Age at menopause influences the risk of numerous serious illnesses as well as mortality risk. It is estimated that deaths from cardiovascular disease fall by 2% for each year that menopause is delayed. There is evidence from family history studies and heritability estimates that genetic factors contribute significantly to the start of menopause. This study tested the hypothesis that age at natural menopause is heritable by analyzing data from the Framingham Heart Study, begun in 1948. The study sample used in multivariable analyses was based on 1022 families that include 984 members of the original cohort and 680 women offspring.
Mean age at natural menopause was similar in the original cohort (49.1 years) and offspring women (49.4 years). In multivariable-adjusted analyses, correlation coefficients for age at natural menopause were 0.21 for mother-daughter pairs, 0.22 for sister-sister pairs, and 0.12 for aunt-niece pairs. Respective estimates of heritability were 0.42, 0.44, and 0.48. Heritability estimates for multivariable-adjusted age at natural menopause were 0.74 in the original cohort (95% confidence interval [CI], 0.31-1.00), 0.48 (95% CI, 0.15-0.81) for the offspring, and 0.52 (95% CI, 0.35-0.69) for the pooled sample of offspring and cohort women. At least 50% of inter-individual variability in menopausal age appears to be attributable to genetic effects. The contribution of genetic factors to overall variation in age at natural menopause in offspring was 45%. In the original cohort, genetic factors accounted for 74% of variation in the age at natural menopause.
The investigators conclude that a substantial proportion of variability in age at natural menopause can be ascribed to genetic factors. A better understanding of these factors may have important clinical implications.