First Investigation of Testosterone Therapy in Women with Chronic Heart Failure Shows Benefits
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A dose of testosterone appears to be beneficial in elderly women with advanced chronic heart failure (CHF) – a condition in which the heart can no longer pump enough blood to meet the body’s needs, according to a new study published in the October 12, 2010, issue of the Journal of the American College of Cardiology.
The study – the first to look at this potential new therapy in women with CHF – shows that low-dose testosterone supplementation, in addition to standard medical care, can improve insulin resistance, muscle strength and functional capacity, the amount of physical exertion an individual can sustain before muscle exhaustion or related symptoms (e.g., labored breathing, shortness of breath) develop.
“This therapy improves important clinical measures – exercise capacity, muscle strength and insulin sensitivity – which all play a role in determining the prognosis and survival of female patients with chronic heart failure,” said Ferdinando Iellamo, M.D., professor of motor science, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Pisana, University Tor Vergata. “While more research is needed, testosterone supplementation could be considered for female patients whose testosterone levels are at or below the normal range, provided that no contraindications to testosterone administration do exist.”
In this study, 36 elderly women with advanced CHF were randomized 2:1 to receive a skin patch either with 300 mcg of testosterone or a placebo, applied twice weekly for 24 weeks. Primary end points of this double-blind study were distance traveled during a 6-minute walk test and insulin sensitivity.
Authors report a significant 36 percent relative increase in 6-min walking time, improvements in peak oxygen consumption (VO2), and declines in insulin resistance among women who received testosterone supplementation. In addition, both muscle strength and performance improved in patients supplemented with testosterone.
Patients with chronic heart failure, particularly the elderly, tend to have a decrease in muscle mass, strength and performance. Many people with CHF also have insulin resistance, leading to an inability of insulin to promote glucose getting into skeletal muscles and perhaps contributing to skeletal fatigue and deterioration. Testosterone supplementation is thought to work by increasing the number and size of muscular fibers that help to improve oxygen utilization and delay the onset of fatigue. This is the likely way by which testosterone supplementation improves muscle strength and performance and, in turn, functional capacity.
“The lack of effects of testosterone on left ventricular function in women, like men, seems to confirm that the effect of testosterone is mediated via a direct action on muscle rather than any changes in LV function,” said Dr. Iellamo. “We have no direct evidence for this yet, but there are animal studies that show that testosterone improves metabolism at the muscular level.”
Larger, long-duration studies are needed to determine the benefits and safety of such a replacement strategy in women with CHF, according to authors and other experts.
“Replacing testosterone that is lacking could be a novel approach, but larger clinical trials involving both men and women are needed to find the right dose and route of administration, as well as to assess not only symptomatic relief, but harder endpoints such as death and hospitalization for severe heart failure,” said Paul W. Armstrong, M.D., Distinguished University Professor, Department of Cardiology, University of Alberta and author of the accompanying editorial.
“Heart failure affects both sexes; although there are some differences between men and women's heart failure syndromes, there are probably more similarities and perhaps we could better capitalize on these as we strive to enhance patient care,” he said.
Dr. Iellamo and his team caution that testosterone supplementation should be regarded, at present, only as an adjunctive therapy and that the results cannot be extrapolated to less severely ill and/or obese female patients with CHF. He and his team reported similar findings in men with CHF.
Drs. Iellamo and Armstrong report no conflicts of interest.
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