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BACKGROUND: During perimenopause, vasomotor symptoms are known to have a detrimental effecton women’s functional ability and quality of life. For symptomatic women not eligible for hormonaltherapy, desvenlafaxine is an option, but its safety margin and tolerability are not yet determined.METHODS: A computer-based literature search was done in the databases of MEDLINE, Cochranelibrary, and HINARI (Health InterNetwork Access to Research Initiative). Meta-analysis was conductedby including double-blind randomized controlled studies on the effectiveness and safety ofdesvenlafaxine in the treatment of hot flashes. The effectiveness, safety and tolerability of desvenlafaxinewere determined by standardized mean differences (SMDs) and Mantel-Haenszel odds ratio. Subgroupanalysis based on doses of desvenlafaxine and linear meta-regression analyses were performed forseveral covariates. Heterogeneity testing, the risk of bias assessment and sensitivity analyses were done.RESULTS: Desvenlafaxine was associated with a statistically significant reduction in the number andseverity of daily moderate to severe hot flashes. The number of nighttime awakenings because of hotflashes was also significantly decreased. However, the rate of desvenlafaxine treatment discontinuationbecause of adverse events was a significantly higher than placebo treated women and the risk ratios ofadverse events like asthenia, hypertension, anorexia, constipation, diarrhea, dry mouth, nausea,dizziness, insomnia, somnolence and mydriasis were very high.CONCLUSION: Desvenlafaxine is effective in the treatment of hot flashes but it is strongly associatedwith several adverse events and treatment discontinuation. Further clinical trials focusing only ondesvenlafaxine related adverse events are highly warranted before it is approved for public use.