SAN FRANCISCO (Reuters Health) - Men who are insulin resistant also tend to have reduced testosterone levels, according to researchers who presented their findings here Friday at the 84th annual meeting of the Endocrine Society.

"Our results indicate that insulin resistance in men is associated with reduced testosterone secretion," lead investigator Dr. Nelly Pitteloud told Reuters Health. "This may be due to alterations in the hypothalamic-pituitary-gonadal (HPG) axis and to reductions in sex-hormone binding globulin (SHBG)." Dr. Pitteloud is a staff endocrinologist at Massachusetts General Hospital in Boston, where she is an instructor in the Reproductive Endocrine Unit and the National Center for Infertility Research.

In this small study, funded by the National Institutes of Health, she and her colleagues sought to determine whether there was a dose-response relationship between increasing insulin resistance and testosterone secretion in otherwise normal men.

Eleven healthy men, who ranged in age from 40 to 55 years old, underwent testosterone and SHBG measurement. The subjects had a mean body mass index (BMI) of 26, ranging from 22.5 to 32.7, and a mean baseline testosterone level of 558 ng/dL. The mean SHBG level was 27 nmol/L.

The subjects underwent a 75-g oral glucose tolerance test to provide an index of whole body insulin sensitivity (composite ISI), based on glucose and insulin levels. The mean composite ISI was 11, with scores ranging from 5 to 15.

In a subset of eight subjects, the investigators further characterized HPG axis function and assessed gonadotropin and testosterone secretion by sampling the subjects' blood every 10 minutes for 12 hours. To evaluate whether there were defects in HPG axis function, Dr. Pitteloud and colleagues used a physiologic probe to assess pituitary and testicular responses in the absence of endogenous reproductive hormones.

The subjects' endogenous gonadotropins and sex steroids were initially suppressed using a gonadotropin-releasing hormone (GnRH) antagonist. The subjects then received intravenous administration of exogenous GnRH at a dose of 750 mg/kg, so that the investigators could assess pituitary sensitivity. To assess Leydig cell function, the subjects underwent a human chorionic gonadotropin stimulation test, using an intramuscular injection of 1000 IU.

The investigators found that composite ISI correlated strongly with SHBG levels (p < 0.05). The relationship between composite ISI and testosterone approached but did not attain statistical significance (p = 0.09). Composite ISI correlated strongly with luteinizing hormone amplitude (p < 0.05), which indicated pituitary responsiveness to insulin.

The relationship between the peak luteinizing hormone response and exogenous GnRH was not significant

In their assessment of testicular responsiveness, the investigators observed a strong correlation between ISI and the testosterone response to human chorionic gonadotropin at 24 hours (p < 0.05).

"It's important to find a treatment to see if reversing insulin resistance can, in turn, improve testosterone secretion," Dr. Pitteloud told Reuters Health. "Men with insulin resistance should be encouraged to lose weight. However, we are also studying whether insulin-sensitizing agents will improve testosterone secretion."

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