IGF–PAPP-A–stanniocalcin axis and androgenic anabolic steroid use in men and women

OBJECTIVE: Anabolic androgenic steroids (AAS) may exert effects through the insulin-like growth factor (IGF) system. We compared the IGF system in male and female recreational athletes who were current or former AAS users and non-users. METHODS: The cross-sectional study included 80 active AAS users (19 women), 26 former users (8 women), and 58 age- and sex-matched non-users (16 women). Participants underwent clinical examination, echocardiography, and measurement of circulating IGF-1, IGF-2, IGF bioactivity, IGF-binding proteins (IGFBPs), pregnancy-associated plasma protein-A (PAPP-A) and -A2 (PAPP-A2), and stanniocalcin-1 (STC1) and -2 (STC2). RESULTS: In active AAS users, IGF-2 levels were reduced by 36.1% vs. former users and 38.4% vs. non-users (P < .001), and IGFBP-3 levels were 13.6% and 35.8% lower (P < .001). STC2 was increased in AAS-using men only, being 24.5% higher than former users (P = .029) and 45.7% higher than non-users (P < .001). PAPP-A was higher in non-using men than women, whereas levels were similar in active users. Differences remained after adjustment for age, sex, body fat, exercise and strength training, family history of coronary disease, smoking, alcohol, and drug use. No group differences were observed for IGF-1, bioactive IGF, IGFBP-2, or PAPP-A2. Cumulative lifetime AAS exposure was associated with IGF-2, IGFBP-3, and STC2 in multivariable models. Higher IGF-2 and IGFBP-3 associated with lower left ventricular mass, higher left ventricular ejection fraction, and better diastolic function, whereas higher STC2 associated with adverse outcomes (all P < .05). CONCLUSIONS: Illicit AAS use is associated with persistent, sex-specific alterations in the IGF-PAPP-A-STC2 axis, potentially contributing to cardiovascular risk in recreational athletes.