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

Merritt MA 1 , Riboli E 2 , Murphy N 3 , Kadi M 4 , Tjønneland A 5 , Olsen A 6 Show all authors , Overvad K 7 , Dossus L 8 , Dartois L 9 , Clavel-Chapelon F 10 , Fortner RT 11 , Katzke VA 12 , Boeing H 13 , Trichopoulou A 14 , Lagiou P 15 , Trichopoulos D 16 , Palli D 17 , Sieri S 18 , Tumino R 19 , Sacerdote C 20 , Panico S 21 , Bueno-de-Mesquita HB 22 , Peeters PH 23 , Lund E 24 , Nakamura A 25 , Weiderpass E 26 , Quirós JR 27 , Agudo A 28 , Molina-Montes E 29 , Larrañaga N 30 , Dorronsoro M 31 , Cirera L 32 , Barricarte A 33 , Olsson Å 34 , Butt S 35 , Idahl A 36 , Lundin E 37 , Wareham NJ 38 , Key TJ 39 , Brennan P 40 , Ferrari P 41 , Wark PA 42 , Norat T 43 , Cross AJ 44 , Gunter MJ 45

Affiliations 

  • 1 Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Norfolk Place, London, W2 1PG, UK. m.merritt@imperial.ac.uk
  • 2 Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Norfolk Place, London, W2 1PG, UK. e.riboli@imperial.ac.uk
  • 3 Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Norfolk Place, London, W2 1PG, UK. neil.murphy08@imperial.ac.uk
  • 4 Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Norfolk Place, London, W2 1PG, UK. mai.kadi09@imperial.ac.uk
  • 5 Danish Cancer Society Research Center, Strandboulevarden 49, DK-2100, Copenhagen, Denmark. annet@cancer.dk
  • 6 Danish Cancer Society Research Center, Strandboulevarden 49, DK-2100, Copenhagen, Denmark. anja@cancer.dk
  • 7 Department of Public Health, Section for Epidemiology, Aarhus University, Bartholins Allé 2 - Building 1260, DK-8000, Aarhus, Denmark. ko@ph.au.dk
  • 8 Inserm, Centre for research in Epidemiology and Population Health (CESP), U1018, Nutrition, Hormones and Women's Health team, F-94805, Villejuif, France. laure.dossus@lyon.unicancer.fr
  • 9 Inserm, Centre for research in Epidemiology and Population Health (CESP), U1018, Nutrition, Hormones and Women's Health team, F-94805, Villejuif, France. Laureen.dartois@igr.fr
  • 10 Inserm, Centre for research in Epidemiology and Population Health (CESP), U1018, Nutrition, Hormones and Women's Health team, F-94805, Villejuif, France. francoise.clavel@gustaveroussy.fr
  • 11 Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany. r.fortner@dkfz-heidelberg.de
  • 12 Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany. v.katzke@dkfz-heidelberg.de
  • 13 Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Arthur-Scheunert-Allee 114-116, 14558, Nuthetal, Germany. boeing@dife.de
  • 14 Hellenic Health Foundation, 13 Kaisareias Street, Athens, GR-115 27, Greece. atrichopoulou@hhf-greece.gr
  • 15 Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, 75 M Asias Street, Goudi GR-115 27, Athens, Greece. plagiou@hsph.harvard.edu
  • 16 Hellenic Health Foundation, 13 Kaisareias Street, Athens, GR-115 27, Greece. dtrichop@hsph.harvard.edu
  • 17 Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute - ISPO, Ponte Nuovo Palazzina 28 A "Mario Fiori", Via delle Oblate 4, 50141, Florence, Italy. d.palli@ispo.toscana.it
  • 18 Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian, 1, 20133, Milan, Italy. sabina.sieri@istitutotumori.mi.it
  • 19 Cancer Registry and Histopathology Unit, "Civic - M.P.Arezzo" Hospital, ASP, Via Dante N° 109, 97100, Ragusa, Italy. rtumino@tin.it
  • 20 Unit of Cancer Epidemiology, Citta' della Salute e della Scienza Hospital- University of Turin and Center for Cancer Prevention (CPO), Via Santena 7, 10126, Turin, Italy. carlotta.sacerdote@cpo.it
  • 21 Dipartimento di Medicina Clinica e Chirurgia, Federico II University, via Pansini 5, 80131, Naples, Italy. spanico@unina.it
  • 22 Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Norfolk Place, London, W2 1PG, UK. bas.bueno.de.mesquita@rivm.nl
  • 23 Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Norfolk Place, London, W2 1PG, UK. p.h.m.peeters@umcutrecht.nl
  • 24 Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Breivika, N-9037, Tromsø, Norway. eiliv.lund@uit.no
  • 25 Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Breivika, N-9037, Tromsø, Norway. nakamura.a.trinite@uit.no
  • 26 Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Breivika, N-9037, Tromsø, Norway. elisabete.weiderpass.vainio@ki.se
  • 27 Public Health Directorate, Asturias, Ciriaco Miguel Vigil St, 9, 33006, Oviedo, Spain. joseramon.quirosgarcia@asturias.org
  • 28 Unit of Nutrition and Cancer, IDIBELL, Catalan Institute of Oncology-ICO, L'Hospitalet de Llobregat, Barcelona, 08908, Spain. a.agudo@iconcologia.net
  • 29 Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria ibs and Hospitales Universitarios de Granada/Universidad de Granada, Cuesta del Observatorio, 4, Campus Universitario de Cartuja, 18080, Granada, Spain. esther.molina.easp@juntadeandalucia.es
  • 30 CIBER de Epidemiología y Salud Pública (CIBERESP), Melchor Fernández Almagro, 3-5, 28029, Madrid, Spain. epidem3-san@ej-gv.es
  • 31 CIBER de Epidemiología y Salud Pública (CIBERESP), Melchor Fernández Almagro, 3-5, 28029, Madrid, Spain. m-dorronsoro@ej-gv.es
  • 32 CIBER de Epidemiología y Salud Pública (CIBERESP), Melchor Fernández Almagro, 3-5, 28029, Madrid, Spain. lluis.cirera@carm.es
  • 33 CIBER de Epidemiología y Salud Pública (CIBERESP), Melchor Fernández Almagro, 3-5, 28029, Madrid, Spain. aurelio.barricarte.gurrea@cfnavarra.es
  • 34 Institute of Clinical Sciences, Malmö and Department of Surgery, Lund University, Skane University Hospital, SE-205 02, Malmö, Sweden. asa.olsson@med.lu.se
  • 35 Institute of Clinical Sciences, Malmö and Department of Surgery, Lund University, Skane University Hospital, SE-205 02, Malmö, Sweden. salma.butt@med.lu.se
  • 36 Department of Clinical Sciences, Obstetrics and Gynecology, Umeå University, SE-901 87, Umeå, Sweden. annika.idahl@obgyn.umu.se
  • 37 Department of Medical Biosciences, Pathology, Umeå University, SE-901 87, Umeå, Sweden. eva.lundin@medbio.umu.se
  • 38 MRC Epidemiology Unit, University of Cambridge, Institute of Metabolic Science, Addenbrooke's Hospital, Hills Road, PO Box 285, Cambridge, CB2 0QQ, UK. nick.wareham@mrc-epid.cam.ac.uk
  • 39 Cancer Epidemiology Unit, Nuffield Department of Population Health, Richard Doll Building, University of Oxford, Oxford, OX3 7LF, UK. tim.key@ceu.ox.ac.uk
  • 40 International Agency for Research on Cancer, 150 Cours Albert-Thomas, 69372, Lyon, Cedex 08, France. brennanp@iarc.fr
  • 41 International Agency for Research on Cancer, 150 Cours Albert-Thomas, 69372, Lyon, Cedex 08, France. ferrarip@iarc.fr
  • 42 Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Norfolk Place, London, W2 1PG, UK. p.wark@imperial.ac.uk
  • 43 Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Norfolk Place, London, W2 1PG, UK. t.norat@imperial.ac.uk
  • 44 Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Norfolk Place, London, W2 1PG, UK. amanda.cross1@imperial.ac.uk
  • 45 Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Norfolk Place, London, W2 1PG, UK. m.gunter@imperial.ac.uk
BMC Med, 2015 Oct 30;13:252.
PMID: 26515238 DOI: 10.1186/s12916-015-0484-3

Abstract

BACKGROUND: 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.

METHODS: 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.

RESULTS: 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).

CONCLUSIONS: 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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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