Slow-Paced Respiration for Treatment of Menopausal Hot Flashes

多达三分之二的美国女性在更年期时会出现潮热，20%的女性潮热严重到需要治疗。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疗法。之前的小型临床试验报告称，慢呼吸(慢节奏呼吸)可以通过减少交感神经系统活动来显著减少潮热的频率，而交感神经系统活动已被发现在潮热女性中会增加。然而，有节奏的呼吸很少用于治疗潮热，因为支持疗效的数据有限，而且没有明确描述如何教授或学习这项技术。为了提供明确的证据证明使用慢节奏呼吸治疗潮热的有效性和可行性，我们建议使用一种简单易用的设备(RESPeRATE，InterCure Inc.)进行一项严格的随机盲法试验，该设备引导用户将呼吸速度降至每分钟10次以下。该设备已上市(好市多，亚马逊)，并获得FDA批准用于治疗轻度高血压，包括一个腰带式呼吸传感器，放置在衣服上的胸部周围，以及一个通过耳机产生音乐模式的小计算机盒。该设备感知用户S的呼吸，将其音乐音调与用户S的吸气和呼气相同步。当用户遵循音乐音调的模式时，呼吸频率减慢，呼气延长。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，并随机让她们在12周内每天使用该设备练习15分钟的慢节奏呼吸，或者使用该设备练习在不调整呼吸的情况下每天15分钟的放松音乐。我们的具体目标是：1)使用RESPeRATE设备确定慢节奏呼吸对减少潮热频率的有效性(使用可移动的胸骨皮肤电导监测仪测量)；2)使用RESPeRATE确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有效性(即，通过有效问卷测量的自我报告的潮热严重程度、潮热烦扰、睡眠困难、更年期相关的生活质量、抑郁症状和焦虑症状)；以及3)确定是否交感神经系统活动减少、副交感神经活动相对增加或慢节奏呼吸参数介导了起搏呼吸潮热频率的改善。这项研究将明确证明，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一种有效和可行的雌激素替代方案。

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.