The Effect of Atorvastatin (and Subsequent Metformin) on Adipose Tissue Acylation-Stimulatory-Protein Concentration and Inflammatory Biomarkers in Overweight/Obese Women With Polycystic Ovary Syndrome.

Background: Atorvastatin has been shown to improve cardiovascular risk (CVR) indices in women with polycystic ovary syndrome (PCOS). Low-grade chronic inflammation of adipose tissue may link PCOS and adverse CVR. In pro-inflammatory states such as PCOS, spontaneous activation of the alternative pathway of complement results in increased generation of acylation stimulating protein (ASP) from adipocytes irrespective of body mass index. Methods: The objective of this study was to determine the effect of atorvastatin on markers of adipose tissue dysfunction and inflammation; acylation-stimulating-protein (ASP), interleukin-6 (IL-6), and monocyte-chemoattractant-protein-1 (MCP-1) in PCOS. This was a randomized, double-blind, placebo-controlled study where 40 medication-naive women with PCOS and biochemical hyperandrogenaemia were randomized to either atorvastatin 20 mg daily or placebo for 12 weeks. Following the 12 week randomization; both group of women with PCOS were subsequently started on metformin 1,500 mg daily for further 12 weeks to assess whether pre-treatment with atorvastatin potentiates the effects of metformin on markers of adipose tissue function We conducted a post-hoc review to detect plasma ASP and the pro-inflammatory cytokines IL6 and MCP-1 before and after 12 and 24 weeks of treatment. Results: There was significant reduction in ASP (156.7 ± 16.2 vs. 124.4 ± 14.8 ng/ml p <0.01), IL-6 (1.48 ± 0.29 vs.0.73 ± 0.34 pg/ml p = 0.01) and MCP-1 (30.4 ± 4.2 vs. 23.0 ± 4.5 pg/ml p = 0.02) after 12 weeks of atorvastatin that was maintained subsequently with 12 weeks treatment with metformin. There was a significant positive correlation between ASP levels with CRP (p < 0.01), testosterone (p < 0.01) and HOMA-IR (p < 0.01); IL-6 levels with CRP (p <0.01) and testosterone (p < 0.01) and MCP-1 with CRP (p < 0.01); testosterone (p < 0.01) and HOMA-IR (p < 0.02). Conclusions: This post-hoc analysis revealed that 12 weeks of atorvastatin treatment significantly decreased the markers of adipose tissue dysfunction and inflammation, namely ASP, IL-6 and MCP-1 in obese women with PCOS. Changes in adipose tissue markers were significantly associative with substantial improvements in HOMA-IR, testosterone and hs-CRP levels. ISRCTN Number: ISRCTN24474824.

The Effect of Exenatide on Cardiovascular Risk Markers in Women With Polycystic Ovary Syndrome.

Background: Polycystic ovary syndrome (PCOS) is associated with an adverse cardiovascular risk profile including a prothrombotic state. Exenatide has been shown to be effective at improving insulin sensitivity and weight loss in PCOS; therefore this study was undertaken to assess its effects on weight, endothelial function, inflammatory markers, and fibrin structure/function in overweight/obese women with PCOS. Methods: Thirty overweight/obese anovulatory women with all 3 Rotterdam criteria received exenatide 5 mcg bd for 4 weeks then 10 mcg bd for 12 weeks. The primary outcome was change in weight; secondary outcomes were changes in endothelial function [Reactive Hyperemia-Peripheral Arterial Tonometry (RH-PAT)], serum endothelial markers (ICAM-1, VCAM-1, E-selectin, and P-selectin), change in inflammation (hsCRP), and alteration in clot structure and function [maximum absorbance (MA), and time from full clot formation to 50% lysis (LT)]. Results: Twenty patients completed the study. Exenatide reduced weight 111.8 ± 4.8 to 108.6 ± 4.6 kg p = 0.003. Serum endothelial markers changed with a reduction in ICAM-1 (247.2 ± 12.9 to 231.3 ± 11.5 ng/ml p = 0.02), p-selectin (101.1 ± 8.2 to 87.4 ± 6.6 ng/ml p = 0.01), and e-selectin (38.5 ± 3.3 to 33.6 ± 2.6 ng/ml p = 0.03), without an overt change in endothelial function. Inflammation improved (CRP; 8.5 ± 1.4 to 5.6 ± 0.8 mmol/L p = 0.001), there was a reduction in clot function (LT; 2,987 ± 494 to 1,926 ± 321 s p = 0.02) but not clot structure. Conclusion: Exenatide caused a 3% reduction in weight, improved serum markers of endothelial function, inflammation, and clot function reflecting an improvement in cardiovascular risk indices in these women with PCOS. This suggests exenatide could be an effective treatment for obese women with PCOS. Clinical Trial Registration: ISRCTN81902209.

The effect of atorvastatin on pancreatic beta cell requirement in women with polycystic ovary syndrome.

BACKGROUND: There is an increased risk of developing T2DM in women with polycystic ovary syndrome (PCOS), and there is evidence that statins improve metabolic parameters in these patients. However, there are some data to show that statins increase the risk of incipient diabetes. MATERIALS AND METHODS: We have previously shown that 12 weeks of atorvastatin improves insulin resistance when measured using HOMA-IR. This post hoc analysis was designed to look at the effect of atorvastatin on pancreatic ß cell function using HOMA-ß in the same study. In this randomised, double-blind placebo controlled study, 40 medication-naïve patients with PCOS were randomised to either atorvastatin 20 mg daily or placebo for 3 months. A 3-month extension study for both groups of patients was undertaken with metformin 1500 mg daily after completing initial 3 months of atorvastatin or placebo. RESULTS: There was a significant reduction in HOMA-ß (240 ± 3.2 vs 177 ± 2.3; P value <0.01) after 12 weeks of atorvastatin treatment, which was maintained by metformin in the subsequent 12 weeks. There were no changes in HOMA-ß after the placebo or after subsequent metformin treatment.There was no linear correlation between reduction in HOMA-ß with improvement of free androgen index (FAI) (r2 = 0.02; P = 0.72), testosterone (r2 = 0.13; P = 0.49), SHBG (r2 = 0.22; P = 0.48), hsCRP (r2 = 0.19; P = 0.64), triglycerides (r2 = 0.09; P = 0.12), total cholesterol (r2 = 0.11; P = 0.32) or LDL-C (r2 = 0.19; P = 0.38). CONCLUSION: Treatment with atorvastatin for 12 weeks in women with PCOS significantly reduced HOMA-ß. This could be potentially due to fall in ß-cell requirement with improvement of insulin resistance rather than a reduction of ß-cell function.

Endocannabinoid receptor blockade reduces alanine aminotransferase in polycystic ovary syndrome independent of weight loss.

BACKGROUND: Evidence suggests that endocannabinoid system activation through the cannabinoid receptor 1 (CB1) is associated with enhanced liver injury, and CB1 antagonism may be beneficial. The aim of this study was to determine the impact of rimonabant (CB1 antagonist) on alanine aminotransferase (ALT), a hepatocellular injury marker, and a hepatic inflammatory cytokine profile. METHODS: Post hoc review of 2 studies involving 50 obese women with PCOS and well matched for weight, randomised to weight reducing therapy; rimonabant (20 mg od) or orlistat (120 mg tds), or to insulin sensitising therapy metformin, (500 mg tds), or pioglitazone (45 mg od). No subject had non-alcoholic fatty liver disease (NAFLD). RESULTS: Treatment with rimonabant for 12 weeks reduced both ALT and weight (p < 0.01), and there was a negative correlation between Δ ALT and Δ HOMA-IR (p < 0.001), but not between Δ ALT and Δ weight. There was a significant reduction of weight with orlistat (p < 0.01); however, orlistat, metformin and pioglitazone had no effect on ALT. The free androgen index fell in all groups (p < 0.05). The inflammatory marker hs-CRP was reduced by pioglitazone (p < 0.001) alone and did not correlate with changes in ALT. The inflammatory cytokine profile for IL-1ß, IL-6, IL-7, IL-10, IL12, TNF-α, MCP-1 and INF-γ did not differ between groups. None of the interventions had an effect on biological variability of ALT. CONCLUSION: Rimonabant through CB1 receptor blockade decreased serum ALT that was independent of weight loss and hepatic inflammatory markers in obese women with PCOS without NAFLD. TRIAL REGISTRATION: ISRCTN58369615 (February 2007; retrospectively registered) ISRCTN75758249 (October 2007; retrospectively registered).

Endocannabinoid receptor blockade increases vascular endothelial growth factor and inflammatory markers in obese women with polycystic ovary syndrome.

CONTEXT: Animal studies suggest that cannabinoid receptor-1 (CB-1) blockade reduces inflammation and neovascularization by decreasing vascular endothelial growth factor (VEGF) levels associated with a reduction in inflammatory markers, thereby potentially reducing cardiovascular risk. OBJECTIVE: To determine the impact of CB1 antagonism by rimonabant on VEGF and inflammatory markers in obese PCOS women. DESIGN: Randomized, open-labelled parallel study. SETTING: Endocrinology outpatient clinic in a referral centre. SUBJECTS: Twenty patients with PCOS (PCOS) and biochemical hyperandrogenaemia with a body mass index of ≥30 kg/m2 were recruited. Patients were randomized to 1·5 g daily of metformin or 20 mg daily of rimonabant. MAIN OUTCOME MEASURES: Post hoc review to detect VEGF and pro-inflammatory cytokines TNF-α, IL-1ß, IL-1ra, IL-2, IL6, IL-8, IL-10 and MCP-1 before and after 12 weeks of treatment. RESULTS: After 12 weeks of rimonabant treatment, there was a significant increase in VEGF (99·2 ± 17·6 vs 116·2 ± 15·8 pg/ml, P < 0·01) and IL-8 (7·4 ± 11·0 vs 18·1 ± 13·2 pg/ml, P < 0·05) but not after metformin (VEGF P = 0·7; IL-8 P = 0·9). There was no significant difference in the pro-inflammatory cytokines TNF-α, IL-1ß, IL-1ra, IL-2, IL6, IL-8, IL-10 and MCP-1 following either treatment. CONCLUSION: This study suggests that rimonabant CB-I blockade paradoxically raised VEGF and the cytokine IL-8 in obese women with PCOS that may have offset the potential benefit associated with weight loss.

A comparison of cardiovascular risk indices in patients with polycystic ovary syndrome with and without coexisting nonalcoholic fatty liver disease.

BACKGROUND: Women with polycystic ovary syndrome (PCOS) have an adverse cardiovascular risk profile and an increased prevalence of nonalcoholic fatty liver disease (NAFLD), which is also associated with an adverse cardiovascular risk profile. OBJECTIVE: To compare the cardiovascular risk profile of women with PCOS alone and women with PCOS and NAFLD. DESIGN, SETTING AND PARTICIPANTS: Twenty-five oligoanovulatory women with PCOS were screened for NAFLD (including liver biopsy if appropriate) and had their cardiovascular risk factors measured which included the inflammatory marker C-reactive protein (CRP), endothelial function {measured using endoPAT 2000 and serum markers [intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin and P-selectin]}, clot structure and function [maximum absorbance (MA) and lysis potential (LT)]. RESULTS: Twelve patients had confirmed PCOS without evidence of NAFLD, and 13 patients had confirmed PCOS with evidence of NAFLD. The PCOS and NAFLD group were heavier (BMI 43·9 ± 2·2 kg/m(2) ) compared with the PCOS alone group (BMI 37·6 ± 1·4 kg/m(2) P = 0·03). There was no difference in CRP (7·57 ± 0·95 vs 6·59 ± 1·87 mm P = 0·62) or endothelial function (RH-PAT 1·96 ± 0·1 vs 1·74 ± 0·16 P = 0·25), ICAM-1 (221 ± 48 vs 250 ± 60 ng/ml P = 0·19), VCAM-1 (2124 ± 78 vs 2314 ± 91 ng/ml P = 0·13), E-selectin (33·9 ± 3·3 vs 39·5 ± 15·5 ng/ml P = 0·31) and P-selectin (101·0 ± 6·6 vs 95·9 ± 10·2 ng/ml P = 0·69). There was no difference in clot formation or lysis. CONCLUSION: The patients with PCOS and NAFLD were heavier compared with patients with PCOS alone. Despite this, we were unable to demonstrate differences in inflammatory markers, endothelial function or clot structure and function, suggesting that severity of steatosis is not the most important determinant of cardiovascular risk in PCOS.

Atorvastatin reduces malondialdehyde concentrations in patients with polycystic ovary syndrome.

BACKGROUND: It has been shown that there is an increase in oxidative stress in polycystic ovary syndrome (PCOS). Statins are considered to have a pleiotropic effect other than their lipid-lowering effect. These effects may be mediated in part by reducing oxidative stress. METHODS: This randomized, double-blind, placebo-controlled study was conducted to assess the effect of atorvastatin on serum malondialdehyde (MDA) concentrations as a marker of oxidative stress in patients with PCOS. Forty medication-naïve patients with PCOS were randomized to either atorvastatin 20 mg daily or placebo for 3 months. A 3-month extension study for both groups of patients was undertaken with metformin 1500 mg daily after completing initial 3 months of atorvastatin or placebo. RESULTS: There was a significant decrease of MDA concentrations with atorvastatin [mean (sem)] [0.29 (0.04) vs. 0.25 (0.02) µmol/liter; P < 0.01] compared with placebo [0.28 (0.02) vs. 0.29 (0.12) µmol/liter; P = 0.52]. Three months treatment with metformin resulted in further reduction of MDA levels with atorvastatin compared with baseline [0.25 (0.02) baseline vs. 0.23 (0.03) µmol/liter for atorvastatin treated; P = 0.02]. There was also a significant correlation between the reduction in MDA with a reduction in high-sensitivity C-reactive protein (r = 0.71, P < 0.01), an increase in 25-hydroxyvitamin D (25OHD; r = -0.68, P = 0.02), and a reduction in testosterone levels (r = 0.63, P = 0.01). Multiple linear regression analysis revealed Δ25OHD, ΔC-reactive protein, and Δtestosterone were independent predictors of changes in MDA after atorvastatin treatment. No correlation was observed between the reductions in serum MDA concentrations with changes in the lipid parameters. CONCLUSIONS: Twelve weeks of atorvastatin led to a significant reduction in oxidative stress as determined by MDA concentrations among patients with polycystic ovary syndrome that was independently predicted by changes in testosterone, 25OHD, and high-sensitivity C-reactive protein.

Atorvastatin therapy decreases androstenedione and dehydroepiandrosterone sulphate concentrations in patients with polycystic ovary syndrome: randomized controlled study.

BACKGROUND: Hyperandrogenaemia in polycystic ovary syndrome (PCOS) represents a composite of raised serum concentrations of testosterone, androstenedione, dehydroepiandrosterone (DHEA) and DHEA sulphate (DHEAS). In patients with PCOS, testosterone and androstenedione are primarily derived from the ovaries and DHEAS is a metabolite predominantly from the adrenals. It has been shown that atorvastatin reduces testosterone concentrations in patients with PCOS. The objective was to study the effect of atorvastatin on serum androstenedione and DHEAS concentrations in patients with PCOS. METHODS: A randomized, double-blind, placebo-controlled study was performed. Forty medication-naive patients with PCOs were randomized to either atorvastatin 20mg daily or placebo for three months. Subsequently, a three-month extension study for all patients was undertaken with metformin 1500 mg daily. The main outcome measures were change in androstenedione and DHEAS concentrations. RESULTS: The mean (SD) baseline androstenedione (5.7 [0.8] versus 5.6 [1.3] nmol/L; P = 0.69) and DHEAS (7.1 [1.0] versus 7.2 [1.2] µmol/L; P = 0.72) concentrations were comparable between two groups. There was a significant reduction of androstenedione (5.7 [0.8] versus 4.7 [0.7] nmol/L; P = 0.03) and DHEAS (7.1 [1.0] versus 6.0 [0.9] µmol/L; P = 0.02) with three months of atorvastatin while there were no significant changes with placebo. Three months' treatment with metformin maintained the reduction of androstenedione and DHEAS concentrations with atorvastatin compared with baseline. There were no changes in either DHEAS or androstenedione concentrations in the initial placebo group after 12 weeks of metformin. CONCLUSIONS: Twelve weeks of atorvastatin significantly reduced both DHEAS and androstenedione contributing to the total reduction of androgen concentrations and indicating that the reduction of the hyperandrogenaemia could be partly due to the action of atorvastatin at both the ovary and the adrenal gland in PCOS.

Guidance on reporting ultrasound exposure conditions for bio-effects studies.

This guidance is intended to encourage best practice among researchers into ultrasound bio-effects in terms of how they determine and report the exposure conditions used in their studies. It covers both diagnostic and therapeutic applications of ultrasound and is intended to be useful to the researchers themselves, to the review boards of ethical and funding committees and to the editors and reviewers of scientific journals. Recommendations are made for reporting formats, depending on the information available, and level of the study.

Atorvastatin increases 25-hydroxy vitamin D concentrations in patients with polycystic ovary syndrome.

BACKGROUND: It has been shown that many women with polycystic ovary syndrome (PCOS) are 25-hydroxyvitamin D (25OHD) insufficient. Both statin treatment and vitamin D supplementation have been shown to improve biochemical hyperandrogenemia, insulin resistance, and markers of inflammation in patients with PCOS, raising the possibility that some of the statin effects are mediated through vitamin D. METHODS: We conducted this randomized, double-blind placebo controlled study to assess the effect of atorvastatin on serum 25OHD concentrations in patients with PCOS. Forty medication-naive patients with PCOS were randomized to either atorvastatin 20 mg daily or placebo for 3 months. After completing the initial 3 months of atorvastatin or placebo, both groups of patients participated in a 3-month extension study with metformin 1500 mg daily. We measured changes in 25OHD concentrations by use of tandem mass spectrometry. RESULTS: Mean (SD) baseline 25OHD concentrations were comparable between the 2 groups [45.9 (2.4) vs 44.8 (1.8) nmol/L; P = 0.7]. There was a significant increase in 25OHD concentrations with atorvastatin [45.9 (2.4) vs 60.8 (3.5) nmol/L] compared with placebo [44.8 (1.8) vs 41.8 (3.2) nmol/L; P = 0.02]. Three-month treatment with metformin maintained the improvement of 25OHD with atorvastatin compared to baseline [45.9 (2.4) vs 61.8 (3.5), P ≤ 0.01). There were no significant changes in 25OHD concentrations in the placebo group after 12 weeks of metformin. CONCLUSIONS: Among patients with polycystic ovary syndrome, 12 weeks of atorvastatin led to a clinically significant rise in 25OHD concentrations. This may represent a beneficial pleiotropic effect of statins on 25OHD concentrations.

Metformin maintains the weight loss and metabolic benefits following rimonabant treatment in obese women with polycystic ovary syndrome (PCOS).

OBJECTIVE: Rimonabant has been shown to reduce weight, free androgen index (FAI) and insulin resistance in obese patients with polycystic ovary syndrome (PCOS) compared to metformin. Studies have shown that significant weight regain occurs following the cessation of rimonabant therapy. This study was undertaken to determine if subsequent metformin treatment after rimonabant would maintain the improvement in weight, insulin resistance and hyperandrogenaemia in PCOS. DESIGN: An extension study for 3 months with the addition of metformin to the randomised open labelled parallel study of metformin and rimonabant in 20 patients with PCOS with a body mass index >or= 30 kg/m(2). Patients who were on 3 months of rimonabant were changed over to metformin for 3 months, whereas those on 3 months of metformin were continued on metformin for another 3 months. MEASUREMENTS: The primary end-point was a change in weight; secondary end-points were a change in FAI and insulin resistance. RESULTS: The mean weight loss of 6.2 kg associated with 3 months of rimonabant treatment was maintained by 3 months of metformin treatment (mean change +0.2 kg, P = 0.96). Therefore, the percentage reduction in weight remained significantly higher in the rimonabant/metformin group compared to metformin only subjects at 6 months compared to baseline (-6.0 +/- 0.1%vs. -2.8 +/- 0.1%, P = 0.04). The percentage change in testosterone and FAI from baseline to 6 months was also greater in the rimonabant/metformin group. [Testosterone (-45.0 +/- 5.0%vs. -16 +/- 2.0%, P = 0.02); FAI (-53.0 +/- 5.0%vs. -17.0 +/- 12.2%, P = 0.02)]. HOMA-IR continued to fall significantly in the rimonabant/metformin group between 0, 3 and 6 months (4.4 +/- 0.5 vs. 3.4 +/- 0.4 vs. 2.7 +/- 0.3, respectively, P < 0.01) but not at all in the metformin only group (3.4 +/- 0.7 vs. 3.4 +/- 0.8 vs. 3.7 +/- 0.8, respectively, P = 0.80). Total cholesterol and LDL reduced significantly in both groups, but improvements in triglycerides and HDL were limited to the rimonabant/metformin group. CONCLUSIONS: In these obese patients with PCOS, metformin maintained the weight loss and enhanced the metabolic and biochemical parameters achieved by treatment with rimonabant, compared to 6 months of metformin treatment alone.

The effect of atorvastatin in patients with polycystic ovary syndrome: a randomized double-blind placebo-controlled study.

CONTEXT: Polycystic ovary syndrome (PCOS) is associated with increased risk of cardiovascular morbidity, whereas statins are proven to reduce cardiovascular mortality and morbidity through lipid-lowering and perhaps through their pleiotropic effects. Statins can also reduce testosterone in vitro by inhibiting ovarian theca-interstitial cell proliferation and steroidogenesis and reducing inflammation in vivo. OBJECTIVE: Our objective was to assess the effect of atorvastatin on inflammatory markers, insulin resistance, and biochemical hyperandrogenemia in patients with PCOS. DESIGN AND SETTING: We conducted a randomized, double-blind, placebo-controlled study at a tertiary care setting in United Kingdom. PATIENTS: Patients included 40 medication-naive patients with PCOS and biochemical hyperandrogenemia. METHODS: Patients were randomized to either atorvastatin 20 mg daily or placebo. MAIN OUTCOME MEASURES: The primary endpoint of the study was a change in the inflammatory marker high-sensitivity C-reactive protein. The secondary endpoints were a change in insulin resistance and total testosterone. RESULTS: After 12 wk atorvastatin, there was a significant reduction (mean +/- sem) in total cholesterol (4.6 +/- 0.2 vs. 3.4 +/- 0.2 mmol/liter, P < 0.01), low-density lipoprotein cholesterol (2.9 +/- 0.2 vs. 1.8 +/- 0.2 mmol/liter, P < 0.01), triglycerides (1.34 +/- 0.08 vs. 1.08 +/- 0.13 mmol/liter, P <0.01), high-sensitivity C-reactive protein (4.9 +/- 1.4 vs. 3.4 +/- 1.1 mg/liter, P = 0.04), free androgen index (13.4 +/- 0.6 vs. 8.7 +/- 0.4, P < 0.01), testosterone (4.1 +/- 0.2 vs. 2.9 +/- 0.1 nmol/liter, P < 0.01) and insulin resistance as measured by homeostasis model assessment for insulin resistance (HOMA-IR) (3.3 +/- 0.4 vs. 2.7 +/- 0.4). There was a significant increase in SHBG (31.1 +/- 1.0 vs. 35.3 +/- 1.2 nmol/liter, P < 0.01). There was a positive correlation between the reduction in HOMA-IR in the atorvastatin group with the reduction in triglycerides and the reduction of free androgen index. There was a significant deterioration of HOMA-IR in the placebo group (3.0 +/- 0.4 vs. 3.8 +/- 0.5). CONCLUSIONS: This study suggests that atorvastatin is effective in reducing inflammation, biochemical hyperandrogenemia, and metabolic parameters in patients with PCOS after a 12-wk period.

A comparison between rimonabant and metformin in reducing biochemical hyperandrogenaemia and insulin resistance in patients with polycystic ovary syndrome (PCOS): a randomized open-label parallel study.

CONTEXT: Weight loss and metformin therapy are reported to be beneficial in improving the biochemical hyperandrogenaemia and insulin resistance of polycystic ovary syndrome (PCOS). Rimonabant has been found to reduce weight and improve the metabolic profile in patients with obesity, type 2 diabetes and metabolic syndrome. OBJECTIVE: To compare the effects of insulin sensitization with metformin to weight reduction by rimonabant on biochemical hyperandrogenaemia and insulin resistance in patients with PCOS. DESIGN: A randomized, open-label parallel study. SETTING: Endocrinology outpatient clinic in a referral centre. SUBJECTS: Twenty patients with PCOS and biochemical hyperandrogenaemia with a body mass index (BMI) >or= 30 kg/m(2) were recruited. INTERVENTION: Patients were randomized to 1.5 g daily of metformin or 20 mg daily of rimonabant. MAIN OUTCOME MEASURES: The primary end-point of the study was a change in total testosterone. RESULTS: After 12 weeks of rimonabant there was a significant reduction (mean +/- SEM) in weight (104.6 +/- 4.6 vs. 98.4 +/- 4.7 kg, P < 0.01), waist circumference (116.0 +/- 3.3 vs. 109.2 +/- 3.7 cm, P < 0.01), hip circumference (128.5 +/- 4.0 vs. 124.1 +/- 4.2 cm, P < 0.03), waist-hip ratio (0.90 +/- 0.02 vs. 0.88 +/- 0.01, P < 0.01) free androgen index (FAI) (26.6 +/- 6.1 vs. 16.6 +/- 4.1, P < 0.01), testosterone [4.6 +/- 0.4 vs. 3.1 +/- 0.3 nmol/l (132.7 +/- 11.5 vs. 89.4 +/- 8.65 ng/dl), P < 0.01] and insulin resistance as measured by the homeostasis model assessment (HOMA) method (4.4 +/- 0.5 vs. 3.4 +/- 0.4, P = 0.05). There was no change in any of these parameters in the metformin-treated group. CONCLUSION: This study suggests that the weight loss through rimonabant therapy may be of use in patients with PCOS and appears superior to insulin sensitization by metformin in reducing the FAI and insulin resistance in obese PCOS patients treated over a 12-week period.