N-acetyl cysteine Compares Favorably to Metformin in Women with PCOS
Author: Javanmanesh F, Kashanian M, Rahimi M, Sheikhansari N.
Reference: A comparison between the effects of metformin and N-acetyl cysteine (NAC) on some metabolic and endocrine characteristics of women with polycystic ovary syndrome.
Design: A double blind randomized clinical trial in women with polycystic ovary syndrome (PCOS). One group received metformin 500 mg, three times a day. The other group (NAC) received oral NAC 600 mg three times a day for 24 weeks. Primary assessments before and after treatment were BMI, fasting blood glucose, abnormal uterine bleeding, fasting blood insulin, HOMA index and lipid profile including triglycerides, HDL, LDL and total cholesterol.
Participants: In total, 120 women diagnosed with PCOS as defined according to the Rotterdam criteria entered the study. Inclusion criteria were women with PCOS and between ages 20 and 36. Women were excluded if they had Cushing syndrome, congenital adrenal hyperplasia, hyperprolactinemia, thyroid disorders, diabetes mellitus, history of peptic ulcer, drug use including infertility drugs or women who were pregnant. Four women were excluded due to pregnant and four due to the use of fertility drugs ; two women in the metformin group and two in the NAC group discontinued due to gastrointestinal problems. Women of the two groups were similar in age range, and did not have statistically significant differences in mean body mass index (BMI), fasting blood sugar (FBS), abnormal uterine bleeding (AUB), fasting blood insulin, HOMA index and lipid profile, upon entrance into the study. In the end, 94 women completed the study, 46 women in the NAC group and 48 women in the metformin group.
Primary outcome: The primary objective was to compare NAC and metformin on some of the metabolic and endocrine characteristics of polycystic ovary syndrome.
Key findings: The women of these two groups showed statistically significant improvement after the 24 weeks of treatment. Women in the NAC group showed more improvement in BMI, FBS, fasting insulin, HOMA index and LDL than did those in the metformin group. After treatment, BMI > 30 = 35.4% metformin vs 15.2% NAC; mean BMI =28.36 metformin vs 27.11 NAC; abnormal uterine bleeding= 50% metformin vs 28.3% NAC; mean FBS= 90.02 metformin vs 86.61 NAC; mean fasting insulin= 10.40 metformin vs 8.89 NAC; mean HOMA index= 2.09 metformin vs 1.71 NAC; mean LDL 141.83 metformin vs 127.89 NAC; mean HDL 40.69 metformin vs 36.02 NAC. Triglycerides and total cholesterol did not show significant differences between the two groups after the 24 weeks of treatment. There were no significant differences between the two groups for side effects.
Practice Implications: Both metformin and NAC improved lipid profile, BMI, AUB , fasting blood sugar and insulin after treatment, but NAC improved all of these parameters more than metformin. This is not the only head to head study with NAC vs metformin. In a similar study, both treatments improved BMI, fasting insulin, HOMA index, free testosterone and abnormal bleeding; however in that study, NAC reduced total cholesterol and LDL, and metformin only reduced total cholesterol. In a comparison study between metformin and NAC on induction of ovulation in women with PCOS, only metformin was effective for induction of ovulation in PCOS resistant patients. Metformin also lowered fasting glucose and insulin but not in the NAC group—which is quite different results than the current study.
Numerous other studies have been done on NAC in women with PCOS. It has been used as an adjuvant with clomiphene in PCOS patients who are resistant to clomiphene alone and the results have yielded an increased ovulation and pregnancy rate. NAC has also been shown to increase ovulation rates, endometrial lining thickness and progesterone levels when used with clomiphene, however another study showed no effect on ovulation rate for NAC. A study on NAC and PCOS women reported no changes in the amount of fasting glucose and fasting insulin, but did report improvement in peripheral insulin sensitivity after oral glucose tolerance testing.
One area of limitation of the current study is that it does not characterize PCOS patients by phenotype in terms of hirsutism, acne or hair loss— all are signs of hyperandrogenism and are common but not required features of PCOS. None the less, in my women’s health practice, NAC (or metformin) has become a fundamental treatment as part of a holistic and comprehensive approach to PCOS.
 Omer G, Muderris II. Clinical, endocrine and metabolic effects of metformin vs NAC in women with PCOS. Eur J Gynecol Reprod Biol 2011;159:127-131.
 Elnashar A, et al. NAC vs metformin in treatment of clomiphene citrate-resistant polycystic ovary syndrome: a prospective randomized controlled study. Fertil Steril 2007;88: 406-9.
 Rizk A, et al. NAC is a novel adjuvant to clomiphene citrate in clomiphene citrate-resistant patients with PCOS. Fertil Steril 2005;83:367-70.
 Badawy A, et al. NAC and clomiphene citrate for induction of ovulation in PCOS: a cross-over trial. Acta ; Obstet Gynecol Scand 2007;86: 218-22.
 Badawy A, et al. Clomiphene citrate plus NAC vs clomiphene citrate for augmenting ovulation in the management of unexplained infertility: a randomized double-blind controlled trial. Fertil Steril 2006;86:647-650.
Fulghesu AM, et. NAC treatment improves insulin sensitivity women with PCOS. Fertil Steril 2002;77:1128-35