Marcello Maggio1, Peter J Snyder2, Francesca De Vita3, Gian Paolo Ceda1, Yuri Milaneschi4, Fulvio Lauretani3, Michele Luci5, Chiara Cattabiani5, Helen Peachey2, Giorgio Valenti5, Anne R Cappola2, Dan L Longo6, Luigi Ferrucci6. 1. Department of Clinical and Experimental Medicine, Section of Geriatrics, University of Parma, Italy Geriatric Rehabilitation Department, University Hospital of Parma, Parma, Italy. 2. Division of Endocrinology, Diabetes, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania. 3. Geriatric Rehabilitation Department, University Hospital of Parma, Parma, Italy. 4. Department of Psychiatry, VU University Medical Center/GGZ inGeest, Amsterdam, the Netherlands National Institute on Aging, National Institutes of Health, Baltimore, Maryland. 5. Department of Clinical and Experimental Medicine, Section of Geriatrics, University of Parma, Italy. 6. National Institute on Aging, National Institutes of Health, Baltimore, Maryland.
Abstract
OBJECTIVE: During the male aging process, testosterone (T) levels progressively fall and inflammatory biomarkers increase. Although a relationship between these 2 phenomena has been tested in previous clinical trials, there is inconclusive evidence about the potential anti-inflammatory action of T. METHODS: A total of 108 healthy males >65 years with serum T concentration <475 ng/dL were recruited by direct mailings to alumni of the University of Pennsylvania and Temple University and randomized to60-cm2 T or a placebo patch for 36 months. Ninety-six subjects completed the trial. Information and stored serum specimens from this trial were used to test the hypothesis of the inhibitory effect of T on inflammation. We evaluated 70 males (42 in the T group) who had banked specimens from multiple time points available forassays of T, C-reactive protein (CRP), tumor necrosis factor (TNF)-α, soluble TNF-α receptor-1 (TNFR1), interleukin-6 (IL-6), and soluble IL-6 receptors (sIL6r and sgp130). RESULTS: The mean age ± SD at baseline was 71.8 ± 4.9 years. Testosterone replacement therapy for 36 months did not induce significant decreases in inflammatory markers. A trend toward a significant increase was observed in the placebo group for TNF-α (P = .03) and sgp130 (P = .01). Significant differences in estimated means of TNFR1 (but not other inflammatory markers), with lower levels in the T group, were observed at the 36-month time point. In T-treated subjects we found an almost significant treatment x time interaction term TNFR1 (P = .02) independent of total body fat content as assessed by dual energy X-ray absorptiometry (DXA). No serious adverse effect was observed. CONCLUSIONS:Transdermal T treatment of older males for 36 months is not associated with significant changes in inflammatory markers.
RCT Entities:
OBJECTIVE: During the male aging process, testosterone (T) levels progressively fall and inflammatory biomarkers increase. Although a relationship between these 2 phenomena has been tested in previous clinical trials, there is inconclusive evidence about the potential anti-inflammatory action of T. METHODS: A total of 108 healthy males >65 years with serum T concentration <475 ng/dL were recruited by direct mailings to alumni of the University of Pennsylvania and Temple University and randomized to 60-cm2 T or a placebo patch for 36 months. Ninety-six subjects completed the trial. Information and stored serum specimens from this trial were used to test the hypothesis of the inhibitory effect of T on inflammation. We evaluated 70 males (42 in the T group) who had banked specimens from multiple time points available for assays of T, C-reactive protein (CRP), tumor necrosis factor (TNF)-α, soluble TNF-α receptor-1 (TNFR1), interleukin-6 (IL-6), and soluble IL-6 receptors (sIL6r and sgp130). RESULTS: The mean age ± SD at baseline was 71.8 ± 4.9 years. Testosterone replacement therapy for 36 months did not induce significant decreases in inflammatory markers. A trend toward a significant increase was observed in the placebo group for TNF-α (P = .03) and sgp130 (P = .01). Significant differences in estimated means of TNFR1 (but not other inflammatory markers), with lower levels in the T group, were observed at the 36-month time point. In T-treated subjects we found an almost significant treatment x time interaction term TNFR1 (P = .02) independent of total body fat content as assessed by dual energy X-ray absorptiometry (DXA). No serious adverse effect was observed. CONCLUSIONS: Transdermal T treatment of older males for 36 months is not associated with significant changes in inflammatory markers.
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