N-acetyl cysteine versus Metformin in treatment of PCOS

1. N - a c e t y l c y s t e i n e v e r s u s
M e t f o r m i n i n t r e a t m e n t o f
P C O S
M Fahmy, H Abdelkader, K Ibraheim
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2. NAC
Acetylated variant of the amino acid L-cysteine
Mechanisms of action
The beneficial effects of NAC are a result of its
ability to
1. Reduce extra-cellular cystine to cysteine
2. Be a source of SH groups: so
stimulate glutathione synthesis,
enhance glutathione-s-transferase activity,
promote detoxification, and
act directly on reactive oxidant radicals
(De Vries et al., 1993).
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3. Effects
A. Metabolic:
1. Antioxidant:
in non-insulin dependent DM (1.2 gm for 1 month)
(De Mattia, et al., 1998).
preserve vascular integrity
(Sekhon et al. 2003)
protect against focal ischemia.
2. Insulin sensitizer:
Increase peripheral insulin sensitivity, whereas the hepatic
insulin extraction was unaffected
(Moghetti et al., 2000).
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4. B. Biological effects:
Antiapoptotic
(Odetti et al., 2003).
Anticytokines (inhibit proinflammatory cytokine release)
(Lappas et al. 2003)
Inhibition of
phosopholipid metabolism&
Protease activity.
NAC may exert the same effects at the ovarian level which may be important
in inducing ovulation
Mucolytic.
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5. To compare the effect of NAC & Metformin on:
• hormonal profile (insulin & testosterone)
• ovulation rate
in CC resistant PCOS
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6. 60 infertile women with CC resistant PCOS (CC 100 mg/day for
at least 3 cycles).
Inclusion criteria:
1. Age: between 19-35 years
2. Duration of infertility > 2 years.
3. Patent tubes and normal uterine cavity documented by a
recent HSG and a recent (within 3 months)
4. Normal semen parameters according to WHO criteria
(1993).
5. No treatment was taken during the last
2 months.
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7. Patients were randomly assigned into 2 groups each
consisting of 30 patients.
Group I: Metformin (Cidophage tablet, CID, SAE)
1500 mg/day.(500 mg/ tablet) from the first day of the
cycle, for 6 weeks
Group II: Acetyl cysteine (SEDICO, SAE) (200 mg
/sachet) 1.8 gm (on 3 divided doses) from the first
day of cycle, for 6 weeks.
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8. Folliculometry was done by serial TVS every other
day from D10 of the cycle.
After 6 weeks the above investigations (fasting
glucose, fasting insulin, total testosterone) were
repeated.
• HOMA-IR= FI (uU/ml) X FG (mmol/L)/22.5
<3.2 insulin resistance
• FG (mg/dl)/FI (uU/ml)
<4.5 insulin resistance
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9. Variable
Metformin
(n= 30)
NAC
(n=30)
P value
Age (Ys)
Range 19:35 20:33
0.736
Mean + SD 26.73 + 5.36 27.33 + 3.35
Duration of
Infertility (Ys)
Range 2:10 3:7
0.866
Mean + SD 5.07 + 2.60 5.07 + 1.47
Body mass index
(kg/m²
Range 27:32 27:30
0.683
Mean + SD 28.8 + 1.52 28.8 + 0.94
Waist / hip ratio
Range 0.70:0.96 0.78:0.90
0.257
Mean + SD 0.81 + 0.07 0.83 + 0.04
Waist
circumference
>100 cm 8 10 0.635
<100cm 22 20 0.575
Menstrual
pattern
Oligomenorrhea 73.4% 80
0.366Regular menses 20% 6.7%
Irregular menses 6.7% 13.3
Hirsutism
Present 86.7% 66.7%
0.195
Absent 13.3% 33.3%
Clinical characteristics of patients in both groups before treatment.
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10. Variable Metformin
(n=30)
NAC
(n=30)
P value
Fasting glucose
(mg/dl)
Range 85:120 75:110 0.07
Mean
±SD
105.93±11.4 91.67±11.3
Fasting insulin
(IU/ml)
Range 10:22 10:75 0.17
Mean ± SD 17.7±3.1 26.87±19.65
Fasting
glucose/fasting
insulin
Range 3.8: 11 1.1: 10.8 0.32
Mean ± SD 6.47± 1.80 4.77±2.59
HOMA-IR Range 2.7: 5.33 1.9: 6.1
0.24
Mean ± SD 4.3 ±1.17 4.53±1.9
Total testosterone
(pg/ml)
Range 49: 164 45:161 0.07
Mean ±SD 116.47±44.67 84.60±27.76
Hormonal profile of both groups
before treatment.
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11. Variable
Metformin
(n=30)
NAC
(n=30)
Before After
P
valu
e
Before After
P
value
Fasting
glucose
mg/dl
Range 85:120 69:102
0.001
75:110 68:100
0.008Mean +
SD
105.93 +
11.4
91.87 +
12.35
91.67 +
11.3
86 + 9.75
Fasting
insulin
IU/ml
Range 10:22 8:18
0.004
10:75 8:55
0.002Mean
+ SD
17.7 + 3.1 14.53 + 2.8
26.87 +
19.65
21 + 11.5
Fasting
glucose/fasting
insulin
Range 3.8:11 4:12.6
0.31
1.1:10.8 1.40:11.1
0.208Mean
+ SD
6.47 + 1.80 6.58 + 2.26 4.77 + 2.59 5.19 + 2.74
Total
testosterone
Pg/ml
Range 49:164 43:130
0.001
45:161 40:150
0.001Mean
+ SD
116.47 +
44.67
88.27 +
31.56
48.60 +
27.76
73.87 +
17.49
Effects of metformin & NAC on hormonal profile
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12. Fasting
glucose/
fasting
insulin
< 4.5
Metformin
(n=30)
NAC
(n=30)
Before After
z-
test
P-
value
Before After
z-
test
P-
value
18 3 2.83 0.01 16 10 1.21 0.22
> 4.5 12 12 2.12 0.03 14 20 1.05 0.29
HOMA-IR
< 3.2
2 6 1.33 0.18 4 8 1.53 0.12
> 3.2 28 24 1.52 0.17 26 22 1.47 0.11
Effect of metformin & NAC on fasting glucose/fasting insulin
ratio & HOMA-IR
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13. Metformin
(n=30)
NAC
(n=30)
16 2
Ovulation
rate
53.3% 6.6%
Z-test 2.02*
P-value 0.004
Ovulation rate in both groups.
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14. Metformin alone is effective drug in inducing
ovulation in CC resistant PCOS while NAC
alone is not.
Further large studies are required to confirm
our results.
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