Letters Section Editor: Robert M. Golub, MD, Senior Editor.
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.
Ding EL, Song Y, Liu S. Endogenous Sex Hormones and Type 2 Diabetes Risk—Reply. JAMA. 2006;296(2):168-170. doi:10.1001/jama.296.2.169-b