A prospective study of insulin-like growth factor 1, its binding protein 3, and risk of endometriosis

Several retrospective case-control studies suggested that insulin-like growth factor 1 (IGF-1) or insulin-like growth factor binding protein 3 (IGFBP-3) was associated with endometriosis. However, results are inconsistent and no prospective study exists. We prospectively evaluated associations between plasma levels of IGF-1 and IGFBP-3 and laparoscopically confirmed endometriosis in a case-control study nested within the Nurses' Health Study II. Between blood collections in 1996-1999 and 2007, we ascertained 310 premenopausal women with incident endometriosis and 615 matched controls. We estimated incidence rate ratios and 95% confidence intervals using multivariable conditional logistic regression. We observed no statistically significant associations between endometriosis and IGF-1 (incidence rate ratio (IRR) = 0.88, 95% confidence interval (CI): 0.61, 1.27; Ptrend = 0.48), IGFBP-3 (IRR = 1.12, 95% CI: 0.80, 1.57; Ptrend = 0.51), and the IGF-1:IGFBP-3 molar ratio (IRR = 0.94, 95% CI: 0.66, 1.34; Ptrend = 0.64), comparing the top with the bottom tertile. IGF-1, IGFBP-3, and the molar ratio appeared to be positively associated with endometriosis risk among women aged <40 years at blood draw (IGF-1: IRR = 1.60, 95% CI: 0.86, 2.98; IGFBP-3: IRR = 1.85, 95% CI: 1.08, 3.16; IGF-1:IGFBP-3: IRR = 1.57, 95% CI: 0.85, 2.88) but not among women aged ≥40 years at blood draw (all Pheterogeneity ≤ 0.05). Overall, these data suggest that, if IGF-1 or IGFBP-3 plays a role in the etiology of endometriosis, it is minimal and perhaps only among younger women.