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High Postmenopausal Sex Hormones Signal Type 2 Diabetes Risk

Posted: Thursday, June 15, 2006

Postmenopausal women with high levels of estradiol and testosterone are at a greatly increased risk of developing type 2 diabetes, according to data on nearly 28,000 women.

Among women enrolled in the Women's Health Study, those with high levels of plasma-free and total estradiol had a nearly 12-fold risk of developing type 2 diabetes compared with women who had the lowest levels, reported epidemiology fellow Eric L. Ding, and colleagues, of the Harvard School of Public Health.

 
"The results are actually quite astonishing," said Ding during a presentation at the American Diabetes Association meeting.
There were 123 cases of type 2 diabetes in women in the highest quintile of sex hormones, compared with 21 in the lowest quintile, and the associations between sex hormone levels and diabetes risk held up even after controlling for multiple risk factors, Ding said.

He and his colleagues conducted a prospective, nested case-control study of plasma estradiol, testosterone, sex hormone-binding globulin, and dehydroepiandrosterone sulfate (DHEAS) as predictors of type 2 diabetes. The study cohort was 27,962 women enrolled in the Women's Health Study, a randomized double-blind, placebo-controlled trial that evaluated the relative benefits of vitamin E and low-dose aspirin for prevention of hearts attacks and stroke.

A subset enrolled in the sex-hormone study were postmenopausal women who were not taking hormone-replacement therapy and who were free of diabetes, cancer, and cardiovascular disease. A total of 359 incident cases of type 2 diabetes were identified, and these were matched with 359 controls.

The investigators found that after adjustment for traditional risk factors and reproductive variables, total and free estradiol and testosterone levels were all strongly associated with a risk of type 2 diabetes. The relative risks for total and free estradiol, respectively, were 11.9 (95% confidence interval, 3.41-41.4, P for trend <0.001) and 11.7 (95% CI, 3.68-37.0, P for trend <0.001). The relative risks for total and free testosterone, respectively, were 3.23 (95% CI, 1.08-9.68, P for trend=0.02) and 12.7 (95%CI, 4.33-37.4, P for trend <0.001).

In addition, the investigators also found that levels of sex-hormone binding globulin were negatively associated with diabetes risk. That is, women with lower levels were at higher risk for type 2 diabetes, a finding that might be expected because SHBG binds and removes free testosterone from circulation.

The relative risk for SHBG levels and type 2 diabetes were 0.05 (95%CI, 0.02-0.18, P for trend <0.001). There was no significant association between DHEAS and diabetes, however.

The associations for estradiol (both free and total), free testosterone, and SHBG remained significant after the data were adjusted for C-reactive protein and for pre-diabetes diagnosis levels of HbA1c. The ratios between total and free estradiol and total and free testosterone, respectively, were not significant, however.

The findings suggest that postmenopausal women who are known to have high levels of free and total estradiol and testosterone should be monitored for signs and symptoms of type 2 diabetes, the authors suggested.

Office Pearl: Explain to interested patients that high levels of estradiol and testosterone, as well as low levels of sex hormone-binding globulin, in postmenopausal women appear to be highly predictive of an increased risk for type 2 diabetes.

 

 

Source: Diabetes In Control: 2006 American Diabetes Association Scientific Sessions; Ding EL et al. "Plasma Sex Hormones and Risk of Developing Type 2 Diabetes in Women." Abstract 79-0R, presented June 10.

 
 
 
 
 
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