Variations in reproductive events across life: a pooled analysis of data from 505 147 women across 10 countries

STUDY QUESTION: How has the timing of women's reproductive events (including ages at menarche, first birth, and natural menopause, and the number of children) changed across birth years, racial/ethnic groups and educational levels?SUMMARY ANSWER: Women who were born in recent generations (1970-84 vs before 1930) or those who with higher education levels had menarche a year earlier, experienced a higher prevalence of nulliparity and had their first child at a later age.WHAT IS KNOWN ALREADY: The timing of key reproductive events, such as menarche and menopause, is not only indicative of current health status but is linked to the risk of adverse hormone-related health outcomes in later life. Variations of reproductive indices across different birth years, race/ethnicity and socioeconomic positions have not been described comprehensively.STUDY DESIGN, SIZE, DURATION: Individual-level data from 23 observational studies that contributed to the International Collaboration for a Life Course Approach to Reproductive Health and Chronic Disease Events (InterLACE) consortium were included.PARTICIPANTS/MATERIALS, SETTING, METHODS: Altogether 505 147 women were included. Overall estimates for reproductive indices were obtained using a two-stage process: individual-level data from each study were analysed separately using generalised linear models. These estimates were then combined using random-effects meta-analyses.MAIN RESULTS AND THE ROLE OF CHANCE: Mean ages were 12.9 years at menarche, 25.7 years at first birth, and 50.5 years at natural menopause, with significant between-study heterogeneity (I2 &gt; 99%). A linear trend was observed across birth year for mean age at menarche, with women born from 1970 to 1984 having menarche one year earlier (12.6 years) than women born before 1930 (13.5 years) (P for trend = 0.0014). The prevalence of nulliparity rose progressively from 14% of women born from 1940-49 to 22% of women born 1970-84 (P = 0.003); similarly, the mean age at first birth rose from 24.8 to 27.3 years (P = 0.0016). Women with higher education levels had fewer children, later first birth, and later menopause than women with lower education levels. After adjusting for birth year and education level, substantial variation was present for all reproductive events across racial/ethnic/regional groups (all P values &lt; 0.005).LIMITATIONS, REASONS FOR CAUTION: Variations of study design, data collection methods, and sample selection across studies, as well as retrospectively reported age at menarche, age at first birth may cause some bias.WIDER IMPLICATIONS OF THE FINDINGS: This global consortium study found robust evidence on variations in reproductive indices for women born in the 20th century that appear to have both biological and social origins.STUDY FUNDING/COMPETING INTEREST(S): InterLACE project is funded by the Australian National Health and Medical Research Council project grant (APP1027196). GDM is supported by the Australian National Health and Medical Research Council Principal Research Fellowship (APP1121844).</p

Unravelling the role of epigenetics in reproductive adaptations to early-life environment

Reproductive function adjusts in response to environmental conditions in order to optimize success. In humans, this plasticity includes age of pubertal onset, hormone levels and age at menopause. These reproductive characteristics vary across populations with distinct lifestyles and following specific childhood events, and point to a role for the early-life environment in shaping adult reproductive trajectories. Epigenetic mechanisms respond to external signals, exert long-term effects on gene expression and have been shown in animal and cellular studies to regulate normal reproductive function, strongly implicating their role in these adaptations. Moreover, human cohort data have revealed differential DNA methylation signatures in proxy tissues that are associated with reproductive phenotypic variation, although the cause–effect relationships are difficult to discern, calling for additional complementary approaches to establish functionality. In this Review, we summarize how adult reproductive function can be shaped by childhood events. We discuss why the influence of the childhood environment on adult reproductive function is an important consideration in understanding how reproduction is regulated and necessitates consideration by clinicians treating women with diverse life histories. The resolution of the molecular mechanisms responsible for human reproductive plasticity could also lead to new approaches for intervention by targeting these epigenetic modifications