Eff ect of metformin therapy in patients with Polycystic
Objective: To determine the eff ect of 12 week of metformin therapy on clinical and
hormonal indices of patients with Polycystic Ovary Syndrome.
Study design: Prospective
Study sett ing: Th
e study was carried out at the outpatient Department of Obstetrics &
Gynaecology and Endocrinology from Sept. 2006 to April 2007. 30 women meeting
the eligibility criteria were enrolled. Th
ey were interviewed using standardized pro-
forma . Data was analyzed by using SPSS version 10. Paired t- test was used for com-
Intervention: Patients were treated with 500mg of tab.metformin three times daily for
Main outcome measures: Hirsuitism, menstrual irregularities, BMI and fasting insulin
levels were assessed before and aft er treatment .
Results: In 21 of 30 patients(70%) normal menstrual cycle resumed. Th
ere was signifi -
cant reduction in the BMI (p< 0.000), and signifi cant reduction in the fasting insulin
Levels (p<0.000). 73.3% presented with hirsuitism and 33.3% showed improvement.
Conclusion: 12 week course of metformin is eff ective in the treatment of menstrual ir-
regularities ,in reducing weight, fasting insulin levels and improving hirsuitism.
Key words: PCOS,insulin resistance, hyperinsulinemia, hyperandrogenism, metform-
number of ways. At one end of the spectrum, the
Polycystic ovary is the most common endocrine disease produces polycystic morphology and at disorder with incidence of 4% to 12% in the re-
the other end there are symptoms like obesity,
productive age.1,2 Polycystic ovarian syndrome is
hyperandrogenism, menstrual cycle disturbanc-
considered a problem arising as a consequence es and infertility. Th
of persistent anovulation with spectrum of eti-
ther singly or in combination. It has been shown
ologies and clinical manifestations that includes that insulin resistance is associated with PCOS.
insulin resistance as well as hyperandrogenism.
In addition, hyperandrogenism and insulin re-
sistance may also be linked to each other.4
Biochemical disturbances include elevated se-
rum concentration of lutenizing hormones, Insulin resistance is defi ned as the decreased
Department of Obstetrics &Gynaecology,
testosterone, androstenedione and insulin. ability of insulin to stimulate glucose disposal in
Hyperinsulinemia appears to be the key to the to target tissues, or a reduced glucose response
to a given amount of insulin.5 In this situation,
the blood insulin levels are chronically higher
Polycystic ovary syndrome can manifest in which inhibits fat cells from giving up their en-
Eff ect of metformin therapy in patients with polycystic ovary syndrome
ergy stores, this in turn is associated with obe-
sity, hypertension, abnormal triglycerides, glu-
Reversed FSH:LH ratio in early follicular
cose intolerance and type 2 diabetes mellitus.
e discovery that insulin resistance has a key •
role in the pathophysiology of PCOS has led to promising form of therapy in the form of insulin Exclusion criteria:sensitizing drugs. Metformin is an insulin sensi-
tizer that reduces insulin resistance and insulin •
secretion followed by a reduction of ovarian an-
Other causes of obesity like hypothyroid-
drogen production. Direct action of metformin
on ovarian theca cells also reduces androgen Intervention:
Patients were treated with 500 mg of metformin
Metformin is an oral biguanide well established three times daily for 12 weeks. Th
for the treatment of hyperglycemia, that does formin was fi xed in all the patients.
not cause hypoglycemia in normoglycemic sub-
Clinical symptoms including hirsutism, men-
e objective of the study was to determine the strual cycle, BMI,fasting insulin levels and fast-
eff ect of twelve weeks of metformin therapy on ing blood glucose were assessed before and aft er clinical and hormonal indices of the women treatment with metformin.
with PCOS. It will not only help treating the Statistical analysis:
presenting complaints but will also prevent the Data was collected on proforma; SPSS version
long term health issues and will improve the 10 was used for analysis. Frequency and per-
centage were used for categorical variables like
presenting complaints, family history of diabe-
tes mellitus, menstrual irregularity. Mean and
quat National Hospital Karachi with patients standard deviation were used for age, menstrual from Gynaecology and Endocrinology clinics cycle, BMI and hirsutism. Paired t- test was used for a period of 8 months. Th
irty women who to compare the pre and post mean diff erences.
met the PCOS eligibility criteria were enrolled. Results:
e women were interviewed using proforma Th e study was done on 30 patients. All of the
to keep the record. Data was analyzed by using patients completed the 12 week course of Met-
SPSS version 10- statistical package. Paired t- formin. All of the patients belonged to reproduc-
test was used to compare the results.
tive age group. Ages of the patients were between
18 to 37 years. 15 patients were with positive family history of diabetes mellitus. Of the 30
Sample technique: Non-probability purposive patients who completed the 12 week course of sampling
metformin, 21 had normal menstrual cyclicity was restored (70%).
22 patients presented with hirsuitism (73.3%).
Inclusion criteria: Women fulfi lling any three According to Ferriman and Gallwey, hirsuitism out of the following criteria:
score ranged from 7 to 18. Hirsutism was not
completely treated in any of the patient although
10 patients (33.3%) showed some improvement.
Treatment with metformin signifi cantly reduced
fasting serum insulin levels from 8.72±3.43 mi-
Figure 1: Menstrual Cycle (before treatment)
like raised levels of LH, testosterone, andros-
tenedione and insulin levels can over a period of time have serious eff ects.
Hyperinsulinemia in non diabetic patient is in-
dependently associated with an increased risk of cardio vascular disease and metabolic abnor-
malities that include glucose intolerance and hy-perlipidemia resulting in hypertension and type
Also in PCOS menstrual irregularities are com-
mon and because of chronic anovulation, infer-tility is a common problem in married couples.
Figure 2: Menstrual Cycle (aft er treatment)
Obesity by itself have long term consequences
on the health of a person, these people are at higher risk of cardio vascular disease and diabe-
So the objective of the study was to see the ef-fect of metformin on the clinical and hormonal
indicies in a person suff ering from PCOS. Met-formin acts by reducing hepatic production of
glucose, improves the tissue sensitivity to in-sulin, facilitating glucose utilization by skeletal
muscles and adipocytes and reduced intestinal glucose absorption.9,10
Table 1: BMI before and aft er treatment with Metformin
We gave 30 females who fulfi lled the criteria of
PCOS, metformin tablets 500 mg, three times a
day for 12 weeks and studied its eff ects on men-
strual cyclicity, BMI, fasting insulin levels, hir-
suitism and fasting blood glucose levels. It was
seen that in 21(70%) out of 30 patients, normal
menstrual cycle was restored aft er a 3 month course of metformin. Other investigators have
cro units/ml to 6.91± 1.93 micro units/ml with p
reported similar results where metformin use re-
value <0.00, which is signifi cant. Metformin also
sulted in decrease levels of androgens, increase
reduced fasting blood sugar from 106.03±17.17 in the levels of sex hormone binding proteins
to 97.40±10.12 with p value <0.00 which is also and resulting in restoration of normal menstrual
cycles.11,12,13,14,15 Another study done in Services Hospital Lahore showed that females treated
Patient also showed signifi cant decrease in their with metformin resumed their normal men-
BMI (p<0.005) from 32.20±2.50 to30.67±2.51
strual cycle and started ovulating within 3 to 9
PCOS can manifest in a number of ways. Th
ere Patient also showed signifi cant decrease in their
is persistant state of anovulation which can BMI (p<0.000) from 32.20±2.50 to 30.67±2.51
manifest with both clinical and biochemical by improving tissue sensitivity to insulin and fa-
Eff ect of metformin therapy in patients with polycystic ovary syndrome
cilitating glucose utilization by skeletal muscles. References:
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HAS 9 Education Outside the Classroom Education Outside the Classroom (EOTC) Safety Management procedures for Kapanui School Rationale • Children learn by safely experiencing and enjoying their environment. These experiences should be appropriate to their needs and prior experience. • Children should have the opportunity to explore the world safely outside the • E.O.T.C is defin