title: Associations between sex steroids and the development of metabolic syndrome: a longitudinal study in European men.
abstract: BACKGROUND
  Low testosterone (T) has been associated with incident metabolic syndrome (MetS), but it remains unclear if this association is independent of sex hormone binding globulin (SHBG). Estradiol (E2) may also be associated with MetS, but few studies have investigated this.
  
  
  OBJECTIVE
  To study the association between baseline sex steroids and the development of incident MetS and to investigate the influence of SHBG, body mass index (BMI) and insulin resistance on this risk.
  
  
  METHODS
  Three thousand three hundred sixty nine community-dwelling men aged 40-79 years were recruited for participation in EMAS. MetS was defined by the updated NCEP ATP III criteria. Testosterone and E2 levels were measured by liquid and gas chromatography/mass spectrometry, respectively. Logistic regression was used to assess the association between sex steroids and incident MetS.
  
  
  RESULTS
  One thousand six hundred fifty one men without MetS at baseline were identified. During follow-up, 289 men developed incident MetS, while 1362 men did not develop MetS. Men with lower baseline total T levels were at higher risk for developing MetS [odds ratio (OR) = 1.72, P < .001), even after adjustment for SHBG (OR = 1.43, P = .001), BMI (OR = 1.44, P < .001) or homeostasis model assessment of insulin resistance (HOMA-IR) (OR = 1.64, P < .001). E2 was not associated with development of MetS (OR = 1.04; P = .56). However, a lower E2/T ratio was associated with a lower risk of incident MetS (OR = 0.38; P < .001), even after adjustment for SHBG (OR = 0.48; P < .001), BMI (OR = 0.60; P = .001) or HOMA-IR (OR = 0.41; P < .001).
  
  
  CONCLUSIONS
  In men, lower T levels, but not E2, are linked with an increased risk of developing MetS, independent of SHBG, BMI or insulin resistance. A lower E2/T ratio may be protective against developing MetS.
authors: Department of Clinical and Experimental Medicine (L.A., B.D., D.V.), KU Leuven, Laboratory of Clinical and Experimental Endocrinology, B-3000 Leuven, Belgium; Department of Cellular and Molecular Medicine (L.A., M.R.L., F.C.), KU Leuven, Laboratory of Molecular Endocrinology, B-3000 Leuven, Belgium; Department of Endocrinology (L.A., B.D., D.V.), University Hospitals Leuven, B-3000 Leuven, Belgium; Andrology Research Unit (F.C.W.W., E.L.C., J.D.F., M.K.R.), Endocrinology and Diabetes Research Group, Institute of Human Development, Faculty of Medical and Human Sciences, The University of Manchester, Manchester M13 9WL, United Kingdom; Manchester Royal Infirmary (F.C.W.W.), Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester M13 9WL, United Kingdom; Arthritis Research UK Centre of Epidemiology (T.W.O., S.R.P.), The University of Manchester, Manchester Academic Health Science Centre, Manchester M13 9WL, United Kingdom; NIHR Manchester Musculoskeletal Biomedical Research Unit (T.W.O.), Central Manchester NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester M13 9WL, United Kingdom; The Endocrinology and Diabetes Research Group (M.K.R.), Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, Manchester Academic Health Science Centre, Manchester M13 9WL United Kingdom; Manchester Diabetes Centre (M.K.R.), Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester M13 9WL, United Kingdom; Department of Clinical and Experimental Medicine (M.R.L.), KU Leuven, Laboratory of Gerontology and Geriatrics, B-3000 Leuven, Belgium; Department of Surgery and Cancer (I.T.H.), Imperial College London, Hammersmith Campus, London W12 ONN, United Kingdom; Department of Endocrinology (T.S.H.), Ashford and St. Peter's NHS Foundation Trust Hospital, Chertsey, Surrey, KT16 0PZ, United Kingdom; Department of Hum
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mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism*; D001823:Body Composition; D015992:Body Mass Index; D005060:Europe / Q000453:epidemiology; D012739:Gonadal Steroid Hormones / Q000097:blood*; D006801:Humans; D015994:Incidence; D007333:Insulin Resistance; D008137:Longitudinal Studies; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood* / Q000453:epidemiology*; D008875:Middle Aged
chemical_list: D012739:Gonadal Steroid Hormones