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High Testosterone in Women Linked with Insulin Resistance and CVD

Dec 21, 2009

In postmenopausal women, high testosterone levels increase the risk for insulin resistance, metabolic syndrome, and coronary heart disease, a new study shows. 

The research team writes, “Our findings suggest that even at the physiologically low levels of testosterone found in these older women, the association between testosterone and insulin resistance found in premenopausal and early postmenopausal women persists into old age.”


The 344 women in the study ranged from 65 to 98 years of age (mean, 74.4 years), according to senior author Dr. Anne R. Cappola, of the University of Pennsylvania School of Medicine in Philadelphia, and colleagues.

Using ultrasensitive assays, the researchers determined that their cohort had a mean total testosterone level of 19.1 ng/dL and a mean free testosterone level of 2.8 pg/mL. Insulin resistance, as assessed by the homeostasis model assessment of insulin resistance, rose in a stepwise manner along with total (p = 0.003) and free (p = 0.02) testosterone.

Higher free (p = 0.002) and total (p < 0.001) testosterone levels were also accompanied by stepwise decreases in insulin sensitivity, as assessed by the Quantitative Insulin Sensitivity Check Index.

Higher levels of total and free testosterone were strongly associated with abdominal obesity and high fasting glucose — two components of the metabolic syndrome strongly linked to insulin resistance.

In adjusted models, women in the top quartile of total testosterone had a three-fold greater odds of developing metabolic syndrome (odds ratio 3.15) compared to those in the bottom quartile. These women were also three times more likely to have coronary heart disease (OR 2.95) than those in the second quartile of total testosterone.

Free testosterone was not significantly associated with metabolic syndrome or coronary heart disease.

Dr. Cappola stated that, “The connection between higher levels of testosterone and these health risks is likely explained by our finding of a greater degree of insulin resistance in women with the highest testosterone levels.”

She noted that because of the observational aspect of the study, “We cannot discern if testosterone is a marker or mediator of cardiovascular disease in this population.”

J Clin Endocrinol Metab 2009;94:4776-4784.