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).

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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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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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To compare the effect of NAC & Metformin on:

• hormonal profile (insulin & testosterone)

• ovulation rate

in CC resistant PCOS

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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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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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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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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.

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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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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

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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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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.

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