Reproductive factors, hormone use and the risk of lung cancer among middle-aged never-smoking Japanese women: A large-scale population-based cohort study

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Abstract
Although a link between female hormonal factors and the risk of lung cancer has been suggested, few studies have examined this association in detail. We investigated the associations between reproductive factors, hormone use and the risk of lung cancer in a population‐based prospective study. Self‐administered questionnaires were distributed to 44,677 lifelong never‐smoking women in 1990–1994 to assess menstrual and reproductive factors and hormone use. After 8–12 years of follow‐up, 153 lung cancer cases were diagnosed. Relative risk (RR) and 95% confidence intervals (CI) were calculated using the Cox proportional hazards model. Age at menopause, age at menarche, number of children, age at first live birth, breast feeding and use of hormones were not associated with a risk of lung cancer, either overall or among postmenopausal women or women with natural menopause. Compared to women with both late age at menarche (≥16) and early age at menopause (≤50), those with either early age at menarche or late age at menopause had a >2‐fold, significant increase in the risk of lung cancer. Induced menopausal women with experience of hormone replacement therapy had a significantly elevated risk compared to naturally menopausal women without female hormone use, with an RR of 2.40 (95% CI 1.07–5.40). These findings suggest that both endogenous and extraneous estrogen may be involved in the etiology of lung cancer.