美PSTF重申：限用激素预防绝经期症状

激素治疗已被美国食品药品管理局(FDA)批准用于预防绝经后女性的骨质疏松，但美国预防服务工作组(PSTF)对最新研究数据进行分析后，认为不应联合使用雌激素和孕激素预防绝经后女性的骨质疏松或其他慢性疾病。

已知雌激素单药治疗和雌激素/孕激素联合治疗可降低骨折风险。在20世纪90年代开展的一系列政府资助的研究(2010年终止随访)中，激素被广泛用于预防绝经后女性的骨骼疾病。然而，近期开展的妇女健康计划(WHI)研究显示，这两种激素治疗还会增加严重不良事件风险，导致研究不得不提前终止。一项随机、安慰剂对照研究表明，雌激素单药治疗与卒中、深静脉血栓形成和胆囊疾病风险显著增加相关，而联合治疗与卒中、浸润性乳腺癌、痴呆、胆囊疾病、深静脉血栓形成和肺栓塞风险增加相关。

美国PSTF此次根据包括WHI研究在内的最新研究数据得出了与2005年相同的结论，即建议不要联合使用雌激素和孕激素或单独使用雌激素预防切除子宫的绝经后女性的慢性疾病。但工作组强调，激素治疗仍适用于治疗潮热或者阴道干涩等绝经后症状。此外，工作组明确表示，其反对使用激素预防疾病的建议不适用于已进行手术绝经的50岁以下女性。

FDA批准的激素用于绝经后女性的适应证包括治疗绝经期症状和预防骨质疏松。黑框警告指出，雌激素在与或不与孕激素合用的情况下均应在最低有效剂量水平使用，并且用药时间应尽可能短。美国PSTF此次得出的结果主要基于WHI研究中所用的剂量和剂型：口服马结合雌激素(0.625 mg/d +醋酸甲羟孕酮，2.5 mg/d)或单纯雌激素0.625 mg/d。工作组非常谨慎地指出，其并不是说激素不应用于治疗血管舒缩症状或阴道萎缩，只是不适用于预防。对于处于绝经过渡期的健康但有症状的女性，激素仍然是适当的治疗选择。

工作组成员均声明无相关经济利益冲突。

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By: JENNIE SMITH, Ob.Gyn. News Digital Network

Combined estrogen and progestin should not be used for the prevention of osteoporosis or other chronic conditions in postmenopausal women, according to recommendations issued by the U.S. Preventive Services Task Force.

Hormone therapy currently has Food and drug Administration approval for use in the prevention of osteoporosis in postmenopausal women.

The task force, an independent body of volunteer experts that advises the Department of Health and Human Services, issued the recommendations Oct. 22 as an update of its 2005 statement on hormone therapy for prevention of disease in postmenopausal women.
 
Using the most recent scientific evidence available, including long-term follow-up data from the Women's Health Initiative (WHI) studies of hormone therapy use in postmenopausal women, the task force reached the same conclusions as it had in 2005, advising against combined estrogen and progestin for prevention of chronic conditions, and also against the use of estrogen alone for the prevention of chronic conditions in postmenopausal women who have had a hysterectomy.

The task force emphasized that hormone therapy was still indicated for the management of menopausal symptoms, such as hot flashes or vaginal dryness. It additionally made clear that its recommendation against hormone therapy for disease prevention does not apply to women younger than 50 years of age who have undergone surgical menopause.

Prior to the WHI studies, a series of government-funded trials that began in the 1990s, with follow-up ending in 2010, hormones had been widely used for the prevention of bone disease in postmenopausal women. Both estrogen and combined estrogen and progestin are known to reduce fracture risk.

However, both forms of hormone therapy were shown during the WHI studies to also increase the risk of serious adverse events, to the point where the trials were stopped early. In one randomized, placebo-controlled trial, estrogen alone was associated with a significantly higher risk of stroke, deep vein thrombosis, and gallbladder disease, while combined therapy was associated with an increased risk of stroke, invasive breast cancer, dementia, gallbladder disease, deep vein thrombosis, and pulmonary embolism.

Reproductive endocrinologist Jan L. Shifren of the department of obstetrics and gynecology and reproductive biology at Harvard Medical School and director of the menopause program at Massachusetts General Hospital, both in Boston, said in an interview that the task force’s updated position largely reflected the current consensus of the ob.gyn. community, "which is that HT should not be used to prevent the diseases of aging."

The task force was "very careful to point out that they are not saying HT should not be used for the treatment of vasomotor symptoms or vaginal atrophy. It’s not that hormones aren’t indicated; they’re just not indicated for prevention. They remain an appropriate treatment for otherwise healthy, very symptomatic women at the menopause transition," said Dr. Shifren, who is not a task force member.

FDA-approved indications for hormone therapy in postmenopausal women include treatment of menopausal symptoms and prevention of osteoporosis. A black box warning indicates that estrogen with or without progestin should be prescribed at the lowest effective dose and for the shortest time possible. The task force’s findings were based on the dosages and formulations used in the WHI trials: oral conjugated equine estrogen (0.625 mg/day plus medroxyprogesterone acetate, 2.5 mg/day) or estrogen 0.625 mg/day alone.

Dr. Shifren said that there are some practitioners "who believe that hormone therapy could still be appropriate for the prevention of osteoporosis in people who absolutely cannot tolerate any other therapy. But what I would argue is that it is incredibly rare that there is a patient who can’t tolerate one of the very many other FDA-approved treatments for the prevention of osteoporosis."

The task force members declared no relevant financial conflicts of interest.