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. 2023 Nov 27:14:1277393.
doi: 10.3389/fendo.2023.1277393. eCollection 2023.

Body composition and testosterone in men: a Mendelian randomization study

Yoshihiro Ikehata  1 , Tsuyoshi Hachiya  2 , Takuro Kobayashi  1 , Hisamitsu Ide  1 , Shigeo Horie  1   2
Affiliations

Body composition and testosterone in men: a Mendelian randomization study

Yoshihiro Ikehata et al. Front Endocrinol (Lausanne). .

Abstract

Background: Testosterone is an essential sex hormone that plays a vital role in the overall health and development of males. It is well known that obesity decreases testosterone levels, but it is difficult to determine the causal relationship between body composition and testosterone.

Methods: To investigate potential causal associations between body composition and testosterone levels by a first time application of Mendelian randomization methods. Exposure variables in men included body composition (fat mass, fat-free mass, and body mass index). In addition to whole body fat and fat-free mass, we examined fat and fat-free mass for each body part (e.g., trunk, left arm, right arm, left leg and right leg) as exposures. Instrumental variables were defined using genome-wide association study data from the UK Biobank. Outcome variables in men included testosterone levels (total testosterone [TT], bioavailable testosterone [BT], and sex hormone-binding globulin [SHBG]). A one-sample Mendelian randomization analysis of inverse-variance weighted and weighted median was performed.

Results: The number of genetic instruments for the 13 exposure traits related to body composition ranged from 156 to 540. Genetically predicted whole body fat mass was negatively associated with TT (β=-0.24, P=5.2×10-33), BT (β=-0.18, P=5.8×10-20) and SHBG (β=-0.06, P=8.0×10-9). Genetically predicted whole body fat-free mass was negatively associated with BT (β=-0.04, P=2.1×10-4), but not with TT and SHBG, after multiple testing corrections. When comparing the causal effect on testosterone levels, there was a consistent trend that the effect of fat mass was more potent than that of fat-free mass. There were no differences between body parts.

Conclusion: These results show that reducing fat mass may increase testosterone levels.

Keywords: BMI; Mendelian randomization; body composition; exercise; fat mass; fat-free mass; testosterone levels.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Study design: One-sample Mendelian randomization analysis of inverse-variance weighted and weighted median to evaluate the association between detailed body composition (body mass index [BMI], fat mass, fat-free mass), and testosterone levels (total testosterone, bioavailable testosterone, and sex hormone-binding globulin) in men. MR-PRESSO was used for the sensitivity analysis.
Figure 2
Figure 2
βcoefficients with 95% CIs of inverse-variance weighted for the effect of one unit increase in fat mass, fat-free mass, and body mass index (BMI) on testosterone levels (total testosterone, bioavailable testosterone, and sex hormone-binding globulin) in men. SHBG, sex hormone-binding globulin.
Figure 3
Figure 3
βcoefficients with 95% CIs of weighted median for the effect of one unit increase in fat mass, fat-free mass, and body mass index (BMI) on testosterone levels (total testosterone, bioavailable testosterone, and sex hormone-binding globulin) in men. SHBG, sex hormone-binding globulin.
See this image and copyright information in PMC

References

    1. Mirone V, Debruyne F, Dohle G, Salonia A, Sofikitis N, Verze P, et al. . European association of urology position statement on the role of the urologist in the management of male hypogonadism and testosterone therapy. Eur Urol (2017) 72(2):164–7. doi: 10.1016/j.eururo.2017.02.022 - DOI - PubMed
    1. Salonia A, Bettocchi C, Boeri L, Capogrosso P, Carvalho J, Cilesiz NC, et al. . European association of urology guidelines on sexual and reproductive health-2021 update: male sexual dysfunction. Eur Urol (2021) 80(3):333–57. doi: 10.1016/j.eururo.2021.06.007 - DOI - PubMed
    1. Wu FC, Tajar A, Beynon JM, Pye SR, Silman AJ, Finn JD, et al. . Identification of late-onset hypogonadism in middle-aged and elderly men. N Engl J Med (2010) 363(2):123–35. doi: 10.1056/NEJMoa0911101 - DOI - PubMed
    1. Zarotsky V, Huang MY, Carman W, Morgentaler A, Singhal PK, Coffin D, et al. . Systematic literature review of the risk factors, comorbidities, and consequences of hypogonadism in men. Andrology (2014) 2(6):819–34. doi: 10.1111/andr.274 - DOI - PubMed
    1. Del Giudice F, Glover F, Belladelli F, De Berardinis E, Sciarra A, Salciccia S, et al. . Association of daily step count and serum testosterone among men in the United States. Endocrine (2021) 72(3):874–81. doi: 10.1007/s12020-021-02631-2 - DOI - PMC - PubMed