Elevated interleukin 8 and matrix metalloproteinase 9 levels are associated with myocardial pathology in users of Anabolic-Androgenic Steroids.

AIM: In the current paper, we aim to explore the effect of both current and former long-term anabolic-androgenic steroid (AAS) use on regulation of systemic inflammatory markers and mediators of extracellular matrix (ECM) remodeling and their association with hormones and echocardiographic myocardial pathology in weightlifters. METHODS: In a cross-sectional study, 93 weightlifting AAS-users, of which 62 were current and 31 were past users, with at least one-year cumulative AAS-use (mean 11±7 accumulated years of AAS-use), were compared to 54 non-using weightlifting controls (WLC) using clinical interview, blood pressure measurements, and echocardiography. RESULTS: Serum levels of interleukin (IL)-6, IL-8, tumor necrosis factor (TNF), interferon (IFN)γ, growth differentiation factor (GDF)-15 and matrix metalloproteinase (MMP-9), sex hormones and lipids were analyzed. Serum levels of IL-8, GDF-15 and MMP-9 were significantly increased in current AAS users compared to former users and WLC. MMP-9, but not IL-8, correlated consistently with sex-hormone levels, and sex-hormone levels correlated consistently with mean wall thickness, in current users. Moreover, HDL cholesterol was significantly lower in current versus former AAS users, in significantly inversely correlated with MMP-9 in current users. Further, in current users, MMP-9 and IL-8 correlated with markers of myocardial strain, and MMP9 also with indices of cardiac mass, which was not seen in former users. Mediation analyses suggested that MMP-9 could partly explain hormone-induced alterations in markers of myocardial damage in current users. CONCLUSION: In conclusion, long-term AAS is associated with increased levels of markers of inflammation and extracellular matrix remodeling, which seems to have a hormone-dependent (MMP-9) and hormone-independent (IL-8) association with markers of myocardial dysfunction.

Long-term use of anabolic-androgenic steroids (AAS) can increase inflammation and mediators of extracellular matrix (ECM) remodeling which potentially could be involved in myocardial pathology seen in these individuals. AAS use increased levels of inflammatory marker IL-8 and marker of ECM remodeling MMP-9.IL-8 and MMP-9 were both associated with myocardial pathology in current, but not former users, suggesting that these markers are association with risk of myocardial damage during AAS use.

Treatment-seeking behavior and cardiovascular morbidity among men with anabolic-androgenic steroid use: A cross-sectional study.

AIMS: To determine associations between anabolic-androgenic steroid (AAS) use-related morbidity including cardiovascular disease (CVD) and engagement to health services. METHODS: In this cross-sectional study, 90 males with at least 12 months cumulative current or former use of AAS were included. The participants were divided into a treatment-seeking group (TSG) and a non-treatment seeking group (non-TSG) based on their responses to a self-report web questionnaire. All participants were screened for symptoms that could be indicative of CVD through a clinical interview, and examined with blood samples, blood pressure measurements and transthoracic echocardiography. RESULTS: In the total sample (n = 90), mean age was 39 ± 11 years with cumulative AAS use of 12 ± 9 years. Among men in the TSG with current use there were higher prevalence of dyspnoea (50% vs 7%) and reduced left ventricular ejection fraction (LVEF) in conjunction with left ventricular hypertrophy (LVH) (36 vs. 9%) and/or high blood pressure (55% vs. 19%) compared to men in the non-TSG. Among men with current AAS use and established LVEF <50% (n = 25) or LVH (n = 21), 44% (11) and 43% (9) respectively, had never engaged health services due to AAS-related adverse effects. Deviant liver- and kidney parameters were frequently observed in the total sample but without between-group differences. CONCLUSIONS: Treatment-seeking behavior among current AAS users may be associated with increased levels of dyspnoea and established CVD. Despite objective signs of severe CVD among a substantial amount of study participants, it is of great concern that the majority had never sought treatment for AAS-related concerns.

Severe biventricular cardiomyopathy in both current and former long-term users of anabolic-androgenic steroids.

AIMS: This study aims to explore the cardiovascular effects of long-term anabolic-androgenic steroid (AAS) use in both current and former weightlifting AAS users and estimate the occurrence of severe reduced myocardial function and the impact of duration and amount of AAS. METHODS AND RESULTS: In this cross-sectional study, 101 weightlifting AAS users with at least 1 year cumulative AAS use (mean 11 ± 7 accumulated years of AAS use) were compared with 71 non-using weightlifting controls (WLC) using clinical data and echocardiography. Sixty-nine were current, 30 former (>1 year since quitted), and 2 AAS users were not available for this classification. Anabolic-androgenic users had higher left ventricular mass index (LVMI) (106 ± 26 vs. 80 ± 15 g/m2, P < 0.001), worse left ventricular ejection fraction (LVEF) (49 ±7 vs. 59 ± 5%, P < 0.001) and right ventricular global longitudinal strain (-17.3 ± 3.5 vs. -22.8 ± 2.0%, P < 0.001), and higher systolic blood pressure (141 ± 17 vs. 133 ± 11 mmHg, P < 0.001) compared with WLC. In current users, accumulated duration of AAS use was 12 ± 7 years and in former 9 ± 6 years (quitted 6 ± 6 years earlier). Compared with WLC, LVMI and LVEF were pathological in current and former users (P < 0.05) with equal distribution of severely reduced myocardial function (LVEF ≤40%) (11 vs. 10%, not significant (NS)). In current users, estimated lifetime AAS dose correlated with reduced LVEF and LVGLS, P < 0.05, but not with LVMI, P = 0.12. Regression analyses of the total population showed that the strongest determinant of reduced LVEF was not coexisting strength training or hypertension but history of AAS use (ß -0.53, P < 0.001). CONCLUSION: Long-term AAS users showed severely biventricular cardiomyopathy. The reduced systolic function was also found upon discontinued use.

In this, to date, largest cardiovascular study comparing 101 weightlifting long-term anabolic­androgenic steroid (AAS) users (11 ± 7 accumulated years of AAS use), with 71 weightlifting controls, we conclude that non-medical use of AAS is associated with adverse cardiovascular effects including enlarged heart muscle, seriously reduced heart function, and increased blood pressure. Both current and former users with accumulated years of AAS use of respectively 12 ± 7 years and 9 ± 6 years (former quitted 6 ± 6 years earlier) had biventricular cardiomyopathy with severely affected left and right myocardium. Of note, 11% of AAS users (10% of current and 11% of former) had severely reduced left ventricular systolic function with ejection fraction < 40%, consistent with heart failure.Regression analyses of the total population showed that the strongest determinant of reduced left ventricle ejection fraction was not coexisting strength training or hypertension but history of AAS use (ß −0.53, P < 0.001).