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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
ABOUBAKR ELNASHAR
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).
ABOUBAKR ELNASHAR
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).
ABOUBAKR ELNASHAR
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.
ABOUBAKR ELNASHAR
To compare the effect of NAC & Metformin on:
• hormonal profile (insulin & testosterone)
• ovulation rate
in CC resistant PCOS
ABOUBAKR ELNASHAR
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.
ABOUBAKR ELNASHAR
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.
ABOUBAKR ELNASHAR
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
ABOUBAKR ELNASHAR
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
0.366 Regular 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.
ABOUBAKR ELNASHAR
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.
ABOUBAKR ELNASHAR
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
0.008 Mean +
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
0.002 Mean
+ 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
0.208 Mean
+ 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
0.001 Mean
+ SD
116.47 +
44.67
88.27 +
31.56
48.60 +
27.76
73.87 +
17.49
Effects of metformin & NAC on hormonal profile
ABOUBAKR ELNASHAR
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
ABOUBAKR ELNASHAR
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.
ABOUBAKR ELNASHAR
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.
ABOUBAKR ELNASHAR
ABOUBAKR ELNASHAR