Life-course origins of the ages at menarche and menopause Original paper

What was reviewed?

This comprehensive review examined the life-course origins and determinants of the ages at menarche (onset of first menstruation) and menopause (end of reproductive function) in women. The authors synthesized evidence from developmental biology, epidemiology, nutrition, demography, sociology, and psychology to explore the patterns, trends, and associations between these two reproductive milestones. The review particularly focused on the possible relationship between the timing of menarche and menopause, and considered the influence of genetic, epigenetic, hormonal, environmental, socioeconomic, nutritional, and psychosocial factors across a woman’s life course. The article also discussed implications for chronic disease risk, quality of life, and public health, and highlighted methodological challenges and recommendations for future research.

Who was reviewed?

The review encompassed a wide array of studies, including population-based cohorts, cross-sectional surveys, and case-control studies from diverse geographic regions and ethnic groups. The included literature spanned women of varying ages, racial and ethnic backgrounds (notably non-Hispanic whites, non-Hispanic blacks, Hispanics, Asians, and others), and socioeconomic strata. Research subjects ranged from girls in childhood and adolescence to postmenopausal women, including special populations exposed to unique environmental or hormonal influences (e.g., women exposed to diethylstilbestrol in utero or those affected by famine). While the majority of genetic studies focused on non-Hispanic white women, the review also highlighted studies involving minority or underserved groups, though it noted a general lack of data for these populations.

Most important findings

The review found that both early and late ages at menarche and menopause are associated with significant health and psychosocial outcomes. Early menarche is linked to increased risks for premature death, breast and endometrial cancers, depression, cardiovascular and metabolic diseases, and adverse psychosocial outcomes (e.g., early smoking, early sexual activity, and teenage pregnancy). Late menarche is associated with depression and reduced bone mineral density. Early menopause confers higher risks for cardiovascular disease, osteoporosis, and premature mortality, whereas late menopause is associated with increased risks for hormone-related cancers but longer life expectancy. Crucially, the review reported no consistent or robust association between age at menarche and age at menopause. Among 36 studies, only ten found a significant direct relationship, two found an inverse relationship, and the remainder reported null findings. Genetic heritability estimates for both menarche and menopause are moderate (44–72%), but known genetic variants explain only a small fraction of the variance. Environmental, socioeconomic, and psychosocial factors, such as childhood nutrition, body mass index, early-life adversity, breastfeeding, and stress, exert significant influence on the timing of both events, but their effects are complex and often population-specific.

Emerging evidence suggests that early-life exposures, such as in utero hormonal disruptions, rapid postnatal growth, and adverse socioeconomic conditions, may set developmental trajectories affecting reproductive aging. Obesity, both in childhood and adulthood, is associated with earlier menarche and later menopause. Socioeconomic status (SES) impacts both menarche and menopause, but the direction and strength of these associations can differ by race/ethnicity and across life stages. Psychosocial stress, especially in childhood, may accelerate both menarche and menopause, potentially through endocrine and epigenetic mechanisms.

Key implications

For clinicians, this review underscores the importance of considering a woman’s full life-course context when evaluating reproductive aging and related health risks. The lack of a strong or consistent association between age at menarche and age at menopause suggests that these events are influenced by partly independent mechanisms, with cumulative exposures over the life course playing critical roles. Interventions aimed at optimizing early-life nutrition, reducing childhood adversity, and addressing obesity and socioeconomic disadvantage may favorably influence reproductive health. For microbiome research, the review highlights potential links between metabolic states (e.g., obesity), inflammation, and reproductive timing, suggesting that microbial signatures associated with chronic inflammation or metabolic dysfunction could be relevant in mapping reproductive aging trajectories. However, direct microbiome associations remain unaddressed in the current literature, pointing to an important area for future research.