TY - JOUR
T1 - Elevated luteinizing hormone despite normal testosterone levels in older men—natural history, risk factors and clinical features
AU - the EMAS Group
AU - Eendebak, Robert J.A.H.
AU - Ahern, Tomas
AU - Swiecicka, Agnieszka
AU - Pye, Stephen R.
AU - O'Neill, Terence W.
AU - Bartfai, Gyorgy
AU - Casanueva, Felipe F.
AU - Maggi, Mario
AU - Forti, Gianni
AU - Giwercman, Aleksander
AU - Han, Thang S.
AU - Słowikowska-Hilczer, Jolanta
AU - Lean, Michael E.J.
AU - Punab, Margus
AU - Pendleton, Neil
AU - Keevil, Brian G.
AU - Vanderschueren, Dirk
AU - Rutter, Martin K.
AU - Tampubolon, Gindo
AU - Goodacre, Royston
AU - Huhtaniemi, Ilpo T.
AU - Wu, Frederick C.W.
N1 - Funding Information:
The European Male Ageing Study is funded by the Commission of the European Communities Fifth Framework Programme “Quality of Life and Management of Living Resources” Grant QLK6-CT-2001-00258 and facilitated by the Manchester Academic Health Sciences Centre and the NIHR Greater Manchester: Clinical Research Network. Additional support was also provided by Arthritis Research United Kingdom and the National Institute for Health Research and the Manchester Academic Health Sciences Centre. The Principal Investigator of EMAS is Professor Frederick Wu, MD; Andrology Research Unit, University of Manchester, Manchester, United Kingdom. The authors wish to thank the men who participated in the eight countries, the research/nursing staff in the eight centres: C Pott (Manchester), E Wouters (Leuven), M Nilsson (MalmD堁M儁ddel Mar Fernandez (Santiago de Compostela), M Jedrzejowska (ŁD唀dDH-M儁d Tabo (Tartu) and A Heredi (Szeged) for their data collection and C Moseley (Manchester) for data entry and project co-ordination. Dr. D Vanderschueren is a senior clinical investigator supported by the Clinical Research Fund of the University Hospitals Leuven, Belgium. Robert J.A.H. Eendebak is supported by a Biotechnology and Biological Sciences Research Council—Doctoral Training Partnership (BBSRC-DTP) PhD fellowship and is grateful for support received from the Fundatie van de Vrijvrouwe van Renswoude and Scholten-Cordes scholarship foundations.
Funding Information:
Funding information The European Male Ageing Study is funded by the Commission of the European Communities Fifth Framework Programme ?Quality of Life and Management of Living Resources? Grant QLK6-CT-2001-00258. The European Male Ageing Study is funded by the Commission of the European Communities Fifth Framework Programme ?Quality of Life and Management of Living Resources? Grant QLK6-CT-2001-00258 and facilitated by the Manchester Academic Health Sciences Centre and the NIHR Greater Manchester: Clinical Research Network. Additional support was also provided by Arthritis Research United Kingdom and the National Institute for Health Research and the Manchester Academic Health Sciences Centre. The Principal Investigator of EMAS is Professor Frederick Wu, MD; Andrology Research Unit, University of Manchester, Manchester, United Kingdom. The authors wish to thank the men who participated in the eight countries, the research/nursing staff in the eight centres: C Pott (Manchester), E Wouters (Leuven), M Nilsson (Malm?), M del Mar Fernandez (Santiago de Compostela), M Jedrzejowska (??d?), H-M Tabo (Tartu) and A Heredi (Szeged) for their data collection and C Moseley (Manchester) for data entry and project co-ordination. Dr. D Vanderschueren is a senior clinical investigator supported by the Clinical Research Fund of the University Hospitals Leuven, Belgium. Robert J.A.H. Eendebak is supported by a Biotechnology and Biological Sciences Research Council?Doctoral Training Partnership (BBSRC-DTP) PhD fellowship and is grateful for support received from the Fundatie van de Vrijvrouwe van Renswoude and Scholten-Cordes scholarship foundations.
Publisher Copyright:
© 2017 John Wiley & Sons Ltd
PY - 2018/3
Y1 - 2018/3
N2 - 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.
AB - 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.
KW - ageing
KW - hypogonadism
KW - luteinizing hormone
KW - physical function
KW - testosterone
UR - http://www.scopus.com/inward/record.url?scp=85038944860&partnerID=8YFLogxK
U2 - 10.1111/cen.13524
DO - 10.1111/cen.13524
M3 - Article
C2 - 29178359
AN - SCOPUS:85038944860
SN - 0300-0664
VL - 88
SP - 479
EP - 490
JO - Clinical Endocrinology
JF - Clinical Endocrinology
IS - 3
ER -