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

Ida Gregersen; Morgan Elizabeth Scarth; Rang Abdullah; Per Medbøe Thorsby; Lisa E Hauger; Kristina H Haugaa; Ellen Lund Sagen; Annika E Michelsen; Thor Ueland; Thor Edvardsen; Pål Aukrust; Vibeke Marie Almaas; Astrid Kristine Bjørnebekk; Bente Halvorsen

doi:10.1093/eurjpc/zwae126

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

Eur J Prev Cardiol. 2024 Apr 4:zwae126. doi: 10.1093/eurjpc/zwae126. Online ahead of print.

Authors

Ida Gregersen¹, Morgan Elizabeth Scarth², Rang Abdullah^{2

3

4}, Per Medbøe Thorsby^{4

5}, Lisa E Hauger^{2

6}, Kristina H Haugaa^{3

4}, Ellen Lund Sagen^{1

4}, Annika E Michelsen^{1

4}, Thor Ueland^{1

4

7}, Thor Edvardsen^{3

4}, Pål Aukrust^{1

4}, Vibeke Marie Almaas³, Astrid Kristine Bjørnebekk², Bente Halvorsen^{1

4}

Affiliations

¹ Research Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway.
² Anabolic Androgenic Steroid Research Group, Section for Clinical Addiction Research, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
³ ProCardio Center for Research Based Innovation, Department of Cardiology, Rikshospitalet, Oslo University Hospital, Oslo, Norway.
⁴ Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
⁵ Hormone Laboratory, Department of Medical Biochemistry and Biochemical Endocrinology and Metabolism Research Group, Oslo University Hospital, Aker, Oslo, Norway.
⁶ National Centre for Epilepsy, Section for Clinical Psychology and Neuropsychology, Oslo University Hospital.
⁷ Thrombosis Research Center (TREC), Division of internal medicine, University hospital of North Norway, Tromsø Norway.

PMID: 38573232
DOI: 10.1093/eurjpc/zwae126

Abstract

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.

Keywords: MMP; anabolic-androgenic steroids; hormones; inflammation; myocardial dysfunction.

Plain language summary

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.