Circulating Estrone Levels Are Associated Prospectively With Diabetes Risk in Men of the Framingham Heart Study

  1. Shalender Bhasin, MD3
  1. 1Department of Mathematics, Boston University, Boston, Massachusetts
  2. 2Center for Health Quality, Outcomes, and Economic Research, Bedford VA Medical Center, Bedford, Massachusetts
  3. 3Section of Endocrinology, Diabetes, and Nutrition, Boston University School of Medicine, Boston, Massachusetts
  4. 4Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts
  5. 5Section of General Internal Medicine, Boston University School of Medicine, Boston, Massachusetts
  6. 6ARUP Laboratories University of Utah, Salt Lake City, Utah
  7. 7Section of Preventative Medicine and Epidemiology, Boston University School of Medicine, Boston, Massachusetts
  8. 8NHLBI's Framingham Heart Study (FHS), Framingham, Massachusetts
  1. Corresponding author: Guneet Kaur Jasuja, guneetk{at}


OBJECTIVE In postmenopausal women and preclinical murine models, estrogen administration reduces diabetes risk; however, the relationship of estradiol and estrone to diabetes in men is poorly understood. We determined the relationship between circulating estradiol and estrone levels and diabetes risk in community-dwelling men of the Framingham Heart Study (FHS).

METHODS Cross-sectional relationships of estradiol and estrone levels with diabetes were assessed at examination 7 (1998–2001) in FHS generation 2 men (n = 1,458); prospective associations between hormone levels at examination 7 and incident diabetes were assessed 6.8 years later at examination 8. Type 2 diabetes mellitus was defined as fasting glucose >125 mg/dL, medication use, or both. Estradiol, estrone, and testosterone levels were measured with liquid chromatography tandem mass spectrometry, and free estradiol and estrone were calculated.

RESULTS In cross-sectional models, men with elevated estrone and estradiol had 40% and 62% increased likelihoods of existing diabetes per cross-sectional doubling of estrone and estradiol levels, respectively. Free estrone (cross-sectional odds ratio 1.28 [95% CI 1.02–1.62], P = 0.04) was associated with impaired fasting glucose at examination 7. There was an increase in risk of existing diabetes with increasing quartiles of total and free estrone and estradiol and an increase in risk of incident diabetes with increasing quartiles of estrone levels. In multivariate longitudinal analyses, a twofold increase in total or free estrone levels at examination 7 was associated with 77 and 93% increases, respectively, in odds of incident diabetes at examination 8.

CONCLUSIONS Although both estradiol and estrone exhibit cross-sectional associations with diabetes in men, in longitudinal analyses estrone is a more sensitive marker of diabetes risk than estradiol.

  • Received November 28, 2012.
  • Accepted February 8, 2013.

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  1. Diabetes Care
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