妇女健康倡议雌激素加孕激素临床试验：一项无法确定相关临床风险的研究。

Women's Health Initiative estrogen plus progestin clinical trial: a study that does not allow establishing relevant clinical risks.

作者信息

Aedo Sócrates, Cavada Gabriel, Blümel Juan E, Chedraui Peter, Fica Juan, Barriga Patricio, Brantes Sergio, Irribarra Cristina, Vallejo María, Campodónico Ítalo

机构信息

1Peñalolén, Campus Oriente, Department of Obstetrics and Gynecology, School of Medicine, University of Chile, Santiago de Chile, Chile 2Department of Public Health and Epidemiology, University of the Andes, Santiago de Chile, Chile 3Campus Sur, Department of Medicine, School of Medicine, University of Chile, Santiago de Chile, Chile 4Institute of Biomedicine, Research Area for Women's Health, Faculty of Medicine, Catholic University of Santiago de Guayaquil, Guayaquil, Ecuador 5Avansalud, Santiago de Chile, Chile 6School of Medicine, University Finis Terrae, Santiago de Chile, Chile 7Quilín Clinic, Clinical University Hospital Network Chile, School of Medicine, University of Chile, Santiago de Chile, Chile.

出版信息

Menopause. 2015 Dec;22(12):1317-22. doi: 10.1097/GME.0000000000000472.

DOI:10.1097/GME.0000000000000472

PMID:25968833

Abstract

OBJECTIVE

This study aims to determine time differences (differences in restricted mean survival times [RMSTs]) in the onset of invasive breast cancer, coronary heart disease, stroke, pulmonary embolism, colorectal cancer, and hip fracture between the placebo group and the conjugated equine estrogens 0.625 mg plus medroxyprogesterone acetate 2.5 mg group of the Women's Health Initiative (WHI) trial based on survival curves of the original report and to provide adequate interpretation of the clinical effects of a given intervention.

METHODS

Distribution of survival function was obtained from cumulative hazard plots of the WHI report; Monte Carlo simulation was performed to obtain censored observations for each outcome, in which assumptions of the Cox model were evaluated once corresponding hazard ratios had been estimated. Using estimation methods such as numerical integration, pseudovalues, and flexible parametric modeling, we determined differences in RMSTs for each outcome.

RESULTS

Obtained cumulative hazard plots, hazard ratios, and outcome rates from the simulated model did not show differences in relation to the original WHI report. The differences in RMST between placebo and conjugated equine estrogens 0.625 mg plus medroxyprogesterone acetate 2.5 mg (in flexible parametric modeling) were 1.17 days (95% CI, -2.25 to 4.59) for invasive breast cancer, 7.50 days (95% CI, 2.90 to 12.11) for coronary heart disease, 2.75 days (95% CI, -0.84 to 6.34) for stroke, 4.23 days (95% CI, 1.82 to 6.64) for pulmonary embolism, -2.73 days (95% CI, -5.32 to -0.13) for colorectal cancer, and -2.77 days (95% CI, -5.44 to -0.1) for hip fracture.

CONCLUSIONS

The differences in RMST for the outcomes of the WHI study are too small to establish clinical risks related to hormone therapy use.

摘要

目的

本研究旨在根据原始报告的生存曲线，确定妇女健康倡议（WHI）试验中安慰剂组与结合马雌激素0.625毫克加醋酸甲羟孕酮2.5毫克组之间，浸润性乳腺癌、冠心病、中风、肺栓塞、结直肠癌和髋部骨折发病的时间差异（受限平均生存时间[RMSTs]差异），并对特定干预措施的临床效果作出充分解读。

方法

生存函数分布取自WHI报告的累积风险图；进行蒙特卡罗模拟以获取每个结局的删失观测值，在估计出相应风险比后评估Cox模型的假设。使用数值积分、伪值和灵活参数建模等估计方法，我们确定了每个结局的RMST差异。

结果

从模拟模型获得的累积风险图、风险比和结局发生率与原始WHI报告相比未显示出差异。安慰剂组与结合马雌激素0.625毫克加醋酸甲羟孕酮2.5毫克组之间（灵活参数建模）的RMST差异，浸润性乳腺癌为1.17天（95%CI，-2.25至4.59），冠心病为7.50天（95%CI，2.90至12.11），中风为2.75天（95%CI，-0.84至6.34），肺栓塞为4.23天（95%CI，1.82至6.64），结直肠癌为-2.73天（95%CI，-5.32至-0.13），髋部骨折为-2.77天（95%CI，-5.44至-0.1）。