title: Effects of transdermal testosterone treatment on inflammatory markers in elderly males.
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 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.
authors.affiliation: Department of Clinical and Experimental Medicine, Section of Geriatrics, University of Parma, Italy Geriatric Rehabilitation Department, University Hospital of Parma, Parma, Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: Maggio
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Snyder
authors.affiliation: Geriatric Rehabilitation Department, University Hospital of Parma, Parma, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: De Vita
authors.affiliation: Department of Clinical and Experimental Medicine, Section of Geriatrics, University of Parma, Italy Geriatric Rehabilitation Department, University Hospital of Parma, Parma, Italy.
authors.forename: Gian Paolo
authors.initials: GP
authors.lastname: Ceda
authors.affiliation: Department of Psychiatry, VU University Medical Center/GGZ inGeest, Amsterdam, the Netherlands National Institute on Aging, National Institutes of Health, Baltimore, Maryland.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Milaneschi
authors.affiliation: Geriatric Rehabilitation Department, University Hospital of Parma, Parma, Italy.
authors.forename: Fulvio
authors.initials: F
authors.lastname: Lauretani
authors.affiliation: Department of Clinical and Experimental Medicine, Section of Geriatrics, University of Parma, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Luci
authors.affiliation: Department of Clinical and Experimental Medicine, Section of Geriatrics, University of Parma, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Cattabiani
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Helen
authors.initials: H
authors.lastname: Peachey
authors.affiliation: Department of Clinical and Experimental Medicine, Section of Geriatrics, University of Parma, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Valenti
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Anne R
authors.initials: AR
authors.lastname: Cappola
authors.affiliation: National Institute on Aging, National Institutes of Health, Baltimore, Maryland.
authors.forename: Dan L
authors.initials: DL
authors.lastname: Longo
authors.affiliation: National Institute on Aging, National Institutes of Health, Baltimore, Maryland.
authors.forename: Luigi
authors.initials: L
authors.lastname: Ferrucci
mesh_terms: D000368:Aged; D015415:Biomarkers; D002097:C-Reactive Protein; D004311:Double-Blind Method; D006801:Humans; D015850:Interleukin-6; D008297:Male; D013739:Testosterone / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha
chemical_list: D015415:Biomarkers; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D013739:Testosterone; D002097:C-Reactive Protein
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