背景:潮热,在更年期期间很常见,影响多达80%的西方更年期妇女,据报道会导致中年睡眠障碍。很少有前瞻性数据可以证实潮热在破坏中年女性睡眠中的具体作用。然而,或确认潮热对临床治疗的反应是否会导致睡眠改善。
目的:研究持续硝酸甘油治疗对频繁潮热的围绝经期和绝经后妇女睡眠质量的影响(预先指定的次要试验终点),并研究该人群潮热与睡眠中断之间的前瞻性关联。
方法:睡眠数据来自随机,双盲,持续经皮硝酸甘油(NTG)治疗抑制绝经前后潮热妇女一氧化氮介导的血管舒张的安慰剂对照试验.参与者被随机分配到不间断使用经皮NTG(0.2-0.6mg/小时)或安慰剂12周。使用基线时的7天症状日记评估夜间潮热从睡眠中唤醒参与者,5周,和12周。睡眠中断(睡眠开始后的唤醒时间,WASO)使用经过验证的睡眠日记进行评估,通过验证的匹兹堡睡眠质量指数(PSQI:范围0[最佳]21[最差])问卷评估全球睡眠质量。混合线性模型检查了睡眠质量和中断的变化,以及夜间热闪光频率和睡眠结果之间的关联强度,超过5周和12周,调整基线值,年龄,种族,和种族。
结果:在141名参与者中(NTG为70名,安慰剂为71名,平均年龄54.6[±3.9]岁),平均基线热闪光频率为每天10.8(±3.5),包括2.6(±1.7)名夜间潮热唤醒参与者。在基线,潮热是夜间觉醒最常见的原因,62.6%的参与者报告每晚至少两次因潮热而醒来。超过5周和12周,两组中引起觉醒的夜间潮热的平均频率均降低(NTG:-0.9次/夜,安慰剂:-1.0发作/晚)。通过平均每晚WASO测量的睡眠中断也减少了(NTG:-10.1分钟,安慰剂:-7.3分钟),平均PSQI得分提高(NTG:-1.3分,安慰剂:-1.2分)。从基线到5周和12周没有检测到睡眠结果变化的显著组间差异,包括PSQI睡眠质量评分作为预先指定的次要试验终点(全部P≥0.05)。在合并样本中,5周和12周夜间热闪光频率的改善与PSQI睡眠质量评分(β=-0.30,P=.01)和WASO反映的睡眠中断(β=-1.88,P=.02)的改善有关。
结论:在一项连续NTG治疗潮热的随机试验中,在绝经妇女中,潮热是夜间觉醒的最常见原因。与安慰剂相比,从基线至第5周和第12周,持续NTG治疗并未使睡眠质量得到更大改善.根据夜间症状日记和问卷,然而,两组患者夜间热闪光频率的较大改善与睡眠质量和睡眠中断的较大改善相关.
BACKGROUND: Hot flashes, common during menopause, affect up to 80% of Western menopausal women and are reported to contribute to sleep disturbances in midlife. Few prospective data are available to confirm the specific role of hot flashes in disrupting sleep in midlife women, however, or confirm whether changes in hot flashes in response to clinical therapies result in improvement in sleep.
OBJECTIVE: To examine the effects of continuous nitroglycerin therapy on sleep quality in peri- and postmenopausal women with frequent hot flashes (pre-specified secondary trial endpoint), and to examine prospective associations between hot flashes and sleep disruption in this population.
METHODS: Sleep data were analyzed from a randomized, double-blinded, placebo-controlled trial of continuous transdermal nitroglycerin (NTG) therapy to suppress nitric oxide-mediated vasodilation in peri- or postmenopausal women with hot flashes. Participants were randomized to uninterrupted use of transdermal NTG (0.2-0.6 mg/hour) or placebo for 12 weeks. Nocturnal hot flashes awakening participants from sleep were evaluated using 7-day symptom diaries at baseline, 5 weeks, and 12 weeks. Sleep disruption (wake time after sleep onset, WASO) was assessed using validated sleep diaries, and global sleep quality was assessed by the validated Pittsburgh Sleep Quality Index (PSQI: range 0 [best] 21 [worst]) questionnaire. Mixed linear models examined changes in sleep quality and disruption, as well as the strength of associations between nocturnal hot flash frequency and sleep outcomes, over 5 and 12 weeks, adjusting for baseline values, age, race, and ethnicity.
RESULTS: Among the 141 participants (70 to NTG and 71 to placebo, mean age 54.6 [±3.9] years), the mean baseline hot flash frequency was 10.8 (±3.5) per day, including 2.6 (±1.7) nocturnal hot flashes awakening participants. At baseline, hot flashes were the most commonly reported reason for nocturnal awakening, with 62.6% of participants reporting waking due to hot flashes at least twice nightly. Over 5 and 12 weeks, mean frequency of nocturnal hot flashes causing awakenings decreased in both groups (NTG: -0.9 episodes/night, placebo: -1.0 episodes/night). Sleep disruption as measured by average nightly WASO also decreased (NTG: -10.1 minutes, placebo: -7.3 minutes), and mean PSQI score improved (NTG: -1.3 points, placebo: -1.2 points). No significant between-group differences in change in sleep outcomes were detected from baseline to 5 and 12 weeks, including PSQI sleep quality score as a pre-specified secondary trial endpoint (P ≥ .05 for all). Greater improvement in nocturnal hot flash frequency over 5 and 12 weeks was associated with greater improvement in PSQI sleep quality score (β= -0.30, P=.01) and sleep disruption reflected by WASO (β= -1.88, P=.02) in the combined sample.
CONCLUSIONS: Among menopausal women in a randomized trial of continuous NTG therapy for hot flashes, hot flashes were the most frequently reported cause of nocturnal awakenings. Compared to placebo, continuous NTG therapy did not result in greater improvements in sleep quality from baseline to 5 and 12 weeks. Based on night-by-night symptom diaries and questionnaires, however, greater improvement in nocturnal hot flash frequency in both groups was associated with greater improvement in sleep quality and disruption.