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In Reply: We agree with Dr Phillips that there is an increasing body of evidence that estradiol may have adverse effects on glycemic control and that there are potentially divergent effects of direct-tissue transdermal estradiol vs oral estrogen therapy. Our systematic review indicated elevated plasma estradiol levels in persons with type 2 diabetes, and estradiol therapy has been shown to induce insulin resistance in men.¹ In addition, 2 short-term randomized trials in postmenopausal women support the variable effects of different estrogen therapies.^2-3 In both of these trials, transdermal estradiol consistently elevated plasma glucose levels compared with oral estrogen (P = .06 and P = .07, respectively; pooled Fisher meta-P = .03). Long-term prospective studies to examine the roles of plasma estradiol and estradiol-testosterone ratio in the development of type 2 diabetes would be valuable.

Dr Bondy suggests that the associations of testosterone and SHBG with diabetes risk are confounded by adiposity . . . [Full Text of this Article]

Eric L. Ding, BA
eding@hsph.harvard.edu
Department of Epidemiology
Harvard School of Public Health
Boston, Mass

Yiqing Song, MD, ScD
Division of Preventive Medicine
Brigham and Women's Hospital
Boston

Simin Liu, MD, ScD, MPH
Program on Genomics and Nutrition
Department of Epidemiology
UCLA School of Public Health
Los Angeles, Calif

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