The association of birthweight with age at natural menopause: a population study of women in Norway

Abstract

Abstract Background Previous studies suggest that birthweight may influence age at natural menopause, but the evidence remains inconclusive. Thus, we aimed to estimate the association of birthweight with age at natural menopause. Methods A retrospective population study of 164 608 women in Norway, aged 48–71 years. Data were obtained by two self-administered questionnaires among participants in BreastScreen Norway during 2006–2014. We used Cox proportional hazard models to estimate hazard ratios and logistic regression models to estimate odds ratios of menopause according to birthweight. Restricted cubic splines were applied to allow for possible non-linear associations, and adjustments were made for year and country of birth. Results Women with birthweight <2500 g were median 51 years at menopause (interquartile range 49–54 years), whereas women with birthweight 3500–3999 g were median 52 years at menopause (interquartile range 49–54 years). The hazard ratio of menopause decreased with increasing birthweight up until 3500 g. At birthweights >3500 g, we estimated no further decrease (P for non-linearity = 0.007). Birthweight at 2500 g increased the odds ratios of menopause before the age of 45 [1.20; 95% confidence interval (CI): 1.14–1.25] and the age of 40 (1.26; 95% CI: 1.15–1.38) compared with birthweight at 3500 g. At birthweights 4000 g and 4500 g, the odds ratio estimates were very similar to the reference group and the CIs overlapped 1.00. Conclusions We found a non-linear dose-relationship of birthweight with age at natural menopause, and low birthweight was associated with early natural menopause. Our findings suggest that growth restriction during fetal life may influence the timing of natural menopause.