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Altered Vascular Function in Young Women with Polycystic Ovary Syndrome

University Department of Medicine and Therapeutics (C.J.G.K., J.M.C.C.), Gardiner Institute, Western Infirmary, Glasgow G11 6NT; Division of Biochemistry and Molecular Biology (A.S., G.W.G.), Institute of Biomedical and Life Science, University of Glasgow, Glasgow G12 8QQ; and Departments of Medicine (J.R.P.) and Obstetrics and Gynaecology (H.L.), Glasgow Royal Infirmary, Glasgow G31 2ER, United Kingdom

Address all correspondence and requests for reprints to: J. M. C. Connell, Professor of Endocrinology, University Department of Medicine and Therapeutics, Gardiner Institute, Western Infirmary, Glasgow G11 6NT, United Kingdom. E-mail: John.M.C.Connell{at}clinmed.gla.ac.uk

Abstract

Polycystic ovary syndrome (PCOS) is characterized by hyperinsulinemic insulin resistance, a metabolic disorder that in other circumstances is associated with increased cardiovascular risk. We compared macrovascular and microvascular function in 19 women with PCOS with 12 control subjects matched as a group for body mass index. Macrovascular function was assessed by recording pulse wave velocity (PWV) across the aorta and brachial artery. Microvascular function was studied by wire myography, by measuring the concentration response curve to norepinephrine (NE) before and after incubation with insulin (100 and 1,000 pM).

PWV at the level of the brachial artery was found to be significantly elevated in the PCOS group [9.08 (range, 8.34–11.15) m/sec^-1 vs. 8.27 (range, 7.5–9.01) m/sec^-1; P = 0.03]. In contrast, PWV measured in the aorta did not differ between the two groups [7.49 ± 1.21 vs. 7.84 ± 1.44 m/sec^-1; P = 0.8].

In vessels from control subjects, insulin reduced the contraction response to NE. At an insulin concentration of 100 pM, NE negative log EC50 (pD₂) was 6.2 ± 0.24 vs. 6.7 ± 0.15 (P = 0.02). At a concentration of 1,000 pM, NE pD₂ was 6.4 ± 0.14 vs. 6.9 ± 0.19 (P = 0.0006). Both concentrations also caused attenuation in maximal tension developed in response to NE (insulin 100 pM, 12 ± 3%, P = 0.002; insulin 1,000 pM, 17 ± 5%, P = 0.009). In contrast, there was no change in the PCOS group with insulin at 100 pM for either pD₂ (6.7 ± 0.24 vs. 6.8 ± 0.27; P = 0.3) or maximum contraction (-0.4 ± 2%; P = 0.8). At 1,000 pM, there was a change in pD₂ (6.4 ± 0.2 vs. 6.8 ± 0.2; P = 0.003) but not maximum contraction (4 ± 3%; P = 0.2).

In conclusion, this study is the first to demonstrate increased vascular stiffness and a functional defect in the vascular action of insulin ex vivo in patients with PCOS. We suggest that these findings are indicative of insulin resistance at a vascular level in women without overt cardiovascular disease.

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