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Reproductive history and risk of type 2 diabetes mellitus in postmenopausal women: findings from the Women's Health Initiative

LeBlanc, Erin S. MD, MPH; Kapphahn, Kristopher MS; Hedlin, Haley PhD; Desai, Manisha PhD; Parikh, Nisha I. MD; Liu, Simin MD, ScD; Parker, Donna R. ScD; Anderson, Matthew MD; Aroda, Vanita MD; Sullivan, Shannon MD; Woods, Nancy F. PhD, RN, FAAN; Waring, Molly E. PhD; Lewis, Cora E. MD, MSPH, FACP, FAHA; Stefanick, Marcia PhD

doi: 10.1097/GME.0000000000000714
Original Articles

Objective: The aim of the study was to understand the association between women's reproductive history and their risk of developing type 2 diabetes. We hypothesized that characteristics signifying lower cumulative endogenous estrogen exposure would be associated with increased risk.

Methods: Prospective cohort analysis of 124,379 postmenopausal women aged 50 to 79 years from the Women's Health Initiative (WHI). We determined age of menarche and final menstrual period, and history of irregular menses from questionnaires at baseline, and calculated reproductive length from age of menarche and final menstrual period. Presence of new onset type 2 diabetes was from self-report. Using multivariable Cox proportional hazards models, we assessed associations between reproductive variables and incidence of type 2 diabetes.

Results: In age-adjusted models, women with the shortest (<30 y) reproductive periods had a 37% (95% CI, 30-45) greater risk of developing type 2 diabetes than women with medium-length reproductive periods (36-40 y). Women with the longest (45+ y) reproductive periods had a 23% (95% CI, 12-37) higher risk than women with medium-length periods. These associations were attenuated after full adjustment (HR 1.07 [1.01, 1.14] for shortest and HR 1.09 [0.99, 1.22] for longest, compared with medium duration). Those with a final menstrual period before age 45 and after age 55 had an increased risk of diabetes (HR 1.04; 95% CI, 0.99-1.09 and HR 1.08; 95% CI, 1.01-1.14, respectively) compared to those with age of final menstrual period between 46 and 55 years. Timing of menarche and cycle regularity was not associated with risk after full adjustment.

Conclusions: Reproductive history may be associated with type 2 diabetes risk. Women with shorter and longer reproductive periods may benefit from lifestyle counseling to prevent type 2 diabetes.

1Kaiser Permanente Center for Health Research, Portland, OR

2Stanford University School of Medicine, Stanford University, Stanford, CA

3University of California, San Francisco, San Francisco, CA

4Warren Alpert Medical School and School of Public Health of Brown University, Providence, RI

5Center for Primary Care and Prevention, Memorial Hospital of Rhode Island, Pawtucket, RI

6Department of Obstetrics & Gynecology, Baylor College of Medicine, Houston, TX

7MedStar, Washington Hospital Center, Washington, DC

8University of Washington School of Nursing, Seattle, WA

9University of Massachusetts Medical School, Worcester, MA

10Division of Preventive Medicine, University of Alabama at Birmingham, Birmingham, AL.

Address correspondence to: Erin S. LeBlanc, MD, MPH, Kaiser Permanente Center for Health Research, 3800N Interstate Ave, Portland, OR 97227. E-mail:

Received 5 January, 2016

Revised 18 May, 2016

Accepted 18 May, 2016

E.S.L. contributed to the study conception, design, and interpretation of results, and developed the first draft of the manuscript. K.K., H.H., and M.D. contributed to the study conception and design, researched and analyzed the data, contributed to interpretation of results, and reviewed/edited the manuscript. The remaining authors contributed to the study conception and design and reviewed/edited the manuscript. The final draft for submission was approved by all authors. E.S.L. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and accuracy of the data analysis.

The full list of WHI investigators is available online at

Funding/support: The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services through contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C.

Financial disclosure/conflicts of interest: E.S.L.'s institute had received research funding from Amgen, AstraZeneca, Bristol Meyers Squibb, and Merck for unrelated projects. Support for M.E.W. was provided by NIH grant KL2TR000160. The other authors had no conflicts to report.

© 2017 by The North American Menopause Society.