Point 12: What do a PCO woman is benefitted
by decrease of serum FSH? How it helps at granulosa cell level?? Ans: The indirect
role of metformin on granulosa
cells by decreseing IGF-1 . This is very impotrtnat and most important opath,
at least I feel in that way that IGF-1 is notorious to cause & propagate PCO.
Metformin , at the ovarian level with
its hyperandrogenic intra
follicular pattern cause improved function by
a decrease in IGF-1
availability that has an
important role in controlling
granulosa cell aromatase levels.
Point 13: PCOS
have higher levels of FSH receptor
expression compared with those from normal
ovaries .Ans:-
It has been shown that
granulosa cells from women with metformin reduces FSH
without altering
cAMP levels. This involves blocking activation of CRE
on promoter ii of CYP19 via inhibition of pCREB and possible disruption
of the formation of the CREB – CRTC
2 co activator complex. This is
via an AMPK independent mechanism .
Metformin is
available as 500, 850 and 1,000 mg
tablets with a target dose
of 1,500-2,550 mg / day Dosage
and side effects
.
Metformin has a dose dependent absorption
in humans and its bioavailability is
limited to 50-60 % because the amount
available may result from pre
systemic clearance or binding to the intestinal wall.
Therapeutic regimens of
metformin administration are not
well standardized and its dose should probably be adjusted according
to the patient’s BMI and insulin
resistance .
For example it was demonstrated
that nonobese women with
PCOS respond better than obese women to metformin treatment
at a dosage of 1,500 mg/ day
for 6 months Nonobese women in fact showed a statistically significant decrease
in serum androgen level and fasting insulin level and also an improvement
in menstrual cyclicity . Moreover it is
possible that women who did not respond to metformin 1.5 g dose
per day might show clinical
changes if the dose is increased to 2 g.
Common side effects are gastrointestinal such as diarrhea nausea vomiting bloating abdominal discomfort flatulence and unpleasant metallic taste in the mouth.
Lactic acidosis
and hypoglycemia are very rare.
To reduce these side
effects. It is recommended to start
metformin with a low dose
and then gradually increase
within a period of 4-6 weeks.
Metformin may cause vitamin B12
malabsorption and so every
patient should be monitored for signs and symptoms
of vitamin B 12 deficiency numbness paresthesia macroglossia
behavioral changes and pernicious anemia.
Metformin prescription should be avoided in women
with renal insufficiency congestive
heart failure sepsis
or hepatic dysfunction
Therefore testing
of hepatic and renal function is
necessary in advance of prescription and thereafter yearly testing
is indicated.
However it has been
demonstrated that metformin use
for up to 6 months dose not adversely
affect renal or liver function
in a large sample
of PCOS women even
those with mildly abnormal
baseline hepatic parameters
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