Adjuvant therapy improves fertility, hormonal profile in PCOS

Adjuvant N-acetyl cysteine and clomiphene citrate improved fertility and hormonal profiles among women with clomiphene citrate-resistant polycystic ovary syndrome compared with metformin, researchers in Iran reported.

“Clomiphene citrate is the traditional first-line ovulation induction agent for treatment of patients with anovulatory infertility due to PCOS,” Maryam Nemati, of the department of obstetrics and gynecology at Shahrekord University of Medical Science, and colleagues wrote. “Approximately 15% to 20% of PCOS patients are [clomiphene citrate]-resistant and fail to [respond] to doses as high as 150 mg daily for 5 days. … Considering the high prevalence of insulin resistance and hyperinsulinemia, as the most common etiological factors for resistance to clomiphene in PCOS patients, many attentions have been placed on drugs with insulin-sensitizing action in clomiphene citrate-resistant PCOS patients.”

The researchers conducted a prospective study of 108 women with clomiphene-resistant PCOS from April 2011 through January 2013. All patients were receiving fertility treatment during the study. One group received 1,800 mg per day of N-acetyl cysteine in three daily doses on the third day of the menstrual cycle (n = 54), while another group received 1,500 mg of metformin, also in three daily doses (n = 54). Both groups also received 100 mg per day of clomiphene citrate. Nemati and colleagues evaluated mean BMI, hirsutism score, luteinizing hormone/follicle-stimulating hormone ratio, endometrial thickness, number of mature follicles, serum luteinizing hormone, follicle-stimulating hormone, estradiol, fasting insulin, fasting blood glucose and total testosterone at 8 and 12 weeks.

At 8 weeks, the researchers reported no significant difference among all variables (P ≥ .05), although they noted that metformin lowered BMI and insulin significantly more than N-acetyl cysteine treatment. However, at 12 weeks, adjuvant N-acetyl cysteine reduced hirsutism score and fasting blood glucose levels significantly more than metformin, the researchers wrote.

Nemati and colleagues reported that women in the metformin group showed a 32% ovulation rate and a 16% pregnancy rate in the first cycle, followed by a 47.6% ovulation rate and 26.1% pregnancy rate in the second cycle. Those treated with N-acetyl cysteine demonstrated a 38% ovulation rate and an 18% pregnancy rate in the first cycle, while in the second cycle, they achieved an ovulation rate of 58.5% and a pregnancy rate of 24.3%.

The researchers noted that N-acetyl cysteine had few side effects and high safety and tolerability. – by Andy Polhamus

Disclosures: The authors report no relevant financial disclosures.