N-acetyl-cysteine treatment improves insulin sensitivity in women with polycystic ovary syndrome

Anna Maria Fulghesu; Mario Ciampelli; Giuseppe Muzj; Chiara Belosi; Luigi Selvaggi; Gian Franco Ayala; Antonio Lanzone

doi:10.1016/s0015-0282(02)03133-3

Therapeutics Supplements and Botanicals

N-acetyl-cysteine treatment improves insulin sensitivity in women with polycystic ovary syndrome

Fulghesu AM, Ciampelli M, Muzj G, Belosi C, Selvaggi L, Ayala GF, Lanzone A

Published June 12, 2002 Fertility and Sterility, 77(6), 1128-1135

DOI 10.1016/s0015-0282(02)03133-3 PMID 12057717

RRM Academy Synopsis

N-acetyl-cysteine improved insulin sensitivity in a small PCOS study

In a small study, N-acetyl-cysteine improved insulin sensitivity in women with PCOS who had a high insulin response. PCOS, now named polyendocrine metabolic ovarian syndrome, PMOS, was the condition studied. Researchers followed 37 women for 5 to 6 weeks. Thirty-one took the supplement and 6 took a placebo. Normal-insulin women and the placebo group showed no significant change.

Key Findings

Among the 31 treated women, total insulin after a glucose drink fell and insulin sensitivity rose. Fasting glucose, fasting insulin and blood sugar after the drink stayed the same.
Among the 17 treated women with a high insulin response, testosterone and the free androgen index fell, and sex hormone-binding globulin rose (P<.05).
The 14 treated women with a normal insulin response and the 6 placebo-treated women, all obese with a high insulin response, showed no significant change.
Total cholesterol, triglycerides and LDL cholesterol fell in the treated group. The authors report this held only in the high-insulin subgroup.
Liver insulin extraction and body mass index were unchanged. The authors observed no side effects, and three women ovulated during treatment.

Interpretation

This prospective trial followed 37 women with PCOS for 5 to 6 weeks, comparing N-acetyl-cysteine to placebo, and tracked insulin, hormone and lipid markers. The hormone shifts in the high-insulin group point to a direct link between insulin levels and androgen levels in PCOS: as insulin sensitivity rose, testosterone fell and sex hormone-binding globulin rose. Three women ovulated during treatment. The authors note the findings are preliminary and call for further study of longer treatment with N-acetyl-cysteine in PCOS. The findings support larger studies of insulin-sensitizing treatment in PCOS.

RRM Context

Restorative reproductive medicine looks for the drivers behind PCOS. The authors link insulin resistance to PCOS. This study measured insulin sensitivity as a root-cause target, and the hormone and lipid changes that followed support that link. A treatment that lowers insulin levels from the inside may correct the hormone imbalance at its source, the pattern restorative reproductive medicine looks to use.

Our editorial summary of this paper, not the article's abstract.

Abstract

Objective

To evaluate the effect of N-acetyl-cysteine (NAC) on insulin secretion and peripheral insulin resistance in subjects with polycystic ovary syndrome (PCOS).

Design

Prospective data analysis.

Setting

Volunteer women in an academic research environment.

Patients

Six lean and 31 obese subjects, aged 19-33 years.

Interventions

Patients were treated for 5-6 weeks with NAC at a dose of 1.8 g/day orally. A dose of 3 g/day was arbitrarily chosen for massively obese subjects. Six of 31 obese patients with PCOS were treated with placebo and served as controls.

Main Outcome Measures

Before and after the treatment period, the hormonal and lipid blood profile and insulin sensitivity, assessed by an hyperinsulinemic euglycemic clamp, were evaluated and an oral glucose tolerance test (OGTT) was performed.

Results

Fasting glucose, fasting insulin, and glucose area under curve (AUC) were unchanged after treatment. Insulin AUC after OGTT was significantly reduced, and the peripheral insulin sensitivity increased after NAC administration, whereas the hepatic insulin extraction was unaffected. The NAC treatment induced a significant fall in T levels and in free androgen index values (P<.05). In analyzing patients according to their insulinemic response to OGTT, normoinsulinemic subjects and placebo-treated patients did not show any modification of the above parameters, whereas a significant improvement was observed in hyperinsulinemic subjects.

Conclusions

NAC may be a new treatment for the improvement of insulin circulating levels and insulin sensitivity in hyperinsulinemic patients with polycystic ovary syndrome.

Topics

Therapeutics › Supplements and Botanicals › Antioxidant Supplements · Reproductive Endocrinology › Thyroid and Metabolic Function › Insulin and Metabolism

Anna Maria Fulghesu, Mario Ciampelli, Giuseppe Muzj, Chiara Belosi, Luigi Selvaggi, Gian Franco Ayala, Antonio Lanzone

A Fulghesu, M Ciampelli, G Muzj, C Belosi, L Selvaggi, G Ayala, A Lanzone

PMID 12057717 12057717 DOI 10.1016/s0015-0282(02)03133-3 10.1016/s0015-0282(02)03133-3 Fulghesu et al. 2002, Fulghesu 2002

Keywords

Acetylcysteine/administration & Dosage/therapeutic Use, Adult, Androgens/blood, Drug Administration Schedule, Female, Glucose Tolerance Test, Humans, Hyperinsulinism/blood, Insulin/blood/metabolism, Insulin Resistance/physiology, Liver/metabolism, Polycystic Ovary Syndrome/drug Therapy/physiopathology, Prospective Studies, Testosterone/blood, Androgens, Insulin, Testosterone, Acetylcysteine

N-acetyl-cysteine treatment improves insulin sensitivity in women with polycystic ovary syndrome

N-acetyl-cysteine improved insulin sensitivity in a small PCOS study

Key Findings

Interpretation

RRM Context

Abstract

Topics

By this author

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Keywords