Age at Menopause, Reproductive Life Span, and Type 2 Diabetes Risk

Results from the EPIC-InterAct study

  1. The InterAct Consortium
  1. 1Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands
  2. 2Medical Research Council Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, U.K.
  3. 3Department of Public Health and Primary Care, University of Cambridge, Addenbrooke's Hospital, Cambridge, U.K.
  4. 4Navarre Public Health Institute, Pamplona, Spain
  5. 5Consortium for Biomedical Research in Epidemiology and Public Health (CIBER Epidemiología y Salud Pública), Madrid, Spain
  6. 6Public Health Division of Gipuzkoa, Basque Government, San Sebastian, Spain
  7. 7Instituto BIO-Donostia, Basque Government, Spain
  8. 8Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany
  9. 9Department of Epidemiology, Murcia Regional Health Council, Murcia, Spain
  10. 10INSERM, Centre for Research in Epidemiology and Population Health (CESP), Centre for Research in Epidemiology and Population Health, U1018: Nutrition, Hormones and Women's Health, Institut Gustave Roussy (IGR), Villejuif, France
  11. 11Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, U.K.
  12. 12University Paris Sud 11, UMRS 1018, Villejuif, France
  13. 13Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program, L'Hospitalet de Lolgbregat, Barcelona, Spain
  14. 14Department of Clinical Sciences, Clinical Research Center, Malmö General Hospital, Lund University, Malmö, Sweden
  15. 15Department of Public Health and Clinical Medicine, Umea University, Umea, Sweden
  16. 16Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan, Italy.
  17. 17Department of Clinical Sciences, Diabetes and Endocrinology, University Hospital Scania, Lund University, Malmö, Sweden
  18. 18Insitute for Molecular Medicine Finland FIMM, University of Helsinki, Helsinki, Finland
  19. 19Division of Cancer Epidemiology, German Cancer Research Centre, Heidelberg, Germany
  20. 20Department of Clinical Sciences, University Hospital Scania, Lund University, Malmö, Sweden
  21. 21Department of Epidemiology, School of Public Health, Aarhus, Denmark
  22. 22Department of Cardiology, Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark
  23. 23Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute, Florence, Italy
  24. 24Department of Clinical and Experimental Medicine, Federico II University, Naples, Italy
  25. 25Consejería de Sanidad, Public Health Directorate, Oviedo-Asturias, Spain
  26. 26Department of Public Health and Clinical Medicine, Family Medicine, Umea University, Umea, Sweden
  27. 27Center for Cancer Prevention (CPO-Piemonte), Torino, Italy
  28. 28Human Genetic Foundation, Torino, Italy
  29. 29Andalusian School of Public Health, Granada, Spain
  30. 30International Agency for Research on Cancer, Dietary Exposure Assessment Group, Lyon, France
  31. 31Danish Cancer Society Research Center, Strandboulevarden Copenhagen, Denmark
  32. 32Cancer Registry and Histopathology Unit, “Civile - M.P. Arezzo” Hospital, Azienda Sanitaria Provinciale No. 7, Ragusa, Italy
  33. 33Associazone Iblea per la Ricerca Epidemiologica–Onlus, Ragusa, Italy
  34. 34National Institute for Public Health and the Environment, Bilthoven, the Netherlands
  35. 35Section of Nutrition and Epidemiology, Division of Human Nutrition, University of Wageningen, Wageningen, the Netherlands
  36. 36Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, U.K.
  1. Corresponding author: Yvonne T. van der Schouw, Y.T.vanderSchouw{at}


OBJECTIVE Age at menopause is an important determinant of future health outcomes, but little is known about its relationship with type 2 diabetes. We examined the associations of menopausal age and reproductive life span (menopausal age minus menarcheal age) with diabetes risk.

RESEARCH DESIGN AND METHODS Data were obtained from the InterAct study, a prospective case-cohort study nested within the European Prospective Investigation into Cancer and Nutrition. A total of 3,691 postmenopausal type 2 diabetic case subjects and 4,408 subcohort members were included in the analysis, with a median follow-up of 11 years. Prentice weighted Cox proportional hazards models were adjusted for age, known risk factors for diabetes, and reproductive factors, and effect modification by BMI, waist circumference, and smoking was studied.

RESULTS Mean (SD) age of the subcohort was 59.2 (5.8) years. After multivariable adjustment, hazard ratios (HRs) of type 2 diabetes were 1.32 (95% CI 1.04–1.69), 1.09 (0.90–1.31), 0.97 (0.86–1.10), and 0.85 (0.70–1.03) for women with menopause at ages <40, 40–44, 45–49, and ≥55 years, respectively, relative to those with menopause at age 50–54 years. The HR per SD younger age at menopause was 1.08 (1.02–1.14). Similarly, a shorter reproductive life span was associated with a higher diabetes risk (HR per SD lower reproductive life span 1.06 [1.01–1.12]). No effect modification by BMI, waist circumference, or smoking was observed (P interaction all > 0.05).

CONCLUSIONS Early menopause is associated with a greater risk of type 2 diabetes.

  • Received May 31, 2012.
  • Accepted September 21, 2012.

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