Reproductive factors and risk of mortality in the European Prospective Investigation into Cancer and Nutrition; a cohort study

Melissa A. Merritt, Elio Riboli, Neil Murphy, Mai Kadi, Anne Tjønneland, Anja Olsen, Kim Overvad, Laure Dossus, Laureen Dartois, Françoise Clavel-Chapelon, Renée T. Fortner, Verena A. Katzke, Heiner Boeing, Antonia Trichopoulou, Pagona Lagiou, Dimitrios Trichopoulos, Domenico Palli, Sabina Sieri, Rosario Tumino, Carlotta Sacerdote, Salvatore Panico, H. Bas Bueno-de-Mesquita, Petra H. Peeters, Eiliv Lund, Aurelie Nakamura, Elisabete Weiderpass, J. Ramón Quirós, Antonio Agudo, Esther Molina-Montes, Nerea Larrañaga, Miren Dorronsoro, Lluís Cirera, Aurelio Barricarte, Åsa Olsson, Salma Butt, Annika Idahl, Eva Lundin, Nicholas J. Wareham, Timothy J. Key, Paul Brennan, Pietro Ferrari, Petra A. Wark, Teresa Norat, Amanda J. Cross, Marc J. Gunter

Reproductive events are associated with important physiologic changes, yet little is known about how reproductive factors influence long-term health in women. Our objective was to assess the relation of reproductive characteristics with all-cause and cause-specific mortality risk. The analysis was performed within the European Investigation into Cancer and Nutrition prospective cohort study, which enrolled >500,000 women and men from 1992 to 2000, who were residing in a given town/geographic area in 10 European countries. The current analysis included 322,972 eligible women aged 25-70 years with 99 % complete follow-up for vital status. We assessed reproductive characteristics reported at the study baseline including parity, age at the first birth, breastfeeding, infertility, oral contraceptive use, age at menarche and menopause, total ovulatory years, and history of oophorectomy/hysterectomy. Hazard ratios (HRs) and 95 % confidence intervals (CIs) for mortality were determined using Cox proportional hazards regression models adjusted for menopausal status, body mass index, physical activity, education level, and smoking status/intensity and duration. During a mean follow-up of 12.9 years, 14,383 deaths occurred. The HR (95 % CI) for risk of all-cause mortality was lower in parous versus nulliparous women (0.80; 0.76-0.84), in women who had ever versus never breastfed (0.92; 0.87-0.97), in ever versus never users of oral contraceptives (among non-smokers; 0.90; 0.86-0.95), and in women reporting a later age at menarche (≥15 years versus <12; 0.90; 0.85-0.96; P for trend = 0.038). Childbirth, breastfeeding, oral contraceptive use, and a later age at menarche were associated with better health outcomes. These findings may contribute to the development of improved strategies to promote better long-term health in women.