• Clinical Research Unit, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
• Department of Epidemiology and Biostatistics, National Clinical Research Center for Cancer, Key Laboratory of Molecular Cancer Epidemiology of Tianjin, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, PR China.
• Department of Epidemiology, Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, IN, USA.
• Department of Epidemiology and Biostatistics, National Clinical Research Center for Cancer, Key Laboratory of Molecular Cancer Epidemiology of Tianjin, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, PR China. Electronic address: daihongji@tijmu.edu.cn.

OBJECTIVES: Although both age at menarche and age at menopause may independently affect the risk of cardiovascular diseases and all-cause mortality, their joint association with mortality is less clear. The objectives of this study were to address the relationship between ages at menarche and at menopause with mortality among postmenopausal women.

STUDY DESIGN: The study included 75,359 U.S. postmenopausal women aged 50-78 years from the Prostate, Lung, Colorectal, and Ovarian (PLCO) cohort. Information on ages at menarche and menopause was self-reported and collected at baseline, by questionnaire.

MAIN OUTCOME MEASURES: All-cause, cardiovascular and cancer mortality.

RESULTS: After a median follow-up of 13 years, we identified 7826 deaths among 75,359 women in the PLCO cohort. Compared with women with an age at menarche of 12-13 years and an age at menopause of 45-54 years, the adjusted hazard ratios (95% confidence interval) for all-cause mortality for women with early menarche (≤11 years) and menopause (≤44 years) and those with late menarche (≥14 years) and menopause (≥55 years) were 1.20 (1.09, 1.32) and 0.82 (0.71, 0.96), respectively. This association remained significant in a sensitivity analysis that excluded women who did not undergo natural menopause. The indexes for the additive effect of the combined association showed no excess risk due to an interaction.

CONCLUSIONS: Early menarche and early menopause seemed to have an exactly additive effect on all-cause mortality. The findings suggest that it is important to evaluate ages at both menarche and menopause rather than to consider either variable on its own in assessing the risk of mortality.