Low testosterone production appears to be a common complication of type 2 diabetes in men, affecting 1 out of 3 diabetic patients, a new study has shown.

Moreover, results of the investigation show that this condition, known clinically as hypogonadism, is caused not by a defect in the testes, where testosterone is produced, but by improper functioning of the pituitary gland, which controls production of testosterone, or of the hypothalamus, the region of the brain that controls the pituitary.

"This starts a whole new story on the crucial complications of type 2 diabetes," said Paresh Dandona, M.D., senior author on the study and director of the Division of Endocrinology, Diabetes and Metabolism at the University at Buffalo and Kaleida Health, where the study was conducted.

Results of the study appear in the November issue of Journal of Clinical Endocrinology and Metabolism.

Sandeep Dhindsa, M.D., UB assistant professor of medicine and first author on the study, said the findings are important because hypogonadism has not been recognized as a complication of type 2 diabetes, and the high prevalence of 30 percent was unexpected.

"The surprisingly high prevalence of low testosterone levels was associated with lower levels of pituitary hormones called gonadotrophins, suggesting that the primary defect in these patients was either in the pituitary or higher up in the hypothalamus," he said. "Since gonadotrophins drive the testes to produce testosterone, this finding gives us an insight into the pathogenesis of this complication of type 2 diabetes."

Earlier studies, including those conducted by this research group, found that diabetic subjects with erectile dysfunction and low testosterone levels often have low levels of pituitary hormones. However, conclusions from prior studies have been fraught with problems with testosterone assays, Dhindsa noted.

"A large portion of testosterone in the blood is bound to proteins, but a small portion is unbound and largely determines the amount of testosterone that is available to the tissues," said Dhindsa. "This active portion is called free testosterone. Assays to accurately determine it are delicate, tedious and time-consuming.

"This investigation set out to determine, in a prospective fashion, the prevalence of low total testosterone, accurately measure free testosterone in male patients with type 2 diabetes and to attempt to determine the seat of the problem in those with low free testosterone." The study involved 103 consecutive males with type 2 diabetes who were referred to the Diabetes-Endocrinology of Western New York for treatment. None of the men had been diagnosed previously with low testosterone levels.

The researchers collected fasting blood samples from the participants and analyzed them for testosterone levels and for hormones associated with testosterone production. They also measured cholesterol and glucose levels, and a blood marker for how well glucose was controlled during previous months, called hemoglobin A1c. Data on height, weight and diabetic complications, including erectile dysfunction, neuropathy, retinopathy and coronary artery disease, were recorded.

Results showed that nearly one-third of the men had hypogonadism. Although obesity is associated with hypogonadism and is prevalent among type 2 diabetics, only 10-15 percent of the variation in low free testosterone levels could be attributable to body mass index, Dhindsa said. More than 30 percent of lean patients also were hypogonadal.

"Equally important, most of the men who had low testosterone levels also had lower levels of gonadotrophins, as compared to men with normal testosterone levels," he noted. "Furthermore, the gonadotrophin concentration in the blood correlated positively with free testosterone levels, supporting the notion that the cause of the defect is in the pituitary or hypothalamus."

The high prevalence of low testosterone in diabetic men is concerning, said Dhindsa, because in addition to lowered libido and erectile dysfunction, the condition is associated with loss of muscle tone, increase in abdominal fat, loss of bone density, and can affect mood and cognition.

"Further studies will help us determine why type 2 diabetic patients are more prone to developing hypogonadism," he said. "While obesity may explain part of the high prevalence of hypogonadism, it is likely that other factors associated with type 2 diabetes also contribute significantly. This area is clearly ripe for further investigation."

Reference Source 125
December 1, 2004

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