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Aim <p>To investigate the association between age at menopause and prevalent circadian syndrome, a construct integrating metabolic dysfunction with circadian rhythm disruption and depressive symptoms.</p> Methods <p>This cross-sectional analysis included 112,918 women with natural menopause from the UK Biobank. Age at menopause was categorized as &lt; 40 years, 40–44 years, 45–49 years, 50–54 years (reference), and ≥ 55 years. Circadian syndrome was defined as the presence of at least four of seven components: reduced high-density lipoprotein cholesterol, elevated triglycerides, elevated waist circumference, hyperglycemia, elevated blood pressure, short sleep, and depression. Missing covariate data were handled using multiple imputation by chained equations. Multivariable logistic regression models were used to evaluate the associations of age at menopause with circadian syndrome and its individual components, and restricted cubic spline analyses were performed to assess the dose-response relationship.</p> Results <p>Among 112,918 participants, 19,730 (17.47%) had circadian syndrome. Compared with menopause at 50–54 years, the adjusted odds ratios (ORs) for circadian syndrome were (OR 1.52, 95% CI 1.37–1.68) for menopause before 40 years, (OR 1.24, 95% CI 1.17–1.31) for 40–44 years, (OR 1.06, 95% CI 1.02–1.10) for 45–49 years, and (OR 1.16, 95% CI 1.11–1.21) for ≥ 55 years. Restricted cubic spline analyses showed a significant non-linear association between age at menopause and circadian syndrome (<i>P</i> for overall association &lt; 0.001; <i>P</i> for non-linearity &lt; 0.001). In component-specific analyses, premature menopause showed the strongest associations with short sleep (OR 1.55, 95% CI 1.34–1.79), depression (OR 1.41, 95% CI 1.26–1.57), reduced high-density lipoprotein cholesterol (OR 1.39, 95% CI 1.27–1.53), and elevated triglycerides (OR 1.38, 95% CI 1.27–1.50). Subgroup analyses suggested interactions by smoking status and age at menarche. Findings were largely consistent in complete-case and HRT-adjusted sensitivity analyses.</p> Conclusion <p>Age at menopause was non-linearly associated with the odds of prevalent circadian syndrome in this cross-sectional study. The association was strongest for premature menopause, while later menopause was also associated with modestly higher odds. Future prospective studies are needed to clarify the temporal relationships between menopause timing and circadian syndrome, and to determine which components drive the observed associations.</p>

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The association between age at menopause and circadian syndrome: a study based on the UK Biobank

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月29日

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  • Tianyuan Su,
  • Lu Ding,
  • Zhiyi Wei,
  • Zhen Chen,
  • Lu Liu,
  • Xue Li,
  • Zhongyan Lian,
  • Ruxianguli Aimuzi,
  • Rong Li

摘要

Aim

To investigate the association between age at menopause and prevalent circadian syndrome, a construct integrating metabolic dysfunction with circadian rhythm disruption and depressive symptoms.

Methods

This cross-sectional analysis included 112,918 women with natural menopause from the UK Biobank. Age at menopause was categorized as < 40 years, 40–44 years, 45–49 years, 50–54 years (reference), and ≥ 55 years. Circadian syndrome was defined as the presence of at least four of seven components: reduced high-density lipoprotein cholesterol, elevated triglycerides, elevated waist circumference, hyperglycemia, elevated blood pressure, short sleep, and depression. Missing covariate data were handled using multiple imputation by chained equations. Multivariable logistic regression models were used to evaluate the associations of age at menopause with circadian syndrome and its individual components, and restricted cubic spline analyses were performed to assess the dose-response relationship.

Results

Among 112,918 participants, 19,730 (17.47%) had circadian syndrome. Compared with menopause at 50–54 years, the adjusted odds ratios (ORs) for circadian syndrome were (OR 1.52, 95% CI 1.37–1.68) for menopause before 40 years, (OR 1.24, 95% CI 1.17–1.31) for 40–44 years, (OR 1.06, 95% CI 1.02–1.10) for 45–49 years, and (OR 1.16, 95% CI 1.11–1.21) for ≥ 55 years. Restricted cubic spline analyses showed a significant non-linear association between age at menopause and circadian syndrome (P for overall association < 0.001; P for non-linearity < 0.001). In component-specific analyses, premature menopause showed the strongest associations with short sleep (OR 1.55, 95% CI 1.34–1.79), depression (OR 1.41, 95% CI 1.26–1.57), reduced high-density lipoprotein cholesterol (OR 1.39, 95% CI 1.27–1.53), and elevated triglycerides (OR 1.38, 95% CI 1.27–1.50). Subgroup analyses suggested interactions by smoking status and age at menarche. Findings were largely consistent in complete-case and HRT-adjusted sensitivity analyses.

Conclusion

Age at menopause was non-linearly associated with the odds of prevalent circadian syndrome in this cross-sectional study. The association was strongest for premature menopause, while later menopause was also associated with modestly higher odds. Future prospective studies are needed to clarify the temporal relationships between menopause timing and circadian syndrome, and to determine which components drive the observed associations.