Insulin-like growth factor binding protein-1 in PCOS: a systematic review and meta-analysis.

BACKGROUND Despite extensive research, the pathogenesis of polycystic ovary syndrome (PCOS) remains unclear. Putatively, an elevated circulating concentration of insulin inhibits the production of insulin-like growth factor binding protein-1 (IGFBP-1), thus increasing the level of free IGF-I in serum and stimulating ovarian androgen production. Decreased IGFBP-1 has been reported in PCOS and in obesity; however, there are inconsistencies in the evidence. This systematic review and meta-analysis aimed to determine whether IGFBP-1 is decreased in PCOS when controlling for the influence of BMI. METHODS Articles published between 1988 and 2008 were searched using MEDLINE, PubMed, SCOPUS and Web of Knowledge. Unpublished literature, trials in progress, and recent reviews were also searched. Original articles were selected by two investigators. To be included, the study must have compared serum IGFBP-1 in two populations: either PCOS versus controls, or an overweight subgroup versus the normal weight subgroup in either population. From 617 identified articles, 12 were included in the meta-analysis. Data were abstracted by two reviewers independently and standardized for errors. RESULTS The population difference is presented as the Weighted Mean Difference (95% CI). PCOS subjects had a significantly lower serum concentrations of IGFBP-1 compared with controls [P< 0.00001; -36.6 (-52.0, -21.2) µg/l]. Overweight PCOS subjects also had lower IGFBP-1 levels compared with normal weight PCOS subjects [P < 0.006; -30.6 (-52.3, -8.8) µg/l]. No significant difference was found between overweight PCOS patients and overweight controls [P = 0.23; -5.1 (-13.5, 3.2) µg/l] or between normal weight PCOS patients and normal weight controls [P = 0.50; -3.8 (-14.9, 7.3) µg/l]. Overweight controls had significantly lower IGFBP-1 concentrations than normal weight controls [P = 0.03; -18.0 (-34.4, - 1.5) µg/l]. CONCLUSION These data indicate that a decreased serum level of IGFBP-1 is unlikely to be a mechanism for ovarian hyperandrogenism in PCOS. BMI may be the major determinant of serum IGFBP-1.