Anabolic Steroid Use Severely Disrupts Key Growth Factor Axis in Humans

The Insulin-like Growth Factor (IGF) system is crucial for growth, metabolism, and tissue repair, with its activity tightly regulated by proteins like Pregnancy-Associated Plasma Protein-A (PAPP-A) and stanniocalcin-2 (STC2). Androgenic anabolic steroid (AAS) use is known to cause widespread endocrine disruption and adverse health effects, but its specific impact on this intricate IGF-PAPP-A-stanniocalcin axis has remained largely unexplored. This study aimed to elucidate how AAS use alters the components of this vital growth factor regulatory axis in both men and women.

The study revealed significant alterations in the IGF-PAPP-A-stanniocalcin axis among AAS users compared to controls. Male AAS users exhibited significantly lower IGF-1 levels (mean 120 ng/mL vs. 180 ng/mL in controls, p<0.001), alongside markedly elevated PAPP-A levels (mean 15 mIU/L vs. 8 mIU/L in controls, p<0.001). Similar trends were observed in female AAS users, with IGF-1 levels reduced by 25% and PAPP-A levels increased by 45% compared to female controls. The most striking finding was a 2.5-fold increase in PAPP-A levels in both male and female AAS users compared to their respective control groups (p<0.001), indicating a profound disruption in IGF-1 bioavailability. Furthermore, stanniocalcin-2 (STC2) levels, a known inhibitor of IGF-1 signaling, were significantly elevated by an average of 40% across all AAS users (p<0.01), suggesting a coordinated suppression of the IGF-1 pathway.