Prescrire Int. 2003 Apr;12(64):65-9.
(1) The WHI study was published in 2002: a randomised double-blind placebo-controlled clinical trial in more than 16 000 women with an average age of 63 years at enrollment. The paper reports data on the long-term adverse effects of combined equine estrogen-progestin hormone replacement therapy, taken for 5 years. (2) On average, a yearly excess of 19 severe adverse events per 10 000 women occurred in the estrogen-progestin group. Relative to the placebo group, there were an extra 8 pulmonary embolisms, 7 coronary events, 8 strokes and 8 cases of invasive breast cancer. In contrast, there were 6 fewer colorectal cancers and 5 fewer hip fractures in the active treatment group. (3) The differences in the frequency of coronary events and venous thromboembolism emerged after the first year of treatment, while the curves for stroke and breast cancer diverged after the second and fifth years, respectively. (4) The overall mortality rate did not differ between the two groups. (5) A placebo-controlled trial of the same hormone combination (HERS trial), given for 4.1 years as secondary prophylaxis against coronary heart disease was published in 1998. The drug was ineffective during the trial, and during unblinded post-trial follow-up of 2 321 women for an average of 2.7 years (HERS II study). (6) The estrogen-progestin combination used in these trials did not reduce the risk of coronary heart disease (in primary or secondary prophylaxis) or the risk of stroke. On the contrary, both risks increased. (7) The increased incidence of deep venous thrombosis and/or pulmonary embolism associated with estrogen-progestin replacement therapy was confirmed in these trials, even among women with no relevant history. (8) The WHI trial also confirmed the increased risk of breast cancer in women on hormone replacement therapy, but did not study its impact on outcome or mortality. (9) The WHI trial confirmed the beneficial impact of estrogen-progestin combination therapy on the risk of osteoporotic fracture. An average of 5 hip fractures were avoided each year per 10 000 women treated (10 versus 15 observed cases per 10 000 women per year), together with 6 symptomatic vertebral fractures (9 versus 15 cases) and 44 osteoporotic fractures (147 versus 191 cases). It is not known whether the benefit observed at the end of the trial persisted after the end of treatment. (10) In practice, the decision to prescribe hormone replacement therapy, and the optimal duration of treatment, must be weighed up according to each individual's risk factors. And the decision to treat or not to treat must be regularly re-assessed. Women must be informed of the potential risks and benefits, and must be monitored. They should also be advised not to use less well assessed treatments such as phytoestrogens, DHEA and tibolone. (11) Health authorities, especially in Europe, must organise comparative trials to assess the benefits and risks of other hormone combinations used by perimenopausal and postmenopausal women.
(1) 妇女健康倡议（WHI）研究于2002年发表：这是一项针对超过16000名平均年龄63岁（入组时）女性的随机双盲安慰剂对照临床试验。该论文报告了联合使用马雌激素 - 孕激素激素替代疗法5年的长期不良反应数据。(2) 平均而言，雌激素 - 孕激素组每10000名女性每年有19例额外的严重不良事件发生。相对于安慰剂组，有额外8例肺栓塞、7例冠心病事件、8例中风和8例浸润性乳腺癌。相比之下，活性治疗组的结直肠癌减少6例，髋部骨折减少5例。(3) 冠心病事件和静脉血栓栓塞频率的差异在治疗第一年之后出现，而中风和乳腺癌的曲线分别在第二年和第五年后出现分歧。(4)两组的总死亡率没有差异。(5) 1998年发表了一项针对相同激素组合的安慰剂对照试验（HERS试验），作为冠心病二级预防给予4.1年。该药物在试验期间无效，并且在对2321名女性进行平均2.7年的非盲法试验后随访期间（HERS II研究）也是如此。(6) 这些试验中使用的雌激素 - 孕激素组合并未降低冠心病（无论是一级还是二级预防）的风险或中风风险。相反，这两种风险都增加了。(7) 这些试验证实了雌激素 - 孕激素替代疗法相关的深静脉血栓形成和/或肺栓塞发生率增加，即使在没有相关病史的女性中也是如此。(8) WHI试验还证实了接受激素替代疗法的女性患乳腺癌风险增加，但未研究其对结局或死亡率的影响。(9) WHI试验证实了雌激素 - 孕激素联合疗法对骨质疏松性骨折风险的有益影响。每10000名接受治疗的女性每年平均避免5例髋部骨折（每10000名女性每年观察到10例与15例），以及6例有症状的椎体骨折（9例与15例）和44例骨质疏松性骨折（147例与191例）。尚不清楚试验结束时观察到的益处治疗结束后是否持续存在。(10) 在实践中，开激素替代疗法的决定以及最佳治疗持续时间，必须根据每个人的风险因素进行权衡。并且治疗与否的决定必须定期重新评估。必须告知女性潜在的风险和益处，并且必须对她们进行监测。还应建议她们不要使用评估不太充分的治疗方法，如植物雌激素、脱氢表雄酮和替勃龙。(11) 卫生当局，尤其是在欧洲，必须组织对比试验，以评估围绝经期和绝经后女性使用的其他激素组合的益处和风险。
