RANKL is a new Epigenetic Biomarker for the Vasomotor Symptom During Menopause

Area of Science:

• Epigenetics
• Endocrinology
• Menopause Research

Background:

• Estrogen decline during menopause causes physiological and hormonal shifts.
• Hot flashes are a common and disruptive menopausal symptom.
• Epigenetic modifications, like gene methylation, are increasingly recognized as factors influencing health outcomes.

Purpose of the Study:

• To investigate promoter methylation of RANKL and FSHR genes in premenopausal and postmenopausal women.
• To determine the association between gene methylation and the occurrence of hot flashes.
• To explore the epigenetic profiles related to menopausal symptoms in Turkish Cypriot women.

Main Methods:

• Methylation-specific high-resolution melting (MS-HRM) analysis was used to detect gene promoter methylation.
• Statistical analyses, including Pearson chi-squared and Fisher's exact tests, were employed.
• In vitro studies in mice examined the link between RANKL expression, FSH levels, and hot flashes.

Main Results:

• Methylated RANKL was found in 16 postmenopausal women, with 75% experiencing hot flashes (p=0.024).
• Methylated FSHR was detected in 18 postmenopausal women, with 75% experiencing hot flashes (p=0.028).
• In vitro mouse studies supported the association between RANKL, FSH, and hot flashes.

Conclusions:

• RANKL and FSHR gene promoter methylation are significantly associated with hot flashes in postmenopausal women.
• This study provides crucial epigenetic insights into menopausal symptoms.
• This is the first investigation into RANKL and FSHR methylation in relation to hot flashes in this population.