title: Testosterone, sex hormone-binding globulin and the metabolic syndrome in men: an individual participant data meta-analysis of observational studies.
abstract: BACKGROUND
  Low total testosterone (TT) and sex hormone-binding globulin (SHBG) concentrations have been associated with the metabolic syndrome (MetS) in men, but the reported strength of association varies considerably.
  
  
  OBJECTIVE
  We aimed to investigate whether associations differ across specific subgroups (according to age and body mass index (BMI)) and individual MetS components.
  
  
  METHODS
  Two previously published meta-analyses including an updated systematic search in PubMed and EMBASE.
  
  
  METHODS
  Cross-sectional or prospective observational studies with data on TT and/or SHBG concentrations in combination with MetS in men.
  
  
  METHODS
  We conducted an individual participant data meta-analysis of 20 observational studies. Mixed effects models were used to assess cross-sectional and prospective associations of TT, SHBG and free testosterone (FT) with MetS and its individual components. Multivariable adjusted odds ratios (ORs) and hazard ratios (HRs) were calculated and effect modification by age and BMI was studied.
  
  
  RESULTS
  Men with low concentrations of TT, SHBG or FT were more likely to have prevalent MetS (ORs per quartile decrease were 1.69 (95% CI 1.60-1.77), 1.73 (95% CI 1.62-1.85) and 1.46 (95% CI 1.36-1.57) for TT, SHBG and FT, respectively) and incident MetS (HRs per quartile decrease were 1.25 (95% CI 1.16-1.36), 1.44 (95% 1.30-1.60) and 1.14 (95% 1.01-1.28) for TT, SHBG and FT, respectively). Overall, the magnitude of associations was largest in non-overweight men and varied across individual components: stronger associations were observed with hypertriglyceridemia, abdominal obesity and hyperglycaemia and associations were weakest for hypertension.
  
  
  CONCLUSIONS
  Associations of testosterone and SHBG with MetS vary according to BMI and individual MetS components. These findings provide further insights into the pathophysiological mechanisms linking low testosterone and SHBG concentrations to cardiometabolic risk.
authors.affiliation: Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Judith S
authors.initials: JS
authors.lastname: Brand
authors.affiliation: Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands; Departments of EBH and operating rooms, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
authors.forename: Maroeska M
authors.initials: MM
authors.lastname: Rovers
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Perth, Australia.
authors.forename: Bu B
authors.initials: BB
authors.lastname: Yeap
authors.affiliation: Medizinische Klinik Innenstadt der Universität München, München, Germany.
authors.forename: Harald J
authors.initials: HJ
authors.lastname: Schneider
authors.affiliation: Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.
authors.forename: Tomi-Pekka
authors.initials: TP
authors.lastname: Tuomainen
authors.affiliation: Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Robin
authors.initials: R
authors.lastname: Haring
authors.affiliation: Andrology and Sexual Medicine Unit Department of Clinical Physiopathology, University of Florence, Florence, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Corona
authors.affiliation: Department of Cardiology, Istanbul University, Istanbul, Turkey.
authors.forename: Altan
authors.initials: A
authors.lastname: Onat
authors.affiliation: Department of Internal Medicine and Biomedical Sciences, University of Parma, Parma, Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: Maggio
authors.affiliation: Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana, United States of America.
authors.forename: Claude
authors.initials: C
authors.lastname: Bouchard
authors.affiliation: Department of Medicine and Therapeutics, Chinese University of Hong Kong, Shatin, Hong Kong, Hong Kong.
authors.forename: Peter C Y
authors.initials: PC
authors.lastname: Tong
authors.affiliation: Department of Endocrinology, Changing General Hospital, Singapore, Singapore.
authors.forename: Richard Y T
authors.initials: RY
authors.lastname: Chen
authors.affiliation: Department of Geriatric Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Akishita
authors.affiliation: Department of Medical Oncology, University Medical Center Groningen, Groningen, Netherlands.
authors.forename: Jourik A
authors.initials: JA
authors.lastname: Gietema
authors.affiliation: Department of Endocrinology, Saint-Joseph University, Beirut, Lebanon.
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Gannagé-Yared
authors.affiliation: Center for Family and Community Medicine, Stockholm, Sweden.
authors.forename: Anna-Lena
authors.initials: AL
authors.lastname: Undén
authors.affiliation: Department of Clinical Chemistry, University of Helsinki, Helsinki, Finland.
authors.forename: Aarno
authors.initials: A
authors.lastname: Hautanen
authors.affiliation: Endocrinology Research Center, Moscow, Russia.
authors.forename: Nicolai P
authors.initials: NP
authors.lastname: Goncharov
authors.affiliation: Clinical Center of Endocrinology and Gerontology, Medical University, Sofia, Bulgaria.
authors.forename: Philip
authors.initials: P
authors.lastname: Kumanov
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Perth, Australia.
authors.forename: S A Paul
authors.initials: SA
authors.lastname: Chubb
authors.affiliation: School of Psychiatry and Clinical Neurosciences, University of Western Australia, Perth, Australia.
authors.forename: Osvaldo P
authors.initials: OP
authors.lastname: Almeida
authors.affiliation: Institute of Clinical Psychology, Center of Clinical Epidemiology and Longitudinal Studies, University of Dresden, Dresden, Germany.
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Wittchen
authors.affiliation: Institute of Clinical Psychology, Center of Clinical Epidemiology and Longitudinal Studies, University of Dresden, Dresden, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Klotsche
authors.affiliation: Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Henri
authors.initials: H
authors.lastname: Wallaschofski
authors.affiliation: Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Henry
authors.initials: H
authors.lastname: Völzke
authors.affiliation: Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.
authors.forename: Jussi
authors.initials: J
authors.lastname: Kauhanen
authors.affiliation: MAS-Metabolic Analytical Services Oy, Helsinki, Finland.
authors.forename: Jukka T
authors.initials: JT
authors.lastname: Salonen
authors.affiliation: Clinical Research Branch, National Institute on Aging, Baltimore, Maryland, United States of America.
authors.forename: Luigi
authors.initials: L
authors.lastname: Ferrucci
authors.affiliation: Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Yvonne T
authors.initials: YT
authors.lastname: van der Schouw
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D015992:Body Mass Index; D003430:Cross-Sectional Studies; D006801:Humans; D008297:Male; D024821:Metabolic Syndrome / Q000453:epidemiology*; D008875:Middle Aged; D064887:Observational Studies as Topic; D016017:Odds Ratio; D011446:Prospective Studies; D012738:Sex Hormone-Binding Globulin / Q000032:analysis*; D013739:Testosterone / Q000097:blood*; D055815:Young Adult
chemical_list: D012738:Sex Hormone-Binding Globulin; D013739:Testosterone