Testosterone Therapy for Older Hypogonadal Men: The Debate Continues

By Thomas Crocker
Thursday, March 1, 2018

Long-term testosterone therapy improves urinary and sexual function in hypogonadal men, according to a recent study. Other recent findings, however, continue to fuel debate as to whether the potential benefits of the treatment outweigh the risks.

In middle-aged and older men, low levels of testosterone caused by age-related decline in its production can significantly reduce quality of life. Testosterone deficiency (male hypogonadism) can lead to fatigue, muscle loss, low libido, erectile dysfunction and lower urinary tract symptoms (LUTS), such as weak stream and incomplete bladder emptying.

Testosterone therapy for older, symptomatic, hypogonadal men has long been contentious among clinicians, mainly due to fears of a link to prostate cancer. Studies have proved those concerns to be unfounded, according to Abdulmaged Traish, PhD, Professor of Urology at Boston University School of Medicine, but questions have remained about a possible association between testosterone therapy and LUTS. Traish partnered with colleagues at Boston University and in Germany to conduct a long-term, observational, prospective study of testosterone therapy’s effects on urinary and sexual function, as well as quality of life.

“The myth is that androgen [testosterone] causes abnormal prostate growth,” Traish says. “Benign prostatic hyperplasia takes place only when androgen begins to decline, though. I think this somehow has never been understood. The myth continues, and because it does, we think testosterone therapy is going to make urinary symptoms worse. A few studies before ours didn’t see worsening. Everyone criticizes the duration of [those] studies, so we undertook this one to [find out] if we were to go back and evaluate patients who’ve been on this treatment seven, eight, 10 years, what would we see?”

Encouraging Results

The study examined 656 men, most in their 50s and 60s, who received treatment for hypogonadism at a urology clinic in Germany. A group of 360 men received injectable testosterone undecanoate every 12 weeks for up to 10 years; the in-office nature of the treatment ensured 100 percent patient compliance. The 296 men who chose not to receive testosterone served as a control group. The researchers identified 82 men from each group for comparative examination. The median follow-up period for both groups was eight years.

Men who received testosterone therapy experienced fewer LUTS, as well as improvement in erectile dysfunction and increases in quality of life. Measurements of post-void bladder volume found that the men in the testosterone group were able to empty their bladders more successfully. Men in the non-testosterone group saw LUTS rise, erectile function fall and quality of life decrease. They also experienced increasing difficulty with emptying the bladder.

“The literature is replete with arguments that testosterone increases prostate volume and, therefore, worsens LUTS,” Traish says. “However, our study and several others have demonstrated that testosterone therapy does not worsen LUTS; on the contrary, it improves them.”

One of Traish’s coauthors, urologist Ahmad Haider, Dr. Med., whose clinic in Germany compiled the registry used in the study, says the lengthy follow-up “revealed some hitherto unknown effects of testosterone therapy.”

“I like to think that we see a slow reversal of a situation that has gotten out of balance,” he says.

Dr. Haider gives the example of a man who has become obese over many years as the result of poor diet and inactivity. Obesity is associated with low testosterone.

“The man gets his testosterone normalized, he starts feeling better, his muscle mass comes back slowly, he gets more active ... and things start to slowly improve,” Dr. Haider says. “The fact that we still see improvements after 10 years of treatment speaks to this hypothesis.”

Reasons for Caution

Glenn R. Cunningham, MD, Distinguished Professor Emeritus of Medicine (Endocrinology) at Baylor College of Medicine, who was not involved in the study, points to its non-randomized nature and lower threshold for diagnosing hypogonadism than those of recent clinical trials as reasons for skepticism.

“The testosterone group had a baseline BMI of 33.1, and the control group had a BMI of 29.3,” Dr. Cunningham says. “Total testosterone levels are decreased in obese men [but free testosterone levels may remain in the normal range], so it is likely that many of these men were not hypogonadal.”

Recent findings will likely continue to give physicians pause. In 2017, researchers revealed the results of the one-year, NIH-supported Testosterone Trials, which examined the use of testosterone in nearly 800 hypogonadal men age 65 and older. The treatment increased volumetric bone mineral density and bone strength, as well as hemoglobin levels in men with anemia, compared with controls. However, men in the testosterone group were found to have more noncalcified plaque in their coronary arteries — a risk factor for heart attack — at the end of the study. Other studies have shown that testosterone therapy has no adverse effects on the heart, and may even be protective, according to Traish. Longer, larger studies are needed to corroborate the Testosterone Trials’ findings.

“There’s reasonable evidence out there to give a three- or six-month [testosterone therapy] trial,” Traish says, “and if the patient doesn’t benefit, take him off the therapy.”