相关指标如空腹血糖、糖化血红蛋白、空腹胰岛素,进行性激素、乳腺钼靶、骨密度等相关检查,比较分析治疗前后症状、心血管疾病及乳腺癌、骨质疏松的危险因素变化情况以及阴道流血的模式。三、研究结果完成试验者107例,占随机入组受试者总数的87.0%,三组用药前各指标均无统计学差异。1、治疗3个周期后改良Kupperman评分均明显下降,其后的6个周期分值趋于平稳。治疗3个周期后,3组的完全缓解率、显效率差异均无统计学意义,但 B 组有效率(89.2%)显著高于 A 组(60%,P =0.024)和 C 组(61.9%,P =0.035),A组与C组比较,差异无统计学意义。治疗结束后,3组的完全缓解率、显效率、有效率差异均无统计学意义。2、标准剂量雌激素的两组B组与C组在治疗12个周期后HDL-C均显著性升高,LDL-C水平、空腹血糖、糖化血红蛋白均显著性下降,A组与治疗前比并无显著性差异。三组的TC水平、HOMA-IR均无显著性变化。C组的TG水平在治疗后显著升高了 33.1%(P = 0.026),且A、C两组在治疗后TG的变化水平有统计学差异(P0.001)。尽管B组的TG水平在治疗后升高了 30.0%,但治疗前后差异无统计学意义(P = 0.140),B、C两组在治疗后的变化也无统计学差异(P = 0.342)。3、对3组治疗前后腰椎(L2-L4)、双侧股骨颈及双侧全股骨T值进行前后比较,治疗前3组各部位骨密度T值无显著性差异,治疗后3组组间T值均值亦无显著性差异。4、A、B两添加天然孕酮组,出血率明显随着雌激素剂量的增加而增加(B组44.09%;A组21.60%)。两雌激素剂量相同组B、C组,添加地屈孕酮组者明显高于添加天然孕酮组(C组80.21%;B组44.09%)。对标准剂量雌激素的B、C两组,治疗后内膜厚度均显著性增加。对标准剂量雌激素的两组,加用天然孕酮组平均在加孕酮第8天开始出血,加用地屈孕酮组平均在停地屈孕酮第3天开始出血。出血时间中位数均为5天。5、A、B、C三个组发生乳胀的周期分别占30.2%,47.5%,87.9%,各组间差异均有显著性。随着时间的推移,每组乳胀的发生率也呈逐渐减少的趋势。三组的乳腺密度在治疗前后并无显著性差异。四、研究结论:低剂量MHT与标准剂量MHT均能有效缓更年期症状,预防骨丢失。但标准剂量MHT对血脂和血糖的影响效果优于低剂量MHT,低剂量MHT乳胀的发生率低。天然孕酮可能有拮抗雌激素升高甘油三酯的作用,在对代谢和乳胀方面,天然孕酮优于地屈孕酮。天然孕酮100mg每天的剂量较地屈孕酮1Omg每天的剂量可能不足以支持内膜。
[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，

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