Slow-Paced Respiration for Treatment of Menopausal Hot Flashes

在绝经期的美国女性中，多达三分之二的人会出现潮热，其中20%的人严重到需要治疗。虽然绝经后激素治疗是一种有效的治疗方法，但它与各种严重不良反应的风险增加有关。目前迫切需要有效、安全和易于使用的替代治疗方法。先前的小型临床试验报告称，缓慢呼吸（慢节奏呼吸）可以通过减少交感神经系统的活动来显著减少潮热的频率，而女性潮热时交感神经系统的活动会增加。然而，节奏呼吸很少用于治疗潮热，因为支持疗效的数据有限，并且没有关于如何教授或学习该技术的明确描述。为了提供使用慢节奏呼吸治疗潮热的有效性和可行性的明确证据，我们建议使用一种简单易用的设备（RESPeRATE¿，Intercure Inc.）进行严格的随机盲法试验，指导用户将呼吸速度减慢到每分钟10次以下（BPM）。该设备已在市售（Costco, Amazon），并已获得FDA批准用于治疗轻度高血压。该设备包括一个腰带式呼吸传感器，它被放置在衣服周围的胸部，以及一个通过耳机产生音乐模式的小型计算机化盒子。感应到用户的呼吸，该设备将其音乐音调与用户的吸气和呼气相同步。当使用者跟随音乐音调的模式时，呼吸频率减慢，呼气时间延长。在拟议的临床试验中，我们将招募120名每天至少有4次更年期潮热的女性，并随机分配她们，要么使用该设备每天练习15分钟的慢节奏呼吸，持续12周，要么使用该设备每天练习15分钟的无节奏呼吸的放松音乐，持续12周。我们的具体目标是：1)使用RESPeRATE设备确定慢节奏呼吸减少潮热频率的功效（使用动态胸骨皮肤电导监测仪测量）；2)使用RESPeRATE测定慢节奏呼吸对与潮热相关的其他症状和生活质量结果的疗效（即，自我报告的潮热严重程度、潮热困扰、睡眠困难、绝经相关的生活质量、抑郁症状和焦虑症状，通过有效问卷测量）；3)确定节奏呼吸时潮热频率的改善是否由交感神经系统活动的减少、副交感神经活动的相对增加或慢节奏呼吸参数介导。这项研究将明确地证明这种针对自主神经系统活动的新型行为干预是否为缓解潮热提供了雌激素的有效和可行的替代方法。

Hot flashes occur in as many as two thirds of U.S. women during menopause and are severe enough to require treatment in 20%. Although postmenopausal hormone therapy is an effective treatment, it is associated with increased risk for a variety of serious adverse effects. There is currently an urgent need for alternative treatments that are effective, safe, and easy to use. Prior small clinical trials have reported that slow breathing (slow-paced respiration) can significantly reduce the frequency of hot flashes by reducing sympathetic nervous system activity, which has been found to be increased in women with hot flashes. However, paced respiration is rarely used to treat hot flashes, because data supporting efficacy are limited, and there is no clear description of how to teach or learn the technique. To provide clear evidence of the efficacy and feasibility of using slow-paced respiration to treat hot flashes, we propose to conduct a rigorous randomized, blinded trial using a simple, easy-to-use device (RESPeRATE¿, Intercure Inc.), that guides users to slow their respiration below 10 breaths per minute (BPM). The device, which is commercially available (Costco, Amazon) and approved by the FDA for treatment of mild hypertension, includes a belt-type respiration sensor that is placed around the chest over clothing, along with a small computerized box that generates musical patterns through earphones. Sensing the user¿s respiration, the device synchronizes its musical tones to the user¿s inspiratory and expiratory phases. As the user follows the pattern of the musical tones, respiratory rate is slowed and expiration is prolonged. For the proposed clinical trial, we will enroll 120 women with at least 4 menopausal hot flashes per day and randomize them either to use the device to practice slow-paced respiration for 15 minutes per day for 12 weeks, or to use the device to practice listening to relaxing music without pacing respiration for 15 minutes per day for 12 weeks. Our specific aims are to: 1) determine the efficacy of slow-paced respiration using the RESPeRATE device to reduce the frequency of hot flashes (measured using an ambulatory sternal skin conductance monitor); 2) determine the efficacy of slow-paced respiration using RESPeRATE on other symptom and quality-of-life outcomes associated with hot flashes (i.e., self-reported severity of hot flashes, bothersomeness of hot flashes, difficulty sleeping, menopause-related quality of life, depression symptoms, and anxiety symptoms as measured by validated questionnaires); and 3) determine if improvement in frequency of hot flashes with paced respiration is mediated by reduction in sympathetic nervous system activity, relative increase in parasympathetic activity, or parameters of slow-paced respiration. This research will definitively demonstrate whether this novel behavioral intervention that targets autonomic nervous system activity offers an effective and feasible alternative to estrogen for alleviation of hot flashes.