SAN DIEGO (EGMN) – The scale that weighs risks and benefits tips more favorably for newly menopausal women who begin hormone therapy at age 50-59 years and who use it for 5 years, compared with women who start the therapy in their 60s, according to a systematic review of several studies and position statements.

Younger women who are newly menopausal and who use hormone therapy have a 30%-40% reduction in total mortality, a phenomenon “that’s not seen in older women,” said Dr. Richard J. Santen, professor of medicine at the University of Virginia, Charlottesville, who called the findings “very surprising.”

“Physicians and their patients need to rethink the use of menopausal hormonal therapy” on the basis of these findings, said Dr. Santen, who chaired the 12-member task force that wrote a scientific statement on behalf of the Endocrine Society suggesting that menopausal hormone therapy may benefit women who start it in their 50s rather than in their 60s.

Importantly, the new analysis points to the need to look beyond data from the Women’s Health Initiative, in which the average age was 63 years, in order to advise younger women. “The therapy clearly needs to be individualized, primarily based on symptoms. But if a woman has an underlying risk of breast cancer ... you’re going to be very cautious about this,” Dr. Santen said during a press briefing at the annual meeting of the Endocrine Society.

Dr. Santen and his associates used the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) system to evaluate the benefits and risks associated with menopausal hormone therapy based on published randomized controlled trials, cohort studies, and case-control studies, as well as position statements related to the topic.

“Hormone therapy has gone through a series of twists and turns,” Dr. Santen commented. “The WHI was directed at women starting hormone therapy [more than 10 years] after the menopause. The average age of the women starting the WHI study was 63, and only 3.4% of the women were between the ages of 50 and 55, ... the usual time when women would decide to take hormone therapy.”

With the publication of the WHI data in 2002, “there was a huge scare” because hormone therapy was shown to be associated with an increased risk of heart disease, breast cancer, stroke, blood clots in the legs and lungs, and memory loss. As a result, the use of menopausal hormone therapy declined by about 80%.

Dr. Santen explained that the new analysis is more applicable to the typical menopausal patient whom physicians see in practice: the 53-year-old who had her last period a year ago, and is now trying to make a decision about whether to start menopausal hormonal therapy to relieve her symptoms.

Overall, the researchers found that women who start menopausal hormone therapy at age 50-59 years experienced a 30%-40% decrease in mortality, no increased risk of heart disease, and a 90% reduction of menopausal symptom such as hot flashes or overactive bladder.

“Relief of symptoms is really the key issue,” Dr. Santen said.

Compared with women who did not take hormone therapy, younger women and those who were newly menopausal experienced 10 fewer diagnoses of diabetes per 1,000 women, 4 fewer cases of heart disease (among those on estrogen only), 5 fewer bone fractures, and 2 fewer cases of colon cancer per 1,000 women (among those on estrogen plus progestin only).

Risks associated with menopausal hormone therapy included gallbladder disease (10 more per 1,000 women), blood clots in the legs and lungs (5 more women), and stroke (2 more women).

Women who were on estrogen therapy alone had no increased risk of developing breast cancer, but there were 7 more cases of breast cancer per 1,000 women among those who took estrogen and progestin for 5 years, compared with non-HT users.

“Our tentative conclusion is that estrogen plus progesterone actually didn’t cause tumors; it caused preexisting tumors to grow to a size where they became detectable,” Dr. Santen said. “There have been eight studies in women [aged 40-80 years] at autopsy, to find out how many women have breast cancer that’s undiagnosed. [Those studies found that] 7% of women at autopsy have breast cancer that’s too small to be diagnosed by mammography, MRI, or clinical examination.”

He added that he hopes the scientific statement will lead to a new perspective on menopausal hormone therapy. “This perspective is only in younger women, and we need to consider the risks and benefits for the women who are considering its use,” he said.

The statement is published in the July 2010 issue of the Journal of Clinical Endocrinology and Metabolism.

Dr. Santen reported having no conflicts of interest.

Copyright (c) 2009 Elsevier Global Medical News. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.

圣地亚哥(EGMN)——据纳入数项研究及立场声明的一项系统性综述，在对激素治疗的风险效益比进行权衡后，研究提示，与那些在60岁后才开始接受激素治疗的女性相比，那些在50~59岁便开始接受该治疗且治疗时间超过5年的新近绝经的女性从治疗中获得的益处更多。

 

夏洛茨维尔弗吉尼亚大学的医学教授Richard J. Santen博士说，那些新近绝经且接受激素治疗的年轻女性总死亡率下降了30%~40%，研究者“并未在更年长的女性中观察到”这一现象，他将其称之为“令人极其惊讶的”发现。

 

Santen博士说，基于这一发现，“内科医生及其患者需要重新思考绝经后激素治疗的用法”，他在代表内分泌学会撰写科学报告的12人工作组中担任主席一职，该学会表示，绝经后激素治疗为那些在50岁后就开始接受治疗的女性带来了更多益处，对那些在60岁后才开始治疗的女性而言则并非如此。

 

Santen博士在内分泌学会年会的某次新闻发布会上发言说，重要的是，这一新分析表明，我们需要对那些来自妇女健康倡议(该研究受试者的平均年龄为63岁)的数据进行更加长远的考虑，从而为年轻女性提出建议。“显然需要为患者制定个性化的治疗方案，其主要依据是患者的症状。但是如果某位女性存在潜在的乳腺癌发病风险……你就必须对此采取极其谨慎的态度”。

 

基于已发表的随机对照试验、队列研究和病例对照研究，以及与该主题相关的立场声明，Santen博士及其同事使用了GRADE(推荐等级的评估、制定与评价)系统来评价与绝经后激素治疗相关的益处和风险。

 

Santen 博士评论说：“激素治疗曾经历过一系列的曲解与波折，妇女健康倡议(WHI)针对的是绝经后开始接受激素治疗(超过10年)的女性。参与WHI研究的女性其平均年龄为63岁，且其中仅有3.4%的女性年龄介于50~55岁……女性通常在这一时间范围内做出接受激素治疗的决定”。

 

WHI 2002年发表的相关数据 “引发了巨大的恐慌”，因为据该研究数据显示，激素治疗与心脏病、乳腺癌、卒中、腿部与肺部血液凝结及记忆力减退等症状的发病风险增高存在关联。其结果是，绝经后激素治疗的使用率下降了大约80%。

 

Santen博士解释说，这项新分析更适用于内科医生在诊疗中所面对的典型绝经后患者：某位53岁的患者，在1年前经历了最后一次月经，她是否应当接受绝经后激素治疗以缓解相关症状呢？她现在正尝试就此做出决定。

 

总体来说，研究者发现，绝经后激素治疗开始时间介于50~59岁之间的女性其死亡率下降了30%~40% ，其心脏病患病风险并未增加，此外，这些患者绝经后症状(譬如潮热或膀胱过动症)的发生率下降了90%。

 

Santen博士说：“缓解症状确实是关键问题” 。

 

与那些未接受激素治疗的女性相比，对年轻女性和那些新绝经的女性而言，被诊断患有糖尿病的患者例数每1,000人少10例，心脏病少4例(在那些仅使用雌激素的女性中)，骨折少5例，且其结肠癌发病率也减少了2/1,000例女性(在那些仅使用雌激素+孕激素的女性中)。

 

与绝经后激素治疗相关的风险包括胆囊疾病(每1,000例女性中发病人数多10例)，腿部和肺部血液凝结(多5例)和卒中(多2例)。

 

那些单用雌激素治疗的女性乳腺癌的发病风险并未升高，但是，对那些联用雌激素和孕激素时间达到5年的女性而言，其乳腺癌发病率相较于未使用激素治疗(HT)女性高出7/1,000例女性。

 

Santen 博士说：“我们的初步结论是，雌激素+孕激素实际上并不会导致肿瘤；但该治疗会促使先前业已存在的肿瘤继续增大，直到被检查发现为止，为了查明有多少女性存在未被诊断的乳腺癌，我们曾在尸检时对8例女性(年龄介于40~80岁)进行过研究。这些研究表明，尸检发现有7%的女性乳腺肿瘤体积过小，以至于无法通过乳腺X光造影检查、磁共振成像(MRI)或临床检查发现。

 

他补充说，他希望此项科学报告会为绝经后激素治疗带来新的视角。他说：“这一观点仅适用于年轻女性，我们还需要替那些正考虑应用该疗法的女性权衡其风险与益处”。

 

该报告于2010年6月发表于《临床内分泌与代谢杂志》(the Journal of Clinical Endocrinology and Metabolism)。

 

Santen博士报告说无任何利益冲突。

 

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