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Factors Associated With Circulating Sex Hormones in Men: Individual Participant Data Meta-analyses

Marriott, Ross J; Murray, Kevin; Adams, Robert J; Antonio, Leen; Ballantyne, Christie M; Bauer, Douglas C; Bhasin, Shalender; ... Yeap, Bu B; + view all (2023) Factors Associated With Circulating Sex Hormones in Men: Individual Participant Data Meta-analyses. Annals of Internal Medicine , 176 (9) pp. 1221-1234. 10.7326/m23-0342. Green open access

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Abstract

Background: Various factors modulate circulating testosterone in men, affecting interpretation of testosterone measurements. // Purpose: To clarify factors associated with variations in sex hormone concentrations. // Data Sources: Systematic literature searches (to July 2019). // Study Selection: Prospective cohort studies of community-dwelling men with total testosterone measured using mass spectrometry. // Data Extraction: Individual participant data (IPD) (9 studies; n = 21 074) and aggregate data (2 studies; n = 4075). Sociodemographic, lifestyle, and health factors and concentrations of total testosterone, sex hormone–binding globulin (SHBG), luteinizing hormone (LH), dihydrotestosterone, and estradiol were extracted. // Data Synthesis: Two-stage random-effects IPD meta-analyses found a nonlinear association of testosterone with age, with negligible change among men aged 17 to 70 years (change per SD increase about the midpoint, −0.27 nmol/L [−7.8 ng/dL] [CI, −0.71 to 0.18 nmol/L {−20.5 to 5.2 ng/dL}]) and decreasing testosterone levels with age for men older than 70 years (−1.55 nmol/L [−44.7 ng/dL] [CI, −2.05 to −1.06 nmol/L {−59.1 to −30.6 ng/dL}]). Testosterone was inversely associated with body mass index (BMI) (change per SD increase, −2.42 nmol/L [−69.7 ng/dL] [CI, −2.70 to −2.13 nmol/L {−77.8 to −61.4 ng/dL}]). Testosterone concentrations were lower for men who were married (mean difference, −0.57 nmol/L [−16.4 ng/dL] [CI, −0.89 to −0.26 nmol/L {−25.6 to −7.5 ng/dL}]); undertook at most 75 minutes of vigorous physical activity per week (−0.51 nmol/L [−14.7 ng/dL] [CI, −0.90 to −0.13 nmol/L {−25.9 to −3.7 ng/dL}]); were former smokers (−0.34 nmol/L [−9.8 ng/dL] [CI, −0.55 to −0.12 nmol/L {−15.9 to −3.5 ng/dL}]); or had hypertension (−0.53 nmol/L [−15.3 ng/dL] [CI, −0.82 to −0.24 nmol/L {−23.6 to −6.9 ng/dL}]), cardiovascular disease (−0.35 nmol/L [−10.1 ng/dL] [CI, −0.55 to −0.15 nmol/L {−15.9 to −4.3 ng/dL}]), cancer (−1.39 nmol/L [−40.1 ng/dL] [CI, −1.79 to −0.99 nmol/L {−51.6 to −28.5 ng/dL}]), or diabetes (−1.43 nmol/L [−41.2 ng/dL] [CI, −1.65 to −1.22 nmol/L {−47.6 to −35.2 ng/dL}]). Sex hormone–binding globulin was directly associated with age and inversely associated with BMI. Luteinizing hormone was directly associated with age in men older than 70 years. // Limitation: Cross-sectional analysis, heterogeneity between studies and in timing of blood sampling, and imputation for missing data. // Conclusion: Multiple factors are associated with variation in male testosterone, SHBG, and LH concentrations. Reduced testosterone and increased LH concentrations may indicate impaired testicular function after age 70 years. Interpretation of individual testosterone measurements should account particularly for age older than 70 years, obesity, diabetes, and cancer. // Primary Funding Source: Medical Research Future Fund, Government of Western Australia, and Lawley Pharmaceuticals. (PROSPERO: CRD42019139668)

Type: Article
Title: Factors Associated With Circulating Sex Hormones in Men: Individual Participant Data Meta-analyses
Open access status: An open access version is available from UCL Discovery
DOI: 10.7326/m23-0342
Publisher version: https://doi.org/10.7326/M23-0342
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Ageing; Cohort studies; Testosterone
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > MRC Clinical Trials Unit at UCL
URI: https://discovery.ucl.ac.uk/id/eprint/10176023
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