Clinical Endocrinology (2015) 83, 236–245
doi: 10.1111/cen.12722
ORIGINAL ARTICLE
Genetic and environmental influence on the association between testosterone, sex hormone-binding globulin and body composition in Korean men Kayoung Lee*, Joohon Sung†,‡ and Yun-Mi Song§ *Department of Family Medicine, Busan Paik Hospital, Inje University College of Medicine, Busan, †Department of Epidemiology, School of Public Health, Seoul National University, ‡Institute of Health and Environment, Seoul National University, and §Department of Family Medicine, Samsung Medical Center and Center for Clinical Research, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
Summary Objectives This study aimed to evaluate an association between testosterone, sex hormone-binding globulin and body composition as well as the influence of genetic and environmental factors on the association. Design A cross-sectional study. Setting Community-based study. Participants One thousand and eighty-three Korean men including 144 pairs of monozygotic twins. Main Outcome Measure Levels of serum total testosterone (TT) and sex hormone-binding globulin (SHBG) were measured by chemiluminescence immunoassay, and free testosterone (cFT) was calculated using Vermeulen’s method. Detailed body composition was measured using dual-energy X-ray absorptiometry. We performed linear mixed regression analysis with consideration of familial correlations and covariates. Results Each 1-SD increase in age-adjusted levels of TT, cFT and SHBG was associated with lower levels of adiposity measures and absolute measures of lean body mass. On the other hand, percentage total lean mass increased with increasing levels of TT, cFT and SHBG (P < 005). Bivariate variance-component analyses revealed that most body composition measures had a significant inverse unique environmental correlation with both TT and SHBG, and a significant genetic correlation with TT. A co-twin control study in monozygotic twins showed that withinpair differences in adiposity measures were inversely associated with within-pair differences in the levels of TT and SHBG, while within-pair differences in lean mass were inversely associated with within-pair differences in the levels of TT. Conclusions The significant associations of body composition with testosterone and SHBG were influenced by both genetic
Correspondence: Yun-Mi Song, Department of Family Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Irwon-ro 81, Gangnamgu, Seoul 135-710, Republic of Korea. Tel.: +82 2 3410 2442; Fax: +82 2 3410 0388; E-mail: [email protected]
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and environmental factors. Further efforts to elucidate related genes and modifiable environmental factors are needed. (Received 22 September 2014; returned for revision 10 December 2014; finally revised 10 January 2015; accepted 12 January 2015)
Introduction Ageing accompanies significant changes in body composition, including fatness and lean body mass. Body composition is significantly associated with testosterone and sex hormone-binding globulin (SHBG) in men.1 Testosterone, a representative male sex hormone primarily secreted from the testes, may be associated with ageing, sexual function and various health conditions in men.2 SHBG, a protein mainly synthesized in the liver, binds testosterone with high affinity and regulates its clinical action.3 In many studies, low total testosterone (TT), low free testosterone and low SHBG levels have been associated with a greater risk of obesity or increased visceral fat.1,4 Prospective studies also found that baseline testosterone level was inversely associated with accumulation of visceral fat and waist–hip ratio.5,6 A meta-analysis of randomized clinical trials evaluating the effect of testosterone on body fat has demonstrated greater weight reduction in the testosterone-treated group than in the placebo group.7 Some studies revealed a decrease in central obesity, as measured by waist circumference (WC) or waist–hip ratio, after testosterone replacement, although the effect of testosterone on subcutaneous fat is controversial.8,9 However, other evidence negates the influence of testosterone on fat mass. A study of a mixed ethnic population in the USA found no significant association between baseline sex hormone levels and changes in anthropometric measures over time; they argued instead that the association between hormone levels and body fat is driven by the influence of an adiposity-on hormone rather than by testosterone.4 Obesity was associated with a decrease in testosterone over time in healthy men in another study.10 A study in German men showed that obesity was associ© 2015 John Wiley & Sons Ltd
Testosterone and body composition 237 ated with risk of testosterone deficiency, while men with a normal body mass index (BMI,
doi: 10.1111/cen.12722
ORIGINAL ARTICLE
Genetic and environmental influence on the association between testosterone, sex hormone-binding globulin and body composition in Korean men Kayoung Lee*, Joohon Sung†,‡ and Yun-Mi Song§ *Department of Family Medicine, Busan Paik Hospital, Inje University College of Medicine, Busan, †Department of Epidemiology, School of Public Health, Seoul National University, ‡Institute of Health and Environment, Seoul National University, and §Department of Family Medicine, Samsung Medical Center and Center for Clinical Research, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
Summary Objectives This study aimed to evaluate an association between testosterone, sex hormone-binding globulin and body composition as well as the influence of genetic and environmental factors on the association. Design A cross-sectional study. Setting Community-based study. Participants One thousand and eighty-three Korean men including 144 pairs of monozygotic twins. Main Outcome Measure Levels of serum total testosterone (TT) and sex hormone-binding globulin (SHBG) were measured by chemiluminescence immunoassay, and free testosterone (cFT) was calculated using Vermeulen’s method. Detailed body composition was measured using dual-energy X-ray absorptiometry. We performed linear mixed regression analysis with consideration of familial correlations and covariates. Results Each 1-SD increase in age-adjusted levels of TT, cFT and SHBG was associated with lower levels of adiposity measures and absolute measures of lean body mass. On the other hand, percentage total lean mass increased with increasing levels of TT, cFT and SHBG (P < 005). Bivariate variance-component analyses revealed that most body composition measures had a significant inverse unique environmental correlation with both TT and SHBG, and a significant genetic correlation with TT. A co-twin control study in monozygotic twins showed that withinpair differences in adiposity measures were inversely associated with within-pair differences in the levels of TT and SHBG, while within-pair differences in lean mass were inversely associated with within-pair differences in the levels of TT. Conclusions The significant associations of body composition with testosterone and SHBG were influenced by both genetic
Correspondence: Yun-Mi Song, Department of Family Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Irwon-ro 81, Gangnamgu, Seoul 135-710, Republic of Korea. Tel.: +82 2 3410 2442; Fax: +82 2 3410 0388; E-mail: [email protected]
236
and environmental factors. Further efforts to elucidate related genes and modifiable environmental factors are needed. (Received 22 September 2014; returned for revision 10 December 2014; finally revised 10 January 2015; accepted 12 January 2015)
Introduction Ageing accompanies significant changes in body composition, including fatness and lean body mass. Body composition is significantly associated with testosterone and sex hormone-binding globulin (SHBG) in men.1 Testosterone, a representative male sex hormone primarily secreted from the testes, may be associated with ageing, sexual function and various health conditions in men.2 SHBG, a protein mainly synthesized in the liver, binds testosterone with high affinity and regulates its clinical action.3 In many studies, low total testosterone (TT), low free testosterone and low SHBG levels have been associated with a greater risk of obesity or increased visceral fat.1,4 Prospective studies also found that baseline testosterone level was inversely associated with accumulation of visceral fat and waist–hip ratio.5,6 A meta-analysis of randomized clinical trials evaluating the effect of testosterone on body fat has demonstrated greater weight reduction in the testosterone-treated group than in the placebo group.7 Some studies revealed a decrease in central obesity, as measured by waist circumference (WC) or waist–hip ratio, after testosterone replacement, although the effect of testosterone on subcutaneous fat is controversial.8,9 However, other evidence negates the influence of testosterone on fat mass. A study of a mixed ethnic population in the USA found no significant association between baseline sex hormone levels and changes in anthropometric measures over time; they argued instead that the association between hormone levels and body fat is driven by the influence of an adiposity-on hormone rather than by testosterone.4 Obesity was associated with a decrease in testosterone over time in healthy men in another study.10 A study in German men showed that obesity was associ© 2015 John Wiley & Sons Ltd
Testosterone and body composition 237 ated with risk of testosterone deficiency, while men with a normal body mass index (BMI,
