Testosterone Replacement Therapy Impact on Respiratory Disease Progression

Testosterone replacement therapy has the potential slow the progression of COPD, according to new research, which explored a promising way to lower the risk of hospitalization due to respiratory disease.

Study co-authors Randall Urban, MD, vice president and chief research officer, and Jacques Baillargeon, PhD, a professor of internal medicine, both at the University of Texas Medical Branch, said administering testosterone therapy early on in the progression of COPD could have a positive impact on outcomes in men suffering from the complex and difficult-to-treat disease.

Why did you explore testosterone therapy’s impact on COPD?

Dr. Baillargeon: Our team has done several research projects on testosterone therapy in middle-aged and older men involving large administrative databases, which are nationally representative and have strong statistical power. We knew based on the literature that small-scale, randomized control trials had looked at the effects of testosterone therapy on COPD outcomes in men. We also knew that there were a large proportion of men with COPD who are also hypogonadal, meaning they have chronically low testosterone levels. That's often the result of the medications they're taking for their illness or a number of comorbidities that they have. There was conflicting evidence about the impact that testosterone therapy had on respiratory outcomes in men with COPD, so we thought it would be important to look the therapy’s comparative effectiveness in a large national database.

What did your study reveal about testosterone use in COPD patients?

Dr. Baillargeon: We identified cohorts of men who were hypogonadal, had initiated testosterone therapy, and who had COPD. We compared hospitalizations for respiratory reasons between testosterone users and the nonusers. We found in both cohorts that there was a greater decrease in respiratory hospitalizations among testosterone users than in non-users. We know that low testosterone, if left untreated, causes a number of adverse symptoms, including muscle wasting. The thought is that improving lean muscle mass could ultimately improve respiratory outcomes.

How specifically does testosterone therapy slow the progression of COPD?

Dr. Urban: We don't yet know exactly why. We can speculate that patients with end-stage COPD experience loss of muscle mass and that giving them testosterone therapy might help prevent cachexia associated with severe forms of the disease, but studies have universally shown that testosterone therapy provided no real benefit to those patients. Muscle is always in a dynamic state — new muscle is being made or old muscle is being broken down. Testosterone is a unique compound that helps improve the strength of peripheral and skeletal muscles. It also increases the production of new muscle and inhibits the inflammatory process that stimulate the breakdown of muscle. We feel giving the therapy to patients with end-stage COPD, when loss of muscle mass occurs, is too late to delay the disease’s progression. Our study indicated that there’s an opportunity to explore the benefits of using testosterone therapy earlier in the course of the disease.

What is the study’s main take-home message?

Dr. Baillargeon: COPD is a high-prevalence condition, particularly in older adults, that’s associated with a lot of hospitalizations. We certainly know hypogonadism is a significant comorbidity in this patient population. It’s encouraging that testosterone therapy might help reduce the rate of respiratory hospitalizations, but a larger scale clinical trial with a particular focus on understanding the specific biologic mechanisms that underlie these findings is needed.

In the meantime, what practical advice can you give to providers based on your study’s findings?

Dr. Urban: Providers should check the testosterone levels of patients in the early stages of COPD and consider initiating therapy in those with low levels. We’ve published research that showed administering testosterone in 2-week cycles provided anabolic benefit, increased muscle mass, and minimized side effects. Those findings also raised the potential of using cycle dosing in women to avoid secondary sexual characteristic problems such as hair growth and male patterns. The early use of low-dose cycling of testosterone in COPD patients might slow the disease’s progression, but we don’t yet have clinical proof of that impact.

—Dan Cook

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