Efficacy of metformin in obese and non-obese women with polycystic ovary syndrome: a randomized, double-blinded, placebo-controlled cross-over trial

Abstract

BACKGROUND: Our aim was to assess the effects of metformin on menstrual frequency, fasting plasma glucose (FPG), insulin resistance assessed as HOMA-index, weight, waist/hip ratio, blood pressure (BP), serum lipids, and testosterone levels in women with polycystic ovary syndrome (PCOS) METHODS: In a randomized, controlled, doubleblinded setup, 56 women aged 18 -45 with PCOS were treated with either metformin 850 mg or placebo twice daily for 6 months. After a wash-out period of 3 months participants received the alternate treatment for 6 months. The changes in the measured parameters were analysed by intention-to-treat and per protocol RESULTS: There were no changes in menstrual frequency. In the intention-to-treat analysis, weight and systolic BP were reduced on metformin treatment (p50.009 and 0.047, respectively), while high-density lipoprotein (HDL) increased (p50.001). On placebo, weight and FPG increased (p<0.05). Post-hoc subgrouping according to BMI revealed reductions in testosterone (p50.013), FPG (p50.018), insulin (p50.045) and HOMA-index (p50.022) in obese women. Per protocol analysis showed the following differences between the changes on placebo and metformin (mean (5 -95 % percentiles): weight (-4.2 (-7.0, -1.9) kg, p<0.001), FPG (-0.23 (-0.44, -0.01) mmol/l, p50.041), insulin (-4.17 (-8.10, -0.23) mIU/l, p50.039) and HOMA index (-1.50 (-2.53, -0.47) mIU/l*mmol/l, p50.006). Weight, FPG and HOMA index were lower after metformin than after placebo. CONCLUSIONS: Metformin treatment lowered weight and systolic blood pressure and increased HDL in women with PCOS. In post-hoc analysis it increased insulin sensitivity and lowered testosterone in obese women. Non-obese women did not benefit from metformin.

A clinical study on the short-term effect of berberine in comparison to metformin on the metabolic characteristics of women with polycystic ovary syndrome

“…Although, our 3-month treatment period led to decrease in concentrations of insulin and androgens as it was reported elsewhere (11,12,32,33), we could not confirm significant effect of MET on weight change and lipid profile as it was shown by others (11,12,34). Three months may be too short a time to demonstrate the effect of MET on metabolic abnormalities sufficiently.…”

“…Insulin resistance (IR) is known to play a critical role in the pathophysiology of PCOS (6,7). The administration of insulin sensitizer metformin (MET) is recognized as a successful treatment for many metabolic and reproductive dysregulations characteristic of women with PCOS (8)(9)(10)(11)(12)(13).…”

Polycystic ovaries and obesity

“…The reduction, however, was greater when metformin was combined with lifestyle interventions, particularly in PCOS women with a BMI >39 kg/m 2 [70], but in a subsequent study including women with a BMI >30 kg/m 2 metformin was without any effect [86]. If metformin has any body-weight-lowering effects, it happens only in obese and not in lean patients [71]. It is still uncertain whether metformin can be used in adolescents.…”

Adiponectin levels in women with polycystic ovary syndrome: impact of metformin treatment in a randomized controlled study

“…The aim of this study was to evaluate the effect of metformin in PCOS, and results with regard to hormonal and metabolic parameters have been published elsewhere (17). In this report, we describe our PCOS population with regard to correlations between adiponectin and anthropometric, hormonal, and metabolic factors.…”