O-9: Increased Serum IGF-1 Levels After Bilateral Oophorectomy in Postmenopausal Women: A Case for Ovarian Preservation?

Abstract

Background: IGF-1 has been implicated in colorectal cancer, with elevated levels associated with increased risk of disease. Hormone replacement therapy in postmenopausal women (PMW) decreases both IGF-1 and colon cancer risk. However, the impact of postmenopausal oophorectomy, and thus reduction of estrogenic precursors, on IGF-1 levels has not been evaluated.Objective: To determine if oophorectomy in PMW results in increased levels of IGF-1, thus potentially increasing future risks of colon cancer, and to quantify potential relationships between IGF-1 levels and hormonal markers of ovarian function.Methods: Thirteen PMW, aged 56.7±8.2 years, with FSH 50.4±12.8 U/L, and amenorrhea of 59.1±46.2 months, undergoing TAH-BSO, were recruited. Blood was obtained preoperatively and postoperatively. Intraoperatively, blood was obtained from both ovarian veins and from a peripheral vein. Serum levels of IGF-1 and IGFBP-3 were quantified by use of highly specific chemiluminescence immunoassays. T, DHEA, A, E2, and E1 were analyzed by RIA with preceding organic solvent extraction and column chromatography. Paired samples t-test and Pearson correlation were used for statistical analysis.Results: IGF-1 levels increased significantly following TAH-BSO (109±42 vs. 135±51 ng/mL, p<0.05), whereas IGFBP-3 showed no significant change (1080±558 vs. 1126±640 ng/mL, p>0.05). All ovarian hormones demonstrated higher levels in the ovarian veins than in the peripheral circulation (p<0.05), and levels of T and A decreased significantly following TAH-BSO (p<0.05). IGF-1 levels correlated with E2 (r=0.80, p<0.01) preoperatively, and with E1 (r=0.72, p<0.05) postoperatively. No statistically significant correlations between IGF-1 and T, DHEA, or A, or between IGFBP-3 and any hormone, were observed preoperatively or postoperatively.Conclusions: 1) IGF-1 levels increase following oophorectomy in PMW, suggesting a potential increase in the risk of colon cancer in women undergoing bilateral oophorectomy during menopause. 2) IGF-1 levels correlate with E2 and E1 in PMW, suggesting that IGF-1 may retain its stimulatory role on estrogen production in the menopause. 3) Because of the association between elevated IGF-1 levels and increased colon cancer risk, preservation of postmenopausal ovaries may be beneficial. Background: IGF-1 has been implicated in colorectal cancer, with elevated levels associated with increased risk of disease. Hormone replacement therapy in postmenopausal women (PMW) decreases both IGF-1 and colon cancer risk. However, the impact of postmenopausal oophorectomy, and thus reduction of estrogenic precursors, on IGF-1 levels has not been evaluated. Objective: To determine if oophorectomy in PMW results in increased levels of IGF-1, thus potentially increasing future risks of colon cancer, and to quantify potential relationships between IGF-1 levels and hormonal markers of ovarian function. Methods: Thirteen PMW, aged 56.7±8.2 years, with FSH 50.4±12.8 U/L, and amenorrhea of 59.1±46.2 months, undergoing TAH-BSO, were recruited. Blood was obtained preoperatively and postoperatively. Intraoperatively, blood was obtained from both ovarian veins and from a peripheral vein. Serum levels of IGF-1 and IGFBP-3 were quantified by use of highly specific chemiluminescence immunoassays. T, DHEA, A, E2, and E1 were analyzed by RIA with preceding organic solvent extraction and column chromatography. Paired samples t-test and Pearson correlation were used for statistical analysis. Results: IGF-1 levels increased significantly following TAH-BSO (109±42 vs. 135±51 ng/mL, p<0.05), whereas IGFBP-3 showed no significant change (1080±558 vs. 1126±640 ng/mL, p>0.05). All ovarian hormones demonstrated higher levels in the ovarian veins than in the peripheral circulation (p<0.05), and levels of T and A decreased significantly following TAH-BSO (p<0.05). IGF-1 levels correlated with E2 (r=0.80, p<0.01) preoperatively, and with E1 (r=0.72, p<0.05) postoperatively. No statistically significant correlations between IGF-1 and T, DHEA, or A, or between IGFBP-3 and any hormone, were observed preoperatively or postoperatively. Conclusions: 1) IGF-1 levels increase following oophorectomy in PMW, suggesting a potential increase in the risk of colon cancer in women undergoing bilateral oophorectomy during menopause. 2) IGF-1 levels correlate with E2 and E1 in PMW, suggesting that IGF-1 may retain its stimulatory role on estrogen production in the menopause. 3) Because of the association between elevated IGF-1 levels and increased colon cancer risk, preservation of postmenopausal ovaries may be beneficial.