Postmenopausal women with higher levels of bioavailable
testosterone and 17beta-estradiol and lower levels of sex hormone-binding
globulin had significantly greater risk for developing incident type 2 diabetes
in a new study.
Adiposity and insulin resistance explained the
association between testosterone and type 2 diabetes but only partially
explained the association with estradiol and SHBG.
Researchers examined the association between endogenous
sex hormones and incident type 2 diabetes in 1,612 postmenopausal women aged 45
to 84 years. All women were included in the Multi-Ethnic Study of
Atherosclerosis (MESA), a multicenter, longitudinal cohort study of the
prevalence and correlates of subclinical cardiovascular disease from 2000 to
2006.
The women were not taking hormone replacement therapy,
had no prevalent CVD or diabetes and had complete detection of sex hormones.
During follow-up, researchers identified 116 incident
cases of type 2 diabetes.
Hazard ratios for developing incident diabetes were
greater for women with higher quartiles of bioavailable testosterone and
estradiol and lower quartiles of SHBG (P<.001 for all).
However, after adjusting for BMI and insulin resistance,
bioavailable testosterone was no longer associated with incident type 2
diabetes. The associations of estradiol and SHBG with diabetes were explained
in part by BMI and insulin resistance but persisted in fully adjusted models
(P<.02 for both). Dehydroepiandrosterone was not associated with
incident diabetes.
The researchers concluded that further studies are
required to establish hormone thresholds at which diabetes risk is increased to
identify high-risk postmenopausal women.
“It is not known how medications inhibiting the
production of adrenally produced sex hormones or aromatase activity may affect
development of type 2 diabetes,” they wrote. “In the future, studies
investigating the effects of such medications on glucose metabolism and
diabetes risk may facilitate the development of novel glucose-lowering
therapies and diabetes prevention measures.”
Kalyani R. J Clin Endocrinol Metab.2009; 94:
4127–4135.