Abstract Although incidence of gastric cancer has been declining, it is still the second leading cause of cancer deaths worldwide. In women, incidence is about half of that in men. Menstrual factors and steroid sex hormones may modify risk for this deadly cancer. A prospective analysis of menstrual and reproductive factors, exogenous hormone use, and gastric cancer risk in women was conducted in the European Prospective Investigation into Cancer (EPIC), a prospective cohort study of individuals aged 35 to 70 years from 10 European countries. The cohort for these analyses included 345,990 women of whom 183 developed primary incident gastric adenocarcinoma (GA) after 8.8 years of follow-up. Hazard ratios (HR) and 95% confidence intervals (CI) for menstrual factors and GA risk were estimated using Cox proportional hazards models with adjustment for age, center, smoking status, education, body mass index, and total calorie-adjusted intake of vegetables, fruits and nuts, and red and processed meats. We analyzed the following factors: age at menarche, age at menopause, parity, age at first full-term pregnancy, history of breast feeding, spontaneous and induced abortion, hysterectomy, ovariectomy, oral contraceptive (OC) use, and hormone replacement therapy (HRT). We estimated total cumulative years of menstrual cycling (fertility life) as the difference between age at menopause (age at recruitment for pre- and perimenopausal women) and age at menarche minus the total amount of time pregnant (number of full-term pregnancies x 9 months). All relative risk estimates were analyzed according to menopausal status, anatomical site (cardia vs non-cardia), histological subtype (diffuse vs intestinal), and Helicobacter pylori (Hp) infection status. Women who reported surgical removal of one or both ovaries were at an increased risk of GA compared with women with intact ovaries (HR=1.72, 95% CI=1.196-2.56), and this association was stronger in ovariectomized women who reported never using exogenous hormones such as HRT and OC (HR=2.40, 95% CI=1.37-4.20). Total years of fertile life (26-30, 31-34, 35-38, 39+ vs <26 years) was inversely associated with GA risk (HR=0.66, 95%CI=0.37-1.17; HR=0.64, 95%CI=0.37-1.11; HR=0.58, 95%CI=0.33-1.01; and HR=0.51, 95%CI=0.27-0.98, respectively). Although some estimates were imprecise, the patterns of association were similar when the analyses were restricted to postmenopausal women, women with non-cardia GA, women with diffuse subtype, and women with Hp infection. Our study showed that surgical removal of the ovaries increased the risk of GA and that this risk was even greater in women who did not receive hormone replacement. Our study also showed that women with greater total years of fertile life have a lower risk of GA. In conclusion, our results support the hypothesis that steroid sex hormones lower the risk of gastric adenocarcinoma in women. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5751.