Metformin in PCO---How it helps-the cellular dynamics of metformin ? Should we prescribe to all PCO women or be selective?? How long top prescribe ??

Metformin in PCO : When & how

Point 1:-Till date there is no   universal  consensus  on metformin benefits in PCOS  but many researchers, and clinicians  too  firmly believe  that if used judiciously there are many    beneficial  effects of metformin  therapy  in patients   with PCOS.

Point 2: Can we prescribe metformin in nondiabetic PCO women? : Ans . Possibly yes. The positive    effects of metformin have been   demonstrated in nondiabetic women   with PCOS   and they are   associated   with increased   menstrual cyclicity improved   ovulation     and reduction in circulating   androgen levels.

Point 3: Is it approved in US/UK  for PCO women ?? Ans: No. To date   neither   in Europe  nor in the  United  States   metformin   has been   approved for  the treatment   of insulin   resistance  associated  with PCOS  its use should be restricted to those   patients   with IGT   however it is largely  prescribed as an off label drug .

Point 5: What we the clinicians mean by the term as “Off level “use of any drug?? Ans:-For   off label  use of any  medication it is extremely  important   to fulfill several criteria   for safe  use :

The condition should  have health  consequences   significant   enough to   warrant     treatment .The   treatment    should have   demonstrated safety and efficacy .The proposed  treatment   should be  superior   to the presently available   alternatives 

 Point 6: How does Metformin works in the system?? It is an antihyperglycemic  agent   Ans:- Metformin   is a second   generation  biguanide  used as  an  oral antihyperglycemic  agent   and it is  approved  by the US  Food   and Drug   Administration   as treatment   for type ll diabetes  mellitus . It is   considered an insulin   sensitizing  agent because   it lowers   glucose   levels  without   increasing    insulin secretion but   improving   insulin sensitivity 

 Point 7:-What are the actions of metformin at cellular level?? Metformin increases  fatty  acid oxidation in hepatocytes & skeletal muscle   cells   Ans:-Metformin causes 1) increases   peripheral  insulin sensitivity by   activating  glucose   transporters   which  allows      passage of glucose into hepatic  and muscle cells 2)  inhibition of hepatic   glucose production 3)

reduction of circulating free fatty    acid concentration  which  helps    in reducing    gluconeogenesis .

  Point 8: What else are the actions of metformin in cellular dynamics?? Ans :- 1) decreased  glucose   production at liver 2) inhibits  hepatic   gluconeogenesis  .  Metformin  activates  the adenosine monophosphate  activated protein kinase pathway    phosphorylaction of threonine in AMPK   is necessary   for  metformin  action resulting   in decreased  glucose   production  and increased  fatty  acid oxidation in hepatocytes  skeletal muscle   cells   and mouse   ovarian tissue.

Furthermore metformin  inhibits  hepatic   gluconeogenesis  through  an AMP   activated protein    kinase   dependent regulation  of the orphan  nuclear    receptor   small heterodimer partner.