DataSheet_1_Body composition and testosterone in men: a Mendelian randomization study.docx

BackgroundTestosterone 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.MethodsTo 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.ResultsThe 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.ConclusionThese results show that reducing fat mass may increase testosterone levels.</p

Table_1_Body composition and testosterone in men: a Mendelian randomization study.xlsx

BackgroundTestosterone 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.MethodsTo 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.ResultsThe 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.ConclusionThese results show that reducing fat mass may increase testosterone levels.</p

Patient characteristics.

<p>Abbreviations: PSA is prostate-specific antigen; TZ is transition zone; IPSS is International Prostate Symptom Score; QOL is Quality of Life score: OABSS is Overactive Bladder Symptom Score</p><p>Patient characteristics.</p

Bladder blood flow measured by LDF.

<p>Every region of the bladder including left wall, right wall, and bladder trigone showed a significant increase in blood flow as measured by LDF. *: p<0.001 Student’s t-test</p

Multiple regression analysis for the improvement of the storage symptoms.

<p>Multiple regression analysis for the improvement of the storage symptoms.</p

The improvement rate of IPSS and OABSS.

<p>(A) shows the improvement rate of storage symptoms in IPSS for both the increased perfusion group and the no change group. (B) shows the improvement rate of OABSS storage symptoms for the increased perfusion group and the no change group.*: p<0.001 Student’s t-test</p

Longitudinal change in IPSS (A), QOL score (B), and OABSS (C).

<p>There was significant improvement 1 week after surgery (*: p<0.05 Dunnett's test, compared with baseline). Note that the improvement of the OABSS is slower than the IPSS score.</p

Change in individual parameters before and after HoLEP.

<p>Data are derived from the Wilcoxon’s signed rank test</p><p>Change in individual parameters before and after HoLEP.</p

Laser Doppler flowmeter (LDF; OMEGA FLOW FLO-C1 BV, OMEGAWAVE, Tokyo, Japan).

<p>1A: LDF employs a beam of low intensity monochromatic infrared light emitted from a laser diode within the flowmeter to measure the real-time micro-perfusion rate at tissue depths of 1 mm. B: The probe is placed a few mm away from the bladder mucosa while the bladder is filled with 150 ml saline at room temperature.</p

The change in voided volume.

<p>The change in voided volume is shown before and after surgery for both the increased perfusion group and the no change group. *: p<0.0001 Student’s t-test</p