Low Testosterone Should Arouse Clinical Interest

Among the ravages that diabetes and obesity inflict on the body, none presents a greater clinical challenge than derangements of the endocrine system.

Low testosterone, or hypogonadism, is a common but confounding condition that experts say often is underappreciated in primary care.

The links between diabetes, obesity, and hypogonadism are numerous and strong. About one-third of men with diabetes have low levels of testosterone.¹ Men with diabetes aged ≥45 years may be more than twice as likely to have low testosterone as those without diabetes, according to an analysis of the Hypogonadism in Males (HIM) study recently reported at the American Diabetes Association's Annual Meeting and Scientific Sessions in San Diego.

According to research presented in May at the American Association of Clinical Endocrinologists' (AACE) Annual Meeting, the prevalence of hypotestosteronemia (low blood testosterone) is 50% among men with diabetes, 42% among men with hypertension, and 40% among men with hyperlipidemia.

Similar results were observed in the HIM study. Nearly 38% of the men had low testosterone, but among those with diabetes the proportion was 50%, according to co-investigator Sherwyn L. Schwartz, MD, director of the Diabetes and Glandular Disease Clinic in San Antonio, Texas.

WARNING FLAG

About 13 million American men have low testosterone, typically defined as a total testosterone level ≤300 ng/dl, according to AACE. Normally, testosterone levels are 300–1,000 ng/dl.

Men's testosterone levels naturally begin to decline at ages 25–30 years, dropping about 10% per decade. In addition, as men get older, the concentration of sex hormone–binding globulin (SHBG) in the blood increases, reducing the level of unbound, bioavailable testosterone in circulation.

Common symptoms of hypogonadism include decreased libido, erectile dysfunction (ED) (“The Little Blue Pill,” see page 8), fatigue or weakness, and mood changes.

THERAPEUTIC OPTIONS

After a diagnosis of hypogonadism, clinicians first should encourage patients to adopt lifestyle changes to reduce weight and increase physical activity. About one-third of obese patients will have a low total testosterone but a normal bioavailable testosterone—that's a key point about how to measure testosterone, says Richard J. Santen, MD, of the University of Virginia in Charlottesville.

“When you lose weight, the binding protein SHBG and total testosterone go up, but in fact, the biologically available testosterone doesn't,” Santen says. So losing weight to increase testosterone is good advice if a patient goes from 400 lb to 200 lb, but less so for 250 lb to 150 lb, he says.

Endocrinologist William Rosner, MD, of the College of Physicians and Surgeons at Columbia University in New York, suggests referring a patient to a specialist if first-line approaches such as weight loss and increased physical activity fail to bring up testosterone levels.

Virtually all men with low testosterone levels and primary testicular dysfunction should be considered for testosterone replacement, says Bradley Anawalt, MD, of the University of Washington in Seattle and the Veterans Affairs Puget Sound Health Care System. Testosterone is good for bones, muscle, a sense of well-being, and mood and sexual function.

“Many, if not most, men with low testosterone and pituitary disease with low or normal gonadotropins also will benefit for the same reasons,” Anawalt says.

Supplemental testosterone can be given in a variety of formulations—a topical gel or transdermal patch that releases the hormone throughout the day, an injection administered in the clinic every 10–21 days, or a sustained-release buccal tablet. Rosner says the choice of formulation for testosterone replacement therapy is up to patient preference, based on convenience, palatability, and cost. “All of the formulations are equally efficacious,” he says.

There is some controversy about what to do with the large proportion of men >60 years who have low testosterone levels and normal gonadotropins, and whether those conditions might be due to aging and might benefit from treatment. “That's going to involve a conversation between the clinician and patient weighing the risks and benefits for a given indidividual,” Anawalt says.

Prescribing testosterone may not always be appropriate. Supplemental testosterone can increase prostate size and the risk of prostate cancer.

More important, hormone replacement may mask a pituitary tumor. Carson says that looking at thyrotropin and prolactin may provide clues to pituitary tumor, as well as symptoms such as headache, fatigue, and gynecomastia (“The Low Testosterone Workup,” see page 9).

Side effects of testosterone therapy include an increased red cell count, and testosterone may cause acne and breast discomfort. Men who are overweight or have lung disease may develop or have worsened sleep apnea. ▪