Ind J Clin Biochem (Oct-Dec 2010) 25(4):367–370
Effect of Metformin on Hormonal and Biochemical Profilein PCOS Before and After Therapy
Bratati Singh • Suchismita Panda • Rachita Nanda •Sanghamitra Pati • Manaswini Mangaraj •Pratima Kumari Sahu • Prakash Chandra Mohapatra
Received: 18 September 2009 / Accepted: 24 September 2010 / Published online: 19 November 2010Ó Association of Clinical Biochemists of India 2010
Insulin resistance and the resultant hyperinsuli-
nemia exacerbate the reproductive abnormalities of Poly-cystic Ovarian Syndrome by increasing ovarian androgen
Polycystic Ovarian Syndrome is the most common repro-
productions and decreasing serum sex hormone binding
ductive endocrine disorder among women of reproductive
globulin. The present study was conducted to estimate
age, affecting 5–10% of population worldwide . It is the
serum insulin and testosterone level in 44 PCOS cases and
commonest multisystem endocrinopathy having diverse eti-
32 control patients. Simultaneously the role of metformin
opathogenesis in women, causing menstrual irregularities,
(an insulin sensitizing agent) in modulating insulin resis-
hirsutism and anovulatory infertility. In Indian population the
tance and serum androgen level was also analyzed. A sig-
incidence has been estimated to be between 4 and 11% among
nificant rise in serum insulin and testosterone (P \ 0.001)
women of reproductive age group . PCOS is associated
was observed in cases in comparison to control. Fasting
with insulin resistance, obesity, dyslipidemia and infertility
Plasma Glucose to insulin ratio, a marker of insulin resis-
Recently some theories depict genetic and intraovarian
tance revealed a significant fall in PCOS group. Follow up of
origin associated with environmental factors such as diet and
cases with metformin for 3 months revealed a significant
altered life style ]. Several data support the hypothesis
fall in serum insulin (P \ 0.05) with improvement in insulin
that insulin resistance and associated hyperinsulinemia play a
resistance along with a nonsignificant fall in testosterone
pathogenic role in PCOS ]. Hyperinsulinemia may promote
level. Serum insulin registered a significant positive corre-
abnormal ovarian androgen secretion and therewith abnormal
lation (P \ 0.05) with serum testosterone revealing its
follicular development leading to dysfunctional ovarian and
etiological association. Thus administration of drugs ame-
menstrual activity . These observations suggested the role
liorating insulin levels is expected to provide new thera-
of insulin sensitizing agents like metformin in improving
these manifestations . Some researchers demonstratedimprovement in reproductive abnormalities in their group of
patients while others failed to observe any clinical or
This discrepancy in the above observations created an
interest for evaluating the role of insulin resistance for var-ious biochemical & pathological manifestations of PCOS as
B. Singh Á S. Panda Á R. Nanda Á S. Pati Á M. Mangaraj Á
well as the role of metformin as an insulin sensitizing agent
for altering these manifestations in these cases.
Department of Biochemistry, SCB Medical College,Cuttack 753007, Orissa, India
Department of Biochemistry, IMS & SUM Hospital,Siksha O Anusandhan University, Bhubaneswar,
The study was conducted in the Department of Biochemistry,
Orissa 751003, Indiae-mail: email@example.com
S.C.B. Medical College, Cuttack from February 2006 to July
Ind J Clin Biochem (Oct-Dec 2010) 25(4):367–370
2007. 44 PCOS patients within age group 15–35 years
patients had BMI C 25 kg/m2 showing obesity, whereas
attending the OPD & indoor of O&G Department of S.C.B
only 25% of controls had obesity with BMI C 25 kg/m2.
Medical College, Cuttack & 32 age matched healthy female
Table revealed no significant difference in FPG & 2 h
controls from hospital staffs were included in this study
PGPG in PCOS patients as compared to control. That may
be due to relatively young age group patients in this study,
The diagnosis of PCOS was made from the history of
because b-cell dysfunction worsens with age ]. Marked
chronic oligomenorrhoea (cycle length [ 35 days, or less
dyslipidemia was obvious in these patients in comparison to
than 9 cycles per year), amenorrhoea (cycle length [
control, which may be attributed to insulin resistance ].
12wks), infertility with hirsutism or acne, and with an ultr-
The hormone profile reveals a marked rise in fasting
asonographic findings of polycystic ovaries [
serum insulin in these PCOS cases in comparison to control
Women with prior history of glucose intolerance
(P \ 0.001), which was in agreement with other workers
(including gestational diabetes) or NIDDM, hyperprolac-
showing the role of hyperinsulinemia in the pathogenesis
tinemia, thyroid dysfunction, late onset congenital adrenal
of PCOS ]. Marked rise in serum total testosterone in
hyperplasia, cushing’s syndrome or patients taking medi-
these cases (P \ 0.001) may be due to excess ovarian
cations to alter the hormonal or biochemical profiles were
production of androgens, which is central to the diagnosis
excluded from the study. All patients included in the study
of PCOS [Yet some researchers have shown appar-
ently normal testosterone concentrations in their PCOS
Blood was collected from both controls and cases and was
cases, which may be attributed to their low to normal sex
estimated for routine biochemical parameters (Fasting
plasma glucose, 2 h PGPG & lipid profile) using automated
Mean value of fasting plasma glucose to insulin ratio
analyzer Flexor-XL. Specific tests for serum Insulin and
(G/I), a good measure of insulin sensitivity was observed
serum Testosterone were also performed using ELISA
to be 4.34 in PCOS cases. Taking this fasting G/I ratio
of B4.5 as abnormal [50% of cases and 9.4% of
Out of these 44 PCOS patients, 22 women were admin-
controls were determined as insulin resistant, having this
istered with metformin (an insulin sensitizing agent) at a
dose of 500 mg tds for a period of 3 months. After com-
After administration of metformin to 22 PCOS cases at a
pletion of treatment, the biochemical parameters, serum
dose of 500 mg TDS for a period of 3 months, only 10% of
insulin and serum testosterone values were analyzed again
PCOS patients revealed improvement in glucose tolerance,
and compared with their pre-intervention values respec-
whereas no significant alteration was noted in mean FPG &
tively. The results obtained were analyzed by student’s t
PGPG values. Serum HDL registered a significant rise
test, Wilcoxon signed ranks test and Mann–Whitney U test,
(P \ 0.05) in these cases after metformin therapy. All
Pearson correlation coefficient using SPSS-15. This study
other lipid parameters documented no marked difference
protocol has been approved by the institutional ethical
after therapy. Similar observations have been registered by
committee, S.C.B Medical College Cuttack.
other workers [who were in agreement that metforminreduces insulin resistance which in turn modifies dyslipi-demia in PCOS cases (Table ).
Overall change in BMI was statistically insignificant
after therapy. However percentage of patients presented
In the present study about 43.2% of PCOS cases were in
with obesity having BMI C 25 kg/m2 was reduced from
the age group of 21–25 years. 38.6% of these PCOS
36.4 to 27.3%. Obesity was worsened with increase in BMI
Ind J Clin Biochem (Oct-Dec 2010) 25(4):367–370
hormonal changes before andafter therapy in 22 pcos cases
only in one patient, which might have been due to
decreased physical activity during treatment period.
After 3 months of metformin therapy, serum hormone
status documented a marked fall in fasting serum insulin(P \ 0.001), similar to the results of other researchers
[and was in concurrence with the opinion that beingan insulin sensitizer, metformin exerts its effect by pro-
moting peripheral glucose utilization. Others have docu-mented no significant change in serum insulin level after
therapy [Study of Barbieri et al. ] demonstrated thedirect stimulatory effect of insulin on ovarian androgen
production in PCOS women. Insulin infusion studies haveshown a clear association existing between serum insulin
Serum Testosterone in ng/ml
and testosterone levels in cases of PCOS, suggestive of acause and effect relationship. The present study alsorevealed a decline in serum testosterone level, yet it was
Serum insulin in µIU/ml
Our study also revealed insulin resistance measured as
fasting glucose to insulin ratio to be reduced from 77.27%
Fig. 1 Correlation of serum insulin with serum testosterone before
of cases to 40.1% after metformin therapy, showing an
improvement in insulin sensitivity. The median value ofthis ratio raised from 4.19 before therapy to 4.68 after
3 months of metformin therapy crossing the limit value of4.5 which was statistically significant (P \ 0.05) and in
PCOS has been a subject of research and debate over past
six decades. Insulin resistance accompanied by compen-
Significant positive association (r = 0.44, P \ 0.05)
satory hyperinsulinemia is a common feature of PCOS and
between fasting serum insulin and serum total testosterone
both obese and non-obese women with the syndrome are
before metformin therapy in PCOS cases in the present
more insulin resistant and hyperinsulinemic than age and
study (Fig. shows the etiological role of hyperinsuli-
weight matched normal women ]. Insulin resistance in
nemia in stimulating ovarian androgen production
muscles and adipose tissues increases plasma FFA and
However following metformin therapy the association was
insulin concentration, that stimulate synthesis and secretion
though positive, yet it was not significant.
of VLDL in the liver resulting in hypertriglyceridemia,which in turn enhances post-prandial accumulation of
Table 3 FPG/insulin ratio before and after therapy (n = 22)
lipoproteins (LDL, VLDL) in plasma with lowering of
HDL cholesterol , ]. Hyperinsulinemia plays a path-
ogenetic role in PCOS cases by increasing ovarian andro-gen production and decreasing the serum sex hormone
binding globulin concentration [Insulin may directly
stimulate ovarian cytochrome P450c17a, resulting in
increased 17-a hydroxylase and to a lesser extent, 17,
Ind J Clin Biochem (Oct-Dec 2010) 25(4):367–370
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