Slow-Paced Respiration for Treatment of Menopausal Hot Flashes

潮热发生在多达三分之二的美国妇女在更年期和严重到需要治疗的20%。 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。 之前的小型临床试验已经报道，缓慢呼吸（慢节奏呼吸）可以通过减少交感神经系统活动来显著降低潮热的频率，已经发现潮热女性的交感神经系统活动增加。 然而，起搏呼吸很少用于治疗潮热，因为支持疗效的数据有限，并且没有明确描述如何教授或学习该技术。 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，我们建议使用简单易用的设备（RESPeRATE）进行严格的随机盲法试验（Intercure Inc.），它可以引导用户将呼吸速度降低到每分钟10次呼吸（BPM）以下。 该设备已上市（Costco，Amazon），并经FDA批准用于治疗轻度高血压，包括一个带式呼吸传感器，放置在衣服上的胸部周围，沿着一个小型计算机化盒子，通过耳机产生音乐模式。 感应到用户的呼吸，该设备将其音乐音调转换为用户的吸气和呼气阶段。 当使用者跟随音乐音调的模式时，呼吸速率减慢并且呼气延长。 对于拟议的临床试验，我们将招募120名每天至少有4次更年期潮热的女性，并将她们随机分配使用该设备每天练习慢节奏呼吸15分钟，持续12周，或使用该设备每天练习听放松的音乐15分钟，不进行呼吸起搏，持续12周。 我们的具体目标是：1）确定使用RESPeRATE设备的慢节奏呼吸降低潮热频率（使用非卧床胸骨皮肤电导监测器测量）的功效; 2）确定使用RESPeRATE的慢节奏呼吸对与潮热相关的其他症状和生活质量结果（即，自我报告的潮热严重程度、潮热的烦恼、睡眠困难、更年期相关的生活质量、抑郁症状和焦虑症状，如通过有效的问卷测量的）;和3）确定随着起搏呼吸的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起搏呼吸的参数介导。 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可行的雌激素替代品。

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.