Association between premature ovarian insufficiency and biological aging

Eur J Endocrinol. 2025 May 30;192(6):744-753. doi: 10.1093/ejendo/lvaf102.

Abstract

Objective: This study aimed to analyze whether premature ovarian insufficiency (POI) is associated with accelerated biological aging, whether the degree of biological aging is exacerbated by an earlier age at menopause, and whether menopausal hormone therapy (MHT) in the POI population is associated with reduced biological aging.

Design: This is a cross-sectional study. A total of 229 779 participants aged 40 years and older in the UK Biobank (2006-2010) and NHANES (1999-2018) were included in the study.

Methods: Menopause information was collected through questionnaires. Biological age acceleration was defined by the Klemera-Doubal method, which is calculated through biomarkers, in reference to chronological age. Biological age acceleration > 0 was defined as biological aging. Association between POI and biological aging analyzed using multivariate linear regression and logistic regression models.

Results: The results showed that participants with POI had an increased risk of biological aging (UK Biobank: OR = 1.50 [95% CI: 1.24-1.82]; NHANES: OR = 1.20 [95% CI: 1.07-1.34]) and decrease in leukocyte telomere length compared with those without POI (UK Biobank: 0.0109 [95% CI: 0.0079-0.0109]). Participants with POI who underwent MHT had reduced risk of aging compared with those who did not (UK Biobank: OR = 0.63 [95% CI: 0.43-0.92]; NHANES: OR = 0.75 [95% CI: 0.61-0.92]).

Conclusion: This study showed that participants with POI had a significantly increased risk of biological aging compared with those without POI. Participants with POI who received MHT had a reduced risk of aging compared with those who did not.

Keywords: biological age; biological aging; menopausal hormone therapy; premature ovarian insufficiency.

MeSH terms

  • Adult
  • Aged
  • Aging* / physiology
  • Cross-Sectional Studies
  • Female
  • Humans
  • Menopause / physiology
  • Menopause, Premature
  • Middle Aged
  • Nutrition Surveys
  • Primary Ovarian Insufficiency* / epidemiology
  • Primary Ovarian Insufficiency* / physiopathology