Background: IGF-I immunoassays are primarily used to estimate IGF-I bioactivity. Recently, an IGF-I specific Kinase Receptor Activation Assay (KIRA) has been developed as an alternative method. However, no normative values have been established for the IGF-I KIRA.

Objective: To establish normative values for the IGF-I KIRA in healthy adults.

Design: Cross-sectional study in healthy non-fasting blood donors.

Study participants: 426 healthy individuals (310 M, 116 F; age range: 18 – 79 yrs)

Main outcome Measures: IGF-I bioactivity determined by the KIRA. Results were compared with total IGF-I, measured by five different IGF-I immunoassays.

Results: Mean (± SD) IGF-I bioactivity was 423 (± 131) pmol/L and decreased with age ( = -3.4 pmol/L/yr, p < 0.001). In subjects younger than 55 yrs mean IGF-I bioactivity was significantly higher in women than in men. Above this age this relationship was inverse, suggesting a drop in IGF-I bioactivity after menopause. This drop was not reflected in total IGF-I levels. IGF-I bioactivity was significantly related to total IGF-I (r_s varied between 0.46 – 0.52; P-values < 0.001).

Conclusions: We established age-specific normative values for the IGF-I KIRA. We observed a significant drop in IGF-I bioactivity in women between 50 and 60 years, which was not perceived by IGF-I immunoassays. The IGF-I KIRA, when compared to IGF-I immunoassays, theoretically has the advantage that it measures net effects of IGF-binding proteins on IGF-I receptor activation. However, it has to be proven whether information obtained by the IGF-I KIRA is clinically more relevant than measurements obtained by IGF-I immunoassays.