N-acetylcysteine (NAC) is an antioxidant that can reduce extracellular cystine and stimulate glutathione synthesis. It has various metabolic effects such as improving insulin sensitivity and protecting vascular integrity. Studies show NAC is effective in improving ovulation when used as an adjuvant to clomiphene citrate in women with polycystic ovary syndrome or those undergoing infertility treatments. NAC may increase fertility outcomes and decrease the amount of fertility medications needed. Adverse effects are mild and include nausea, vomiting and diarrhea.

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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. EFFECTS OF NAC ON PCOS
NAC: 1.8 g/d for 5-6 W
(Fulghesu et al, 2002)
1. In hyperinsulinemic subjects:
• Significant increase in insulin sensitivity
Significant reduction in insulin levels
• Significant reduction in T & FAI
2. In normoinsulinemie & placebo-treated subjects:
No significant changes
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6. DIAGNOSIS OF PCOS
Rotterdam criteria (2003)
2 of the following 3 manifestations:
1. Irregular or absent ovulation
2. Hyperandrogenism (clinical or biochemical) &/or
3. Polycystic ovaries.
Other conditions with similar signs must be ruled
out.
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7. DIAGNOSIS OF INSULIN RESISTANCE
A. Clinical: specific but not sensitive
1. BMI: > 27 k/m2 is often IR & > 30 K/m2 is almost always IR
(Weyer et al, 1999).
It is reasonable that all over weight anovulatory females with
PCOC are hyperinsluinaemic
(Speroff,2005).
BMI > 25 is found in 35-50% of PCOS
(Frank, 1995).
BMI: 25-29.9: overweight; >30: obese.
2. Waist to hip ratio: >0.85.
Central or android obesity is better indicator than BMI
(Hoeger,2001).
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8. 3. Waist cir.: >100 cm
WC > 90 is predictive of abnormal endocrinologic & metabolic
function & is associated with increased risk of CVD.
4. Acanthosis nigricans (grey-brown velvety discoloration on
neck, axilla or groin.
5. Numerous achrochordons (skin tags)
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9. B. Laboratory:
1. Fasting insulin:
normal levels are variable 10-20 u/ml. The cutoff value for insulin
resistance 13u/ml
(Ludvig et al, 19950)
2. Fasting glucose insulin ratio < 4.5.
It should be measured in all anovulatory females
(Speroff,2005)
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10. 3. Homeostasis model assessment- insulin resistance (HOMA-
IR)
HOMA-IR = fasting insulin (µU/ml) × fasting glucose (mmol/ l)/
22.5.
HOMA-IR < 3.2
(Morques – Vidal et al, 2002).
4-Quantitative insulin sensitivity check index (QUICKI):-
1/ [Log (Fasting insulin) + Log (Fasting glucose)]
QUICKI index is < 0.333
(Katz et al., 2000).
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11. 6. Glucose or insulin response to an oral or IV glucose
challenge
7. Glucose response to an IV insulin.
8. Euoglycemic hyperinsulinaemic clamp:
the gold standard. Specific, sensitive but complex &
expensive
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12. A. Medical
(1) Respiratory: -mucolytic
(2) HIV: -enhances the immune response of
peripheral blood T cells.
(3) Cancer: - Chemo-preventive agent.
(4) Heart disease: It protects against ischemic and
reperfusion damage
(5) Influenza: Reduces symptomatology
(Deflora et al., 1997)
(6) Cigarette smoking: inhibit cigarette smoking (Rogers
et al 1986).
(7) Acetaminophen overdose: The antidote of choice
(Gregory et al., 1998).
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13. B. In obstetrics
1)Habitual abortion
2)Gestational diabetes
3)Pre-eclampsia
4)To improve the outcome of preterm deliveries
associated with inflammation
5. During labor: prevents the oxidative stress and
change in hepatic GSSG that occurs in the fetal –
neonatal transition
(Sastre et al., 1994).
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14. C. In Gynecology
1.Survival factor in female germ cell, and other
cells of the ovarian cortex
2.Idiopathic oligospermia
3. In vitro maturation (IVM)
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15. D). Infertility
1. PCOS:
•NAC plus CC
effective , inexpensive, safe, tolerable adjuvant even
in the absence of insulin resistance
(Elnashar, Badawy Totongy, 2005)
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16. 2. CC R PCOS:
• NAC alone
Metformin 1500 mg/day orally OR Acetyl cysteine 1.8 gm by oral
administration on 3 divided doses for 6 weeks from the first
day of cycle. Metformin alone is effective while NAC alone is
not
(Elnashar et al, 2004)
• NAC plus CC
NAC 1.2 gm/ day with CC 100mg/day for 5 days. Ovulation rate
in 49.3 %
(Rizk et al,2004).
• NAC plus HMG
decreases the number of consumed ampoules and improves PR
(Metawie, 2005)
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17. 3. Non PCOS undergoing ICSI.
NAC 1.2 gm/day plus CC 50 mg/day.
No significant statistical difference was found between
the 2 groups as regards: fertilization, pregnancy,
abortion rates, oocyte maturity
(Toppozada et al, 2004)
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18. 4. Unexplained infertility
•NAC didn’t add to the ovulatory effect of the CC
(Elnashar, Badawy, Totongy, 2005)
Evidence suggests that in healthy individuals, NAC might act as
pro-oxidant and might lower the GSH and increases the amount
of oxidized GSH
(Kleinveld et al. 1992)
•NAC is an effective cheap & safe adjuvant to CC in long
standing unexplained infertility undergoing IUI
(Rezik et al, 2004)
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19. Drug interactions
1. Concomitant oral administration of charcoal and
NAC is not recommended, {charcoal might
interfere with absorption of NAC}
(Renzi et al., 1985).
2. NAC enhance the blood pressure-lowering effects
of angiotensin-converting enzyme (ACE) inhibitors
(Marchetti et al., 1999).
3. The pharmacokinetics of NAC is altered in
patients with chronic liver disease. In general, these
individuals tend to have increased serum
concentrations and decreased ability to clear NAC
from the blood stream following an intravenous dose
(Jones et al., 1997).
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20. Side effects
 NAC is generally safe & well tolerated even in
high doses .
 The most common side effects are :
1-Nausea & vomiting.
2-Diarrhea.
3- Infrequently, anaphylactic reaction.
 NAC has been safely administered during
pregnancy. In general there are no adequate
studies of NAC administration and pregnancy, so
it should only used when clearly indicated
(Threlkeld etal., 1997).
 Contraindicated in active peptic ulcer disease.
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21. NAC is effective adjuvant to CC or HMG in
PCOS &
CC R PCOS
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