Timing of menarche and menopause and epigenetic aging among U.S. adults: results from the National Health and Nutrition Examination Survey 1999-2002

Saher Daredia; Dennis Khodasevich; Nicole Gladish; Hanyang Shen; Jamaji C Nwanaji-Enwerem; Anne K Bozack; Belinda L Needham; David H Rehkopf; Julianna Deardorff; Andres Cardenas

doi:10.1186/s13148-025-01827-x

Timing of menarche and menopause and epigenetic aging among U.S. adults: results from the National Health and Nutrition Examination Survey 1999-2002

Clin Epigenetics. 2025 Feb 21;17(1):31. doi: 10.1186/s13148-025-01827-x.

Authors

Saher Daredia¹, Dennis Khodasevich², Nicole Gladish², Hanyang Shen², Jamaji C Nwanaji-Enwerem^{3

4}, Anne K Bozack², Belinda L Needham⁵, David H Rehkopf^{2

6}, Julianna Deardorff^#⁷, Andres Cardenas^#^{8

9}

Affiliations

¹ Division of Epidemiology, School of Public Health, University of California, Berkeley, USA.
² Department of Epidemiology and Population Health, School of Medicine, Stanford University, Stanford, CA, 94305, USA.
³ Department of Emergency Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA.
⁴ Center of Excellence in Environmental Toxicology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA.
⁵ Department of Epidemiology, Center for Social Epidemiology and Population Health, School of Public Health, University of Michigan, Ann Arbor, USA.
⁶ Department of Pediatrics, School of Medicine, Stanford University, Stanford, USA.
⁷ Division of Community Health Sciences, School of Public Health, University of California, Berkeley, USA.
⁸ Department of Epidemiology and Population Health, School of Medicine, Stanford University, Stanford, CA, 94305, USA. andresca@stanford.edu.
⁹ Department of Pediatrics, School of Medicine, Stanford University, Stanford, USA. andresca@stanford.edu.

^# Contributed equally.

Abstract

Reproductive aging, including timing of menarche and menopause, influences long-term morbidity and mortality in women, yet underlying biological mechanisms remain poorly understood. Using DNA methylation-based biomarkers, we assessed associations of age at menarche (N = 1,033) and menopause (N = 658) with epigenetic aging in a nationally representative sample of women ≥ 50 years. Later age at menopause was associated with lower GrimAge epigenetic age deviation ( $B$ = - 0.10 years, 95% CI: - 0.19, - 0.02). No associations were observed for menarche timing. This suggests a connection between earlier menopause and biological aging, with potential clinical implications for identifying those at high risk for age-related disease.

Keywords: DNA methylation; Epigenetic aging; Menarche; Menopause.

MeSH terms

Age Factors
Aged
Aging* / genetics
Aging* / physiology
DNA Methylation* / genetics
Epigenesis, Genetic*
Female
Humans
Menarche* / genetics
Menopause* / genetics
Menopause* / physiology
Middle Aged
Nutrition Surveys*
United States

Abstract

MeSH terms

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