Effect of Metformin on Microvascular Endothelial Function in Polycystic Ovary Syndrome

Abstract

Objective: To investigate the factors that are associated with the effect of metformin on endothelial dysfunction in polycystic ovary syndrome (PCOS).

Patients and methods: From March 24, 2014, to November 18, 2016, 48 women with PCOS were randomly assigned to 1500 mg/d of metformin (N=29) or no treatment (N=13) for 3 months; 42 patients (29 in the initial treatment group and 13 in the no treatment group) completed the study. Study variables were measured at baseline and after 3 months. Participants who did not receive metformin initially were then treated with metformin for another 3 months, and study variables were measured again. Endothelial function was measured as reactive hyperemia-peripheral arterial tonometry (RH-PAT) from the index finger.

Results: The age and baseline endothelial function (mean ± SD) of the participants were 32.7±6.9 years and 1.8±0.5, respectively. No notable change was observed in endothelial function after 3 months with metformin compared with no treatment. However, after stratifying participants who received metformin based on baseline endothelial function, there was a significant improvement following metformin treatment in participants with abnormal baseline endothelial function (1.3±0.3 vs 1.7±0.3; P<.001) but not in those with normal baseline endothelial function (2.1±0.4 vs 2.0±0.5; P=.11).

Conclusion: Metformin improves endothelial function in women with PCOS and endothelial dysfunction independent of changes in glucose metabolism, dyslipidemia, or presence of prediabetes. Metformin has a direct effect on endothelial function in PCOS, and measurement of endothelial function can stratify and follow response to metformin treatment in PCOS.

Trial registration: clinicaltrials.gov Identifier: NCT02086526.

Conflict of interest statement

Potential Competing Interests: Dr Amir Lerman is a consultant for Itamar Medical Ltd, Shahal Medical Services Ltd, and Volcano Corporation/Philips Healthcare. Dr Lilach Lerman is a consultant for WeiJian Technology Co, Ltd.

Copyright © 2019 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Figures

FIGURE 1.

Participants’ assignments to immediate or delayed metformin treatment. A, Number of participants in each step and treatment received. B, Timing of follow-up visits and workups.

FIGURE 2.

Change in endothelial function following treatment with metformin. Error bars represent 95% CIs of the mean.