BACKGROUND AND PURPOSE:  

• 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 

METHODS:  

• 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 

RESULTS:  

• 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 

CONCLUSION:  

• 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) 

Related ObG Topics:

North American Menopause Society: Hormone Therapy Statement

Insomnia in Menopause: How do Treatments Compare?