Sleep and Methylation of Estrogen Receptor Genes, ESR1 and GPER, in Healthy Middle-Aged and Older Women: Findings from the Women 40+ Healthy Aging Study

Elena S Gardini; Serena Fiacco; Laura Mernone; Ulrike Ehlert

doi:10.2147/NSS.S256102

Sleep and Methylation of Estrogen Receptor Genes, ESR1 and GPER, in Healthy Middle-Aged and Older Women: Findings from the Women 40+ Healthy Aging Study

Nat Sci Sleep. 2020 Jul 27:12:525-536. doi: 10.2147/NSS.S256102. eCollection 2020.

Authors

Elena S Gardini^{1

2}, Serena Fiacco^{1

2}, Laura Mernone^{1

2}, Ulrike Ehlert^{1

2}

Affiliations

¹ Clinical Psychology and Psychotherapy, University of Zurich, Zurich, Switzerland.
² University Research Priority Program (URPP) Dynamics of Healthy Aging, University of Zurich, Zurich, Switzerland.

Abstract

Purpose: Sleep problems in middle-aged and older women are very common and have been associated with menopause-related changes in estrogen levels. However, not all women experience sleep problems as they enter perimenopause, and epigenetic mechanisms might contribute to the differences in sleep quality within this population. In this study, we hypothesized that increased methylation of two estrogen receptor (ER) genes (ESR1 and GPER) would be associated with increased sleep problems in healthy pre-, peri-, and postmenopausal women, either directly or indirectly through the experience of vasomotor symptoms (VMS).

Materials and methods: In 130 healthy women aged 40-73 years, we assessed DNA methylation from dried blood spots (DBS). Women rated their sleep quality using the Pittsburgh Sleep Quality Index (PSQI), and VMS using the Menopause Rating Scale (MRS).

Results: Higher percentage methylation of ESR1 was associated with increased sleep problems, mediated by VMS, even after controlling for age, menopausal status, body mass index, estradiol levels, depressive symptoms, and caffeine consumption. There was no significant association between GPER methylation and either sleep problems or VMS.

Conclusion: The study findings support an association between increased ESR1 methylation and sleep problems through increased VMS among healthy women aged 40-73 years.

Keywords: DNA methylation; ESR1; GPER; VMS; healthy middle-aged and older women; sleep problems.

Associated data

Dryad/10.5061/dryad.51c59zw51

Grants and funding

This work was funded by the University Research Priority Program (URPP), Dynamics of Healthy Aging, University of Zurich, Switzerland. The funding allowed the collection, analysis, interpretation of data and the writing of the report.