Robert J A H Eendebak1, Tomas Ahern1, Agnieszka Swiecicka1, Stephen R Pye2, Terence W O'Neill2, Gyorgy Bartfai3, Felipe F Casanueva4,5, Mario Maggi6, Gianni Forti6, Aleksander Giwercman7, Thang S Han8, Jolanta Słowikowska-Hilczer9, Michael E J Lean10, Margus Punab11, Neil Pendleton12, Brian G Keevil13, Dirk Vanderschueren14, Martin K Rutter15, Gindo Tampubolon16, Royston Goodacre17, Ilpo T Huhtaniemi18,19, Frederick C W Wu1. 1. Manchester Academic Health Sciences Centre, Faculty of Medical and Human Sciences, Institute of Human Development, Centre for Endocrinology and Diabetes, Andrology Research Unit, University of Manchester, Manchester, UK. 2. Arthritis Research UK Centre for Epidemiology, Division of Musculoskeletal & Dermatological Sciences, Faculty of Biology, Medicine and Health, University of Manchester and NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester NHS Foundation Trust, Manchester, UK. 3. Department of Obstetrics, Gynaecology and Andrology, Albert Szent-György Medical University, Szeged, Hungary. 4. Department of Medicine, Santiago de Compostela University, Complejo Hospitalario Universitario de Santiago (CHUS), Santiago de Compostela, Spain. 5. Instituto Salud Carlos III, CIBER de Fisiopatología Obesidad y Nutricion(CB06/03), Santiago de Compostela, Spain. 6. Sexual Medicine and Andrology Unit, Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Florence, Italy. 7. Department of Translational Medicine, Lund University, Malmö, Sweden. 8. Institute of Cardiovascular Research, Royal Holloway University of London (ICR2UL) and Ashford and St Peter's NHS Foundation Trust, Egham, Surrey, UK. 9. Department of Andrology and Reproductive Endocrinology, Medical University of Łódź, Łódź, Poland. 10. Department of Human Nutrition, University of Glasgow, Glasgow, UK. 11. Andrology Unit, United Laboratories of Tartu University Clinics, Tartu, Estonia. 12. Centre for Clinical and Cognitive Neuroscience, University of Manchester, Manchester, UK. 13. Department of Clinical Biochemistry, University Hospital of South Manchester, Manchester, UK. 14. Department of Andrology and Endocrinology, Katholieke Universiteit Leuven, Leuven, Belgium. 15. Manchester Diabetes Centre, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science, Manchester, UK. 16. Cathie Marsh Institute for Social Research. Faculty of Humanities, University of Manchester, Manchester, UK. 17. School of Chemistry, Manchester Institute for Biotechnology, University of Manchester, Manchester, UK. 18. Department of Surgery and Cancer, Institute of Reproductive and Developmental Biology, Imperial College London, Hammersmith Campus, London, UK. 19. Department of Physiology, Institute of Biomedicine, University of Turku, Turku, Finland.
Abstract
OBJECTIVE: Elevated luteinizing hormone (LH) with normal testosterone (T) suggests compensated dysregulation of the gonadal axis. We describe the natural history, risk factors and clinical parameters associated with the development of high LH (HLH, LH >9.4 U/L) in ageing men with normal T (T ≥ 10.5 nmol/L). DESIGN, PATIENTS AND MEASUREMENTS: We conducted a 4.3-year prospective observational study of 3369 community-dwelling European men aged 40-79 years. Participants were classified as follows: incident (i) HLH (n = 101, 5.2%); persistent (p) HLH (n = 128, 6.6%); reverted (r) HLH (n = 46, 2.4%); or persistent normal LH (pNLH, n = 1667, 85.8%). Potential predictors and changes in clinical features associated with iHLH and rHLH were analysed using regression models. RESULTS: Age >70 years (OR = 4.12 [2.07-8.20]), diabetes (OR = 2.86 [1.42-5.77]), chronic pain (OR = 2.53 [1.34-4.77]), predegree education (OR = 1.79 [1.01-3.20]) and low physical activity (PASE ≤ 78, OR = 2.37 [1.24-4.50]) predicted development of HLH. Younger age (40-49 years, OR = 8.14 [1.35-49.13]) and nonsmoking (OR = 5.39 [1.48-19.65]) predicted recovery from HLH. Men with iHLH developed erectile dysfunction, poor health, cardiovascular disease (CVD) and cancer more frequently than pNLH men. In pHLH men, comorbidities, including CVD, developed more frequently, and cognitive and physical function deteriorated more, than in pNLH men. Men with HLH developed primary hypogonadism more frequently (OR = 15.97 [5.85-43.60]) than NLH men. Men with rHLH experienced a small rise in BMI. CONCLUSIONS: Elevation of LH with normal T is predicted by multiple factors, reverts frequently and is not associated with unequivocal evidence of androgen deficiency. High LH is a biomarker for deteriorating health in aged men who tend to develop primary hypogonadism.
OBJECTIVE: Elevated luteinizing hormone (LH) with normal testosterone (T) suggests compensated dysregulation of the gonadal axis. We describe the natural history, risk factors and clinical parameters associated with the development of high LH (HLH, LH >9.4 U/L) in ageing men with normal T (T ≥ 10.5 nmol/L). DESIGN, PATIENTS AND MEASUREMENTS: We conducted a 4.3-year prospective observational study of 3369 community-dwelling European men aged 40-79 years. Participants were classified as follows: incident (i) HLH (n = 101, 5.2%); persistent (p) HLH (n = 128, 6.6%); reverted (r) HLH (n = 46, 2.4%); or persistent normal LH (pNLH, n = 1667, 85.8%). Potential predictors and changes in clinical features associated with iHLH and rHLH were analysed using regression models. RESULTS: Age >70 years (OR = 4.12 [2.07-8.20]), diabetes (OR = 2.86 [1.42-5.77]), chronic pain (OR = 2.53 [1.34-4.77]), predegree education (OR = 1.79 [1.01-3.20]) and low physical activity (PASE ≤ 78, OR = 2.37 [1.24-4.50]) predicted development of HLH. Younger age (40-49 years, OR = 8.14 [1.35-49.13]) and nonsmoking (OR = 5.39 [1.48-19.65]) predicted recovery from HLH. Men with iHLH developed erectile dysfunction, poor health, cardiovascular disease (CVD) and cancer more frequently than pNLH men. In pHLH men, comorbidities, including CVD, developed more frequently, and cognitive and physical function deteriorated more, than in pNLH men. Men with HLH developed primary hypogonadism more frequently (OR = 15.97 [5.85-43.60]) than NLH men. Men with rHLH experienced a small rise in BMI. CONCLUSIONS: Elevation of LH with normal T is predicted by multiple factors, reverts frequently and is not associated with unequivocal evidence of androgen deficiency. High LH is a biomarker for deteriorating health in aged men who tend to develop primary hypogonadism.
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