madman
Super Moderator
Testosterone Replacement Therapy added to Intensive Lifestyle Intervention in Older Men with Obesity and Hypogonadism
ABSTRACT
Background: Obesity and hypogonadism additively contribute to frailty in older men; however, appropriate treatment remains controversial.
Objective: Determine whether testosterone replacement augments the effect of lifestyle therapy on physical function in older men with obesity and hypogonadism.
Design: Randomized, double-blind, placebo-controlled trial.
Setting: VA Medical Center Participants: Eighty-three older (age≥65 years) men with obesity (BMI≥30 kg/m2 ) and persistently low AM testosterone (<10.4 nmol/L) associated with frailty.
Interventions: Participants were randomized to lifestyle therapy (weight management and exercise training) plus either testosterone (LT+Test) or placebo (LT+Pbo) for six months.
Outcome Measures: Primary outcome was a change in the Physical Performance Test (PPT) score. Secondary outcomes included other frailty measures, body composition, BMD, physical functions, hematocrit, PSA, and sex hormones.
Results: PPT score increased similarly in LT+Test and LT+Pbo group (17% vs. 16%; P=.58). VO2peak increased more in LT+Test than LT+Pbo (23% vs. 16%; P=.03). Despite similar -9% weight loss, lean body mass and thigh muscle volume decreased less in LT+Test than LT+Pbo (-2% vs. -3 %; P=.01 and -2% vs -4%; P=04). Hip BMD was preserved in LT+Test compared with LT+Pbo (0.5% vs. -1.1%; P=.003). Strength increased similarly in LT+Test and LT+Pbo (23% vs. 22%; P=.94). Hematocrit but not PSA increased more in LT+Test than LT+Pbo (5% vs 1%; P<.001). Testosterone levels increased more in LT+Test than LT+Pbo (167% vs 27%; P<.001).
Conclusion: In older, obese hypogonadal men, adding testosterone for six months to lifestyle therapy does not further improve overall physical function. However, our findings suggest that testosterone may attenuate the weight loss–induced reduction in muscle mass and hip BMD and may further improve aerobic capacity.
INTRODUCTION
The increasing population of older adults with obesity in the US and other countries (1,2), is a major public health challenge because obesity exacerbates the age-related decline in physical function resulting in frailty and decreased quality of life (QOL) (3-5). However, weight loss therapy of obesity in older adults remains controversial, given the concern that weight loss could worsen the age-related decline in muscle and bone mineral density (BMD) and worsen frailty (6,7). In addition to overeating and exercise insufficiency, the age-related decline in anabolic hormone (i.e., testosterone) may contribute to the age-related loss of muscle and BMD (8,9), which in turn is exacerbated by obesity (10,11). We previously reported that weight loss plus exercise improved physical function and ameliorated frailty in older adults with obesity (12). However, despite weight loss combined with exercise, a potential adverse effect was weight loss-induced reduction in muscle mass and bone mass and thus exacerbating age-related losses (12,13). Importantly, because both obesity and aging lower testosterone levels, we reported a high prevalence of hypogonadism in this population, which did not correct with lifestyle therapy (weight management plus exercise training) (14). Indeed, a high prevalence of hypogonadism (~50%) has been reported in obese men in a large community-based study (15).
The purpose of this randomized, double-blind, comparative efficacy, controlled trial was to determine whether testosterone replacement therapy would augment the effects of lifestyle therapy in older men with obesity and hypogonadism. We hypothesized that lifestyle therapy plus testosterone replacement would improve physical function and preserve muscle and BMD during weight loss more than lifestyle therapy without testosterone in this prevalent, high-risk, but understudied population of older men with obesity and hypogonadism.
The testosterone preparation was Androgel 1.62% (Abbvie) applied topically once daily in the morning. The placebo gel was formulated to have an identical appearance to the active gel. The initial dose was 40.5 mg daily, which was expected to increase the testosterone level within the normal range for young men (19 to 40 years of age). To verify that the testosterone level was in the target range, the testosterone level was measured two weeks after starting the intervention. If the testosterone level was not in the target range, the dose was adjusted by the unblinded physician and a measurement repeated after another two weeks. To maintain blinding when the dose was adjusted in a participant receiving testosterone, the dose was changed simultaneously in a participant receiving a placebo.
DISCUSSION
To our knowledge, this is the first randomized trial of testosterone replacement therapy added to lifestyle therapy in older men with obesity and hypogonadism associated with frailty. Our randomized, controlled trial indicated that testosterone replacement does not further improve overall physical function and reduce frailty in addition to lifestyle therapy. However, testosterone replacement may further increase aerobic capacity and minimize or prevent muscle and BMD loss that occurs with lifestyle therapy in addition to improving sexual function.
In conclusion, our findings demonstrated that in older men with obesity and hypogonadism, testosterone replacement therapy does not significantly add to the improvement in overall physical function and reduction of frailty that occurs with lifestyle therapy alone. However, our findings suggest that testosterone replacement not only may attenuate the weight loss–induced reduction of muscle and BMD that occurs with lifestyle therapy but may improve sexual health and more importantly, may also further improve aerobic capacity. Whether to add testosterone to lifestyle therapy in this population should be decided on an individual basis after carefully weighing the risks and benefits of testosterone therapy.
ABSTRACT
Background: Obesity and hypogonadism additively contribute to frailty in older men; however, appropriate treatment remains controversial.
Objective: Determine whether testosterone replacement augments the effect of lifestyle therapy on physical function in older men with obesity and hypogonadism.
Design: Randomized, double-blind, placebo-controlled trial.
Setting: VA Medical Center Participants: Eighty-three older (age≥65 years) men with obesity (BMI≥30 kg/m2 ) and persistently low AM testosterone (<10.4 nmol/L) associated with frailty.
Interventions: Participants were randomized to lifestyle therapy (weight management and exercise training) plus either testosterone (LT+Test) or placebo (LT+Pbo) for six months.
Outcome Measures: Primary outcome was a change in the Physical Performance Test (PPT) score. Secondary outcomes included other frailty measures, body composition, BMD, physical functions, hematocrit, PSA, and sex hormones.
Results: PPT score increased similarly in LT+Test and LT+Pbo group (17% vs. 16%; P=.58). VO2peak increased more in LT+Test than LT+Pbo (23% vs. 16%; P=.03). Despite similar -9% weight loss, lean body mass and thigh muscle volume decreased less in LT+Test than LT+Pbo (-2% vs. -3 %; P=.01 and -2% vs -4%; P=04). Hip BMD was preserved in LT+Test compared with LT+Pbo (0.5% vs. -1.1%; P=.003). Strength increased similarly in LT+Test and LT+Pbo (23% vs. 22%; P=.94). Hematocrit but not PSA increased more in LT+Test than LT+Pbo (5% vs 1%; P<.001). Testosterone levels increased more in LT+Test than LT+Pbo (167% vs 27%; P<.001).
Conclusion: In older, obese hypogonadal men, adding testosterone for six months to lifestyle therapy does not further improve overall physical function. However, our findings suggest that testosterone may attenuate the weight loss–induced reduction in muscle mass and hip BMD and may further improve aerobic capacity.
INTRODUCTION
The increasing population of older adults with obesity in the US and other countries (1,2), is a major public health challenge because obesity exacerbates the age-related decline in physical function resulting in frailty and decreased quality of life (QOL) (3-5). However, weight loss therapy of obesity in older adults remains controversial, given the concern that weight loss could worsen the age-related decline in muscle and bone mineral density (BMD) and worsen frailty (6,7). In addition to overeating and exercise insufficiency, the age-related decline in anabolic hormone (i.e., testosterone) may contribute to the age-related loss of muscle and BMD (8,9), which in turn is exacerbated by obesity (10,11). We previously reported that weight loss plus exercise improved physical function and ameliorated frailty in older adults with obesity (12). However, despite weight loss combined with exercise, a potential adverse effect was weight loss-induced reduction in muscle mass and bone mass and thus exacerbating age-related losses (12,13). Importantly, because both obesity and aging lower testosterone levels, we reported a high prevalence of hypogonadism in this population, which did not correct with lifestyle therapy (weight management plus exercise training) (14). Indeed, a high prevalence of hypogonadism (~50%) has been reported in obese men in a large community-based study (15).
The purpose of this randomized, double-blind, comparative efficacy, controlled trial was to determine whether testosterone replacement therapy would augment the effects of lifestyle therapy in older men with obesity and hypogonadism. We hypothesized that lifestyle therapy plus testosterone replacement would improve physical function and preserve muscle and BMD during weight loss more than lifestyle therapy without testosterone in this prevalent, high-risk, but understudied population of older men with obesity and hypogonadism.
The testosterone preparation was Androgel 1.62% (Abbvie) applied topically once daily in the morning. The placebo gel was formulated to have an identical appearance to the active gel. The initial dose was 40.5 mg daily, which was expected to increase the testosterone level within the normal range for young men (19 to 40 years of age). To verify that the testosterone level was in the target range, the testosterone level was measured two weeks after starting the intervention. If the testosterone level was not in the target range, the dose was adjusted by the unblinded physician and a measurement repeated after another two weeks. To maintain blinding when the dose was adjusted in a participant receiving testosterone, the dose was changed simultaneously in a participant receiving a placebo.
DISCUSSION
To our knowledge, this is the first randomized trial of testosterone replacement therapy added to lifestyle therapy in older men with obesity and hypogonadism associated with frailty. Our randomized, controlled trial indicated that testosterone replacement does not further improve overall physical function and reduce frailty in addition to lifestyle therapy. However, testosterone replacement may further increase aerobic capacity and minimize or prevent muscle and BMD loss that occurs with lifestyle therapy in addition to improving sexual function.
In conclusion, our findings demonstrated that in older men with obesity and hypogonadism, testosterone replacement therapy does not significantly add to the improvement in overall physical function and reduction of frailty that occurs with lifestyle therapy alone. However, our findings suggest that testosterone replacement not only may attenuate the weight loss–induced reduction of muscle and BMD that occurs with lifestyle therapy but may improve sexual health and more importantly, may also further improve aerobic capacity. Whether to add testosterone to lifestyle therapy in this population should be decided on an individual basis after carefully weighing the risks and benefits of testosterone therapy.
