Sir,
Polycystic ovary syndrome (PCOS) is the most frequently encountered endocrine-metabolic disorder among reproductive-aged females. PCOS is frequently associated with insulin resistance (IR), hyperinsulinemia, obesity, and cardio-metabolic co-morbidities.[1] The general consensus is that obese PCOS women are resistant to insulin and that PCOS appears to intensify the adverse effects of obesity on IR.[2] One of the most common strategies in targeting IR in PCOS is the use of insulin-sensitizers, in particular metformin. A prospective interventional study conducted at Al-Yarmouk Teaching Hospital between January 2019 and April 2020. The study was approved by the Local Ethical Committee. A total of 71 obese PCOS women were included. They were allocated into three sub-groups according to the WHO classification of obesity into: Class I (BMI of 30-34.99 kg/m2), Class II (BMI of 35-39.99 kg/m2), and Class III (BMI ≥40 kg/m2). Diagnosis of PCOS was made according to modified Rotterdam criteria.[3]
The subjects were assigned to receive metformin 1500 mg daily in three divided doses for three months. Fasting plasma glucose, fasting serum insulin, total serum testosterone, and glycosylated hemoglobin (HbA1c) were measured before and after treatment. BMI, HOMA-IR, and insulin sensitivity (IS) were calculated. Data analysis was done using paired-t-test, ANOVA test, and least significant difference (LSD) test with P value ≤ 0.05 considered significant.
Metformin provided a significant reduction in BMI, serum testosterone, fasting glucose, fasting insulin, and HOMA-IR with a significant improvement in IS and HbA1c in all obesity classes. The percent change in fasting glucose, fasting insulin, HOMA-IR, and IS significantly differ between different obesity classes [Table 1]. Using LSD test, changes were significant when comparing class III with I for fasting glucose (P = 0.028) and class II with I for fasting insulin, HOMA-IR, and IS with P values of 0.011, 0.008, and 0.009, respectively.
Table 1.
The comparison of the three different groups according to BMI, testosterone, fasting glucose, fasting insulin, HOMA-IR, insulin sensitivity and HbA1c before and after metformin use
| Class I (n=44) | Class II (n=20) | Class III (n=7) | P | |
|---|---|---|---|---|
| BMI (Kg/m2) | ||||
| Before | 31.33±1.25 (30.02-34.67) | 36.99±1.54 (35.16-39.79) | 45.40±3.59 (40.63-50.07) | 0.0001* |
| After | 29.74±1.14 (28.04-32.44) | 34.90±1.43 (32.47-38.10) | 42.69±3.76 (37.50-47.27) | 0.0001* |
| %Difference | -5.0±1.5 | -5.6±1.4 | -6.0±1.0 | 0.128 |
| P value | 0.0001# | 0.0001# | 0.0001# | |
| Total testosterone (nmol/L) | ||||
| Before | 1.44±0.35 (0.937-2.348) | 1.91±0.33 (1.20-2.776) | 2.49±0.26 (1.978-2.70) | 0.0001* |
| After | 1.28±0.33 (0.79-2.00) | 1.67±0.29 (0.90-2.30) | 2.13±0.21 (1.874-2.40) | 0.0001* |
| %Difference | -11.5±3.1 | -12.8±3.8 | -14.5±5.3 | 0.090 |
| P value | 0.0001# | 0.0001# | 0.0001# | |
| Fasting glucose (mmol/L) | ||||
| Before | 5.40±0.33 (4.7-5.9) | 5.65±0.30 (5.0-6.2) | 5.74±0.15 (5.6-5.9) | 0.002* |
| After | 5.19±0.27 (4.6-5.7) | 5.39±0.25 (4.8-5.8) | 5.41±0.13 (5.3-5.6) | 0.006* |
| %Difference | -3.9±2.0 | -4.6±1.5 | -5.7±1.2 | 0.048* |
| P value | 0.0001# | 0.0001# | 0.0001# | |
| Fasting insulin (μU/mL) | ||||
| Before | 14.64±4.65 (6.69-26.54) | 18.33±4.64 (10.80-25.90) | 23.32±4.53 (17.698-28.598) | 0.0001* |
| After | 10.96±3.67 (6.10-20.10) | 12.93±3.65 (6.30-18.20) | 17.79±4.34 (11.80-23.50) | 0.0001* |
| %Difference | -25.1±6.2 | -29.7±6.7 | -24.4±4.8 | 0.023* |
| P value | 0.0001# | 0.0001# | 0.0001# | |
| HOMA-IR | ||||
| Before | 3.54±1.19 (1.427-6.841) | 4.60±1.20 (2.634-6.563) | 5.97±1.27 (4.404-7.499) | 0.0001* |
| After | 2.54±0.90 (1.274-5.002) | 3.10±0.91 (1.596-4.539) | 4.29±1.10 (2.779-5.640) | 0.0001* |
| %Difference | -28.2±6.4 | -32.9±6.4 | -28.7±4.0 | 0.023* |
| P value | 0.0001# | 0.0001# | 0.0001# | |
| Insulin sensitivity | ||||
| Before | 0.31±0.10 (0.146-0.701) | 0.23±0.07 (0.152-0.379) | 0.17±0.04 (0.133-0.227) | 0.0001* |
| After | 0.43±0.13 (0.199-0.785) | 0.35±0.11 (0.220-0.626) | 0.25±0.07 (0.177-0.3598) | 0.0001* |
| %Difference | 40.4±13.1 | 50.4±15.5 | 40.8±8.5 | 0.024* |
| P value | 0.0001# | 0.0001# | 0.0001# | |
| HbA1c (%) | ||||
| Before | 5.37±0.32 (4.5-6.0) | 5.51±0.32 (5.1-6.3) | 5.83±0.41 (5.2-6.4) | 0.003* |
| After | 5.14±0.30 (4.4-5.8) | 5.26±0.29 (4.9-6.0) | 5.57±0.35 (5.0-6.0) | 0.003* |
| %Difference | -4.2±1.5 | -4.5±1.0 | -4.4±1.7 | 0.727 |
| P value | 0.001# | 0.001# | 0.001# |
-Data were presented as Mean±SD (Range), *Significant difference among more than two independent means using ANOVA-test at 0.05 level., #Significant difference between two dependent means using Paired-t-test at 0.05 level.
This study shows that short-term treatment with metformin is sufficient in attenuating IR besides reducing weight which is in concordance with previous reports.[4] Women with PCOS are at greater risk for cardiovascular events, prediabetes, and type 2 diabetes mellitus as they share people with diabetes a similar pattern of impaired glucose metabolism; putting in mind these facts, metformin role in diabetes prevention, and the American Diabetes Association recommendation for using metformin in people with prediabetes in particular for those with BMI ≥35kg/m2,[5] all these consolidate our findings. Till now there is no clear answer for how long we need to treat women with PCOS using metformin. When we consider the short duration of metformin treatment in this study and the long-term sequels of PCOS especially in obese women, extending the treatment duration is crucial for the aim of reducing these risks. The strength of this study is in support of using metformin selectively for obese PCOS women with BMI of ≥35 kg/m2. Limitation includes small sample size. Further studies with larger sample sizes and for longer duration of therapy are needed, this represents another scope of a second research we are processing now.
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Conflicts of interest
There are no conflicts of interest.
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