Testosterone and cardiovascular disease.
OBJECTIVE
Use of testosterone among men is increasing rapidly. Low serum testosterone is positively associated with cardiovascular disease and its risk factors. No large randomized controlled trial (RCT) has assessed the effects of testosterone on cardiovascular outcomes. Here recent evidence accumulating from other sources - pharmacoepidemiology, Mendelian randomization studies and meta-analysis of small RCTs - is reviewed to inform current testosterone usage.


RESULTS
In a large, well conducted pharmacoepidemiology study specifically testosterone prescription was associated with myocardial infarction. Two Mendelian randomization studies did not corroborate beneficial effects of higher endogenous testosterone on cardiovascular risk factors, but suggested higher endogenous testosterone raised LDL cholesterol and lowered HDL cholesterol. A comprehensive meta-analysis of RCTs summarizing 27 trials including 2994 men found increased risk of cardiovascular-related events on testosterone (odds ratio 1.54, 95% confidence interval 1.09-2.18).


CONCLUSIONS
Contrary to expectations from observational studies, current indications suggest testosterone causes ischemic cardiovascular disease with corresponding implications for practice. A large RCT would undoubtedly settle the issue definitively. Given mounting evidence of harm and the urgency of the situation assembling all the evidence from completed RCTs of testosterone or androgen deprivation therapy and use of Mendelian randomization might generate a definitive answer most quickly.
aCity University New York School of Public Health and Hunter College, New York, USA bSchool of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
C Mary
CM
Schooling
D000728:Androgens / Q000009:adverse effects* / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000097:blood* / Q000139:chemically induced / Q000503:physiopathology; D008076:Cholesterol, HDL / Q000097:blood / Q000187:drug effects*; D008078:Cholesterol, LDL / Q000097:blood / Q000187:drug effects*; D020249:Hormone Replacement Therapy / Q000009:adverse effects*; D006801:Humans; D008297:Male; D057182:Mendelian Randomization Analysis; D009203:Myocardial Infarction / Q000097:blood* / Q000139:chemically induced / Q000503:physiopathology; D017410:Practice Guidelines as Topic; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D013739:Testosterone / Q000009:adverse effects* / Q000172:deficiency / Q000627:therapeutic use
D000728:Androgens; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D013739:Testosterone