Metformin versus flutamide in the treatment of metabolic consequences of non-obese young women with polycystic ovary syndrome: a randomized prospective study

Abstract

In addition to the reproductive consequences, polycystic ovary syndrome (PCOS) is characterized by a metabolic disorder in which hyperinsulinemia and insulin resistance are central features. The effects and possible benefits from insulin-sensitizing drugs are not well known, especially in non-obese women with PCOS. This study was designed to evaluate the effects of metformin and flutamide on metabolic parameters and insulin resistance in non-obese women with PCOS. Thirty non-obese women newly diagnosed with PCOS and 15 age- and weight-matched healthy volunteers as controls were included in the study. Patients were assigned randomly to receive flutamide 250 mg daily or metformin 850 mg three times daily. Glucose, insulin, insulin resistance, androgen levels and glucose and insulin responses to an oral glucose tolerance tests (OGTT) were assessed before and after a 4-week therapy period. A positive correlation was found between body mass index and insulin level in patients with PCOS and controls. Follicle stimulating hormone, luteinizing hormone, free testosterone and dehydroepiandrosterone sulfate levels decreased significantly, but insulin resistance levels were not changed after flutamide therapy. Body weight, free testosterone, insulin and insulin resistance levels decreased significantly after metformin therapy. In conclusion, metformin treatment improved insulin sensitivity and decreased androgen levels, and flutamide decreased androgen levels but failed to improve insulin sensitivity in the non-obese women with PCOS.

Increased micronucleus frequencies in peripheral blood lymphocytes in women with polycystic ovary syndrome

“…In the past decade, the association between hyperandrogenism, hyperinsulinemia and PCOS was demonstrated (19)(20)(21). Our findings, summarized in Table 1, are consistent with those of the previous studies, except for HOMA-IR.…”

Sustainability of 8% weight loss, reduction of insulin resistance, and amelioration of atherogenic-metabolic risk factors over 4 years by metformin-diet in women with polycystic ovary syndrome

“…We [27] have previously reported that women with PCOS in the bottom pretreatment quintile for IR (the leanest at pretreatment) nevertheless experienced significant metabolic and menstrual benefits. In nonobese women with PCOS, Sahin et al [55] reported significant decrements in weight, free testosterone, and measures of IR. In nonobese (mean BMI, 21.4) adolescents with anovulatory hyperandrogenism given 1.275 g MET, Ibanez et al [56] reported that 78% ovulated within 6 months.…”

Evidence-Based and Potential Benefits of Metformin in the Polycystic Ovary Syndrome: A Comprehensive Review

“…The authors (154) found that metformin use was significantly associated with decreased body weight and BMI in the overweight and obese groups. On the other hand, the use of metformin was observed to decrease body weight, even in nonobese PCOS women (335). Other investigators reported a significant reduction in waist circumference, but no significant change was observed in weight in obese subjects treated with metformin (147).…”

“…To date, there is an increasing interest for combined therapies. A prospective study (335) designed to evaluate the effects of metformin plus flutamide on metabolic parameters and insulin resistance in nonobese women with PCOS showed a similar reduction in free testosterone after administration of both 2250 mg/d metformin and 250 mg/d flutamide. In addition, metformin plus OCs provided benefits on hyperandrogenism and insulin resistance in nonobese PCOS women not desiring pregnancy, but the effects on central adiposity and dyslipidemia were weaker (336).…”