Genetic Variation and Hot Flashes: A Systematic Review

Abstract

Context: Approximately 70% of women report experiencing vasomotor symptoms (VMS, hot flashes and/or night sweats). The etiology of VMS is not clearly understood but may include genetic factors.

Evidence acquisition: We searched PubMed and Embase in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidance. We included studies on associations between genetic variation and VMS. We excluded studies focused on medication interventions or prevention or treatment of breast cancer.

Evidence synthesis: Of 202 unique citations, 18 citations met the inclusion criteria. Study sample sizes ranged from 51 to 17 695. Eleven of the 18 studies had fewer than 500 participants; 2 studies had 1000 or more. Overall, statistically significant associations with VMS were found for variants in 14 of the 26 genes assessed in candidate gene studies. The cytochrome P450 family 1 subfamily A member 1 (CYP1B1) gene was the focus of the largest number (n = 7) of studies, but strength and statistical significance of associations of CYP1B1 variants with VMS were inconsistent. A genome-wide association study reported statistically significant associations between 14 single-nucleotide variants in the tachykinin receptor 3 gene and VMS. Heterogeneity across trials regarding VMS measurement methods and effect measures precluded quantitative meta-analysis; there were few studies of each specific genetic variant.

Conclusions: Genetic variants are associated with VMS. The associations are not limited to variations in sex-steroid metabolism genes. However, studies were few and future studies are needed to confirm and extend these findings.

Keywords: gene; genome-wide association study; hot flashes; menopause; night sweats; vasomotor.