Background Estrogen receptor alpha (ERα) contributes to maintain biological processes preserving health during aging. DNA methylation changes of ERα gene (ESR1) were established as playing a direct role in the regulation of ERα levels. In this study, we hypothesized decreased DNA methylation of ESR1 associated with postmenopause, lower estradiol levels and increased age among healthy middle-aged and older women.

Methods We assessed DNA methylation of ESR1 promoter region from dried blood spots and estradiol from saliva samples, among 130 healthy women aged 40-73 years.

Results We found that postmenopause and lower estradiol levels were associated with lower DNA methylation of a distal regulatory region, but not with DNA methylation of proximal promoters.

Conclusion Our results indicate possible adaptive changes of ESR1 methylation in women healthy aging.