Table 1.
Effects of androgens on the cardiovascular system
| First author, Year | Primary CV endpoint | Findings |
|---|---|---|
| Beneficial effects of endogenous testosterone | ||
| Dockery 2003 | Vascular function | Free testosterone was associated with increased systemic arterial compliance (r = 0.507; p < 0.001) |
| Deenadayalu 2012 | Testosterone induces coronary artery relaxation by activating calcium-activated potassium channels | |
| Campelo 2012 | Testosterone directly acts on endothelial nitric oxide production to modulate endothelial cell growth and platelet aggregation | |
| Li 2014 | Dihydrotestosterone increases endothelial progenitor cell proliferation and adhesive ability, promoting cardiovascular health | |
| Norata 2006 | By inhibiting the expression of inflammatory molecules (e.g., IL-6, Cox-2, and PAI-1), dihydrotestosterone may positively modulate endothelial function | |
| Callies 2003 | Myocardial protection | Testosterone administration improves recovery from myocardial ischemia |
| Malkin 2004 | Hypogonadal men receiving testosterone replacement therapy had delayed time to ischemia, which was assessed by time to 1 mm ST depression (p = 0.0002) | |
| Tsang 2008 | Testosterone stimulates cardiac α1-adrenoceptors, reducing myocardial injury induced by ischemia and noradrenaline | |
| Dobrzycki 2003 | Compared to patients with higher levels of free-testosterone (86.10 pmo/l), patients with low free-testosterone levels (23.85 pmol/l) had significantly lower ejection fraction (51.85 vs. 61.30) | |
| Agledahl 2009 | Cardiovascular events | Elderly men with low testosterone had faster tissue-induced coagulation (5.1 ± 1.0 min vs. 5.7 ± 1.3, p = 0.039), suggesting that physiological levels of testosterone has anti-thrombotic properties |
| Ohlsson 2011 | Elderly men with high serum testosterone (> 550 ng/dl) had a reduced 5-year risk of CV events than those with lower serum testosterone (HR, 0.70; 95% CI), even after adjusting for traditional CV risk factors | |
| Effects of supplemental testosterone | ||
| Baillargeon 2014 | Beneficial effect on the CV system | Testosterone therapy was modestly protective against MI in men with high MI risk (HR, 0.69; 95% CI, 0.53–0.92). There was no increased risk for MI in men treated with intramuscular testosterone (HR, 0.84; 95% CI, 0.69–1.02) |
| Cheetham 2017 | Testosterone prescriptions among men with androgen deficiency were associated with decreased risk of stroke events (stroke and TIA) (HR, 0.72; 95% CI, 0.62–0.84) and combined cardiac events (acute MI, SCD, UA, and revascularization procedures) (HR, 0.66; 95% CI, 0.60–0.72) | |
| Crisostomo 2006 | Adverse effect on the CV system | In an animal study, postischemic recovery of LVDP was significantly higher in females (71.7 ± 3.3%) and castrated males (64.5 ± 6.0%) than in females and castrated males who received acute testosterone infusion (26.1 ± 7.5%; 7.1 ± 1.3%), respectively |
| Xu 2013 | Exogenous testosterone increased the risk of a cardiovascular-related event (OR, 1.54; 95% CI 1.09–2.18) | |
| Vigen 2013 | Testosterone replacement therapy was associated with increased risk of mortality, myocardial infarction, and stroke, regardless of presence of preexisting coronary artery disease (HR, 1.29; 95% CI, 1.04 to 1.58) | |
| Gagliano-Jucá 2020 | Testosterone administration was associated with increases in leukocyte and platelet counts (p < 0.001), both of which have known associations with cardiovascular and thromboembolic risks | |
| Effects of testosterone deficiency | ||
| Shores 2006 | Adverse effect on the CV system | Male veterans with low testosterone levels had an increased mortality rate compared to those with equivocal or normal testosterone levels |
| Laughlin 2008 | Low free testosterone levels in older men increased the risk of cardiovascular and respiratory related mortality (HR, 2.29; 95% CI, 1.25–4.20) | |
| Vlachopoulos 2013 | Subjects in the lowest total testosterone tertile (< 4.0 ng/ml) had an increased the risk for MACE compared to those in the highest TT tertile (> 4.9 ng/ml) after adjusting for age, systolic blood pressure, and risk factors. (all p < 0.05). MACE included CV death, stroke, TIA, CAD, and PAD | |
| Babcock 2022 | Brachial artery flow-mediated dilation was reduced in middle-aged and older men with lower testosterone compared to those with higher testosterone (p = 0.021). Low testosterone levels may contribute to accelerated vascular aging, which may increase risk for age-associated cardiovascular disease | |
Abbreviation: CAD, coronary artery disease; CI, confidence interval; CV, cardiovascular; CVM, cardiovascular mortality; CrVD, cerebrovascular death; DM, diabetes mellitus; HF, heart failure; HR, hazard ratio; LVDP, left ventricular diastolic pressure; MACE, major adverse cardiovascular event; MI, myocardial infarction; PAD, peripheral artery disease; SCD, sudden cardiac death; TIA, transient ischemic attack; TT, total testosterone; UA, unstable angina