Metformin improves polycystic ovary syndrome symptoms irrespective of pre-treatment insulin resistance

Abstract

Objective: Insulin resistance (IR) and obesity are common features of the polycystic ovary syndrome (PCOS). Insulin-sensitizing agents have been shown to improve both reproductive and metabolic aspects of PCOS, but it remains unclear whether it is also beneficial in lean patients without pretreatment IR. The aim of this study was to determine the influence of metformin on the clinical and biochemical parameters of PCOS irrespective of the presence of basal obesity and IR. Design: The effect of 6 months of metformin treatment was prospectively assessed in 188 PCOS patients, divided into three groups according to body mass index (BMI; lean: BMI!25 kg/m 2 , overweight: BMI 25-29 kg/m 2 , and obese: BMIR30 kg/m 2 ). Outcome parameters, which were also assessed in 102 healthy controls, included body weight, homeostasis model assessment for IR (HOMA-IR), fasting glucose and insulin levels, area under the curve of insulin response (AUCI), hyperandrogenism, and menstrual irregularities. Results: In comparison with the respective BMI-appropriate control groups, only obese but not lean and overweight PCOS patients showed differences in fasting insulin and HOMA-IR. Metformin therapy significantly improved all outcome parameters except fasting glucose levels. Subgroup analyses revealed that in the group of lean PCOS patients without pre-treatment IR, metformin significantly improved HOMA-IR (1.7G1.0 vs 1.1G0.7 mmol/l!mmol/l 2 ) and fasting insulin levels (7.7G4.2 vs 5.4G3.9 mU/l), in addition to testosterone levels (2.6G0.9 vs 1.8G0.7 nmol/l), anovulation rate (2.3 vs 59.5%), and acne (31.8 vs 11.6%; all P!0.017). In the overweight and obese PCOS groups, metformin also showed the expected beneficial effects. Conclusion: Metformin improves parameters of IR, hyperandrogenemia, anovulation, and acne in PCOS irrespective of pre-treatment IR or obesity.European Journal of Endocrinology 157 669-676

Metformin: an old medication of new fashion: evolving new molecular mechanisms and clinical implications in polycystic ovary syndrome

“…However, previous studies did not confirm the predictive value of IR indices for ovulation induction by metformin (167,169,174). This discrepancy may reside in the use of surrogate mathematical indices for the assessment of IR (175).…”

Polycystic ovaries and obesity

“…Higher circulatory RBP4 levels have been found in PCOS women compared with controls. Furthermore, compared to controls, a significant up-regulation of RBP4 mRNA and higher protein levels in subcutaneous and omental adipose tissue were found in PCOS women [41]. A correlation between RBP4 levels in blood and BMI in PCOS patients is inconclusive as yet in various studies.…”

Insulin and hyperandrogenism in women with polycystic ovary syndrome

“…This drug also reduces appetite in many PCOS women and is thus often [133], but not always [134], associated with more weight loss. Metformin has been shown to be effective in all women with PCOS, even those without insulin resistance and hyperinsulinemia [47, [135][136][137], but tends to be more effective in lean as compared to obese PCOS women [138]. The effects of metformin in PCOS are probably mainly mediated through a reduction in insulin levels, which is observed both in insulin-sensitive and insulin-resistant PCOS women because of the reduction in hepatic glucose production.…”