Table 1 conveys the characteristics of the two groups initially selected.
Table 1: Baseline characteristics of patients with PCOS included in the randomized controlled study.
Variable
|
Metformin (n=21)
|
Placebo (n=24)
|
P -Value
|
Age (in years)
|
30.3 ± 4.5
|
30.9 ± 6.4
|
0.641
|
Weight in Kg
|
73.2 ± 12.7
161,4 ± 6,5
28.1 ± 4.3
|
73,5 ± 13,7
160,9 ± 6.0
28.3 ± 4.9
|
0.873
0.707
0.900
|
Height (cm)
|
Body Mass Index (Kg/m2)
|
Abdominal Circumference (cm)
|
91.2 ± 10.8
|
90.7 ± 13.9
|
0.932
|
Systolic Arterial Pressure
Diastolic
|
111.3 ± 9.7
72,8 ± 7,6
|
115,4 ± 13,8
72,8 ± 10,3
|
0.230
0.951
|
Smoking (n, %)
|
2 (10%)
|
4 (17%)
|
0.670
|
Alcohol Consumption (n,%)
|
4 (19%)
|
6 (25%)
|
0.729
|
Cholesterol (mg/dL) Total HDL-C
|
181,5 ± 44,6
48.4 ± 13.9
|
194,5 ± 32,5
46,7 ± 11,3
|
0.260
0.622
|
Triglycerides (mg/dL)
|
110,4 ± 65,1
|
135,7 ± 77,1
|
0.171
|
LAP Index
|
43.4 ± 29.1
|
57.1 ± 53.3
|
0.469
|
Fasting blood sugar (mg/dL)
|
88,9 ± 7,9
|
87,7 ± 6,5
|
0.962
|
Insulin(μIU/mL)
|
13.7 ± 7.9
|
14.6 ± 10.7
|
0.724
|
TSH (μIU/mL)
|
2.02 ± 0,81
|
3.07 ± 3.34
|
0.890
|
PCOS Phenotype (n,%) Hyperandrogenism +anovulation + PCO Anovulation + PCO Hyperandrogenism +PCO
|
14 (70%)
5 (25%)
1 (5%)
|
10 (45%)
11 (50%)
1 (5%)
|
0.237
|
Infertility (n, %)
|
20 (95%)
|
17 (74%)
|
0.097
|
Pregnancy
|
0,33 ± 0,73
|
0,50 ± 1,06
|
0.820
|
Prior metformin use (n, %)
|
10 (48%)
|
6 (26%)
|
0.242
|
Total testosterone (ng/dL)
|
49.5 ± 29.9
|
48.4 ± 29.6
|
0.606
|
Prolactin (ng/ml)
|
13.7 ± 4.3
|
13.9 ± 4.2
|
0.820
|
LAP: lipidic accumulation product; PCO: polycystic ovaries or augmented at ovaries ultrasound
Twenty patients were evaluated, 5 (25%) of which belonged to the group that took metformin and 15 (75%) who belonged to the placebo group. Thirteen patients (65%) presented hyperandrogenic phenotype and 7 (35%) were non-hyperandrogenic
Table 2 presents the values of Follistatin and Oxyntomodulin before and after treatment. The group that used metformin presented average values of Follistatin equal to 1,53 ± 0,21 (median 1,44) before treatment and 1,58 ± 0,19 (median 1,51) after treatment, while the placebo group average values equal to 1,40 ± 0,13 (median 1,34) before treatment and 1,42 ± 0,13 (median 1,39) after treatment.
Table 2 – Descriptive analysis of the levels of Follistatin and Oxyntomodulin before and after treatment for the metformin and placebo groups.
|
Before Treatment
|
After treatment
|
Follistatin
|
|
|
Metformin Group
|
|
|
± SD* Average
|
1,53 ± 0,21
|
1,58 ± 0,19
|
Median (1stQ – 3rd Q)†
|
1,44 (1,36 – 1,74)
|
1,51 (1,43 – 1,76)
|
Minimum– maximum
|
1,33 – 1,84
|
1,40 – 1,86
|
Placebo Group
|
|
|
± SD * Average
|
1,40 ± 0,13
|
1,42 ± 0,13
|
Median (1st Q – 3rd Q)†
|
1,34 (1,33 – 1,42)
|
1,39 (1,33 – 1,46)
|
Minimum– maximum
|
1,31 – 1,79
|
1,26 – 1,73
|
Oxyntomodulin
|
|
|
Metformin Group
|
|
|
± SD * Average
|
23,72 ± 9,92
|
27,31 ± 9,25
|
Median (1st Q – 3rd Q)†
|
26,83 (13,34 – 32,54)
|
22,88 (20,91 – 35,93)
|
Minimum– maximum
|
11,07 – 33,62
|
20,21 – 42,69
|
Placebo Group
|
|
|
± SD * Average
|
21,56 ± 7,28
|
23,90 ± 11,99
|
Median (1st Q – 3rd Q)†
|
24,03 (15,14 – 29,38)
|
21,93 (13,04 – 29,62)
|
Minimum– maximum
|
8,34 – 29,96
|
10,09 – 47,52
|
* SD: standard deviation; † Median (1st quartile – 3rd quartile)
As far as Oxyntomodulin is concerned, the group that used metformin reached average values equal to a 23,72 ± 9,92 (median 26,83) before treatment and 27,31 ± 9,25 (median 22,88) after treatment. The placebo group presented average values of 21,56 ± 7,28 (median 24,03) and 23,90 ± 11,99 (median 21,93), before and after treatment respectively.
There was no significant difference in the Follistatin and Oxyntomodulin values before and after treatment in the Metformin group (p=0,625 e p=0,625, respectively). Table 3 presents the variation in the Follistatin and Oxyntomodulin levels before and after treatment for both groups. There was no significant difference in the interpretation of the levels of Follistatin and Oxyntomodulin between the Metformin and Placebo groups (p=0,497 e p=0,864, respectively.
Table 3 – Comparison of the variation in the levels of Follistatin and Oxyntomodulin before and after treatment between the Metformin and Placebo groups.
|
Variation in Metformin Group
|
Variation in Placebo Group
|
Valor-p‡
|
Follistatin
|
|
|
|
± SD* Average
|
0,04 ± 0,13
|
0,02 ± 0,11
|
0,497
|
Median (1st Q – 3rd Q)†
|
0,02 (-0,07 – 0,17)
|
-0,02 (-0,05 – 0,05)
|
Minimum– maximum
|
-0,14 – 0,22
|
-0,14 – 0,29
|
Oxintomodulin
|
|
|
|
± SD* Average
|
3,59 ± 11,15
|
2,35 ± 9,35
|
0,864
|
Median (1st Q – 3rd Q)†
|
7,26 (-7,86 – 13,20)
|
0,45 (-4,42 – 3,30)
|
Minimum– maximum
|
-11,25 – 15,86
|
-7,32 – 23,98
|
* SD: standard deviation; † Median (1st quartile – 3rd quartile); ‡ Mann-Whitney Test
Figure 1 shows the boxplots for the variation in the levels of Follistatin and Oxyntomodulin between the groups. The Metformin group presented an average variation of 0,02 while the placebo group had an average variation of -0,02. Regarding Oxyntomodulin, the Metformin group obtained average variation of 7,26, while for the placebo group it was 0,45.
Table 4 presents the levels of Follistatin and Oxyntomodulin by phenotype. The participants with hyperandrogenic phenotype showed average levels of Follistatin and Oxyntomoduline equal to 1,49 ± 0,17 and 21,82 ± 8,49, respectively. Patients with other phenotypes obtained average values of 1,33 ± 0,02 for Follistatin and 22,62 ± 6,89 for Oxyntomodulin. There was a significant difference (p=0,004) in the Follistatin levels for the hyperandrogenic and non-hyperandrogenic phenotype participants, which was more remarkable for hyperandrogenic ones. There was no significant difference (p=0,991) in the levels of Oxyntomodulin between the different phenotypes.
Table 4 – Comparison of the levels of Follistatin and Oxyntomodulin between the Hyperandrogenic phenotype and the non-hyperandrogenic phenotype groups.
|
Hyperandrogenic Phenotype
|
Non-Hyperandrogenic Phenotype
|
p‡-Value
|
Follistatin
|
|
|
|
Mean ± SD*
|
1,49 ± 0,17
|
1,33 ± 0,02
|
0,004
|
Median (1st Q – 3rd Q)†
|
1,42 (1,36 – 1,58)
|
1,33 (1,31 – 1,34)
|
Minimum– maximum
|
1,33 – 1,84
|
1,31 – 1,38
|
Oxintomodulina
|
|
|
|
± SD* Average
|
21,82 ± 8,49
|
22,62 ± 6,89
|
0,991
|
Median (1st Q – 3rd Q)†
|
24,03 (14,00 – 29,82)
|
26,32 (15,14 – 29,38)
|
Minimum– maximum
|
8,34 – 33,62
|
13,87 – 29,73
|
* SD: standard deviation; † Median (1st quartile – 3rd quartile); ‡ Mann-Whitney Test
Figure 2 shows the boxplots for Follistatin and Oxyntomodulin levels between the phenotypes.
Participants with hyperandrogenic phenotype groups presented average values of Follistatin and Oxyntomodulin equal to 1,42 and 24,03, respectively, and participants with other phenotypes showed levels of 1,33 and 26,32, respectively. Participants with hyperandrogenic phenotypes also presented values with considerably greater amplitude than participants with other phenotypes (0,51 e 0,07).