Screen, test, treat: low testosterone and diabetes

Men with diabetes have a two times greater risk of having total testosterone less than 300 ng/dL.

Issue: October 2006

Understanding the effect of hypogonadism on men with diabetes and having knowledge of the current screening tools and treatment options available are important aspects of diabetes education.

“Four to 5 million men in the United States have hypogonadism and only about 5% are currently being treated,” said B. Farrell, BSN, RN, CDE, at the American Association of Diabetes Educators 33rd Annual Meeting and Exhibition. “Hypogonadism is often underdiagnosed. It is important that testosterone be monitored, especially in men presenting with classical signs and symptoms,” she said.

Farrell, who is currently employed by Solvay Pharmaceuticals Inc., and Donna M. Rice, MBA, RN, CDE, president of the AADE, presented information on testosterone and its emerging relationship to obesity and type 2 diabetes.

Increased risk

Obesity and diabetes are often linked to low testosterone levels. Obesity is associated with decreased sex hormone binding globulin (SHBG) levels and decreased total testosterone. SHBG binds estrogens and androgens and regulates free and bound hormone, according to Farrell.

Free and bioavailable testosterone levels are also low in more severely obese men. When morbidly obese men undergo significant weight reduction, SHBG levels and total, free and bioavailable testosterone increase.

Emerging data have continued to strengthen the association between type 2 diabetes, cardiovascular disease and low testosterone, Farrell said. Studies have shown that low total testosterone may predict potential development of type 2 diabetes. Similarly, men with type 2 diabetes have significantly low levels of free and total testosterone compared with nondiabetic men, she said.

One study found that when 110 men with diabetes were compared with 875 nondiabetic men, 21% of those with diabetes had total testosterone less than 350 ng/dL compared with 13% of those without diabetes.

In 2004, an epidemiological study found that the age-adjusted prevalence of low total testosterone levels in men was 38.4%. Odds of having total testosterone less than 300 ng/dL or being currently treated for low testosterone were two times greater if diabetes was present and 2.5 times greater if BMI was 25 or greater.

Finally, another study examined 103 men with type 2 diabetes: 43.7% had low total testosterone; 33% had low free testosterone and 36% had low bioavailable testosterone.

“This [relationship] is yet to be fully understood,” Farrell said. “Men who are complaining of decreased libido, diminished erectile function, changes in energy and mood and those with osteopenia or osteoporosis should be evaluated for hypogonadism.”

Screening for low T

Donna M. Rice, MBA, RN, CDE [photo]
Donna M. Rice

“There are a few questions that you can ask about sexual dysfunction or low testosterone,” Rice said. “You can incorporate these simple questions into a screening tool for patients.”

These questions can include asking about sex drive, energy levels and strength of erections, she said.

“You can give patients a questionnaire to take home or to bring back to their primary care doctor or internist,” Rice said.

Certain symptoms should raise a red flag for low testosterone. These symptoms vary, but can include loss of muscle mass and strength, loss of libido and erectile function, depression, fatigue, osteoporosis, loss of body hair, breast discomfort, hot flashes and sweats, height loss and regression of secondary sexual characteristics.

After these signs and symptoms associated with low testosterone are identified it is important to do thorough diagnostic testing to confirm low testosterone, Rice said.

Plasma total testosterone should be tested, preferably using a morning sample. Testosterone less than 300 ng/dL suggests hypogonadism. The Endocrine Society recommends that these levels be confirmed with a second test.

If low testosterone is confirmed then luteinizing hormone and follicle-stimulating hormone — two hormones synthesized by the hypothalamus — should be tested.

“It is necessary to measure LH and FSH because that helps us access whether it is primary hypogonadism or secondary hypogonadism,” Farrell said. “For instance, in primary hypogonadism [patients] will have a low testosterone and elevated LH and FSH. In secondary hypogonadism, [patients] will have low to normal testosterone but also have low LH and FSH.”

Primary hypogonadism is testicular failure, which can be either congential, such as Klinefelter’s syndrome, or acquired through obesity, castration, mumps or other causes.

Secondary hypogonadism is pituitary failure, which can also be congenital, such as Kallmann syndrome, or acquired through masses, rheumatoid arthritis, Crohn’s disease and certain medications or endocrine disorders.

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Testosterone replacement

After low testosterone is determined patients should be made aware of the treatment options, regimens and side effects.

“Patients should be educated about specific adverse effects, frequency of administration, flexibility of doses, reversibility in case of adverse effects and costs,” Farrell said.

Currently the treatments available are oral agents (not available in the United States), pellet implants, scrotal patches, injectables, transdermal patches and gels, and buccal tablets. Each method has its own special considerations.

Pellets require a surgical incision and may become infected. Scrotal patches require high maintenance and were found to have low adherence.

Injectables need to be injected deeply and there are peaks and valleys in serum testosterone levels, Farrell said. Levels are high after injection and then slowly decline until the next treatment. This may produce fluctuation in mood and libido and there may be pain at the injection site.

Transdermal patches can produce skin irritation at the application site. Transdermal gels — which can be applied to the shoulders, upper arms or abdominal area — are associated with a potential risk for transference to a partner or child when vigorous skin contact is made, she said.

Buccal tablets sometimes produce gum irritation and an alteration of taste.

No matter which treatment, when clinicians recommend testosterone therapy, the Endocrine Society suggests aiming to achieve testosterone levels in a range that is mid-normal. Testosterone levels should be monitored every two to three months after initiation of therapy and treatment doses adjusted as necessary. – by Leah Smith

Farrell is a senior medical liaison for Solvay Pharmaceuticals.

For more information:

Farrell JB, Rice DM. The trilogy: diabetes, obesity, and low testosterone. Presented at: American Association of Diabetes Educators 33rd Annual Meeting and Exhibition; August 11, 2006; Los Angeles.