Endothelial (Dys)function in Women With Androgen Excess Polycystic Ovary Syndrome: Effects of Body Composition and Ethinyl Estradiol Supplementation

Abstract

Polycystic ovary syndrome (PCOS) has been associated with endothelial dysfunction. However, whether endothelial dysfunction occurs as a result of obesity in androgen excess PCOS (AE‐PCOS) remains unclear. The purpose of this study was to compare endothelial function between lean and overweight/obese (OW/OB) women with AE‐PCOS. We hypothesis that OW/OB women with AE‐PCOS would demonstrate impaired endothelial function relative to lean women with AE‐PCOS as well as both lean and OW/OB controls without any form of PCOS. We also tested the hypothesis that short‐term ethinyl estradiol (EE) supplementation improves endothelial function in both lean and OW/OB women with AE‐PCOS. We assessed conduit vessel endothelial function in 14 women with AE‐PCOS (lean: n=7; OW/OB: n=7) and 12 controls (CTRL; lean: n=6, OW/OB: n=6) using flow‐mediated dilation (FMD). FMD responses were assessed twice: before (baseline; BSL) and on the last day of 7‐day oral EE (post‐EE; 30mg/day) and quantified as the peak increase in diameter during reactive hyperemia (%FMD), shear rate, and low flow‐mediated vasoconstriction (LFMC). BSL %FMD was attenuated in lean AE‐PCOS relative to both lean CTRL (5.2 ± 1.5% vs10.3 ± 2.6%, P<0.01) and OW/OB AE‐PCOS (5.2 ± 1.5% vs6.6 ± 0.9%, P=0.04). A negative correlation between BSL %FMD and free testosterone was observed in lean AE‐PCOS only (R2=0.68, P=0.02). %FMD was unchanged from BSL to post‐EE in lean AE‐PCOS (5.17±1.5 vs5.17±1.1, P=0.99). Post‐EE, %FMD was lower in lean CTRL (10.3±2.6% vs7.6±1.2%, P=0.03), but increased in both OW/OB CTRL (7.3±0.1.2% vs 10.4±2.5%) and OW/OB women with AE‐PCOS (6.6±0.92% vs 9.6±1.7%; main effect of EE, P<0.01). Post‐EE %FMD changes from BSL were associated with EE‐induced changes in LFMC and shear rate. Our data indicate that lean women with AE‐PCOS exhibit more severe conduit vessel endothelial dysfunction than OW/OB women with AE‐PCOS. Our data also indicate that short‐term EE supplementation affects LFMC and shear rate (and therefore %FMD) differently across healthy lean women and OW/OB women with and without AE‐PCOS.