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Pharmacologic and hormonal treatments for menopausal sleep disturbances: A network meta-analysis of 43 randomized controlled trials and 32,271 menopausal women.

Sleep medicine reviews
June 1, 2021
Yu-Shian Cheng et al. (15 authors)
Journal ArticleResearch Support, Non-U.S. Gov'tReviewNetwork Meta-AnalysisHuman Study
Study Details

Study Goal

The researchers aimed to investigate the efficacy and tolerability of pharmacologic and hormonal interventions, including melatonin-fluoxetine, for menopausal sleep disturbances.

Results Summary

The study found that melatonin-fluoxetine showed a therapeutic effect against sleep disturbances compared to placebo, with a significant standardized mean difference (SMD = -2.47). However, dropout rates were comparable between interventions and placebo/control, and no specific adverse events for melatonin were highlighted.

Population

Women during or after the menopausal transition (mean age: 61.24 ± 4.23 years).

Effective Dosage

Not specified

Duration

Mean duration: 90.83 ± 66.29 weeks

Interactions

None mentioned

Extracted Claims (11)
InterventionDirectionEndpointPopulationDosageImpactClaim #
melatonin-fluoxetine
decrease
sleep disturbances
women during/after menopausal transition
SMD = -2.47 (95% CI:-4.19-0.74)
showed therapeutic effect
#1
gabapentin
decrease
vasomotor symptoms
women during/after menopausal transition
SMD = -1.04 (95% CI:-1.90-0.18)
demonstrated superior benefits
#2
oral combined hormone therapy
decrease
vasomotor symptoms
women during/after menopausal transition
SMD = -0.62 (95% CI:-1.06-0.18)
demonstrated superior benefits
#3
bazedoxifene-conjugated estrogens
decrease
vasomotor symptoms
women during/after menopausal transition
SMD = -0.50 (95% CI:-0.96-0.04)
demonstrated superior benefits
#4
raloxifene-only
decrease
sleep disturbances
women during/after menopausal transition
SMD = -1.86 (95% CI:-3.09-0.63)
benefits
#5
raloxifene-oral estrogen
decrease
sleep disturbances
women during/after menopausal transition
SMD = -2.64 (95% CI:-4.64-0.63)
benefits
#6
interventions
no change
overall dropout rates
women during/after menopausal transition
-
dropout rates were comparable
#7
eszopiclone
increase
adverse event-related discontinuation
women during/after menopausal transition
RR = 3.84 (95% CI: 1.14-12.87)
associated with higher rates
#8
oral combined hormone therapy
increase
adverse event-related discontinuation
women during/after menopausal transition
RR = 2.51 (95% CI: 1.04-6.07)
associated with higher rates
#9
combined estrogen-progesterone therapy
decrease
menopausal sleep disturbances associated with vasomotor symptoms
women during/after menopausal transition
-
support
#10
hypnotics
no change
menopausal sleep disturbances
women during/after menopausal transition
-
showed no significant effects
#11
Abstract

This network meta-analysis aimed at investigating efficacy/tolerability of pharmacologic/hormonal interventions for menopausal sleep disturbances. Major databases were searched for randomized controlled trials (RCTs) examining pharmacologic or hormonal interventions with either placebo or active controlled designs. Primary outcomes were improvements in sleep disturbance severity/tolerability (i.e., overall dropout rates), whereas secondary outcome was adverse event-related discontinuation rates. Analysis of 43 RCTs with 25 treatment arms involving 32,271 women during/after menopausal transition (age: 61.24 ± 4.23, duration: 90.83 ± 66.29 wks) showed therapeutic effect of melatonin-fluoxetine [SMD = -2.47 (95% CI:-4.19-0.74)] against sleep disturbances compared to placebo. Subgroup analysis of 15 RCTs on vasomotor symptoms demonstrated superior benefits of gabapentin [SMD = -1.04 (95% CI:-1.90-0.18)], oral combined hormone therapy [SMD = -0.62 (95% CI:-1.06-0.18)], and bazedoxifene-conjugated estrogens [SMD = -0.50 (95% CI:-0.96-0.04)] to placebo/control. Despite benefits of raloxifene-only [SMD = -1.86 (95% CI:-3.09-0.63)] and raloxifene-oral estrogen [SMD = -2.64 (95% CI:-4.64-0.63)], patient selection may be a confounder. Dropout rates were comparable between interventions and placebo/control. Eszopiclone [RR = 3.84 (95% CI: 1.14-12.87)] and oral combined hormone therapy [RR = 2.51 (95% CI: 1.04-6.07)] were associated with higher rates of adverse event-related discontinuation. The results support combined estrogen-progesterone therapy for menopausal sleep disturbances associated with vasomotor symptoms but showed no significant effects of hypnotics in this clinical setting.

Medical Subject Headings (MeSH)
AgedFemaleHumansMenopauseMiddle AgedRandomized Controlled Trials as TopicSleep
Study Links
Quality Scores
SafetyNot Assessed
Efficacy75/10
Quality85/10
Citation Metrics
Total Citations21
Citations/Year5.3
Relative Citation Ratio2.25
NIH Percentile77.9%
Research Impact Scores
APT Score0.75
Weight Score2.71
Normalized Score0.67
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