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Insulin Resistance Tied to Low Testosterone in Men: Presented at ENDO

By Paula Moyer

Special to DG News

SAN FRANCISCO, CA -- June 24, 2002 - Men who are insulin resistant are also more likely to have reduced testosterone secretions.

The findings of this small study, funded by the National Institutes of Health, were presented at ENDO 2002, the 84^th annual meeting of the Endocrine Society by lead investigator Nelly Pitteloud. Dr. Pitteloud is an instructor in the Reproductive Endocrine Unit and the National Center for Infertility Research at Massachusetts General Hospital in Boston, Massachusetts.

She and 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 range from 40 to 55 years old underwent measurements of testosterone and sex-hormone binding globulin (SHBG).

The subjects had a mean body mass index (BMI) of 26 ± 1 kg/m2, ranging from 22.5 kg/m2 to 32.7 kg/m2, and a mean baseline testosterone level of 558 ± 38 ng/dL. The mean SHBG level was 27 ± 5 nmol/L.

The subjects underwent a 75 g oral glucose tolerance test (OGTT) to provide an index of whole body insulin sensitivity (composite ISI) based on glucose and insulin levels. The mean composite ISI was 11 ± 1, with scores ranging from 5 to 15.

In a subset of eight subjects, the investigators further characterised the subjects' hypothalamic-pituitary-gonadal (HPG) axis by blood sampling every 10 minutes for 12 hours in order to assess gonadotropin and testosterone secretion. In order to evaluate the extent of the defect in the subjects' HPG axis, Dr. Pitteloud and colleagues used a physiologic probe to assess pituitary and testicular responses in the absence of endogenous reproductive hormones.

Initially, endogenous gonadotropins and sex steroids were suppressed using a gonadotropin-releasing hormone (GnRH) antagonist consisting of a subcutaneous injection of 75 mcg/kg of Acyline. Second, subjects received intravenous administration of exogenous GnRH at a dose of 750 ng/kg, so that the investigators could assess pituitary sensitivity. Finally, so that the investigators could assess Leydig cell function, the subjects underwent a human chorionic gonadotropin (hCG) stimulation test consisting of an intramuscular injection of 1,000 IU.

The investigators found that composite ISI correlated strongly with SHBG levels (r=0.82, p<0.05). The relationship to testosterone approached but did not attain statistical significance (r=0.48, p=0.09). Regarding pituitary responsiveness, the composite ISI correlated strongly with luteinising hormone (LH) amplitude (r=0.8, p<0.05).

However, the relationship with the peak LH response to exogenous GnRH was not statistically significant. The investigators observed no correlation between ISI and LH pulse frequency. In their assessment of testicular responsiveness, the investigators observed a strong correlation between ISI and the testosterone response to hCG at 24 hours (p=0.82, p<0.05).

"Our results indicate that insulin resistance in men is associated with reduced testosterone secretion," Dr. Pitteloud said. "This may be due to alterations in the HPG axis and to reductions in SHBG. It's important to find a treatment to see if reversing insulin resistance can in turn improve testosterone secretion. Men with insulin resistance should be encouraged to lose weight, but we are also studying whether insulin-sensitising agents will improve testosterone secretion."

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