Heritability of age at natural menopause in the Framingham Heart Study.
Level 3 - non-randomized controlled study
Prospective multigenerational family cohort study evaluating genetic variance components.
PubMed 15769979 · doi:10.1210/jc.2005-0181
What was done
Researchers estimated the heritability of age at natural menopause (defined as natural cessation of menses for 1 year or more) using data from 1,500 original cohort women and 932 offspring cohort women across 1,296 extended families in the multigenerational Framingham Heart Study. Family correlation coefficients were calculated for mother-daughter, sister-sister, and aunt-niece pairs. Variance-components methods in the SOLAR software package were used to estimate heritability, adjusting for generation, cigarette smoking, body mass index, and parity.
What was found
The mean age at natural menopause was 49.1 years in the original cohort and 49.4 years in the offspring cohort. Multivariable-adjusted correlation coefficients were 0.21 for mother-daughter pairs, 0.22 for sister-sister pairs, and 0.12 for aunt-niece pairs. The crude heritability estimate was 0.49 (95% CI, 0.37 to 0.61) and the multivariable-adjusted heritability estimate was 0.52 (95% CI, 0.35 to 0.69).
Why it matters
This study provides population-based, multigenerational evidence that roughly half of the variation in the timing of natural menopause is attributable to genetic factors, confirming findings previously seen largely in twin registries.
Limits
The abstract does not specify the racial or ethnic demographics of the cohort, limiting generalizability. Age at natural menopause relied on self-reported cessation of menses, introducing potential recall error. Specific genetic variants or biological pathways were not identified.
Cited by
- supports Maternal age at menopause is a strong predictor of a woman's age of menopause onset.