Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause
Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause
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DOI：
10.1001/jama.297.13.1465
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发表时间：
2007-04-04
影响因子：
120.7
通讯作者：
Stefanick, Marcia L.
中科院分区：
文献类型：
--
作者：
Rossouw, Jacques E.;Prentice, Ross L.;Stefanick, Marcia L.
背景：激素治疗的起始时间可能影响其对心血管疾病的疗效。目的探讨激素治疗对心血管疾病风险的影响是否随绝经年龄或绝经年限的不同而不同。对妇女健康倡议（WHI）激素治疗随机对照试验的二次分析，其中10739名接受子宫切除术的绝经后妇女随机分为结合马雌激素（CEE）或安慰剂组，16608名未接受子宫切除术的绝经后妇女随机分为CEE加醋酸甲孕酮（CEE + MPA）或安慰剂组。1993年9月至1998年10月，研究人员从美国40个临床中心招募了年龄在50岁至79岁之间的女性。主要结局指标联合试验中激素治疗对冠心病（CHD）和卒中的影响趋势的统计检验。结果在联合试验中，激素治疗组有396例冠心病和327例卒中，而安慰剂组有379例冠心病和239例卒中。对于绝经时间小于10年的女性，冠心病的危险比（HR）为0.76(95%可信区间[CI]， 0.50-1.16)；10 - 19岁，1.10 (95% CI, 0.84-1.45)；20年或更长时间，1.28 (95% CI, 1.03-1.58) (P为趋势=。02)。绝经10年内女性患冠心病的绝对超额风险估计为- 6 / 10000人年；对于绝经后10至19年的妇女，每1万人中有4人；对于绝经20年以上的女性，每1万人中有17人。在50 - 59岁年龄组，冠心病的HR为0.93 (95% CI, 0.65-1.33)，绝对超额风险为- 2 / 10000人年；60 - 69岁，0.98 （95% CI, 0.79-1.21）和-1 / 10000人年；70 ~ 79岁，1.26 （95% CI, 1.00 ~ 1.59）和19 / 10000人年（P为趋势=）。16)。激素治疗增加了卒中的风险（HR, 1.32; 95% CI, 1.12-1.56）。绝经后的风险不因年龄或时间的不同而有显著差异。激素治疗对总死亡率的影响在年轻女性中比老年女性更有利（50-59岁的HR为0.70,60-69岁的HR为1.05,70-79岁的HR为1.14），P为趋势=。06)。结论临近绝经期开始激素治疗的妇女冠心病风险降低，而离绝经期较远的妇女冠心病风险增加，但这一趋势检验不符合我们的统计学显著性标准。在总死亡率方面也观察到类似的不显著趋势，但中风的风险升高与绝经后的时间无关。这些数据应考虑到短期治疗更年期症状。
Context The timing of initiation of hormone therapy may influence its effect on cardiovascular disease.Objective To explore whether the effects of hormone therapy on risk of cardiovascular disease vary by age or years since menopause began.Design, Setting, and Participants Secondary analysis of the Women's Health Initiative (WHI) randomized controlled trials of hormone therapy in which 10 739 postmenopausal women who had undergone a hysterectomy were randomized to conjugated equine estrogens (CEE) or placebo and 16 608 postmenopausal women who had not had a hysterectomy were randomized to CEE plus medroxyprogesterone acetate ( CEE + MPA) or placebo. Women aged 50 to 79 years were recruited to the study from 40 US clinical centers between September 1993 and October 1998.Main Outcome Measures Statistical test for trend of the effect of hormone therapy on coronary heart disease (CHD) and stroke across categories of age and years since menopause in the combined trials.Results In the combined trials, there were 396 cases of CHD and 327 cases of stroke in the hormone therapy group vs 379 cases of CHD and 239 cases of stroke in the placebo group. For women with less than 10 years since menopause began, the hazard ratio (HR) for CHD was 0.76 (95% confidence interval [CI], 0.50-1.16); 10 to 19 years, 1.10 ( 95% CI, 0.84-1.45); and 20 or more years, 1.28 ( 95% CI, 1.03-1.58) ( P for trend=. 02). The estimated absolute excess risk for CHD for women within 10 years of menopause was - 6 per 10 000 person-years; for women 10 to 19 years since menopause began, 4 per 10 000 person-years; and for women 20 or more years from menopause onset, 17 per 10 000 person-years. For the age group of 50 to 59 years, the HR for CHD was 0.93 ( 95% CI, 0.65-1.33) and the absolute excess risk was - 2 per 10 000 person-years; 60 to 69 years, 0.98 ( 95% CI, 0.79-1.21) and - 1 per 10 000 person-years; and 70 to 79 years, 1.26 ( 95% CI, 1.00-1.59) and 19 per 10 000 person-years (P for trend=. 16). Hormone therapy increased the risk of stroke ( HR, 1.32; 95% CI, 1.12-1.56). Risk did not vary significantly by age or time since menopause. There was a nonsignificant tendency for the effects of hormone therapy on total mortality to be more favorable in younger than older women ( HR of 0.70 for 50-59 years; 1.05 for 60-69 years, and 1.14 for 70-79 years; P for trend=. 06).Conclusions Women who initiated hormone therapy closer to menopause tended to have reduced CHD risk compared with the increase in CHD risk among women more distant from menopause, but this trend test did not meet our criterion for statistical significance. A similar nonsignificant trend was observed for total mortality but the risk of stroke was elevated regardless of years since menopause. These data should be considered in regard to the short-term treatment of menopausal symptoms.