Genetically predicted testosterone and cardiovascular risk factors in men: a Mendelian randomization analysis in the Guangzhou Biobank Cohort Study
Abstract
BACKGROUND: Observationally lower testosterone is associated with an unhealthier cardiovascular (CVD) risk profile, but this association is open to confounding and reverse causality. The authors examined the association of testosterone with well-established cardiovascular disease (CVD) risk factors (blood pressure, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL)cholesterol and fasting glucose) and the Framingham score using a Mendelian randomization analysis with a separate-sample instrumental variable estimator. METHODS: To minimize reverse causality, a genetic score predicting testosterone was developed in 289 young Chinese men from Hong Kong, based on three selected testosterone-related single nucleotide polymorphisms (rs10046, rs1008805 and rs1256031). Multivariable censored and linear regressions were used to examine the association of genetically predicted testosterone levels with CVD risk factors and Framingham score among 4212 older Chinese men from the Guangzhou Biobank Cohort Study. RESULTS: Predicted testosterone was unrelated to systolic blood pressure [-0.11 mmHg, 95% confidence interval (CI) -0.70 to 0.48], diastolic blood pressure (0.04 mmHg, 95% CI -0.27 to 0.36), fasting glucose (0.02 mmol/l, 95% CI -0.02 to 0.06) or Framingham score (0.02, 95% CI -0.0001 to 0.03) but associated with higher LDL-cholesterol (0.02 mmol/l, 95% CI 0.01 to 0.04) and lower HDL-cholesterol (-0.01 mmol/l, 95% CI -0.02 to -0.001), after adjustment for potential confounders (age, education, smoking status, use of alcohol and body mass index). CONCLUSIONS: Our findings did not corroborate observed protective effects of testosterone on cardiovascular risk factors or risk of ischaemic heart disease among men, but raises the possibility that higher testosterone may be associated with an unhealthier lipid profile.
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Testosterone lowers HDL cholesterol in men.
“testosterone lowers HDL cholesterol in men, which may partly explain why we did not find an increase in HDL cholesterol in men in this systematic review and meta-analysis.”
From Overall and sex-specific effect of berberine for dyslipidemia: systematic review and meta-analysis of placebo-controlled trials (2022) · cites this paper as [41]
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“(16) Furthermore, our previous Mendelian randomization study(41) and a systematic review and meta-analysis of testosterone clinical trials,(42) indicates that .”
BackgroundSelf-citation
- Authors
- Zhao, J., Jiang, C., Lam, T. H., Liu, B., Cheng, K. K., Xu, L., Au Yeung, S. L., Zhang, W., Leung, G. M., & Schooling, C. M.
- Affiliations
- City University of New York (US)
- Corresponding author
- Schooling, C Mary
- Venue
- International Journal of Epidemiology
- Publisher
- Oxford University Press (OUP)
- Published
- 2013-12-02
- Volume
- 43
- Issue
- 1
- Pages
- 140-148
- ISSN
- 0300-5771 (ISSN-L)
- 1464-3685
- OpenAlex
- W2101969517
- Cited by
- 53
- References
- 52
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 2 · 2022: 3 · 2021: 7 · 2020: 5 · 2019: 5 · 2018: 6 · 2017: 4 · 2016: 6 · 2015: 9 · 2014: 4
- FWCI
- 4.96
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- International Journal of Epidemiology (publishedVersion)
- PubMed (publishedVersion)
- The HKU Scholars Hub (University of Hong Kong) (submittedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- Funders
- University of Birmingham
- University of Hong Kong
- Guangzhou Municipal Science and Technology Bureau
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Keywords
- testosterone, cardiovascular risk factors, LDL cholesterol, HDL cholesterol, blood pressure, fasting blood glucose, Framingham risk score, ischemic heart disease, genetic score, single nucleotide polymorphisms, Chinese men, lipid profile
- MeSH terms
- Adult, Aged, Aged, 80 and over, Blood Pressure, Cardiovascular Diseases, Cholesterol, Genotype, Hong Kong, Humans, Male, Middle Aged, Predictive Value of Tests, Surveys and Questionnaires, Risk Factors, Smoking, Socioeconomic Factors, Testosterone, Cohort Studies, Body Mass Index, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Asian People, Mendelian Randomization Analysis
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