Identification of late-onset hypogonadism in middle-aged and elderly men

Frederick C W Wu, Abdelouahid Tajar, Jennifer M. Beynon, Stephen R. Pye, Alan J. Silman, Joseph D. Finn, Terence W. O'Neill, G. Bártfai, Felipe F. Casanueva, Gianni Forti, Aleksander Giwercman, Thang S. Han, Krzysztof Kula, Michael E J Lean, Neil Pendleton, Margus Punab, Steven Boonen, Dirk Vanderschueren, Fernand Labrie, Ilpo T. Huhtaniemi

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Abstract

BACKGROUND: The association between aging-related testosterone deficiency and late-onset hypogonadism in men remains a controversial concept. We sought evidence-based criteria for identifying late-onset hypogonadism in the general population on the basis of an association between symptoms and a low testosterone level. METHODS: We surveyed a random population sample of 3369 men between the ages of 40 and 79 years at eight European centers. Using questionnaires, we collected data with regard to the subjects' general, sexual, physical, and psychological health. Levels of total testosterone were measured in morning blood samples by mass spectrometry, and free testosterone levels were calculated with the use of Vermeulen's formula. Data were randomly split into separate training and validation sets for confirmatory analyses. RESULTS: In the training set, symptoms of poor morning erection, low sexual desire, erectile dysfunction, inability to perform vigorous activity, depression, and fatigue were significantly related to the testosterone level. Increased probabilities of the three sexual symptoms and limited physical vigor were discernible with decreased testosterone levels (ranges, 8.0 to 13.0 nmol per liter [2.3 to 3.7 ng per milliliter] for total testosterone and 160 to 280 pmol per liter [46 to 81 pg per milliliter] for free testosterone). However, only the three sexual symptoms had a syndromic association with decreased testosterone levels. An inverse relationship between an increasing number of sexual symptoms and a decreasing testosterone level was observed. These relationships were independently confirmed in the validation set, in which the strengths of the association between symptoms and low testosterone levels determined the minimum criteria necessary to identify late-onset hypogonadism. CONCLUSIONS: Late-onset hypogonadism can be defined by the presence of at least three sexual symptoms associated with a total testosterone level of less than 11 nmol per liter (3.2 ng per milliliter) and a free testosterone level of less than 220 pmol per liter (64 pg per milliliter).

Original languageEnglish
Pages (from-to)123-135
Number of pages13
JournalNew England Journal of Medicine
Volume363
Issue number2
DOIs
Publication statusPublished - Jul 8 2010

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Hypogonadism
Testosterone
Erectile Dysfunction
Population
Fatigue
Mass Spectrometry

ASJC Scopus subject areas

  • Medicine(all)

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Wu, F. C. W., Tajar, A., Beynon, J. M., Pye, S. R., Silman, A. J., Finn, J. D., ... Huhtaniemi, I. T. (2010). Identification of late-onset hypogonadism in middle-aged and elderly men. New England Journal of Medicine, 363(2), 123-135. https://doi.org/10.1056/NEJMoa0911101

Identification of late-onset hypogonadism in middle-aged and elderly men. / Wu, Frederick C W; Tajar, Abdelouahid; Beynon, Jennifer M.; Pye, Stephen R.; Silman, Alan J.; Finn, Joseph D.; O'Neill, Terence W.; Bártfai, G.; Casanueva, Felipe F.; Forti, Gianni; Giwercman, Aleksander; Han, Thang S.; Kula, Krzysztof; Lean, Michael E J; Pendleton, Neil; Punab, Margus; Boonen, Steven; Vanderschueren, Dirk; Labrie, Fernand; Huhtaniemi, Ilpo T.

In: New England Journal of Medicine, Vol. 363, No. 2, 08.07.2010, p. 123-135.

Research output: Contribution to journalArticle

Wu, FCW, Tajar, A, Beynon, JM, Pye, SR, Silman, AJ, Finn, JD, O'Neill, TW, Bártfai, G, Casanueva, FF, Forti, G, Giwercman, A, Han, TS, Kula, K, Lean, MEJ, Pendleton, N, Punab, M, Boonen, S, Vanderschueren, D, Labrie, F & Huhtaniemi, IT 2010, 'Identification of late-onset hypogonadism in middle-aged and elderly men', New England Journal of Medicine, vol. 363, no. 2, pp. 123-135. https://doi.org/10.1056/NEJMoa0911101
Wu, Frederick C W ; Tajar, Abdelouahid ; Beynon, Jennifer M. ; Pye, Stephen R. ; Silman, Alan J. ; Finn, Joseph D. ; O'Neill, Terence W. ; Bártfai, G. ; Casanueva, Felipe F. ; Forti, Gianni ; Giwercman, Aleksander ; Han, Thang S. ; Kula, Krzysztof ; Lean, Michael E J ; Pendleton, Neil ; Punab, Margus ; Boonen, Steven ; Vanderschueren, Dirk ; Labrie, Fernand ; Huhtaniemi, Ilpo T. / Identification of late-onset hypogonadism in middle-aged and elderly men. In: New England Journal of Medicine. 2010 ; Vol. 363, No. 2. pp. 123-135.
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AU - Wu, Frederick C W

AU - Tajar, Abdelouahid

AU - Beynon, Jennifer M.

AU - Pye, Stephen R.

AU - Silman, Alan J.

AU - Finn, Joseph D.

AU - O'Neill, Terence W.

AU - Bártfai, G.

AU - Casanueva, Felipe F.

AU - Forti, Gianni

AU - Giwercman, Aleksander

AU - Han, Thang S.

AU - Kula, Krzysztof

AU - Lean, Michael E J

AU - Pendleton, Neil

AU - Punab, Margus

AU - Boonen, Steven

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N2 - BACKGROUND: The association between aging-related testosterone deficiency and late-onset hypogonadism in men remains a controversial concept. We sought evidence-based criteria for identifying late-onset hypogonadism in the general population on the basis of an association between symptoms and a low testosterone level. METHODS: We surveyed a random population sample of 3369 men between the ages of 40 and 79 years at eight European centers. Using questionnaires, we collected data with regard to the subjects' general, sexual, physical, and psychological health. Levels of total testosterone were measured in morning blood samples by mass spectrometry, and free testosterone levels were calculated with the use of Vermeulen's formula. Data were randomly split into separate training and validation sets for confirmatory analyses. RESULTS: In the training set, symptoms of poor morning erection, low sexual desire, erectile dysfunction, inability to perform vigorous activity, depression, and fatigue were significantly related to the testosterone level. Increased probabilities of the three sexual symptoms and limited physical vigor were discernible with decreased testosterone levels (ranges, 8.0 to 13.0 nmol per liter [2.3 to 3.7 ng per milliliter] for total testosterone and 160 to 280 pmol per liter [46 to 81 pg per milliliter] for free testosterone). However, only the three sexual symptoms had a syndromic association with decreased testosterone levels. An inverse relationship between an increasing number of sexual symptoms and a decreasing testosterone level was observed. These relationships were independently confirmed in the validation set, in which the strengths of the association between symptoms and low testosterone levels determined the minimum criteria necessary to identify late-onset hypogonadism. CONCLUSIONS: Late-onset hypogonadism can be defined by the presence of at least three sexual symptoms associated with a total testosterone level of less than 11 nmol per liter (3.2 ng per milliliter) and a free testosterone level of less than 220 pmol per liter (64 pg per milliliter).

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