孕激素治疗、血管内皮功能与心血管危险因素：健康早绝经后妇女 3 个月随机、安慰剂对照试验。
Progesterone therapy, endothelial function and cardiovascular risk factors: a 3-month randomized, placebo-controlled trial in healthy early postmenopausal women.
机构信息
Centre for Menstrual Cycle and Ovulation Research (CeMCOR), University of British Columbia, Vancouver, British Columbia, Canada ; Division of Endocrinology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada ; School of Population and Public Health, University of British Columbia and Vancouver Coastal Health Research Institute, Vancouver, British Columbia, Canada.
Centre for Menstrual Cycle and Ovulation Research (CeMCOR), University of British Columbia, Vancouver, British Columbia, Canada ; Division of Endocrinology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
出版信息
PLoS One. 2014 Jan 21;9(1):e84698. doi: 10.1371/journal.pone.0084698. eCollection 2014.
BACKGROUND
Progesterone is effective treatment for hot flushes/night sweats. The cardiovascular effects of progesterone therapy are unknown but evidence suggests that premenopausal normal estradiol with also normal progesterone levels may provide later cardiovascular protection. We compared the effects of progesterone to placebo on endothelial function, weight, blood pressure, metabolism, lipids, inflammation and coagulation.
METHODS AND RESULTS
We conducted a randomized, double-blind, 3-month placebo-controlled trial of progesterone (300 mg daily) among 133 healthy postmenopausal women in Vancouver, Canada from 2003-2009. Endothelial function by venous occlusion plethysmography was a planned primary outcome. Enrolled women were 1-11 y since last menstruation, not using hormones (for >6 months), non-smoking, without diabetes, hypertension, heart disease or their medications. Randomized (1∶1) women (55 ± 4 years, body mass index 25 ± 3) initially had normal blood pressure, fasting lipid, glucose and electrocardiogram results. Endothelial function (% forearm blood flow above saline) was not changed with progesterone (487 ± 189%, n = 18) compared with placebo (408 ± 278%, n = 16) (95% CI diff [-74 to 232], P = 0.30). Progesterone (n = 65) and placebo (n = 47) groups had similar changes in systolic and diastolic blood pressure, resting heart rate, weight, body mass index, waist circumference, total cholesterol, low-density lipoprotein cholesterol and triglyceride levels. High-density lipoprotein was lower (-0.14 mmol/L, P = 0.001) on progesterone compared with placebo. Fasting glucose, hs-C-reactive protein, albumin and D-dimer changes were all comparable to placebo. Framingham General Cardiovascular Risk Profile scores were initially low and remained low with progesterone therapy and not statistically different from placebo.
CONCLUSIONS
Results indicate that progesterone has short-term cardiovascular safety. Endothelial function, weight, blood pressure, waist circumference, inflammation and coagulation were unchanged as were lipids except for HDL-C. The statistically significant decrease in HDL-C levels was not clinically important (based on lack of Cardiovascular Risk Profile change).
TRIAL REGISTRATION
ClinicalTrials.gov NCT00152438.
背景
孕激素是治疗热潮/盗汗的有效方法。孕激素治疗的心血管影响尚不清楚，但有证据表明，绝经前正常雌二醇和正常孕激素水平可能提供后期心血管保护。我们比较了孕激素和安慰剂对内皮功能、体重、血压、代谢、血脂、炎症和凝血的影响。
方法和结果
我们于 2003 年至 2009 年在加拿大温哥华进行了一项随机、双盲、3 个月安慰剂对照的孕激素（每日 300 毫克）治疗 133 例健康绝经后妇女的试验。通过静脉闭塞体积描记法评估内皮功能是一项预设的主要结局。入组的妇女绝经后 1-11 年，>6 个月未使用激素，不吸烟，无糖尿病、高血压、心脏病或其药物治疗。随机（1∶1）的妇女（55 ± 4 岁，体重指数 25 ± 3）最初血压、空腹血脂、血糖和心电图结果正常。与安慰剂（408 ± 278%，n = 16）相比，孕激素（487 ± 189%，n = 18）并未改变内皮功能（前臂血流百分比高于盐水）（95%CI 差值[-74 至 232]，P = 0.30）。孕激素组（n = 65）和安慰剂组（n = 47）的收缩压和舒张压、静息心率、体重、体重指数、腰围、总胆固醇、低密度脂蛋白胆固醇和甘油三酯水平均有相似变化。与安慰剂相比，孕激素组的高密度脂蛋白水平较低（-0.14mmol/L，P = 0.001）。空腹血糖、高敏 C 反应蛋白、白蛋白和 D-二聚体的变化与安慰剂相似。弗雷明汉心血管总体风险评分最初较低，且用孕激素治疗后仍较低，与安慰剂无统计学差异。
结论
结果表明孕激素具有短期心血管安全性。内皮功能、体重、血压、腰围、炎症和凝血均无变化，除高密度脂蛋白胆固醇外，血脂也无变化。高密度脂蛋白胆固醇水平的统计学显著下降无临床意义（基于心血管风险评分无变化）。
试验注册
ClinicalTrials.gov NCT00152438。
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