MON-233 Effect of Weight Loss and Hormonal Suppression Alone and in Combination on Bioactive Gut and Ovarian Peptide Hormones in Women with Polycystic Ovary Syndrome

Abstract

BACKGROUND: Serum peptide biomarkers are frequently abnormal in women with PCOS reflecting underlying reproductive and metabolic dysfunction. The effects of treatment on these biomarkers is poorly described. METHODS: We performed a secondary analysis on obese women with PCOS who had participated in a RCT(JCEM, PMID: 26401593) where they were randomized into a 16 wk intervention to either continuous oral contraceptives(OCP, EE 20 mcg/NETA 1 mg, N= 34), an intensive life style intervention with oral weight loss drugs(WL, either orlistat or sibutramine, N=31), or the combination of the two(COMB, N=29) with OGTT and DXA body composition determination. We hypothesized that the OCP treatment group would experience primarily a treatment related alteration in ovarian biomarkers (Follistatin(FS), Activin, Inhibin A and B), whereas the weight loss group would experience a treatment related change in gut hormones [IGF-1, IGFBP-2 and Oxyntomodulin(OXM)]. Hormones were measured using Ansh Labs assays at baseline and 16 wks. General linear models with correlated errors were used for within and between group comparisons. With the exception of Follistatin, IGF-1 and Inhibin B, hormonal data were log transformed due to non-normal distributions. RESULTS: Activin A and the Inhibins were suppressed significantly by OCP with no effect of WL alone. FS nearly doubled from baseline with OCP alone[mean difference(MD) = 3.3 ng/mL, 95% CI, 2.7 -3.9 ng/mL] or in COMB(MD=2.9 ng/mL, 95%CI, 2.3 -3.6 ng/mL), both significant compared with WL alone (both P < 0.001, where WL itself had no significant change at end vs baseline). By far the most profound and unexpected suppression occurred with OXM, where on OCP alone(median change from baseline= -75.4 pg/mL, P< .001) and COMB (median change from baseline= -21.9 pg/mL, P < .001) with no effect of WL alone. OCP significantly suppressed IGF-1 levels from baseline(MD=-44 pg/mL, 95% CI, -80 to-8 pg/mL) and WL significantly increased it(MD=42 pg/mL, 95% CI, 4 -80 pg/mL) leading to a significant between group difference(P=0.001) with COMB showing no within or between group change. This was paralleled by significant OCP suppression in IGFBP-2 levels from baseline(P=003) also noted in the COMB group(P =.03). There was a significant between group difference in IGFBP-2 on OCP and COMB vs WL alone. CONCLUSION: Bioactive peptides in obese women with PCOS are significantly modulated by common treatments, though not necessarily as expected. The novel and unexpected profound suppression of OXM by OCP could lead to increased weight gain through decreased OXM-mediated anorexia and energy expenditure (though mean weight in the OCP group was unchanged over the 16 weeks). Increased IGF-1 action with WL, despite weight loss and improved AUC glucose levels on OGTT, may be due to the significant tissue remodeling(less fat, increased lean/bone mass noted on follow-up DXA scan) with our lifestyle regimen.