Associations Between Sex Steroids and the Development of Metabolic Syndrome: A Longitudinal Study in European Men

Author:

Antonio Leen123,Wu Frederick C. W.45,O'Neill Terence W.67,Pye Stephen R.6,Carter Emma L.4,Finn Joseph D.4,Rutter Martin K.489,Laurent Michaël R.210,Huhtaniemi Ilpo T.11,Han Thang S.12,Lean Michael E. J.13,Keevil Brian G.14,Pendleton Neil15,Rastrelli Giulia1617,Forti Gianni16,Bartfai Gyorgy18,Casanueva Felipe F.19,Kula Krzysztof20,Punab Margus21,Giwercman Aleksander22,Claessens Frank2,Decallonne Brigitte13,Vanderschueren Dirk13,

Affiliation:

1. Department of Clinical and Experimental Medicine (L.A., B.D., D.V.), KU Leuven, Laboratory of Clinical and Experimental Endocrinology, B-3000 Leuven, Belgium

2. Department of Cellular and Molecular Medicine (L.A., M.R.L., F.C.), KU Leuven, Laboratory of Molecular Endocrinology, B-3000 Leuven, Belgium

3. Department of Endocrinology (L.A., B.D., D.V.), University Hospitals Leuven, B-3000 Leuven, Belgium

4. 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

5. Manchester Royal Infirmary (F.C.W.W.), Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester M13 9WL, United Kingdom

6. 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

7. NIHR Manchester Musculoskeletal Biomedical Research Unit (T.W.O.), Central Manchester NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester M13 9WL, United Kingdom;

8. 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;

9. Manchester Diabetes Centre (M.K.R.), Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester M13 9WL, United Kingdom

10. Department of Clinical and Experimental Medicine (M.R.L.), KU Leuven, Laboratory of Gerontology and Geriatrics, B-3000 Leuven, Belgium

11. Department of Surgery and Cancer (I.T.H.), Imperial College London, Hammersmith Campus, London W12 ONN, United Kingdom;

12. Department of Endocrinology (T.S.H.), Ashford and St. Peter's NHS Foundation Trust Hospital, Chertsey, Surrey, KT16 0PZ, United Kingdom

13. Department of Human Nutrition (M.E.J.L.), University of Glasgow, Glasgow G12 8TA, United Kingdom

14. Department of Clinical Biochemistry (B.G.K.), University Hospital of South Manchester, Manchester M23 9TL, United Kingdom

15. School of Community Based Medicine (N.P.), The University of Manchester, Salford Royal NHS Trust, Salford M6 8HD, United Kingdom

16. Endocrinology Unit, Department of Experimental Clinical And Biochemical Sciences (G.R., G.F.), University of Florence, 50121 Florence, Italy

17. Department of Sexual Medicine and Andrology Unit (G.R.), Department of Experimental, Clinical and Biochemical Sciences, University Of Florence, 50121 Florence Italy;

18. Department of Obstetrics (G.B.), Gynaecology and Andrology, Albert Szent-György Medical University, H-6721 Szeged, Hungary

19. Department of Medicine (F.F.C.), Santiago de Compostela University, Complejo Hospitalario Universitario de Santiago

20. CIBER de Fisiopatología Obesidad y Nutricion (CB06/03), Instituto Salud Carlos III; 15705 Santiago de Compostela, Spain; Department of Andrology and Reproductive Endocrinology (K.K.), Medical University of Łódź, 90-149 Łódź, Poland

21. Andrology Unit (M.P.), United Laboratories of Tartu University Clinics, 51054 Tartu, Estonia

22. Reproductive Medicine Centre (A.G.), Skåne University Hospital, University of Lund, SE-22184 Lund Sweden

Abstract

Context: 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.

Publisher

The Endocrine Society

Subject

Biochemistry (medical),Clinical Biochemistry,Endocrinology,Biochemistry,Endocrinology, Diabetes and Metabolism

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