Polycystic Ovarian Syndrome (PCOS) is a complex heterogenous disease, its main features include excess androgen levels, ovulatory dysfunction, and polycystic ovaries, and is known to be one of the most common endocrine disorders. About 5–10% of all women are infected with PCOS. Clomiphene citrate (CC) is used as the first-line medication for induction of ovulation in anovulatory women and has variable success rates. however, its success rate is the lowest in women with PCOS and insulin resistance. There is evidence that insulin sensitivity reduces hyperandrogenism and hyperinsulinemia and is particularly effective in ovulation induction among patients with PCOS treatment with CC only. The antioxidant effects of N-acetylcysteine (NAC) and its protective properties of focal ischemia have been reported in previous studies which are likely to be a positive effect of NAC on endometrial thickness.
In addition to the effects of insulin reduction and androgen deprivation, other biological effects of NAC, such as antiapoptotic and antioxidant effects, inhibition of phospholipid metabolism, proinflammatory cytokine release and protease activity, can lead to better folliculogenesis and ovulation rate in PCOS women. Adding NAC to CC has increases the number of dominant follicles and improves endometrial thickness with increase in pregnancy rates.
NAC administration increases ovulation rate and eliminate negative impact of CC on endometrial thickness through antioxidant effects and the potential insulin-sensitizing effects of NAC may lead to better induction of ovulation in PCOS women. Most of the beneficial effects of orally administered NAC are hypothesized due to its ability to either reduce extracellular cystine to cysteine or to be a source of sulfhydryl metabolites. As a source of sulfhydryl groups, NAC can stimulate glutathione synthesis, enhance glutathione-S transferase activity, promote detoxification, and act directly on reactive oxidant radicals. Many studies reported no incidence of OHSS in patient taking NAC.
There are sufficient data about combining therapy of NAC and CC in PCOS women. Results from few research studies supports NAC as a better adjuvant with CC. In a study done by Saghar et al. he noted that the rate of ovulation was 45.12% in the CC + NAC group versus 28% in the CC only group with better endometrial thickness in the CC + NAC group 6.6 ± 1.69 mm versus 5.4 ± 1.61 mm in the CC only group and higher pregnancy rates 20.73 in the CC + NAC group versus 9.4%in the CC only group.1
In another one study done by Rizk et al. he found that a combination of CC and 1.2 g/d NAC for induction of ovulation significantly increases the E2 level at the time of HCG administration, ovulation (49.3% in CC + NAC group compared with 1.3% in the placebo group) and pregnancy rate (21.3% in CC + NAC group compared with 0% in the placebo group) but did not reveal any significant change in endometrial thickness.2
Badawy et al. noted that compared with placebo, the addition of NAC to a CC regimen in patients with PCOS increased ovulation rates significantly (52.1% in CC + NAC group compared with 17.9% in the CC only group), pregnancy rate (11.5% in CC + NAC group compared with 0% in the CC only group) and endometrial thickness (7.3 ± 3.1 mm in CC + NAC group compared with 4.3 ± 1.2 mm in the CC only group).3
To conclude, NAC as an adjuvant to CC for induction of ovulation improves ovulation and pregnancy rates in PCOS women and have beneficial impacts on endometrial thickness. NAC is well-tolerated, safe, and inexpensive and may be a novel adjuvant treatment to improve the induction of ovulation outcomes in PCOS patients.
References:
- Saghar S, Azadeh AS, Nasrin S, et al. N-acetylcysteine as an adjuvant to clomiphene citrate for successful induction of ovulation in infertile patients with polycystic ovary syndrome. J Obstet Gynaecol Res 2012;38:1182–6.
- Rizk AY, Bedaiwy MA, Al-Inany HG. N- acetyl-cysteine is a novel adjuvant to clomiphene citrate in clomiphene citrate resistant patients with polycystic ovary syndrome. Fertil Steril 2005;83: 367–70.
- Badawy A, State O, Abdelgawad S. N-acetyl cysteine and clomiphene citrate for induction of ovulation in polycystic ovary syndrome: a cross-over trial. Acta Obstet Gynecol Scand 2007;86: 218–22.
Dr. P. Prasanna., MS (OG), DGO,DNB, FRM, FMAS
Assistant Professor,
Institute Of Obstetrics and Gynaecology,
Madras Medical college,
Chennai.
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N-acetylcysteine (NAC) is commonly used as a safe mucolytic drug with antioxidant and insulin regulatory effects. NAC may also improve the circulating level of insulin and insulin sensitivity in hyperinsulinemic women with PCOS and ameliorate the homocysteine and lipid profile in PCOS. NAC has been used effectively as an adjuvant to letrozole for ovulation induction in women with PCOS, and oral NAC administration has been proposed for the prevention of endothelial damage due to antioxidant agent. In recent years, a limited number of studies have shown the possible benefits of NAC administration in improving insulin sensitivity and better induction of ovulation outcomes in patients with PCOS.
(Mostajeran F, Tehrani HG, Rahbary B. Adv Biomed Res. 2018;7:100.)
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N-Acetyl Cysteine (NAC) with the chemical structure of sulfhydryl groups is derived from L- amino acid cysteine and the first time were used as a mucolytic drug in some respiratory diseases such as chronic bronchitis. NAC decreased blood levels of homocysteine by increasing glutathione synthesis which is an antioxidant. On the other hand, NAC significantly reduces the serum testosterone level, insulin resistance, and serum lipids. It was shown that the combination of NAC and CC enhance ovulation rate and pregnancy rate in CC-resistant PCOS patients. By administering NAC with CC in PCOS patients without CC resistance, a considerable improvement in the ovulation rate, serum estrogen and progesterone, endometrial thickness, and pregnancy rate were observed.
(Behrouzi Lak T, Hajshafiha M, Nanbakhsh F, Oshnouei S. Int J Reprod Biomed. 2017;15(4):203-208.)
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Women with PCOS have unique concerns unlike any other medical condition due to the intersection of reproductive and metabolic hormones. On the other hand, some authors believe that the hyperinsulinemia, secondary to insulin resistance, stimulates the secretion of both urine and adrenal androgen and suppresses the synthesis of sex hormone-binding globulins by the liver, causing a consequent increase of biologically active androgens in the circulation. N-Acetyl Cysteine (NAC) with the chemical structure of sulfhydryl groups is derived from L- amino acid cysteine and the first time were used as a mucolytic drug in some respiratory diseases such as chronic bronchitis. oral NAC administration has been proposed for the prevention of endothelial damage due to antioxidant agent. In recent years, a limited number of studies have shown the possible benefits of NAC administration in improving insulin sensitivity and better induction of ovulation outcomes in patients with PCOS.
(Mostajeran F, Tehrani HG, Rahbary B. Adv Biomed Res. 2018;7:100.)
Click To Know more about the role of N-acetylcysteine for ovulation in PCOS
# N-acetylcysteine #Women_Health #PCOS #Shield_Connect #Gynecology
#Mother #Ovulation #Adjuvant_Therapy
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# N-acetylcysteine #Women_Health #PCOS #Shield_Connect #Gynecology
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