Age at Menopause: Imputing Age at Menopause for Women With a Hysterectomy With Application to Risk of Postmenopausal Breast Cancer

Purpose: Age at menopause, a major marker in the reproductive life, may bias results for evaluation of breast cancer risk after menopause. Methods: We followed 38,948 premenopausal women in 1980 and identified 2,586 who reported hysterectomy without bilateral oophorectomy and 31,626 who reported natural menopause during 22 years of follow-up. We evaluated risk factors for natural menopause, imputed age at natural menopause for women reporting a hysterectomy without bilateral oophorectomy, and estimated the hazard of reaching natural menopause in the next 2 years. We applied this imputed age at menopause to both increase sample size and to evaluate the relation between postmenopausal exposures and risk of breast cancer. Results: Age, cigarette smoking, age at menarche, pregnancy history, body mass index, history of benign breast disease, and history of breast cancer were each significantly related to age at natural menopause; duration of oral contraceptive use and family history of breast cancer were not. The imputation increased sample size substantially, and although some risk factors after menopause were weaker in the expanded model (height, and alcohol use), use of hormone therapy is less biased. Conclusions: Imputing age at menopause increases sample size, broadens generalizability making it applicable to women with hysterectomy, and reduces bias.