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

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:

• sleep problems
• VMS
• ESR1
• GPER
• DNA methylation
• healthy middle-aged and older women

Acknowledgments

This study was supported by the University Research Priority Program Dynamics of Healthy Aging, University of Zurich. The data reported and analyzed in this paper were generated in collaboration with the Genetic Diversity Centre (GDC), ETH Zurich. We also wish to thank Gary G. Chen (NGS support) and Sarah Mannion (proofreading).

Disclosure

The authors report no conflicts of interest in this work.

Additional information

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.