Age at Menopause, Leukocyte Telomere Length, and Coronary Artery Disease in Postmenopausal Women.
Level 3 - non-randomized controlled study
Prospective cohort analysis combined with Mendelian randomization
PubMed 37489536 · doi:10.1161/CIRCRESAHA.123.322984
What was done
Analyzed 130,254 postmenopausal women from the UK Biobank (n = 122,224) and the Women's Health Initiative (n = 8,030) with reproductive history and leukocyte telomere length (LTL) measurements. Multivariable linear regression examined the association between age at menopause and LTL, stratified by surgical versus natural menopause. Mendelian randomization was used to assess causal links between LTL and age at natural menopause. Multivariable Cox regression and mediation analyses evaluated the joint associations of premature menopause and LTL with incident coronary artery disease.
What was found
Premature menopause (<40 years) was present in 4,809 women (3.7%). Earlier menopause was significantly associated with shorter LTL (meta-analyzed beta = -0.02 SD per 5 years earlier menopause, 95% CI [-0.02, -0.01], P = 7.2 × 10^-12). This was stronger in natural menopause (meta-analyzed beta = -0.04 SD per 5 years earlier, 95% CI [-0.04, -0.03], P < 2.2 × 10^-16) and independent of hormone therapy. Mendelian randomization supported a causal association of shorter genetically predicted LTL with earlier age at natural menopause. Both LTL and age at menopause were independently associated with incident coronary artery disease, with LTL showing a small but statistically significant mediation effect.
Why it matters
The study suggests accelerated biological aging via telomere shortening partially underlies the increased risk of coronary artery disease seen in women who experience premature menopause.
Limits
The abstract omits numeric effect sizes (e.g., hazard ratios and exact mediation percentages) for the coronary artery disease outcomes. Findings rely on observational data subject to unmeasured confounding and self-reported reproductive history.
Cited by
- supports Women with a longer reproductive lifespan (later menopause) have longer telomeres.