Biochemical markers of recombinant human insulin‐like growth factor‐I (rhIGF‐I)/rhIGF binding protein‐3 (rhIGFBP‐3) misuse in athletes

Abstract

Insulin-like growth factor-I (IGF-I) is reportedly misused by elite athletes, either alone or with growth hormone (GH). The GH-2000 and GH-2004 research groups previously developed a method for detecting GH misuse based on the GH-sensitive markers IGF-I and procollagen type III amino-terminal propeptide (P-III-NP). Both markers increase in response to rhIGF-I/rhIGF binding protein-3 (rhIGFBP-3) administration in recreational athletes. The aim of this pilot study was to assess the effect of rhIGF-I/rhIGFBP-3 administration on other serum markers of the GH-IGF axis and on other bone and collagen markers. Twenty-six female and 30 male recreational athletes were randomized to 28 days' treatment with placebo or rhIGF-I/rhIGFBP-3 complex, followed by 56 days' washout. GH-IGF axis markers (IGFBP-2, IGFBP-3, acid-labile subunit (ALS) and IGF-II) and bone and collagen markers (procollagen type I carboxy-terminal propeptide (PICP), type I collagen cross-linked carboxy-terminal telopeptide (ICTP) and osteocalcin) were measured using commercial immunoassays. In women in the high dose treatment group, mean IGF-II decreased by 53% (P=0.0028) on Day 21. Mean IGFBP-2 increased by 119% (P=0.0039) and mean ALS decreased by 40% (P=0.0022) on Day 21. There were no significant changes in IGFBP-3, osteocalcin, ICTP or PICP. In men in the high dose group, mean IGF-II decreased by 51% on Day 21 (P<0.0001). Mean IGFBP-2 increased by 125% on Day 21 (P=0.0003). There were no significant changes in IGFBP-3, ALS, osteocalcin, ICTP or PICP. Serum IGFBP-2 and IGF-II may be useful markers of rhIGF-I/rhIGFBP-3 administration in both women and men while ALS may also be a useful marker in women; these markers are now undergoing further evaluation.

Novel markers to detect recombinant human insulin‐like growth factor‐I (rhIGF‐I)/rhIGF binding protein‐3 (rhIGFBP‐3) misuse in athletes

“…By contrast, there were no significant changes in IGFBP-3 or bone turnover markers in either sex, which may reflect the separate actions of GH and IGF-I. [9] The aim of the current study was to extend the pilot data by measuring analytes that responded in the pilot study to assess whether the measurement of IGF-II, IGFBP-2, or ALS either alone or in combination with either IGF-I or P-III-NP, could improve the sensitivity and specificity of a test to detect IGF-I misuse in athletes.…”

“…In women, mean IGF-II decreased by 53% (P = 0.0028) while mean IGFBP-2 increased by 119% (P = 0.0039) and mean ALS decreased by 40% (P = 0.0022). [9] In men, mean IGF-II decreased by 51% (P < 0.0001) and mean IGFBP-2 increased by 125% (P = 0.0003) but there was no significant change in ALS. By contrast, there were no significant changes in IGFBP-3 or bone turnover markers in either sex, which may reflect the separate actions of GH and IGF-I.…”

“…Using the samples obtained from the rhIGF‐I/rhIGFBP‐3 administration study, we undertook a pilot study in which we measured IGF‐II, IGFBP‐2, IGFBP‐3, acid‐labile subunit (ALS) as well as markers of bone and soft tissue turnover in samples obtained after 21 days administration of 60 mg/day of rhIGF‐I/rhIGFBP‐3. In women, mean IGF‐II decreased by 53% ( P = 0.0028) while mean IGFBP‐2 increased by 119% ( P = 0.0039) and mean ALS decreased by 40% ( P = 0.0022) . In men, mean IGF‐II decreased by 51% ( P < 0.0001) and mean IGFBP‐2 increased by 125% ( P = 0.0003) but there was no significant change in ALS.…”

“…In men, mean IGF‐II decreased by 51% ( P < 0.0001) and mean IGFBP‐2 increased by 125% ( P = 0.0003) but there was no significant change in ALS. By contrast, there were no significant changes in IGFBP‐3 or bone turnover markers in either sex, which may reflect the separate actions of GH and IGF‐I …”

Annual banned‐substance review: analytical approaches in human sports drug testing

“…Alternative biomarkers for the administration of IGF‐I/IGFBP were sought and found in IGFBP‐2 and IGF‐II, with IGFBP‐2 being increased by approximately 120% and IGF‐II being depleted by ca. 50% . In women, the acid‐labile subunit (ALS) could possibly serve as additional marker also.…”