Reproductive factors, hormone use, and risk for lung cancer in postmenopausal women, the Nurses' Health Study.

Background: There is increasing evidence suggesting that female hormones may play a significant role in lung cancer development. We evaluated the associations between reproductive factors, exogenous hormone use, and lung cancer incidence in the Nurses' Health Study.

Methods: We assessed age at menopause, age at menarche, type of menopause, parity, age at first birth, postmenopausal hormone (PMH) use, and past oral contraceptive use in 107,171 postmenopausal women. Cox models were used to estimate the hazard ratios for each exposure, adjusting for smoking and other covariates.

Results: We identified 1,729 lung cancer cases during follow-up from 1984 to 2006. Menopause onset before 44 years of age (hazard ratio, 1.39; 95% confidence interval, 1.14-1.70) and past oral contraceptive use for >5 years (hazard ratio, 1.22; 95% confidence interval, 1.05-1.42) were associated with increased lung cancer risk. These associations were strongest in current smokers and small cell histology. In never smokers, increased parity was associated with decreased risk among parous women (P trend = 0.03), whereas in current smokers, older age at first birth was associated with increased risk (P trend = 0.02). PMH use was not associated with overall lung cancer incidence. However, nonsignificant results of increased risk in adenocarcinoma were seen with current PMH use.

Conclusions: Our findings suggest female hormones may influence lung carcinogenesis, although the effect is likely modest, varied by histologic subtype, and altered by smoking.

Impact: Further investigation of the pathophysiology of female hormones in lung cancer subtypes and their interaction with smoking will lead to better understanding of lung carcinogenesis.