Role of sex hormone-binding globulin in the free hormone hypothesis and the relevance of free testosterone in androgen physiology

Narinx, Nick; David, Karel; Walravens, J.; Vermeersch, Pieter; Claessens, Frank; Fiers, Tom; Lapauw, Bruno; LʼAbbate, Antonio; Vanderschueren, Dirk

doi:10.1007/s00018-022-04562-1

Cited by 28 publications

(14 citation statements)

References 249 publications

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“…Regarding FT, it has also been found to be associated with bone health, frailty, and other clinical endpoints [ 45 , 46 ]. And a previous study reported that determining the FT level avoids under- and over-diagnosis of male hypogonadism and facilitates adequate prescription of hormonal replacement therapy [ 47 ]. Therefore, the variations in SHBG and FT concentrations in serum can not only be associated with adverse health outcomes but also impact the sex hormones’ utility as sensitive biomarkers for several clinical outcomes.…”

Section: Discussionmentioning

confidence: 99%

Associations between urinary concentrations of bisphenols and serum concentrations of sex hormones among US. Males

et al. 2022

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Background Bisphenol A (BPA) exposure and its structural analogs (BPS and BPF) might cause endocrine alterations and adverse physiological effects. Few studies to date have directly explored the association between its structural analogs (BPS, BPF) and sex hormones in adult male participants. Therefore, we aimed to assess the associations between BPA, BPS, BPF, and sex hormones in American adult men. Methods We used data from the U.S. National Health and Nutrition Examination Survey 2011–2016. We excluded participants without data available on sex hormones and urinary bisphenols. Furthermore, participants consuming sex hormone medications were excluded. Multivariable regression models were performed to assess the association between bisphenols and sex hormones. Results In this study, 2367 participants were included. Of 2367, in 1575 participants, the data on BPS and BPF were available. We found that a per unit increase in BPF was associated with 0.575 ng/dL higher total testosterone (TT) (Model 2: 95% CI: 0.047, 1.103, P = 0.033). However, there was no significant association between BPA or BPS and TT. Furthermore, increased BPA and BPS levels were associated with higher levels of sex hormone-binding globulin (SHBG) (Model 2: β = 0.364, 95% CI: 0.158, 0.571; β = 0.25, 95% CI: 0.071, 0.429, respectively). Additionally, participants in the highest BPA exposure quartile (quartile 4) had 4.072 nmol/L higher levels of SHBG than those in quartile 1 (Model 2: 95% CI: 0.746, 7.397, P = 0.017; P for trend =0.005). Both BPA and BPS were negatively associated with free testosterone (FT, nmol/L) after full adjustment (Model 2, β = − 0.01%, P = 0.0211, P = 0.0211; Model 2, β = − 0.01%, P = 0.0258, respectively). However, BPF was positively associated with FT (Model 2, β = 0.0029%, P = 0.0028). Conclusion Our study indicated that exposure to both BPA and its substitutions could alter sex hormone levels. This finding supports the possibility that human exposure to bisphenols at environmental levels might affect the endogenous hormone balance.

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Section: Discussionmentioning

confidence: 99%

Associations between urinary concentrations of bisphenols and serum concentrations of sex hormones among US. Males

et al. 2022

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“…23 One plausible cause of the negative associations between SHBG and abdominal muscle radiodensities could be that an increase in SHBG concentrations may in uence the binding capacity and magnitude of available free testosterone and could suggest a partial explanation to some of the weaker association found for other sex hormones . 24 This study has a number of strengths, including usage of data from a large and diverse cohort, detailed sampling of information with validated instruments as well as standardized sampling of blood specimens according to guidelines. 25 Furthermore, by assessing muscle composition with CT, we were able to estimate its quality.…”

Section: Discussionmentioning

confidence: 99%

Sex Hormones and Abdominal Muscle Area and Radiodensity in Men: The Multi-Ethnic Study of Atherosclerosis

Osmancevic,

Allison,

Miljkovic

et al. 2024

Preprint

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Information on the associations of testosterone levels with abdominal muscle volume and quality in men is limited, while the role of estradiol and SHBG on these muscle characteristics are unclear. To investigate the association between fasting serum sex hormones and CT-derived abdominal muscle area and radiodensity in adult men. Cross sectional observational study using data from the Multi-Ethnic Study of Atherosclerosis. A community-based sample of 907 men aged 45–84 years; 878 men with complete data were included in the analysis. CT scans of the abdomen were interrogated for muscle characteristics. Multivariable linear regressions were used to test the associations. After adjustment, higher levels of both total testosterone and estradiol were associated with higher abdominal muscle area (1.79, 0.1–3.4, & 1.79, 0.4–3.2, respectively). In the final analyses, levels of total testosterone showed a positive association, while an inverse relationship was observed for SHBG with abdominal muscle radiodensity (0.3, 0.0–0.6, & -0.34, -0.6 - -0.1, respectively). Our results indicate a complex association between sex hormones and abdominal muscle characteristics in men. Specifically, total testosterone and estradiol were associated with abdominal muscle area, while only total testosterone was associated with muscle radiodensity and SHBG was inversely associated with muscle radiodensity.

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“…Additionally, adipose tissue expresses 17[-hydroxysteroid dehydrogenase which converts less active forms of sex hormones into testosterone and oestradiol, which are more biologically potent 91 . The bioavailability of circulating testosterone and oestradiol is modulated by sex hormone-binding globulin (SHBG), which binds to these hormones, limiting their diffusion into target tissues 92 . Higher adiposity has a strong inverse correlation with SHBG concentration, relating to increased liver fat, insulin and proinflammatory cytokines 93 .…”

Section: Molecular Mechanismsmentioning

confidence: 99%

Adiposity and cancer: meta-analysis, mechanisms, and future perspectives

Watts,

Moore,

Gunter

et al. 2024

Preprint

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Obesity is a recognised risk factor for many cancers and with rising global prevalence, has become a leading cause of cancer. Here we summarise the current evidence from both population-based epidemiologic investigations and experimental studies on the role of obesity in cancer development. This review presents a new meta-analysis using data from 40 million individuals and reports positive associations with 19 cancer types. Utilising major new data from East Asia, the meta-analysis also shows that the strength of obesity and cancer associations varies regionally, with stronger relative risks for several cancers in East Asia. This review also presents current evidence on the mechanisms linking obesity and cancer and identifies promising future research directions. These include the use of new imaging data to circumvent the methodological issues involved with body mass index and the use of omics technologies to resolve biologic mechanisms with greater precision and clarity.

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Role of sex hormone-binding globulin in the free hormone hypothesis and the relevance of free testosterone in androgen physiology

Cited by 28 publications

References 249 publications

Associations between urinary concentrations of bisphenols and serum concentrations of sex hormones among US. Males

Associations between urinary concentrations of bisphenols and serum concentrations of sex hormones among US. Males

Sex Hormones and Abdominal Muscle Area and Radiodensity in Men: The Multi-Ethnic Study of Atherosclerosis

Adiposity and cancer: meta-analysis, mechanisms, and future perspectives

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