title: Natural history, risk factors and clinical features of primary hypogonadism in ageing men: Longitudinal Data from the European Male Ageing Study.
abstract: OBJECTIVE
  In ageing men, the incidence and clinical significance of testosterone (T) decline accompanied by elevated luteinizing hormone (LH) are unclear. We describe the natural history, risk factors and clinical features associated with the development of biochemical primary hypogonadism (PHG, T < 10·5 nmol/l and LH>9·4U/l) in ageing men.
  
  
  METHODS
  A prospective observational cohort survey of 3,369 community-dwelling men aged 40-79 years, followed up for 4·3 years. Men were classified as incident (i) PHG (eugonadal [EUG, T ≥ 10·5 nmol/l] at baseline, PHG at follow-up), persistent (p) PHG (PHG at baseline and follow-up), pEUG (EUG at baseline and follow-up) and reversed (r) PHG (PHG at baseline, EUG at follow-up). Predictors and changes in clinical features associated with the development of PHG were analysed by regression models.
  
  
  RESULTS
  Of 1,991 men comprising the analytical sample, 97·5% had pEUG, 1·1% iPHG, 1·1% pPHG and 0·3% rPHG. The incidence of PHG was 0·2%/year. Higher age (>70 years) [OR 12·48 (1·27-122·13), P = 0·030] and chronic illnesses [OR 4·24 (1·08-16·56); P = 0·038] predicted iPHG. Upon transition from EUG to PHG, erectile function, physical vigour and haemoglobin worsened significantly. Men with pPHG had decreased morning erections, sexual thoughts and haemoglobin with increased insulin resistance.
  
  
  CONCLUSIONS
  Primary testicular failure in men is uncommon and predicted by old age and chronic illness. Some clinical features attributable to androgen deficiency, but not others, accompanied the T decline in men who developed biochemical PHG. Whether androgen replacement can improve sexual and/or physical function in elderly men with PHG merits further study.
authors.affiliation: Andrology Research Unit, Centre for Endocrinology & Diabetes, Institute of Human Development, Old St Mary's Building, The University of Manchester, Manchester, UK.
authors.forename: Tomás
authors.initials: T
authors.lastname: Ahern
authors.affiliation: Andrology Research Unit, Centre for Endocrinology & Diabetes, Institute of Human Development, Old St Mary's Building, The University of Manchester, Manchester, UK.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Swiecicka
authors.affiliation: Andrology Research Unit, Centre for Endocrinology & Diabetes, Institute of Human Development, Old St Mary's Building, The University of Manchester, Manchester, UK.
authors.forename: Robert J A H
authors.initials: RJ
authors.lastname: Eendebak
authors.affiliation: Andrology Research Unit, Centre for Endocrinology & Diabetes, Institute of Human Development, Old St Mary's Building, The University of Manchester, Manchester, UK.
authors.forename: Emma L
authors.initials: EL
authors.lastname: Carter
authors.affiliation: Andrology Research Unit, Centre for Endocrinology & Diabetes, Institute of Human Development, Old St Mary's Building, The University of Manchester, Manchester, UK.
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Finn
authors.affiliation: Arthritis Research UK Centre for Epidemiology & NIHR Manchester Musculoskeletal Biomedical Research Unit, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Pye
authors.affiliation: Arthritis Research UK Centre for Epidemiology & NIHR Manchester Musculoskeletal Biomedical Research Unit, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.
authors.forename: Terence W
authors.initials: TW
authors.lastname: O'Neill
authors.affiliation: Department of Andrology and Endocrinology, Katholieke Universiteit Leuven, Leuven, Belgium.
authors.forename: Leen
authors.identifier: http://orcid.org/0000-0002-1079-2860
authors.initials: L
authors.lastname: Antonio
authors.affiliation: Department of Clinical Biochemistry, University Hospital of South Manchester, Manchester, UK.
authors.forename: Brian
authors.initials: B
authors.lastname: Keevil
authors.affiliation: Department of Obstetrics, Gynaecology and Andrology, Albert Szent-György Medical University, Szeged, Hungary.
authors.forename: György
authors.initials: G
authors.lastname: Bartfai
authors.affiliation: Department of Medicine, Complejo Hospitalario Universitario de Santiago (CHUS), CIBER de Fisiopatología Obesidad y Nutricion (CB06/03), Santiago de Compostela University, Instituto Salud Carlos III, Santiago de Compostela, Spain.
authors.forename: Felipe F
authors.initials: FF
authors.lastname: Casanueva
authors.affiliation: Sexual Medicine and Andrology Unit, Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Florence, Italy.
authors.forename: Gianni
authors.initials: G
authors.lastname: Forti
authors.affiliation: Reproductive Medicine Centre, Malmö University Hospital, University of Lund, Lund, Sweden.
authors.forename: Aleksander
authors.initials: A
authors.lastname: Giwercman
authors.affiliation: Institute of Cardiovascular Research, "Royal Holloway University of London (ICR2UL), Egham & Agham and St Peter's NHS Foundation Trust, Egham, Surrey, UK.
authors.forename: Thang S
authors.initials: TS
authors.lastname: Han
authors.affiliation: Department of Andrology and Reproductive Endocrinology, Medical University of Łódź, Łódź, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Kula
authors.affiliation: Department of Human Nutrition, University of Glasgow, Glasgow, UK.
authors.forename: Michael E J
authors.initials: ME
authors.lastname: Lean
authors.affiliation: School of Community Based Medicine, Hope Hospital, The University of Manchester, Salford, UK.
authors.forename: Neil
authors.initials: N
authors.lastname: Pendleton
authors.affiliation: United Laboratories of Tartu University Clinics, Andrology Unit, Tartu, Estonia.
authors.forename: Margus
authors.initials: M
authors.lastname: Punab
authors.affiliation: Sexual Medicine and Andrology Unit, Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Florence, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Rastrelli
authors.affiliation: Andrology Research Unit, Centre for Endocrinology & Diabetes, Institute of Human Development, Old St Mary's Building, The University of Manchester, Manchester, UK.|Manchester Diabetes Centre, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science, Manchester, UK.
authors.forename: Martin K
authors.initials: MK
authors.lastname: Rutter
authors.affiliation: Department of Andrology and Endocrinology, Katholieke Universiteit Leuven, Leuven, Belgium.
authors.forename: Dirk
authors.initials: D
authors.lastname: Vanderschueren
authors.affiliation: Department of Surgery and Cancer, Institute of Reproductive and Developmental Biology, Imperial College London, Hammersmith Campus, London, UK.|Department of Physiology, Institute of Biomedicine, University of Turku, Turku, Finland.
authors.forename: Ilpo T
authors.initials: IT
authors.lastname: Huhtaniemi
authors.affiliation: Andrology Research Unit, Centre for Endocrinology & Diabetes, Institute of Human Development, Old St Mary's Building, The University of Manchester, Manchester, UK.
authors.forename: Frederick C W
authors.initials: FC
authors.lastname: Wu
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000375:Aging / Q000473:pathology / Q000502:physiology*; D000728:Androgens / Q000172:deficiency; D002908:Chronic Disease; D015331:Cohort Studies; D006801:Humans; D007006:Hypogonadism / Q000209:etiology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors; D013739:Testosterone / Q000172:deficiency
chemical_list: D000728:Androgens; D013739:Testosterone