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During menopausal transition, decreased level of estrogen brings a number of physiological problems and hormonal changes. In this study, promoter methylation of RANKL and FSHR genes were identified in 30 premenopausal and 35 postmenopausal women using methylation-specific high resolution melting (MS-HRM) analysis. The statistical analyses and their association with patient characteristics were performed by Pearson χ2 and Fisher’s exact test (p RANKL gene was detected in 16 postmenopausal cases, and 12 (75.0%) of the RANKL methylated cases had hot flashes (p = 0.024). The methylated FSHR gene was detected in 18 postmenopausal cases, and 13 (75.0%) of the methylated cases had hot flashes (p = 0.028). In vitro studies demonstrated the association between RANKL expression, FSH level and hot flashes in the mouse. Although lack of epigenetic studies in this field proves our results crucial and therefore, our results showed magnitude of epigenetic profiles of Turkish Cypriot post-menopausal women. This was the first study which has investigated the RANKL and FSHR methylation and their relationship with hot flashes in postmenopausal women.