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Mendelian randomization studies of testosterone exposure: A systematic review
Annika Magdalena Rhomberg-Kauert1, Morten Tulstrup2, Christoffer Badsted2
1Department of Clinical Pharmacology, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Bispebjerg Bakke 23, 2400 Copenhagen, Denmark; Medical University of Vienna, Spitalgasse 23, 1090 Vienna, Austria.
Steroids
|April 16, 2025
Summary
Mendelian randomization studies reveal higher testosterone levels are linked to increased risks of cardiovascular issues and prostate cancer in men. The impact on type 2 diabetes remains unclear, with limited research on other health areas.
Area of Science:
- Endocrinology
- Genetics
- Public Health
Background:
- Testosterone plays a crucial role in male reproductive health, cardiovascular function, and metabolism.
- Understanding testosterone's health effects is vital due to testosterone therapy and anabolic steroid misuse.
- Mendelian randomization (MR) offers a robust method to investigate causal links, overcoming limitations of observational studies and short-term clinical trials.
Purpose of the Study:
- To systematically review Mendelian randomization studies examining the causal associations between testosterone exposure and various health outcomes in males.
- To synthesize current evidence on testosterone's impact on cardiovascular, metabolic, oncological, and other health domains.
Main Methods:
- A systematic literature search was conducted using MEDLINE for studies published up to October 2024.
- Included studies utilized Mendelian randomization analysis to assess testosterone's relationship with health outcomes in males.
- Twenty-nine relevant Mendelian randomization studies were identified and analyzed.
Main Results:
- Higher testosterone levels were predominantly associated with adverse cardiovascular outcomes, including thromboembolism, ischemic heart disease, and heart failure.
- Elevated genetically predicted free testosterone consistently correlated with an increased risk of prostate cancer.
- The association between testosterone and type 2 diabetes was inconclusive, with limited exploration of neuropsychiatric, musculoskeletal, dermatological, infectious, and respiratory health.
Conclusions:
- This review highlights significant causal relationships between testosterone exposure and specific health outcomes, particularly cardiovascular risks and prostate cancer.
- The findings contribute to understanding testosterone's health implications, though substantial heterogeneity exists across studies.
- Further research is needed to clarify testosterone's role in metabolic health and explore its effects on less-studied health domains.
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