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Which Menopausal Hormone Therapies Improve Sleep Quality? 


  • Poor sleep quality is common in recently menopausal women  
  • Cintron et al. (Menopause, 2018) compared the impact of different hormone therapy (HT) formulations on sleep domains 


  • Data derived from the Kronos Early Estrogen Prevention Study (KEEPS) 
  • KEEPs is a randomized, double-blind, controlled multisite trial that enrolled women 
    • Between 42 and 58 years of age 
    • Between 6 and 36 months since their last menses 
    • Who had serum follicle-stimulating hormone level ≥35 mIU/mL and/or estradiol level <40 pg/mL 
  • Participants completed the Pittsburgh Sleep Quality Index at baseline  
  • Patients randomized 4:4:5 to received   
    • Oral conjugated equine estrogen (o-CEE) 0.45 mg/d plus a placebo (PBO) transdermal patch  
    • Transdermal 17β-estradiol (t-E2) 50 μg/d plus a PBO pill  
    • PBO pills and patch   
  • Active treatment groups received 200 mg cyclic progesterone and PBO group received a PBO capsule for the first 12 days of each month  
  • Intervention occurred at 6, 18, 36, and 48 months  
  • Global Pittsburgh Sleep Quality Index (PSQI) scores (0 to 21 points) and individual sleep domain scores (0 to 3 points) were compared and correlated with vasomotor symptom (VSM) scores based on hot flashes and night sweats  
  • Poor sleep quality was defined by a PSQI global score >8 


  • Global PSQI scores were similar across groups at baseline 
  • Compared with baseline values, both HT groups and the PBO group showed a reduction in average PSQI global scores over 4 years of treatment (each P < 0.001) 
  • PSQI scores were improved in both HT formulations when compared to PBO  
    • O-CEE: Average PSQI change −1.27 (P=0.001 compared to PBO)  
    • T-E2: Average PSQI change −1.32 (P=0.002 compared to PBO)  
  • With HT use, domain scores for sleep satisfaction and latency improved 
  • The domain score for sleep disturbances improved more with t-E2 than o-CEE or PBO  
  • Global sleep scores were significantly correlated with vasomotor symptom severity 
    • Hot flashes: rs = 0.170, P < 0.001  
    • Night sweats: rs = 0.177, P < 0.001  
  • Change in scores for all domains except sleep latency and sleep efficiency correlated with change in severity of VMS 
  • Multivariable analysis demonstrated that improvement in VMS does not fully account for the improved sleep outcomes among women in the HT group 
    • Improved sleep mediated through VMS relief in those with moderate/severe symptoms but not those with none to mild symptoms 


  • Sleep quality improved with both HT formulations (transdermal slightly better than oral)  
  • Sleep disturbance improved more with transdermal patch which may reflect more consistent hormonal levels (e.g. if oral medication was taken in the morning)  
  • Sleep duration was not affected by HT, indicating that other life factors may be involved 

Learn More – Primary Sources:  

Effects of oral versus transdermal menopausal hormone treatments on self-reported sleep domains and their association with vasomotor symptoms in recently menopausal women enrolled in the Kronos Early Estrogen Prevention Study (KEEPS)