Low Free Testosterone is Associated with Hypogonadal Signs and Symptoms in Men with Normal Total Testosterone.

Leen Antonio; Frederick C. W. Wu; Terence W. O'Neill; Stephen R. Pye; Tomas B Ahern; Michaël R Laurent; Ilpo T Huhtaniemi; Michael E J Lean; Brian G Keevil; Giulia Rastrelli; Gianni Forti; György Bartfai; Felipe F Casanueva; Krzysztof Kula; Margus Punab; Aleksander Giwercman; Frank Claessens; Brigitte Decallonne; Dirk Vanderschueren

doi:10.1210/jc.2015-4106

Low Free Testosterone is Associated with Hypogonadal Signs and Symptoms in Men with Normal Total Testosterone.

Leen Antonio, Frederick C. W. Wu, Terence W. O'Neill, Stephen R. Pye, Tomas B Ahern, Michaël R Laurent, Ilpo T Huhtaniemi, Michael E J Lean, Brian G Keevil, Giulia Rastrelli, Gianni Forti, György Bartfai, Felipe F Casanueva, Krzysztof Kula, Margus Punab, Aleksander Giwercman, Frank Claessens, Brigitte Decallonne, Dirk Vanderschueren

Research output: Contribution to journal › Article › peer-review

Abstract

CONTEXT: During ageing, total testosterone (TT) declines and SHBG increases, resulting in a greater decrease in calculated free testosterone (cFT). Currently, guidelines suggest using TT to diagnose androgen deficiency and to reserve cFT only for men with borderline TT. OBJECTIVE: To investigate if either low cFT or low TT is more strongly associated with androgen-related clinical endpoints. METHODS: 3334 community-dwelling men, aged 40-79, were included. Differences in clinical variables between the referent group of men with both normal TT (≥10.5 nmol/L) and normal cFT (≥220 pmol/L) with those who had normal TT/low cFT, low TT/normal cFT and low TT/low cFT, were assessed by regression models adjusted for age, centre, BMI and comorbidities. RESULTS: 2641 men had normal TT [18.4±5.5 (mean±SD) nmol/L]/normal cFT (326±74 pmol/L), 277 men had normal TT (14.2±3.7)/low cFT (194±23), 96 men had low TT (9.6±0.7)/normal cFT (247±20) and 320 men had low TT (7.8±2.5)/low cFT (160±55). Men with normal TT/low cFT were older and in poorer health. They had higher SHBG and LH, and reported more sexual and physical symptoms, while haemoglobin and bone ultrasound parameters were lower compared to the referent group. Men with low TT/normal cFT were younger and more obese. They had lower SHBG, but LH was normal, while features of androgen deficiency were lacking. CONCLUSIONS: Low cFT, even in the presence of normal TT, is associated with androgen deficiency-related symptoms. Normal cFT, despite low TT, is not associated with cognate symptoms. Therefore cFT levels should be assessed in men with suspected hypogonadal symptoms.

Original language	English
Pages (from-to)	2647-2657
Journal	The Journal of Clinical Endocrinology and Metabolism
Volume	101
Issue number	7
Early online date	24 Feb 2016
DOIs	https://doi.org/10.1210/jc.2015-4106
Publication status	Published - 2016

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10.1210/jc.2015-4106

Arthritis Research UK Centre of Excellence in Epidemiology.
Symmons, D. (PI), Bruce, I. (CoI), Dixon, W. (CoI), Felson, D. (CoI), Hyrich, K. (CoI), Lunt, M. (CoI), Mcbeth, J. (CoI), O'Neill, T. (CoI) & Verstappen, S. (CoI)
1/08/13 → 31/07/18
Project: Research

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Antonio, L., Wu, F. C. W., O'Neill, T. W., Pye, S. R., Ahern, T. B., Laurent, M. R., Huhtaniemi, I. T., Lean, M. E. J., Keevil, B. G., Rastrelli, G., Forti, G., Bartfai, G., Casanueva, F. F., Kula, K., Punab, M., Giwercman, A., Claessens, F., Decallonne, B., & Vanderschueren, D. (2016). Low Free Testosterone is Associated with Hypogonadal Signs and Symptoms in Men with Normal Total Testosterone. The Journal of Clinical Endocrinology and Metabolism, 101(7), 2647-2657. https://doi.org/10.1210/jc.2015-4106

@article{0ac095b7a2434858b4c1d1bc845525f0,

title = "Low Free Testosterone is Associated with Hypogonadal Signs and Symptoms in Men with Normal Total Testosterone.",

abstract = "CONTEXT: During ageing, total testosterone (TT) declines and SHBG increases, resulting in a greater decrease in calculated free testosterone (cFT). Currently, guidelines suggest using TT to diagnose androgen deficiency and to reserve cFT only for men with borderline TT. OBJECTIVE: To investigate if either low cFT or low TT is more strongly associated with androgen-related clinical endpoints. METHODS: 3334 community-dwelling men, aged 40-79, were included. Differences in clinical variables between the referent group of men with both normal TT (≥10.5 nmol/L) and normal cFT (≥220 pmol/L) with those who had normal TT/low cFT, low TT/normal cFT and low TT/low cFT, were assessed by regression models adjusted for age, centre, BMI and comorbidities. RESULTS: 2641 men had normal TT [18.4±5.5 (mean±SD) nmol/L]/normal cFT (326±74 pmol/L), 277 men had normal TT (14.2±3.7)/low cFT (194±23), 96 men had low TT (9.6±0.7)/normal cFT (247±20) and 320 men had low TT (7.8±2.5)/low cFT (160±55). Men with normal TT/low cFT were older and in poorer health. They had higher SHBG and LH, and reported more sexual and physical symptoms, while haemoglobin and bone ultrasound parameters were lower compared to the referent group. Men with low TT/normal cFT were younger and more obese. They had lower SHBG, but LH was normal, while features of androgen deficiency were lacking. CONCLUSIONS: Low cFT, even in the presence of normal TT, is associated with androgen deficiency-related symptoms. Normal cFT, despite low TT, is not associated with cognate symptoms. Therefore cFT levels should be assessed in men with suspected hypogonadal symptoms.",

author = "Leen Antonio and Wu, {Frederick C. W.} and O'Neill, {Terence W.} and Pye, {Stephen R.} and Ahern, {Tomas B} and Laurent, {Micha{\"e}l R} and Huhtaniemi, {Ilpo T} and Lean, {Michael E J} and Keevil, {Brian G} and Giulia Rastrelli and Gianni Forti and Gy{\"o}rgy Bartfai and Casanueva, {Felipe F} and Krzysztof Kula and Margus Punab and Aleksander Giwercman and Frank Claessens and Brigitte Decallonne and Dirk Vanderschueren",

year = "2016",

doi = "10.1210/jc.2015-4106",

language = "English",

volume = "101",

pages = "2647--2657",

journal = "The Journal of Clinical Endocrinology and Metabolism",

issn = "1945-7197",

publisher = "Endocrine Society",

number = "7",

}

Antonio, L, Wu, FCW , O'Neill, TW, Pye, SR, Ahern, TB, Laurent, MR, Huhtaniemi, IT, Lean, MEJ, Keevil, BG, Rastrelli, G, Forti, G, Bartfai, G, Casanueva, FF, Kula, K, Punab, M, Giwercman, A, Claessens, F, Decallonne, B & Vanderschueren, D 2016, 'Low Free Testosterone is Associated with Hypogonadal Signs and Symptoms in Men with Normal Total Testosterone.', The Journal of Clinical Endocrinology and Metabolism, vol. 101, no. 7, pp. 2647-2657. https://doi.org/10.1210/jc.2015-4106

TY - JOUR

T1 - Low Free Testosterone is Associated with Hypogonadal Signs and Symptoms in Men with Normal Total Testosterone.

AU - Antonio, Leen

AU - Wu, Frederick C. W.

AU - O'Neill, Terence W.

AU - Pye, Stephen R.

AU - Ahern, Tomas B

AU - Laurent, Michaël R

AU - Huhtaniemi, Ilpo T

AU - Lean, Michael E J

AU - Keevil, Brian G

AU - Rastrelli, Giulia

AU - Forti, Gianni

AU - Bartfai, György

AU - Casanueva, Felipe F

AU - Kula, Krzysztof

AU - Punab, Margus

AU - Giwercman, Aleksander

AU - Claessens, Frank

AU - Decallonne, Brigitte

AU - Vanderschueren, Dirk

PY - 2016

Y1 - 2016

N2 - CONTEXT: During ageing, total testosterone (TT) declines and SHBG increases, resulting in a greater decrease in calculated free testosterone (cFT). Currently, guidelines suggest using TT to diagnose androgen deficiency and to reserve cFT only for men with borderline TT. OBJECTIVE: To investigate if either low cFT or low TT is more strongly associated with androgen-related clinical endpoints. METHODS: 3334 community-dwelling men, aged 40-79, were included. Differences in clinical variables between the referent group of men with both normal TT (≥10.5 nmol/L) and normal cFT (≥220 pmol/L) with those who had normal TT/low cFT, low TT/normal cFT and low TT/low cFT, were assessed by regression models adjusted for age, centre, BMI and comorbidities. RESULTS: 2641 men had normal TT [18.4±5.5 (mean±SD) nmol/L]/normal cFT (326±74 pmol/L), 277 men had normal TT (14.2±3.7)/low cFT (194±23), 96 men had low TT (9.6±0.7)/normal cFT (247±20) and 320 men had low TT (7.8±2.5)/low cFT (160±55). Men with normal TT/low cFT were older and in poorer health. They had higher SHBG and LH, and reported more sexual and physical symptoms, while haemoglobin and bone ultrasound parameters were lower compared to the referent group. Men with low TT/normal cFT were younger and more obese. They had lower SHBG, but LH was normal, while features of androgen deficiency were lacking. CONCLUSIONS: Low cFT, even in the presence of normal TT, is associated with androgen deficiency-related symptoms. Normal cFT, despite low TT, is not associated with cognate symptoms. Therefore cFT levels should be assessed in men with suspected hypogonadal symptoms.

AB - CONTEXT: During ageing, total testosterone (TT) declines and SHBG increases, resulting in a greater decrease in calculated free testosterone (cFT). Currently, guidelines suggest using TT to diagnose androgen deficiency and to reserve cFT only for men with borderline TT. OBJECTIVE: To investigate if either low cFT or low TT is more strongly associated with androgen-related clinical endpoints. METHODS: 3334 community-dwelling men, aged 40-79, were included. Differences in clinical variables between the referent group of men with both normal TT (≥10.5 nmol/L) and normal cFT (≥220 pmol/L) with those who had normal TT/low cFT, low TT/normal cFT and low TT/low cFT, were assessed by regression models adjusted for age, centre, BMI and comorbidities. RESULTS: 2641 men had normal TT [18.4±5.5 (mean±SD) nmol/L]/normal cFT (326±74 pmol/L), 277 men had normal TT (14.2±3.7)/low cFT (194±23), 96 men had low TT (9.6±0.7)/normal cFT (247±20) and 320 men had low TT (7.8±2.5)/low cFT (160±55). Men with normal TT/low cFT were older and in poorer health. They had higher SHBG and LH, and reported more sexual and physical symptoms, while haemoglobin and bone ultrasound parameters were lower compared to the referent group. Men with low TT/normal cFT were younger and more obese. They had lower SHBG, but LH was normal, while features of androgen deficiency were lacking. CONCLUSIONS: Low cFT, even in the presence of normal TT, is associated with androgen deficiency-related symptoms. Normal cFT, despite low TT, is not associated with cognate symptoms. Therefore cFT levels should be assessed in men with suspected hypogonadal symptoms.

U2 - 10.1210/jc.2015-4106

DO - 10.1210/jc.2015-4106

M3 - Article

C2 - 26909800

SN - 1945-7197

VL - 101

SP - 2647

EP - 2657

JO - The Journal of Clinical Endocrinology and Metabolism

JF - The Journal of Clinical Endocrinology and Metabolism

IS - 7

ER -

Low Free Testosterone is Associated with Hypogonadal Signs and Symptoms in Men with Normal Total Testosterone.

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Arthritis Research UK Centre of Excellence in Epidemiology.

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