Testosterone therapy shows promise for treating type 2 diabetes in men

More than a decade ago, Edward M. Lichten, MD, an obstetrician-gynecologist in Birmingham, Mich., was prescribed testosterone to address symptoms of his own declining hormone levels. His patients noticed a change for the better and asked him to help their husbands. Dr. Lichten did, and noticed a change among them, too, particularly those with type 2 diabetes -- their blood sugar control improved dramatically.

"I have had patients who could reduce the amount of insulin they took by 50% within the first 30 days," said Dr. Lichten, whose patient population is now primarily male. He also will be consulting on an upcoming study of this strategy at Providence Hospital in Southfield, Mich.

With more evidence showing that low testosterone levels in men correlate to a higher risk of type 2 diabetes, some physicians are contemplating whether supplementation of this hormone could be a possible treatment. Research confirming its effectiveness is limited. Most recently, early findings from a British study reported in the June European Journal of Endocrinology suggested that testosterone therapy reduced insulin resistance and improved blood sugar control for hypogonadal men with type 2 diabetes. Body fat and cholesterol levels also went down.

This report of the ongoing study included 24 patients treated for three months; additional studies are also examining the approach from various angles.

A systematic review published in the March 15 Journal of the American Medical Association found that men with high testosterone levels had a lower risk of developing diabetes.

Another article, published in the Aug. 14/28 Archives of Internal Medicine, associated low levels with an increased risk of death. Men with low testosterone also were more likely to have diabetes, although the exact mechanism of this link is unclear.

"Testosterone could be low as a consequence of diabetes, or low testosterone could predispose men to type 2 diabetes," said Frances Hayes, MD, assistant professor of reproductive endocrinology at Harvard Medical School in Boston. "Testosterone is playing some role."

Moving forward -- with some caution

Prescribing testosterone to men with type 2 diabetes also is not completely out of line with what physicians already are doing in some instances.

Testosterone replacement therapy is increasingly common, and, according to a report issued by IMS Health, a pharmaceutical market research and consulting firm, the number of patients who are using this therapy grew by 29%in 2002.

Endocrine Society guidelines also suggest measuring serum testosterone in all male patients with type 2 diabetes.

"Men with type 2 diabetes have an increased prevalence of low testosterone levels, and this means that some of these men may be candidates for testosterone treatment," said Glenn Cunningham, MD, one of the guideline's authors and professor of medicine and molecular and cellular biology at Baylor College of Medicine in Houston.

The challenge now facing physicians is the urgent need for larger studies into the risks and benefits of using the hormone to affect the course of type 2 diabetes.

In addition to Dr. Lichten's study, Solvay Pharmaceuticals launched a trial in March 2005 to determine if the company's testosterone gel, Androgel, could help manage blood sugar levels in men with type 2 diabetes and low testosterone.

Another study, this one funded by the National Institute of Child Health and Human Development and led by Dr. Hayes, is investigating whether the hormone can increase insulin sensitivity in men who have the metabolic syndrome.

"We don't know what the long-term effects are of raising testosterone in older subjects. It may be completely safe. We just don't know yet one way or the other," Dr. Hayes said.

Results are not expected from these studies for several years, and many physicians expressed caution.

"[On] the issue of whether testosterone will improve patients' insulin sensitivity and diabetic control, the jury is still out," Dr. Cunningham said. "The studies have not really been large enough or strong enough to know."

Wary of oversell

Most doctors also are not forgetting the upheaval that occurred after the release of Women's Health Initiative results in 2002. Before these data's emergence, hormones had been used widely by postmenopausal women because prior observational studies had suggested that this practice would improve their overall health.

"Because the studies of hormone therapy in women were done in a particular fashion, they overestimated some of the positive effects," said Ernest Yoder, MD, PhD, chair of the Dept. of Internal Medicine at Providence Hospital, and who is likely to be involved in Dr. Lichten's planned study.

"Hopefully, we're not going to make the same mistakes and have something become a standard of practice without clinical trials," Dr. Yoder said.

Also, while the findings of some studies suggest that this strategy might be beneficial, others continue to raise questions about the value of testosterone supplementation.

A study in the Oct. 19 New England Journal of Medicine, involving healthy rather than diabetic men, for instance, found that low-dose supplementation had no impact on their insulin sensitivity.