Rossouw Jacques E, Prentice Ross L, Manson JoAnn E, Wu Lieling, Barad David, Barnabei Vanessa M, Ko Marcia, LaCroix Andrea Z, Margolis Karen L, Stefanick Marcia L
Women's Health Initiative Branch, National Heart, Lung, and Blood Institute, Bethesda, Md 20892, USA.
JAMA. 2007 Apr 4;297(13):1465-77. doi: 10.1001/jama.297.13.1465.
The timing of initiation of hormone therapy may influence its effect on cardiovascular disease.
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.
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.
In the combined trials, there were 396 cases of CHD and 327 cases of stroke in the hormone therapy group vs 370 [corrected] 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).
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.
clinicaltrials.gov Identifier: NCT00000611.
激素治疗开始的时机可能会影响其对心血管疾病的作用。
探讨激素治疗对心血管疾病风险的影响是否因年龄或绝经开始后的年限而异。
设计、地点和参与者：对女性健康倡议（WHI）激素治疗随机对照试验进行二次分析，其中10739名接受子宫切除术的绝经后女性被随机分配至结合马雌激素（CEE）组或安慰剂组，16608名未接受子宫切除术的绝经后女性被随机分配至CEE加醋酸甲羟孕酮（CEE+MPA）组或安慰剂组。1993年9月至1998年10月期间，从美国40个临床中心招募了年龄在50至79岁的女性参与该研究。
在合并试验中，对激素治疗对冠心病（CHD）和中风的影响在年龄类别和绝经后年限方面进行趋势的统计检验。
在合并试验中，激素治疗组有396例冠心病病例和327例中风病例，而安慰剂组有370[校正后]例冠心病病例和239例中风病例。对于绝经开始后不到10年的女性，冠心病的风险比（HR）为0.76（95%置信区间[CI]，0.
