Effects of Oral Contraception and Lifestyle Modification on Incretins and TGF-ß Superfamily Hormones in PCOS

Abstract

Objective: To examine the effects of common treatments for polycystic ovary syndrome (PCOS) on a panel of hormones (reproductive/metabolic).

Design: Secondary analysis of blood from a randomized controlled trial of three 16-week preconception interventions designed to improve PCOS-related abnormalities: continuous oral contraceptive pills (OCPs, N = 34 subjects), intensive lifestyle modification (Lifestyle, N = 31), or a combination of both (Combined, N = 29).

Materials and methods: Post-treatment levels of activin A and B, inhibin B, and follistatin (FST), as well as Insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein 2 (IGFBP-2), glucagon, glucagon-like peptide 1 (GLP-1) and 2, and oxyntomodulin were compared to baseline, and the change from baseline in these parameters were correlated with outcomes.

Results: Oral contraceptive pill use was associated with a significant suppression in activin A, inhibin A, and anti-mullerian hormone (AMH), but a significant increase in FST. IGF-1, IGFBP-2, glucagon, and GLP-2 levels were significantly decreased. Oxyntomodulin was profoundly suppressed by OCPs (ratio of geometric means: 0.09, 95% confidence interval [CI]: 0.05, 0.18, P < 0.001). None of the analytes were significantly affected by Lifestyle, whereas the effects of Combined were similar to OCPs alone, although attenuated. Oxyntomodulin was significantly positively associated with the change in total ovarian volume (rs = 0.27; 95% CI: 0.03, 0.48; P = 0.03) and insulin sensitivity index (rs = 0.48; 95% CI: 0.27, 0.64; P < 0.001), and it was inversely correlated with change in area under the curve (AUC) glucose [rs = -0.38; 95% CI: -0.57, -0.16; P = 0.001]. None of the hormonal changes were associated with live birth, only Activin A was associated with ovulation (risk ratio per 1 ng/mL increase in change in Activin A: 6.0 [2.2, 16.2]; P < 0.001).

Conclusions: In women with PCOS, OCPs (and not Lifestyle) affect a wide variety of reproductive/metabolic hormones, but their treatment response does not correlate with live birth.

Trial registration: ClinicalTrials.gov NCT00704912.

Keywords: hyperandrogenism; incretins; inflammation; insulin resistance; obesity.

Figure 1.

Scatterplots of change in follistatin with change in testosterone, total ovarian volume, area under the curve (AUC) glucose, and insulin sensitivity index. Spearman correlations are noted on each figure.

Figure 2.

Scatterplots of change in oxyntomodulin with change in total ovarian volume, area under the curve (AUC) glucose, and insulin sensitivity index. Spearman correlations are noted on each figure.