The effect of menopause on the relation between weight gain and mortality among women

Objective: To examine the effect of menopause on the relation between weight gain and all-cause mortality. Design: Prospective cohort study of 6,030 adults (ages 25-82 years) who never smoked cigarettes, had no history of coronary heart disease, cancer, or stroke, and were enrolled in a 29-year follow-up in which anthropometric data were given at baseline and at 17 years after baseline. Results: Weight gain that occurred over a 17-year interval (baseline to 17 years after baseline) increased the mortality risk of men and middle-aged women, but decreased the mortality risk of older women. Further study of the women revealed that a strong protective effect of weight gains was only evident among the leanest (≤25 kg/m²) postmenopausal women. Specifically, weight gains of 10 kg or more (median = 13 kg) produced an almost threefold decrease in mortality risk among the leanest (≤25 kg/m²) postmenopausal women [hazard ratio (HR) (95% confidence interval; CI) = 0.35 (0.13, 0.96)], but did not confer strong protection for heavier (>25 kg/m²) postmenopausal women [HR (95% CI) = 0.81 (0.41, 1.58)] or for premenopausal women [HR (95% CI) = 1.05 (0.49, 2.25) for ≤25 kg/m², 0.95 (0.38, 2.37) for >25 kg/m²]. We found that the protective effect of weight gain among the leanest postmenopausal women was primarily due to a more than threefold decrease in cardiovascular disease mortality risk. One possible explanation for these findings is that weight gain increases the level of adipose-tissue-derived estrogen among lean postmenopausal women. Conclusion: Moderate menopausal weight gain may be well tolerated in lean women.