Background: Insulin resistance is a common feature of Polycystic Ovarian Syndrome and is present in approximately 40-50% of this disorder. Response to insulin sensitisers appear to be maximal in women with disturbed insulin sensitivity. This argues in favour of its usefulness in patients with marked hyperandrogenism and insulin resistance. In this study, only metformin is used as an insulin sensitising drug.
Methods: The study analysed the usefulness of short term metformin therapy to reduce features of hyperandrogenism and hyperinsulinemia in PCOS patients. Out of 96 patients of PCOS, 48 cases were treated with metformin (1500 mg / day) for 3 months to 1 year and 48 controls were advised dietary modification and exercise. The changes in weight, BMI, menstrual cycles, ovulatory response and hormonal changes were compared in case and control.
Results: Study reveals marked improvements in all parameters amongst the cases who received metformin therapy.
Conclusion: Metformin may be a highly effective treatment protocol for the improvement of clinical, biochemical and hormonal profile in PCOS.
Keywords: Polycystic ovary, Metformin, Hyperinsulinemia, Hyperandrogenism
Polycystic Ovarian Syndrome is a heterogeneous disorder affecting 5-10% of women of reproductive age. Insulin resistance plays an important role in dysregulation of folliculogenesis, anovulation and hyperandrogenemia in this disorder. Given the central role of insulin in the aetiology of PCOS, insulin sensitising agents have the potential to ameliorate insulin resistance and alleviate the spectrum of endocrine, meatabolic and reproductive abnormalities in women with PCOS.
Metformin, an insulin sensitising drug was given to PCOS patients for 3 months to one year with an aim to achieve the following
The prospective study was carried out in Malda Medical College and hospital from 1st July 2014 to 31st May 201. 96 patients with menstrual irregularities, ultrasound finding of polycystic ovaries and anovulation on folliculometry along with raised or altered LH, LH: FSH, insulin, testosterone levels were selected for the study. 48 cases received metformin (1500 mg/ day) for 3 months to 1 year depending on the response. The changes in weight, BMI, menstrual cycles, ovulatory response, and hormonal changes were critically analysed. These results were compared with rest 48 control patients of the same weight and BMI range who were advised dietary modification and exercise and the efficacy of metformin was assessed.
Tables 1-4
Menstrual disorder |
Total number |
Cycle restored |
Cycle not restored |
|||
Hypomenorrhoea |
Case |
4 |
4 |
100% |
_ |
_ |
Control |
4 |
2 |
50% |
2 |
50% |
|
Oligomenorrhoea |
Case |
30 |
22 |
73.3% |
8 |
26.7% |
Control |
30 |
10 |
33.3% |
20 |
66.7% |
|
Oligomenorrhoea |
Case |
14 |
10 |
71.4% |
4 |
28.6% |
Control |
10 |
2 |
20% |
8 |
80% |
|
Amenorrhoea |
Case |
0 |
0 |
0 |
0 |
0 |
Control |
4 |
0 |
0 |
4 |
100% |
|
Total |
|
|
36 |
75% |
12 |
25% |
|
|
14 |
29.2% |
34 |
70.8% |
Effect |
Case |
Control |
||||||
No Hirsutism |
Hirsutism |
No Hirsutism |
Hirsutism |
|||||
Before Treatment |
38 |
79.2% |
10 |
20.8% |
38 |
79.2% |
10 |
20.8% |
After |
38 |
79.2% |
10 |
20.8% |
38 |
79.2% |
10 |
20.8% |
Table 2 Effect on Hirsutism on treatment in case & control
Mean |
Case ( 48 ) |
Control ( 48 ) |
||
parameters |
Before treatment |
After treatment |
Before treatment |
After treatment |
Wt ( kg ) |
53.29 |
51.86 |
53.17 |
52.63 |
BMI ( kg/ m2) |
23.01 |
22.36 |
23.05 |
23.66 |
LH ( mIu/ ml ) |
19.63 |
7.34 |
14.01 |
13.59 |
LH:FSH |
2.32:1 |
1.07:1 |
2.09:1 |
2.19:1 |
Fasting insulin (mIU/ml ) |
12.48 |
7.33 |
10.35 |
10.51 |
Testosterone |
0.68 |
0.54 |
0.63 |
0.64 |
Table 3 Evaluation of changes in mean values in different parameters amongst case & control before and after treatment
Duration of ovulation |
Total |
Ovulation |
Anovulation |
||
3 Months to 6 Months |
24 |
16 |
66.7% |
8 |
33.3% |
3-6 Months with Clomiphene |
4 |
4 |
100% |
_ |
_ |
6 Months to 12 Months |
18 |
14 |
77.8% |
4 |
22.2% |
6 -12 Months with Clomiphene |
2 |
2 |
100% |
_ |
_ |
Table 4 Response of Metformin on ovulation
75% cases in our study showed cycle restoration in contrast to 29.2% in control. Marked improvements in all parameters like weight, BMI, LH, LH: FSH, fasting insulin, and testosterone were found in cases who received metformin therapy. Metformin could not show any improvement in hirsutism score. 36 (75%) out of 48 cases became ovulatory with metformin treatment. 6 of them needed additional clomiphene. 16 (44.4%) cases ovulated with 3-6 months of metformin and 14 (38.9%) needed them for 6-12 months.
Metformin either by weight reduction or by modest reduction of insulin and androgen level helps in restoration of menstrual cycles, ovulation and normalise LH: FSH, insulin and testosterone level as evident in our study. Metformin has also been found to potentiate the action of ovulation inducing drugs. Metformin may be considered as a useful drug reserved for infertile PCOS patients who are not responding to clomiphene citrate.
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