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J Clin Endocrinol Metab. 2020 Apr 1;105(4). pii: dgaa081. doi: 10.1210/clinem/dgaa081.

Vasomotor Symptoms and Accelerated Epigenetic Aging in the Women's Health Initiative (WHI).

Author information

1
Departments of Psychiatry and Epidemiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
2
Cousins Center for Psychoneuroimmunology, Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California at Los Angeles School of Medicine, Los Angeles, California.
3
Department of Pathology, Yale School of Medicine, New Haven, Connecticut.
4
Department of Neurosurgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
5
Department of Medicine, David Geffen School of Medicine at the University of California at Los Angeles School of Medicine, Los Angeles, California.
6
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
7
Department of Obstetrics, Gynecology & Reproductive Sciences, Yale School of Medicine, New Haven, Connecticut.
8
Department of Preventive Medicine, Northwestern Feinberg School of Medicine, Chicago, Illinois.
9
Department of Family Medicine and Public Health, University of California, San Diego School of Medicine, La Jolla, California.
10
Department of Biostatistics, University of California at Los Angeles, Los Angeles, California.

Abstract

PURPOSE:

The hallmark menopausal symptom, vasomotor symptoms (VMS), has been linked to adverse health indicators. However, the relationship between VMS and biological aging has not been tested. We examined associations between menopausal VMS and biological aging as assessed by 2 DNA methylation-based epigenetic aging indicators previously linked to poor health outcomes.

METHODS:

Participants were members of the Women's Health Initiative Observational Study integrative genomics substudy (N = 1206) who had both ovaries and were not taking hormone therapy. Relationships between VMS at enrollment (presence, severity) or VMS timing groups (no VMS: not at menopause onset nor at study enrollment; early VMS: at menopause onset but not at enrollment; persistent VMS: at menopause onset and study enrollment; and late VMS: at enrollment but not at menopause onset) and epigenetic clock indicators predictive of physical aging and early death (DNAm PhenoAge, DNAm GrimAge) were tested in linear regression models adjusting for age, race/ethnicity, hysterectomy, education, body mass index, smoking, and, in additional models, sleep disturbance.

RESULTS:

Women were on average 65 years of age at enrollment. Severe hot flashes at enrollment were associated with higher DNAm PhenoAge [relative to no hot flashes: B (SE) = 2.79 (1.27), P = 0.028, multivariable]. Further, late-occurring VMS were associated with both higher DNAm PhenoAge [B (SE) = 2.15 (0.84), P = 0.011] and DNAm GrimAge [B (SE) = 1.09 (0.42), P = 0.010, multivariable] relative to no VMS.

MAIN CONCLUSIONS:

Among postmenopausal women, severe or late-occurring VMS were associated with accelerated epigenetic age, controlling for chronological age. Postmenopausal women with severe or late-occurring VMS may have greater underlying epigenetic aging.

KEYWORDS:

vasomotor symptoms; aging; biologic aging; epigenetics; hot flashes; menopause

PMID:
32080740
PMCID:
PMC7069347
[Available on 2021-02-21]
DOI:
10.1210/clinem/dgaa081

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