Endocrine Abstracts

Background: PCOS is a metabolic disorder associated with long-term health risks including insulin resistance, type 2 diabetes and dyslipidaemia. Metformin improves insulin sensitivity in PCOS and reduces circulating concentrations of markers of endothelial dysfunction, although it is unclear whether this translates into improvements in vascular function.

Objective: To determine whether metformin therapy improves arterial stiffness and endothelial function in young women with PCOS.

Methods: Ethical and MHRA approval was obtained for this study of 30 subjects with PCOS (age 18–30 on no treatment), providing over 80% power to detect a shift of 0.5 times the S.D. of within-group changes (ISRCT number 46268487). Subjects were assigned to consecutive 12-week treatment periods of metformin (stepwise increase to 500 mg tds) or placebo in a randomised, double-blind, crossover design, separated by an 8 week washout. Primary outcome parameters were measures of arterial stiffness (augmentation index (AIx), central blood pressure, brachial and aortic pulse wave velocity (b/aPWV)) and endothelial function. Serum testosterone, anthropometry, lipids, insulin resistance (HOMA-IR) and high sensitivity CRP were also assessed.

Results: Treatment was well tolerated with only 1 withdrawal. Metformin improved the maximum change in AIx after salbutamol (an endothelium-dependent vasodilator; −5.4%, 95% CI for the difference (CI_diff) −8.7 to −2.1%; P=0.003) and all measures of arterial stiffness including AIx (−6.1%, 95% CI_diff −8.5 to −3.7%; P<0.001) and aPWV, an independent risk factor for cardiovascular mortality (−0.76 m/s, 95% CI_diff −1.12 to −0.4 m/s; P<0.001). Metformin also reduced weight (−2.05 kg, 95% CI_diff −2.9 to −1.2 kg; P<0.001), waist circumference (−4.9 cm, 95% CI_diff −7 to −2.8 cm; P<0.001) and triglycerides (−0.16 mmol/l, 95% CI_diff −0.56 to −0.26 mmol/l; P=0.004) but did not affect other lipids, CRP, testosterone or HOMA-IR.

Conclusions: Short-term metformin therapy improves arterial stiffness and endothelial function in young women with PCOS independently of changes in insulin sensitivity.