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Purpose <p>The timing of the biological reproductive span, defined by age at menarche and age at menopause which mark overall reproductive lifespan, has emerged as a clinically relevant red flag of cardio-metabolic vulnerability in women. Beyond reproductive function, these milestones reflect interconnected trajectories of ovarian, metabolic, and vascular ageing, offering a life-course framework for cardiovascular risk identification.</p> Methods <p>The present narrative review synthesized evidence from PubMed, Scopus, and Web of Science through December 2025 using terms related to reproductive timing, ovarian aging, cardiovascular disease, and metabolic risk. Observational studies, meta-analyses, mechanistic investigations, and clinical guidelines were included. Evidence was critically appraised to integrate epidemiological associations with biological mechanisms and clinical implications.</p> Results <p>Early menarche is consistently associated with insulin resistance, dyslipidemia, hypertension, type 2 diabetes, coronary heart disease, stroke, and increased mortality. A U-shaped relationship has also been reported, with very late menarche conferring excess risk. Early menopause and primary ovarian insufficiency (POI) increase cardiovascular risk through early estrogen deprivation, endothelial dysfunction, inflammation, and accelerated vascular aging. A shortened reproductive lifespan independently predicts higher cardiovascular events and mortality. These associations reflect not only cumulative estrogen exposure but also shared genetic susceptibility, adiposity-related pathways, early-life programming, and chronic metabolic stress.</p> Conclusion <p>Reproductive timing represents a key sex-specific dimension of cardiovascular risk. Although POI is recognized in guidelines, systematic consideration of age at menarche and reproductive lifespan may improve early detection, risk stratification, and personalized prevention across the female life course. Recognizing reproductive history as a determinant of cardiovascular ageing is essential to advancing truly sex-specific prevention.</p>

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Early in, early out: reproductive lifespan timing and cardiometabolic risk in women

  • 期刊论文

  • 发表日期：

    2026年4月10日

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  • Valeria Calcaterra,
  • Rossella E. Nappi,
  • Laura Cucinella,
  • Ilaria Anna Maria Scavone,
  • Giorgia E. Parrotta,
  • Gianvincenzo Zuccotti

摘要

Purpose

The timing of the biological reproductive span, defined by age at menarche and age at menopause which mark overall reproductive lifespan, has emerged as a clinically relevant red flag of cardio-metabolic vulnerability in women. Beyond reproductive function, these milestones reflect interconnected trajectories of ovarian, metabolic, and vascular ageing, offering a life-course framework for cardiovascular risk identification.

Methods

The present narrative review synthesized evidence from PubMed, Scopus, and Web of Science through December 2025 using terms related to reproductive timing, ovarian aging, cardiovascular disease, and metabolic risk. Observational studies, meta-analyses, mechanistic investigations, and clinical guidelines were included. Evidence was critically appraised to integrate epidemiological associations with biological mechanisms and clinical implications.

Results

Early menarche is consistently associated with insulin resistance, dyslipidemia, hypertension, type 2 diabetes, coronary heart disease, stroke, and increased mortality. A U-shaped relationship has also been reported, with very late menarche conferring excess risk. Early menopause and primary ovarian insufficiency (POI) increase cardiovascular risk through early estrogen deprivation, endothelial dysfunction, inflammation, and accelerated vascular aging. A shortened reproductive lifespan independently predicts higher cardiovascular events and mortality. These associations reflect not only cumulative estrogen exposure but also shared genetic susceptibility, adiposity-related pathways, early-life programming, and chronic metabolic stress.

Conclusion

Reproductive timing represents a key sex-specific dimension of cardiovascular risk. Although POI is recognized in guidelines, systematic consideration of age at menarche and reproductive lifespan may improve early detection, risk stratification, and personalized prevention across the female life course. Recognizing reproductive history as a determinant of cardiovascular ageing is essential to advancing truly sex-specific prevention.