Metformin and DCI in PCO

 

 Oxidative stress in PCOS patients which is influenced by the following factors: age, hyperhomocysteinemia, hyperandrogenemia and insulin resistance . 

Leptin has peripheral actions to stimulate vascular inflammation, oxidative stress and cardiovascular disease . Leptin via Janus kinases(JNK) pathway [one of the intracellular signaling pathways; mitogen-activated protein (MAP)-kinase] increases the transcription factors activity of NF-kB (nuclear factor-kB) and AP-1(activator protein-1), thereby increases reactive oxygen species (ROS) through induction of cellular oxidation . A significant positive relationship between increased levels of MDA, as a marker of lipid-peroxidation and of increased oxidative stress, and the total testosterone and insulin levels in PCOS patients was observed in this study, confirming the existence of increased oxidative stress in patients with PCOS.

Following treatment with Met & NAC , the level of MDA in the MTF+NAC group was not significantly different from the NAC group, but has a significant reduction compared to MTF group. This could be due to the fact that MTF may raise oxidative stress through increased homocysteine levels which is associated with increased generation of superoxide anions and decreased activity of antioxidant enzymes. 

Since NAC, as an antioxidant, inhibits the transcription factors activity of NF-kB and AP-1, it influences the activity of the signaling pathway of MAP-kinase and results in a reduction in the oxidative stress ; therefore, it is possible that NAC can decrease elevated oxidative stress in PCOS patients taking MTF.

Drug co-treatment remains to be explored and needs future validation. Can we combine Met with NAC/ Myoinositol??.

Metformin lowers the level of serum androgens through direct inhibition of androgen production in human ovarian theca cells and also by improving insulin sensitivity, indirectly. On the other hand, NAC decreases the expression of several key enzymes involved in Testosterone production such as 17β-hydroxysteroid dehydrogenase (17β-HSD) and 3β-hydroxysteroid dehydrogenase (3β-HSD) leading to a decrease in the levels of T production. However, in contrary t  expectations, MTF (metformin) and NAC combination did not cause a significant decrease in testosterone levels, probably due to the effects of drug interference.

 

Role of Leptin:- leptin concentrations correlated significantly and positively with TT in PCOS patients, which likely suggests that a decrease in leptin levels can reduce steroidogenesis.

 

An abnormal lipid profile & role of Met & NAC:- is a common finding in PCOS which elevates levels of total cholesterol, triglycerides, and LDL, while decreases levels of HDL .An improved lipid profile may be obtained following NAC and MTF administration by means of reduced TG and total cholesterol. These effects were not observed in combination therapy,