A new adjuvant for treatment of PCOS

1. N-acetyl cysteineN-acetyl cysteine
A novel adjuvant to CCA novel adjuvant to CC

2. INTRODUCTIONINTRODUCTION
• Clomiphene citrate therapy has variable
success rates in anovulatory women
• Currently there is increasing evidence that
insulin sensitizers are effective in inducing
ovulation in PCOS patients [Lord et al,
2003]

3. NACNAC :: multiple biological effectsmultiple biological effects
• a safe mucolytic drug
• insulin sensitizing effect
• induced a significant fall in testosterone
levels and in free androgen index values
[Fulghesu, 2002 ].
• antioxidant [De Mattia, 1998 ]
• antiapoptotic [Odetti, 2003 ]

4. Objective:Objective:
• to evaluate the effect of NAC adjuvant
therapy in women with PCOS resistant to
CC.

5. DesignDesign
• prospective RCT,
• placebo-controlled,
• double blind
• Allocation was done using opaque sealed
envelopes

6. ParticipantsParticipants
• assigned randomly to receive either
• NAC 1.2 gm/day (group I) with CC 100
mg/day
• or placebo (group II) with CC 100 mg/day
• for 5 days starting at day 3 of the cycle.

7. • Monitoring by TVS and serum E2 levels.
• Monitoring intervals were determined by
patient response.
• Human chorionic gonadotropin was
administered when at least one follicle
measured 18 mm

8. • Timed intercourse was advised 24-36
hours after hCG injection.
• A serum hCG level was determined 14
days after hCG injection if menses had not
yet occurred

9. OutcomesOutcomes
• Primary:
Ovulation rate
Secondary:
pregnancy rate
Tolerability

10. ResultsResults
• 150 women with PCO resistant to CC
were randomized to
• (CC +NAC: n = 75;
• (CC + placebo: n = 75)

11. Baseline featuresBaseline features of Both groupsof Both groups
Variable Group I (n=75) Group II (n=75) P
Age (years) 28.9 ±4.7 28.4±5.7 NS
Duration of infertility(years) 5.0 ±2.9 4.4±2.6 NS
Wt (Kg) 101.3 ±12.4 99.2±12.3 NS
Height (m) 164.1 ±5.31 162.5±5.7 NS
LH (IU/mL) 10.4±2.2 10.8±2.4 NS
FSH (IU/mL) 4.7±2.5 5.2±4.8 NS
LH/FSH ratio 2.2 2.1 NS
Fasting insulin (U/mL) 18.8 ±4.7 17.2±4.4 NS
Fasting Glucose (mg/dL) 81.9±12.6 85.9±14.1 NS

12. Clinical outcomes of both groupsClinical outcomes of both groups..
Variable Group I
(n=75)
Group II
(n=75)
P
E2 at time of HCG(pg/mL) 360.3±367.9 120±10.0 P = .0007
Ovulation rate 49.3% 0.1% P < 0.0001
Follicles >18 mm 2.4±0.97 * P = .0004
End. Thickness (mm) 5.9±0.7 4.9±1.9 P < 0.01
Pregnancy 16 0 P =0.000065
Multiple Pregnancy 5 0

13. Pregnancy rates in patients who receivedPregnancy rates in patients who received
NAC according to their insulinNAC according to their insulin
18.50%
19.00%
19.50%
20.00%
20.50%
21.00%
21.50%
22.00%
22.50%
23.00%
Pregnancy rate
Insulin >20 u/mL
Insulin < 20 u/mL

15. ConclusionConclusion
• NAC is a novel adjuvant treatment for
obese PCOS patients.
• It is a safe, well tolerated and inexpensive
agent.