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.
PATIENT(S): Six lean and 31 obese subjects, aged 19-33 years.
INTERVENTION(S): 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 MEASURE(S): 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.
RESULT(S): 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.
CONCLUSION(S): NAC may be a new treatment for the improvement of insulin circulating levels and insulin sensitivity in hyperinsulinemic patients with polycystic ovary syndrome.
PMID 12057717 12057717 DOI 10.1016/s0015-0282(02)03133-3 10.1016/s0015-0282(02)03133-3
Cite this article
Fulghesu, A. M., Ciampelli, M., Muzj, G., Belosi, C., Selvaggi, L., Ayala, G. F., & Lanzone, A. (2002). N-acetyl-cysteine treatment improves insulin sensitivity in women with polycystic ovary syndrome. Fertility and sterility, 77(6), 1128-1135. https://doi.org/10.1016/s0015-0282(02)03133-3
Fulghesu AM, Ciampelli M, Muzj G, Belosi C, Selvaggi L, Ayala GF, et al. N-acetyl-cysteine treatment improves insulin sensitivity in women with polycystic ovary syndrome. Fertil Steril. 2002;77(6):1128-1135. doi:10.1016/s0015-0282(02)03133-3
Fulghesu, A. M., et al. "N-acetyl-cysteine treatment improves insulin sensitivity in women with polycystic ovary syndrome." Fertility and sterility, vol. 77, no. 6, 2002, pp. 1128-1135.
To determine whether self-selected women with polycystic ovary syndrome (PCOS) are abnormal compared with a control population. Case-control. Support group meeting organized and initiated by patients. PATIENT(S): Forty-five self-selected women with PCOS and 80 control women. INTERVENTION(S): Self-selected women with PCOS at a peer support conference completed a questionnaire, had a brief physical, and gave a fasting blood sample. MAIN OUTCOME MEASURE(S): Historical, biometric, and assay results. RESULT(S): Sixty percent of the women attending the conference participated in the study. Most had been diagnosed with PCOS on the basis of ovarian morphology (35%). They were more likely to be nulliparous and have a history of oligomenorrhea (96%). They were hyperandrogenemic (significantly elevated testosterone and DHEAS levels) compared with control women. Self-selected women with PCOS displayed multiple metabolic abnormalities compared with control women, including elevations in blood pressure, waist-hip ratio, fasting insulin, fasting total cholesterol, and fasting low-density lipoprotein cholesterol levels, as well as a significant decrease in fasting glucose-insulin ratio and high-density lipoprotein cholesterol levels. CONCLUSION(S): Self-selected women with PCOS have reproductive and metabolic abnormalities. The majority of these women received inadequate treatment despite having risk factors for endometrial cancer, diabetes, and/or heart disease. Our study also suggests that women attending or participating in a PCOS support group are willing and likely to participate in clinical studies.
To determine the metabolic and reproductive effectiveness of rosiglitazone in polycystic ovary syndrome (PCOS). Case report. Academic clinical practice and General Clinical Research Center. PATIENT(S): A 25-year-old woman with PCOS. INTERVENTION(S): Rosiglitazone maleate, 4 mg daily for 5 months until conception. MAIN OUTCOME MEASURE(S): Insulin sensitivity by steady-state plasma glucose technique; serum androgens, progesterone, and hCG; and pelvic ultrasound images. RESULT(S): Rosiglitazone treatment for 5 months improved insulin sensitivity, lowered serum free testosterone, and resulted in spontaneous ovulation and conception. CONCLUSION(S): Rosiglitazone is a promising insulin sensitizer for treatment of PCOS. Clinical trials are warranted.
Insulin resistance (IR) plays a pivotal role in PCOS. Insulin-sensitizer agents such as metformin and inositols have been shown to improve the endocrine and metabolic aspects of PCOS. The purpose of this study is to compare their effects on the clinical and metabolic features of the women with PCOS. Fifty PCOS women with IR and/or hyperinsulinemia were randomized to treatment with metformin (1500 mg/day) or myo-inositol (4 g/day). IR was defined as HOMA-IR >2.5, while hyperinsulinemia was defined as a value of AUC for insulin after a glucose load over the cutoff of our laboratory obtained in normal women. The Matsusa Index has been calculated. The women have been evaluated for insulin secretion, BMI, menstrual cycle length, acne and hirsutism, at baseline and after 6 months of therapy. The results obtained in both groups were similar. The insulin sensitivity improved in both treatment groups. The BMI significantly decreased and the menstrual cycle was normalized in about 50% of the women. No significant changes in acne and hirsutism were observed. The two insulin-sensitizers, metformin and myo-inositol, show to be useful in PCOS women in lowering BMI and ameliorating insulin sensitivity, and improving menstrual cycle without significant differences between the two treatments.
PCOSNeuroendocrine MechanismsInsulin SensitizersPulse Frequency
Kalro BN et al., 2001·Obstet Gynecol Clin North Am
Although central and peripheral factors have been implicated in the neuromodulation of GnRH in PCOS, there are no definitive or conclusive data to establish a primary causal role for any one factor. Because increased GnRH pulse frequency is at least a contributor to the secretion of excess LH and insufficient FSH that are the proximate cause of chronic anovulation in PCOS, strategies to slow the GnRH pulse generator are likely to promote ovulation in women with PCOS. Several pharmacologic agents, such as dopamine agonists and antagonists, have been tried, but the lack of consistent effects in women with PCOS limits their clinical utility. Current treatment strategies include the use of the combined oral contraceptive pills, antiandrogens or androgen receptor blockers, and insulin sensitizers. Oral contraceptive preparations are effective in suppressing ovarian hyperandrogenemia, regulating menstrual cycles, and reducing the risk of endometrial hyperplasia. Androgen blockade and antiandrogens provide symptomatic relief from androgen-induced acne and hirsutism and have been reported to restore ovulation in women with PCOS. Whether this effect is mediated peripherally or centrally remains to be clarified. The most recent class of pharmacologic agents to gain popularity are the "insulin modifiers." With increasing evidence that insulin resistance constitutes a key metabolic element, it seems logical that improving insulin sensitivity and glucose disposal might wholly, or partially, reverse certain features of PCOS, including anovulation. To date, insulin modifiers have proved most promising in improving the clinical features and promoting fertility, but whether this effect is centrally mediated is yet to be elucidated.