据3月5日《美国医学协会期刊》（JAMA）上的项随访研究指出，作为某临床试验的一部分，妇女在停止服用雌激素加孕酮的激素疗法之后，她们与安慰剂组的妇女相比较，前者罹患癌症的风险可能会增加。这两组人的发生心血管疾病及骨折的风险相似，但是接受激素疗法妇女的总体综合风险指数较高，这在许多包括死亡为组合终点的利弊平衡关系上得到反映。
妇女健康创制案（WHI）的雌激素加孕酮的试验中包括1万6608名绝经后妇女，这些妇女被评估接受共轭雌激素 (CEE) 加甲孕酮 (MPA)的治疗是否能够预防心脏病和髋骨骨折，及其罹患乳腺癌的风险是否会增加。该试验在2002年停止，因为当时的数据显示，该疗法会增加罹患乳腺癌的风险及该疗法没有显示大体上的健康裨益。进一步的分析显示，CEE 加 MPA治疗组的妇女具有较高的罹患心血管疾病（CVD）、冠心病（CHD）、中风及静脉血栓栓塞性疾病的风险，而其罹患骨折与结肠直肠癌的风险则较低。
美国北卡罗来纳大学的Gerardo Heiss及其同僚对1万5730位参加试验并在停止激素疗法之后于2002年7月到2005年3月间有随访的受试者的风险与裨益进行了检验。
研究人员发现，那些停止激素疗法（CEE 加 MPA）的随访受试者组的“所有癌症”后果的按年度计算的事件发生率比安慰剂组的受试者要高（每年1.56% [n=281] 相对于每年1.26% [n=218]）。这反映了CEE 加 MPA组具有较高的罹患侵润性乳腺癌及其它癌症的风险，这两组的结肠直肠癌的发病率没有显著的差别，但子宫内膜癌的发病率在CEE 加 MPA组则较低。尽管在随访期间，这些受试者罹患乳腺癌的风险仍然处于增高的状态，但这一风险比在试验阶段即将结束前要低。
作者在文章中写道：“对随机分配的CEE 加 MPA 组相对于安慰剂组的延迟与持续性利弊的分析为绝经后妇女的最佳应用CEE加MPA增加了新的资讯。在终止CEE加MPA疗法之后的[平均]2.4年的过程中，我们观察到了与激素疗法相关的利弊的快速改变，而对该试验参与者进行持续的随访将对CEE加MPA的可能的延迟效应提供有益的资讯。在终止使用CEE加MPA之后的3.5到8.5年中，看来仍然值得对这些病患的持续较高的恶性肿瘤风险保持临床上的警惕性。”（来源：EurekAlert!中文版）
生物谷推荐原始出处：
（JAMA），2008;299(9):1036-1045，Gerardo Heiss，Marcia L. Stefanick
Health Risks and Benefits 3 Years After Stopping Randomized Treatment With Estrogen and Progestin
Gerardo Heiss, MD; Robert Wallace, MD; Garnet L. Anderson, PhD; Aaron Aragaki, MS; Shirley A. A. Beresford, PhD; Robert Brzyski, MD; Rowan T. Chlebowski, MD; Margery Gass, MD; Andrea LaCroix, PhD; JoAnn E. Manson, MD; Ross L. Prentice, PhD; Jacques Rossouw, MD; Marcia L. Stefanick, PhD; for the WHI Investigators
Context The Women's Health Initiative (WHI) trial of estrogen plus progestin vs placebo was stopped early, after a mean 5.6 years of follow-up, because the overall health risks of hormone therapy exceeded its benefits.
Objective To report health outcomes at 3 years (mean 2.4 years of follow-up) after the intervention was stopped.
Design, Setting, and Participants The intervention phase was a double-blind, placebo-controlled, randomized trial of conjugated equine estrogens (CEE) 0.625 mg daily plus medroxyprogesterone acetate (MPA) 2.5 mg daily, in 16 608 women aged 50 through 79 years, recruited by 40 centers from 1993 to 1998. The postintervention phase commenced July 8, 2002, and included 15 730 women.
Main Outcome Measures Semi-annual monitoring and outcomes ascertainment continued per trial protocol. The primary end points were coronary heart disease and invasive breast cancer. A global index summarizing the balance of risks and benefits included the 2 primary end points plus stroke, pulmonary embolism, endometrial cancer, colorectal cancer, hip fracture, and death due to other causes.
Results The risk of cardiovascular events after the intervention was comparable by initial randomized assignments, 1.97% (annualized rate) in the CEE plus MPA (343 events) and 1.91% in the placebo group (323 events). A greater risk of malignancies occurred in the CEE plus MPA than in the placebo group (1.56% [n = 281] vs 1.26% [n = 218]; hazard ratio [HR], 1.24; 95% confidence interval [CI], 1.04-1.48). More breast cancers were diagnosed in women who had been randomly assigned to receive CEE plus MPA vs placebo (0.42% [n = 79] vs 0.33% [n = 60]; HR, 1.27; 95% CI, 0.91-1.78) with a modest trend toward a lower HR during the follow-up after the intervention. All-cause mortality was somewhat higher in the CEE plus MPA than in the placebo group (1.20% [n = 233] vs 1.06% [n = 196]; HR, 1.15; 95% CI, 0.95-1.39). The global index of risks and benefits was unchanged from randomization through March 31, 2005 (HR, 1.12; 95% CI, 1.03-1.21), indicating that the risks of CEE plus MPA exceed the benefits for chronic disease prevention.
Conclusions The increased cardiovascular risks in the women assigned to CEE plus MPA during the intervention period were not observed after the intervention. A greater risk of fatal and nonfatal malignancies occurred after the intervention in the CEE plus MPA group and the global risk index was 12% higher in women randomly assigned to receive CEE plus MPA compared with placebo.
