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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

Authors Gardini ES, Fiacco S, Mernone L, Ehlert U

Received 6 April 2020

Accepted for publication 6 July 2020

Published 27 July 2020 Volume 2020:12 Pages 525—536


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Dr Sutapa Mukherjee

Elena S Gardini,1,2 Serena Fiacco,1,2 Laura Mernone,1,2 Ulrike Ehlert1,2

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

Correspondence: Ulrike Ehlert
Clinical Psychology and Psychotherapy, University of Zurich, Binzmühlestrasse 14, Zurich 8050, Switzerland
Tel +41 44 635 73 50
Fax +41 44 635 73 59

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

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