The effects of metformin on endothelial dysfunction, lipid metabolism and oxidative stress in women with polycystic ovary syndrome

Abstract

Polycystic ovary syndrome (PCOS) is a heterogeneous disorder, which is considered not only a reproductive disease but also a metabolic disorder associated with long-term health risks. The aim of this study was to assess the effects of metformin on insulin resistance, oxidant-antioxidant status, endothelial dysfunction, lipid metabolism and their contribution to the risks of cardiovascular disease in women with PCOS. Fifteen women with PCOS and 17 healthy women were included in this case-control study. Nitric oxide (NO), endothelin-1 (ET-1), malondialdehyde (MDA), Apo A1, Apo B, small, dense LDL cholesterol (sdLDL-C), lipid levels and paraoxonase 1 (PON1) activity were measured in serum/plasma obtained from study groups. Insulin resistance (HOMA index - Homeostasis Model Assessment) and serum sex hormone profiles were also evaluated. Significantly decreased NO levels and PON1 activities, but increased MDA, ET-1 and sdLDL-C were found in PCOS patients compared to those of controls. Serum MDA, ET-1, HOMA and sdLDL-C levels decreased and PON1 activity and NO levels increased significantly after the metformin treatment. There was a positive correlation between MDA and free testosterone (fT), ET-1 and fT; and a negative correlation between PON1 activity and fT. Insulin resistance, dyslipidemia, endothelial dysfunction and oxidative stress might contribute to the excess risk of cardiovascular disease reported in PCOS. Metformin seemed to decrease oxidative stress and improve insulin resistance, dyslipidemia and endothelial dysfunction in PCOS patients.

Transcription Factor NRF2 as a Therapeutic Target for Chronic Diseases: A Systems Medicine Approach

“…Glucose metabolism and inflammation may not be the only pathomechanisms affected by metformin/NRF2. In fact, other salutary effects have been described for redox (Kocer et al, 2014;Kelleni et al, 2015) and protein homeostasis (Tsai et al, 2017).…”

PON1 polymorphisms are associated with polycystic ovary syndrome susceptibility, related traits, and PON1 activity in Indian women with the syndrome

“…A few groups of investigators have also explored the relationship of these polymorphisms with PCOS and its related traits (23)(24)(25)(26). Treatment with metformin and hormonal supplements (ethinyloestradiol þ cyproterone acetate) has been shown to increase PON1 activity and subsequently decrease oxidative stress in women with PCOS (27,28). However, to our knowledge, no conclusive study exploring the association of PON1 polymorphisms and its activity with PCOS risk, and their relationship with cardiovascular and metabolic dysfunction is available.…”

Effect of Hawthorn Leaf Flavonoids in Dehydroepiandrosterone-Induced Polycystic Ovary Syndrome in Rats

“…For instance, Victor et al [27] showed that IR in PCOS patients enhanced oxidative stress and leukocyte adhesion. Kocer et al [28] demonstrated that metformin improved PCOS, probably by decreasing oxidative stress and improving IR. Consistent with this, we demonstrated that oral administration of HLF significantly suppressed the upregulation of both TNF-α and IL-6 induced by DHEA, which might mechanistically contribute to its preventive effect against PCOS progression.…”