據(jù)3月5日《美國醫(yī)學(xué)協(xié)會(huì)期刊》（JAMA）上的項(xiàng)隨訪研究指出,，作為某臨床試驗(yàn)的一部分,，婦女在停止服用雌激素加孕酮的激素療法之后，她們與安慰劑組的婦女相比較,，前者罹患癌癥的風(fēng)險(xiǎn)可能會(huì)增加,。這兩組人的發(fā)生心血管疾病及骨折的風(fēng)險(xiǎn)相似，但是接受激素療法婦女的總體綜合風(fēng)險(xiǎn)指數(shù)較高,，這在許多包括死亡為組合終點(diǎn)的利弊平衡關(guān)系上得到反映,。
婦女健康創(chuàng)制案（WHI）的雌激素加孕酮的試驗(yàn)中包括1萬6608名絕經(jīng)后婦女，這些婦女被評(píng)估接受共軛雌激素 (CEE) 加甲孕酮 (MPA)的治療是否能夠預(yù)防心臟病和髖骨骨折,，及其罹患乳腺癌的風(fēng)險(xiǎn)是否會(huì)增加,。該試驗(yàn)在2002年停止,，因?yàn)楫?dāng)時(shí)的數(shù)據(jù)顯示,，該療法會(huì)增加罹患乳腺癌的風(fēng)險(xiǎn)及該療法沒有顯示大體上的健康裨益。進(jìn)一步的分析顯示,，CEE 加 MPA治療組的婦女具有較高的罹患心血管疾?。–VD）、冠心?。–HD）,、中風(fēng)及靜脈血栓栓塞性疾病的風(fēng)險(xiǎn)，而其罹患骨折與結(jié)腸直腸癌的風(fēng)險(xiǎn)則較低,。
美國北卡羅來納大學(xué)的Gerardo Heiss及其同僚對(duì)1萬5730位參加試驗(yàn)并在停止激素療法之后于2002年7月到2005年3月間有隨訪的受試者的風(fēng)險(xiǎn)與裨益進(jìn)行了檢驗(yàn),。
研究人員發(fā)現(xiàn)，那些停止激素療法（CEE 加 MPA）的隨訪受試者組的“所有癌癥”后果的按年度計(jì)算的事件發(fā)生率比安慰劑組的受試者要高（每年1.56% [n=281] 相對(duì)于每年1.26% [n=218]）,。這反映了CEE 加 MPA組具有較高的罹患侵潤性乳腺癌及其它癌癥的風(fēng)險(xiǎn),，這兩組的結(jié)腸直腸癌的發(fā)病率沒有顯著的差別，但子宮內(nèi)膜癌的發(fā)病率在CEE 加 MPA組則較低,。盡管在隨訪期間,，這些受試者罹患乳腺癌的風(fēng)險(xiǎn)仍然處于增高的狀態(tài)，但這一風(fēng)險(xiǎn)比在試驗(yàn)階段即將結(jié)束前要低,。
作者在文章中寫道：“對(duì)隨機(jī)分配的CEE 加 MPA 組相對(duì)于安慰劑組的延遲與持續(xù)性利弊的分析為絕經(jīng)后婦女的最佳應(yīng)用CEE加MPA增加了新的資訊,。在終止CEE加MPA療法之后的[平均]2.4年的過程中，我們觀察到了與激素療法相關(guān)的利弊的快速改變,，而對(duì)該試驗(yàn)參與者進(jìn)行持續(xù)的隨訪將對(duì)CEE加MPA的可能的延遲效應(yīng)提供有益的資訊,。在終止使用CEE加MPA之后的3.5到8.5年中,，看來仍然值得對(duì)這些病患的持續(xù)較高的惡性腫瘤風(fēng)險(xiǎn)保持臨床上的警惕性。”（來源：EurekAlert!中文版）
生物谷推薦原始出處：
（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.
