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Elevated luteinizing hormone despite normal testosterone levels in older men-natural history, risk factors and clinical features

Eendebak, Robert J.A.H. ; Ahern, Tomas ; Swiecicka, Agnieszka ; Pye, Stephen R. ; O'Neill, Terence W. ; Bartfai, Gyorgy ; Casanueva, Felipe F. ; Maggi, Mario ; Forti, Gianni and Giwercman, Aleksander LU , et al. (2018) In Clinical Endocrinology 88(3). p.479-490
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... (More)

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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publishing date
type
Contribution to journal
publication status
published
subject
keywords
Ageing, Hypogonadism, Luteinizing hormone, Physical function, Testosterone
in
Clinical Endocrinology
volume
88
issue
3
pages
479 - 490
publisher
Wiley-Blackwell
external identifiers
  • pmid:29178359
  • scopus:85038944860
ISSN
0300-0664
DOI
10.1111/cen.13524
language
English
LU publication?
yes
id
419fe45d-c7f9-4429-97ab-c2cabe2bcd49
date added to LUP
2018-01-23 13:27:01
date last changed
2020-09-23 06:51:51
@article{419fe45d-c7f9-4429-97ab-c2cabe2bcd49,
  abstract     = {<p>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 &gt;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 &gt;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.</p>},
  author       = {Eendebak, Robert J.A.H. and Ahern, Tomas and Swiecicka, Agnieszka and Pye, Stephen R. and O'Neill, Terence W. and Bartfai, Gyorgy and Casanueva, Felipe F. and Maggi, Mario and Forti, Gianni and Giwercman, Aleksander and Han, Thang S. and Słowikowska-Hilczer, Jolanta and Lean, Michael E.J. and Punab, Margus and Pendleton, Neil and Keevil, Brian G. and Vanderschueren, Dirk and Rutter, Martin K. and Tampubolon, Gindo and Goodacre, Royston and Huhtaniemi, Ilpo T. and Wu, Frederick C.W.},
  issn         = {0300-0664},
  language     = {eng},
  number       = {3},
  pages        = {479--490},
  publisher    = {Wiley-Blackwell},
  series       = {Clinical Endocrinology},
  title        = {Elevated luteinizing hormone despite normal testosterone levels in older men-natural history, risk factors and clinical features},
  url          = {http://dx.doi.org/10.1111/cen.13524},
  doi          = {10.1111/cen.13524},
  volume       = {88},
  year         = {2018},
}