Elsevier

Mayo Clinic Proceedings

Volume 94, Issue 12, December 2019, Pages 2455-2466
Mayo Clinic Proceedings

Original article
Effect of Metformin on Microvascular Endothelial Function in Polycystic Ovary Syndrome

https://doi.org/10.1016/j.mayocp.2019.06.015Get rights and content

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.

Section snippets

Study Design and Treatment Allocation

We conducted an open-label study of women with PCOS randomized to metformin vs no treatment at Mayo Clinic in Rochester, Minnesota, from March 24, 2014, to November 18, 2016 (clinicaltrials.gov Identifier: NCT02086526). The study protocol was approved by the Institutional Review Board of Mayo Clinic. Written informed consent was obtained from each participant before study enrollment. Participants could not be taking any other medications for the treatment of PCOS for at least 3 months before

Results

In this study, 48 women with PCOS were randomly assigned to metformin (33 patients) or no treatment (15 patients). Four participants in the metformin treatment group (12.1%) and 2 participants in the no treatment group (13.3%) did not complete the trial (Figure 1A). Of the participants in the no treatment group who completed the trial, 13 continued the study to take metformin for 3 months (delayed start group). Among those, 12 participants completed therapy.

Table 1 shows the characteristics of

Discussion

The current study documents that treatment with metformin can improve peripheral endothelial function, but specifically in the subset of women with PCOS and endothelial dysfunction. This improvement in endothelial function was not mediated through changes in androgens, glucose metabolism, or insulin resistance. In addition, endothelial dysfunction was highly prevalent in our study population—15 of 42 women with PCOS (35.7%) had endothelial dysfunction (Table 2).

To our knowledge, only one

Conclusion

Metformin improves peripheral endothelial function in women with PCOS and endothelial dysfunction independent of changes in glucose metabolism, dyslipidemia, or presence of prediabetes. The study findings suggest that metformin has a direct effect on endothelial function in PCOS and that measurement of peripheral microvascular endothelial function can stratify and follow response to metformin treatment in PCOS.

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    For Limelight, see page 2369

    Grant Support: This study was supported in part by a St. Jude Medical Foundation Career Development Award in Cardiovascular Research, National Institutes of Health Building Interdisciplinary Careers in Women’s Health Award K12HD065987, and the National Center for Advancing Translational Sciences.

    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.

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