Association between female-specific reproductive factors and leukocyte telomere length.
Level 4 - case-series / case-control
Cross-sectional observational study of baseline data from a cohort
PubMed 37671590 · doi:10.1093/humrep/dead176
What was done
This cross-sectional study analyzed data from 224,965 women aged 40 to 69 years from the UK Biobank (recruited between 2006 and 2010). Female-specific reproductive factors—including age at menarche, age at natural menopause, reproductive lifespan, parity, age at first live birth, history of stillbirth or miscarriage, and use of oral contraceptives and hormone replacement therapy—were self-reported. Leukocyte telomere length was measured using a validated polymerase chain reaction assay. Multivariable linear regression and restricted cubic spline models assessed associations between reproductive factors and leukocyte telomere length after adjusting for potential confounders.
What was found
Early menarche under 12 years (percent change per unit change in leukocyte telomere length Z score: -1.29%, 95% CI: -2.32% to -0.26%), early menopause under 45 years (-7.18%, 95% CI: -8.87% to -5.45%), short reproductive lifespan under 30 years (-6.10%, 95% CI: -8.14% to -4.01%), multiparity (-3.38%, 95% CI: -4.38% to -2.37%), early age at first live birth under 20 years (-4.46%, 95% CI: -6.00% to -2.90%), oral contraceptive use (-1.10%, 95% CI: -2.18% to -0.02%), and hormone replacement therapy use (-3.72%, 95% CI: -4.63% to -2.80%) were significantly associated with shorter leukocyte telomere length. History of miscarriage and stillbirth showed no significant association. Nonlinear relationships with leukocyte telomere length were observed for age at menarche, age at natural menopause, reproductive lifespan, and age at first live birth (P-nonlinear < 0.05).
Why it matters
This study links several female reproductive milestones and exogenous hormone exposures to shorter leukocyte telomere length. It highlights cellular aging as a plausible biological mechanism connecting reproductive history with chronic disease risk later in life.
Limits
The study population was predominantly of European ancestry, which may limit generalizability to other ethnic groups. Reproductive histories were self-reported and subject to recall bias. The observational, cross-sectional design prevents causal inference and cannot determine the temporal sequence of telomere shortening.
Cited by
- supports Women with a longer reproductive lifespan (later menopause) have longer telomeres.