Are the effects of risk factors for timing of menopause modified by age? Results from a British birth cohort study

Objectives: This study investigated the influence of mother's age at menopause, early life and adult behavioral factors on the timing of menopause until age 57 years, and whether these effects vary according to the women's age at menopause. Design: A nationally representative cohort of 1,583 British women born in March 1946 with prospective data across the life course. For factors that vary with age at menopause, analyses were stratified by age at menopause younger than 50 years or 50 years or older. Results: Cox regression models indicated that for women with earlier menopause, those who were heaviest at 2 years had a 59% lower hazard ratio for menopause than those who were the lightest (hazard ratio [HR] = 0.41, 95% CI: 0.16-1.01), whereas this figure was 35% lower (HR = 0.65; 95% CI: 0.42- 1.00) for the later menopause group. For women in the earlier group with parental divorce during childhood, the FIR was 6.5 (95% CI: 2.0-21.3) times higher than that of other women. This rate decreased to 2.5 (95% CI: 1.5-4.2) for those with later menopause. In both groups, increasing mother's age at menopause was associated with decreasing HR (P < 0.0001). For all women, being breast-fed (P = 0.05), increasing cognitive ability (P = 0.009), and increasing parity (P < 0.001) delayed menopause. Conclusions: This study found that the impact of weight at 2 years, parental divorce during childhood, and mother's age at menopause varied according to the women's age at menopause. There was further evidence that being breast-fed,higher childhood cognitive ability, and increasing parity delayed menopause. These results suggest the interaction of genetic and environmental factors in determining age at menopause.