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Hypothalamic-pituitary-testicular axis disruptions in older men are differentially linked to age and modifiable risk factors: The European Male Aging Study

Wu, Frederick C W; Tajar, Abdelouahid; Pye, Stephen R; Silman, Alan J; Finn, Joseph D; O'Neill, Terence W; Bartfai, Gyorgy; Casanueva, Felipe; Forti, Gianni and Giwercman, Aleksander LU , et al. (2008) In Journal of Clinical Endocrinology and Metabolism 93(7). p.2737-2745
Abstract
CONTEXT The cause of declining testosterone (T) in aging men and their relationships with risk factors are unclear. OBJECTIVE To investigate the relationships between lifestyle and health with reproductive hormones in aging men. DESIGN Baseline cross-sectional survey on 3200 community - dwelling men aged 40 - 79 yr from a prospective cohort study in 8 European countries. RESULTS Four predictors were associated with distinct modes of altered function:- Age: lower free T (FT) (-3.12 pmol/L/ yr, p<0.001) with raised luteinizing hormone (LH) suggesting impaired testicular function. Obesity: lower total T (TT) (-2.32 nmol/L) and FT (-17.60 pmol/L) for BMI >/=25 - <30 kg/m(2) and lower TT (-5.09 nmol/L,) and FT (-53.72 pmol/L) for BMI... (More)
CONTEXT The cause of declining testosterone (T) in aging men and their relationships with risk factors are unclear. OBJECTIVE To investigate the relationships between lifestyle and health with reproductive hormones in aging men. DESIGN Baseline cross-sectional survey on 3200 community - dwelling men aged 40 - 79 yr from a prospective cohort study in 8 European countries. RESULTS Four predictors were associated with distinct modes of altered function:- Age: lower free T (FT) (-3.12 pmol/L/ yr, p<0.001) with raised luteinizing hormone (LH) suggesting impaired testicular function. Obesity: lower total T (TT) (-2.32 nmol/L) and FT (-17.60 pmol/L) for BMI >/=25 - <30 kg/m(2) and lower TT (-5.09 nmol/L,) and FT (-53.72 pmol/L) for BMI >/=30 kg/m(2) (p <0.001 - 0.01, referent: BMI <25 kg/m(2)) with unchanged/decreased LH, indicating hypothalamus/pituitary dysfunction. Co-morbidity: lower TT (-0.80 nmol/L, p <0.01) with unchanged LH in younger men but higher LH in older men. Smoking: higher sex hormone binding globulin (SHBG) (5.96 nmol/L, p <0.001) and LH (0.77 U/L, p <0.01) with increased TT (1.31 nmol/L, p<0.001) but not FT, compatible with a resetting of T-LH negative feedback due to elevated SHBG. CONCLUSIONS Complex multiple alterations in the hypothalamic-pituitary-testicular axis function exist in ageing men against a background of progressive age-related testicular impairment. These changes are differentially linked to specific risk factors. Some risk factors operate independently of but others interact with age, in contributing to the T decline. These potentially modifiable risk factors suggest possible preventative measures to maintain T during in aging men. (Less)
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Contribution to journal
publication status
published
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Journal of Clinical Endocrinology and Metabolism
volume
93
issue
7
pages
2737 - 2745
publisher
The Endocrine Society
external identifiers
  • pmid:18270261
  • wos:000257513700048
  • scopus:47549107694
ISSN
1945-7197
DOI
10.1210/jc.2007-1972
language
English
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yes
id
9ca037f2-e4ac-4545-9b09-3fcca9017236 (old id 1042014)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/18270261?dopt=Abstract
date added to LUP
2008-03-06 13:58:54
date last changed
2017-11-12 03:42:11
@article{9ca037f2-e4ac-4545-9b09-3fcca9017236,
  abstract     = {CONTEXT The cause of declining testosterone (T) in aging men and their relationships with risk factors are unclear. OBJECTIVE To investigate the relationships between lifestyle and health with reproductive hormones in aging men. DESIGN Baseline cross-sectional survey on 3200 community - dwelling men aged 40 - 79 yr from a prospective cohort study in 8 European countries. RESULTS Four predictors were associated with distinct modes of altered function:- Age: lower free T (FT) (-3.12 pmol/L/ yr, p&lt;0.001) with raised luteinizing hormone (LH) suggesting impaired testicular function. Obesity: lower total T (TT) (-2.32 nmol/L) and FT (-17.60 pmol/L) for BMI &gt;/=25 - &lt;30 kg/m(2) and lower TT (-5.09 nmol/L,) and FT (-53.72 pmol/L) for BMI &gt;/=30 kg/m(2) (p &lt;0.001 - 0.01, referent: BMI &lt;25 kg/m(2)) with unchanged/decreased LH, indicating hypothalamus/pituitary dysfunction. Co-morbidity: lower TT (-0.80 nmol/L, p &lt;0.01) with unchanged LH in younger men but higher LH in older men. Smoking: higher sex hormone binding globulin (SHBG) (5.96 nmol/L, p &lt;0.001) and LH (0.77 U/L, p &lt;0.01) with increased TT (1.31 nmol/L, p&lt;0.001) but not FT, compatible with a resetting of T-LH negative feedback due to elevated SHBG. CONCLUSIONS Complex multiple alterations in the hypothalamic-pituitary-testicular axis function exist in ageing men against a background of progressive age-related testicular impairment. These changes are differentially linked to specific risk factors. Some risk factors operate independently of but others interact with age, in contributing to the T decline. These potentially modifiable risk factors suggest possible preventative measures to maintain T during in aging men.},
  author       = {Wu, Frederick C W and Tajar, Abdelouahid and Pye, Stephen R and Silman, Alan J and Finn, Joseph D and O'Neill, Terence W and Bartfai, Gyorgy and Casanueva, Felipe and Forti, Gianni and Giwercman, Aleksander and Huhtaniemi, Ilpo T and Kula, Krzysztof and Punab, Margus and Boonen, Steven and Vanderschueren, Dirk},
  issn         = {1945-7197},
  language     = {eng},
  number       = {7},
  pages        = {2737--2745},
  publisher    = {The Endocrine Society},
  series       = {Journal of Clinical Endocrinology and Metabolism},
  title        = {Hypothalamic-pituitary-testicular axis disruptions in older men are differentially linked to age and modifiable risk factors: The European Male Aging Study},
  url          = {http://dx.doi.org/10.1210/jc.2007-1972},
  volume       = {93},
  year         = {2008},
}