Simvastatin improves biochemical parameters in women with polycystic ovary syndrome: results of a prospective, randomized trial. The effect of atorvastatin in patients with polycystic ovary syndrome: a randomized double-blind placebo-controlled study. Comparison of simvastatin and metformin in treatment of polycystic ovary syndrome: prospective randomized trial. The effect of metformin on fat distribution and the metabolic syndrome in women with polycystic ovary syndrome--a randomised, double-blind, placebo-controlled trial. Clinical, metabolic, and endocrine parameters in response to metformin and lifestyle intervention in women with polycystic ovary syndrome: a randomized, double-blind, and placebo control trial. Clinical, metabolic and endocrine parameters in response to metformin in obese women with polycystic ovary syndrome: a randomized, double-blind and placebo-controlled trial. The reproductive and metabolic effect of rosiglitazone on Chinese women with polycystic ovarian syndrome--a double-blind randomized placebo-controlled study. The impact of metformin, oral contraceptives, and lifestyle modification on polycystic ovary syndrome in obese adolescent women in two randomized, placebo-controlled clinical trials. Combined lifestyle modification and metformin in obese patients with polycystic ovary syndrome. A randomized, placebo-controlled, double-blind multicentre study.
To test the hypothesis that statins improve hyperandrogenemia in women with polycystic ovary syndrome (PCOS).
                Prospective, randomized trial.
                Academic medical center.
                Forty-eight women with PCOS.
                Subjects were randomized to a statin group (simvastatin, 20 mg daily plus oral contraceptive pill [OCP]; n = 24) or an OCP group (OCP alone; n = 24).
                Serum T.
                Baseline parameters of both groups were comparable. After 12 weeks of treatment, serum T levels declined by 41% in the statin group and by 14% in the OCP group. In the statin group, there was a greater decrease of LH (43% decrease vs. 9% in the OCP group) and a greater decline of LH/FSH ratio (44% vs. 12%). In the statin group, total cholesterol declined by 10% and low-density lipoprotein (LDL) by 24%. In the OCP group, total cholesterol increased by 8%, and LDL was unchanged.
                This is the first study demonstrating that statin decreases T levels and normalizes gonadotropin levels in women with PCOS. Statin therapy might offer a novel approach, providing endocrine and cardiovascular benefits. 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.
                Our objective was to assess the effect of atorvastatin on inflammatory markers, insulin resistance, and biochemical hyperandrogenemia in patients with PCOS.
                We conducted a randomized, double-blind, placebo-controlled study at a tertiary care setting in United Kingdom.
                Patients included 40 medication-naive patients with PCOS and biochemical hyperandrogenemia.
                Patients were randomized to either atorvastatin 20 mg daily or placebo.
                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).
                This study suggests that atorvastatin is effective in reducing inflammation, biochemical hyperandrogenemia, and metabolic parameters in patients with PCOS after a 12-wk period. Polycystic ovary syndrome (PCOS) is characterized by ovarian dysfunction and hyperandrogenism; it is also associated with increased cardiovascular risks such as adverse lipid profile and endothelial dysfunction. Metformin and, more recently, statins have been shown to improve endocrine and metabolic aspects of PCOS.
                The aim of the study was to compare effects of simvastatin and metformin on PCOS.
                In a prospective trial, women with PCOS (n = 136) were randomized to simvastatin (S), metformin (M), or simvastatin plus metformin (SM) groups. Evaluations were performed at baseline and after 3 months.
                The study was conducted at an academic medical center.
                The change of serum total testosterone was measured.
                The study was completed by 113 subjects. Total testosterone decreased significantly and comparably in all groups: by 17.1, 13.6, and 15.1%, respectively, in the S, M, and SM groups. Significant decreases were also observed in all groups with respect to body mass index, C-reactive protein, and soluble vascular cell adhesion molecule-1. DHEAS declined significantly only in the S group. None of the treatments were associated with significant changes in LH or FSH. Total cholesterol and low-density lipoprotein cholesterol significantly declined only in S and SM groups.
                Simvastatin treatment was superior to metformin alone, whereas a combination of simvastatin and metformin was not significantly superior to simvastatin alone. To establish whether metformin has a significant action in reducing visceral fat and improving other metabolic parameters in women with polycystic ovary syndrome (PCOS).
                Randomised, double-blind, placebo-controlled trial.
                Reproductive medicine clinic.
                Forty women with anovulatory PCOS.
                Participants were randomised into receiving metformin 500 mg three times a day or placebo for 3 months.
                Fat distribution was measured by computed tomography scan. Secondary outcome measures included serum indices of the metabolic syndrome and evidence of ovulation.
                We found no significant differences in any of the measures of fat distribution between the placebo and metformin groups. The metformin group had significantly lower total cholesterol (P= 0.02), low-density lipoprotein cholesterol (P= 0.02) and cholesterol:high-density lipoprotein cholesterol ratio (P= 0.05), but there was no statistically significant treatment effect on androgens, insulin, insulin resistance, triglycerides, ovulation or pregnancy.
                Metformin has no clinically significant effect in reducing visceral fat mass, although it does have a beneficial effect on lipids. This trial lends support to the growing evidence that metformin is not a weight loss drug. Metformin might therefore be used as an adjunct to lifestyle modification in women with PCOS, but not as a substitute for it. The aim of this study was to evaluate the effects of metformin in addition to diet and exercise on endocrine and metabolic disturbances in women with polycystic ovary syndrome (PCOS) in a prospective, double-blind, randomized, placebo (PBO) control trial. Thirty women with insulin resistance and PCOS received lifestyle modification and 1500 mg of metformin or placebo for 4 months. Before and after treatment, body mass index, waist/hip ratio, blood pressure, hirsutism, and menstrual patterns were evaluated. Serum concentrations of gonadotropins, androgens, progesterone, glucose, insulin, and lipids were measured. Lifestyle interventions resulted in similar weight and menstrual cycle's improvements in both groups. A significant reduction in serum fasting insulin, HOMA index, waist and testosterone levels was only observed with metformin. There were no significant changes in androstenedione, dehydroepiandrosterone sulfate, gonadotropins, and lipids levels. No other changes were observed in hirsutism or blood pressure. These findings suggest that metformin has an additive effect to diet and exercise to improve parameters of hyperandrogenism and insulin resistance. Although, a small decrease in body weight trough lifestyle changes could be enough to improve menstrual cycles in insulin-resistant women with PCOS. There is still some controversy concerning the effects of metformin in the treatment of Polycystic Ovary Syndrome (PCOS). The aim of this study was to asses the effect of metformin on clinical, metabolic and hormone parameters in obese women with PCOS. Thirty obese, non-diabetic women with PCOS received 500 mg of metformin or placebo, TID, over 90 days. Assessed parameters included body mass index, waist-to-hip ratio, blood pressure, FSH, LH, total testosterone, SHBG, fasting insulinemia, insulin-to-glucose ratio, total, HDL and LDL cholesterol, triglycerides, and menstrual cycles before and after the use of the drugs. Before treatment, patients did not differ in the two groups. After 90 days of metformin use, PCOS women presented significantly lower levels of total testosterone (p = 0.030) and total cholesterol (p = 0.023) compared to the women that used placebo. The other parameters did not differ between the groups. In conclusion, obese women with PCOS may benefit from the use of metformin through the reduction of hyperandrogenemia, total cholesterol, and possibly by restoration of regular menstrual cycles. Further studies with longer follow-ups are necessary to determine cardiovascular and endometrial metformin benefits and insulin-resistance decrease in women with polycystic ovary syndrome. To investigate whether an insulin sensitizer has any effect on amenorrhea and clinical and biochemical hyperandrogenism in Chinese women with polycystic ovarian syndrome (PCOS).
                Randomized controlled double-blind trial.
                A tertiary referral center, Hong Kong.
                Chinese women who fulfilled the Rotterdam criteria of PCOS (n = 70).
                Rosiglitazone 4 mg daily for the first month followed by 4 mg twice daily for 11 months.
                Menstrual status as well as clinical and biochemical hyperandrogenism.
                There is a significantly higher rate of regular menses among the treatment arm (16 [50.0%] of 32 vs 4 [11.8%] of 34) at 6 months and the improvement appeared to be sustained (10 [41.7%] of 24 vs 6 [20.0%] of 30) at 12 months. There was no change in the acne and hirsutism scores as well as serum T levels in both arms.
                We found a possible benefit in menstrual cyclicity but a lack of improvement in hyperandrogenism in our Chinese population.
                ChiCTR-TRC-09000670 (Chinese Clinical Trial Registry).
                Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved. Polycystic ovary syndrome (PCOS) presents in adolescence, and obesity is a common finding. The benefits and risks of alternate approaches to the management of PCOS in obese adolescent women are not clear.
                We investigated the effects of metformin, oral contraceptives (OCs), and/or lifestyle modification in obese adolescent women with PCOS.
                Two small, randomized, placebo-controlled clinical trials were performed.
                A total of 79 obese adolescent women with PCOS participated.
                In the single treatment trial, subjects were randomized to metformin, placebo, a lifestyle modification program, or OC. In the combined treatment trial, all subjects received lifestyle modification and OC and were randomized to metformin or placebo.
                Serum concentrations of androgens and lipids were measured.
                Lifestyle modification alone resulted in a 59% reduction in free androgen index with a 122% increase in SHBG. OC resulted in a significant decrease in total testosterone (44%) and free androgen index (86%) but also resulted in an increase in C-reactive protein (39.7%) and cholesterol (14%). The combination of lifestyle modification, OC, and metformin resulted in a 55% decrease in total testosterone, as compared to 33% with combined treatment and placebo, a 4% reduction in waist circumference, and a significant increase in HDL (46%).
                In these preliminary trials, both lifestyle modification and OCs significantly reduce androgens and increase SHBG in obese adolescents with PCOS. Metformin, in combination with lifestyle modification and OC, reduces central adiposity, reduces total testosterone, and increases HDL, but does not enhance overall weight reduction. It has been reported that women with polycystic ovary syndrome (PCOS) benefit from metformin therapy.
                A randomized, placebo-controlled, double-blind study of obese (body mass index >30 kg/m2), oligo-/amenorrhoeic women with PCOS. Metformin (850 mg) twice daily was compared with placebo over 6 months. All received the same advice from a dietitian. The primary outcome measures were: (i) change in menstrual cycle; (ii) change in arthropometric measurements; and (iii) changes in the endocrine parameters, insulin sensitivity and lipid profile.
                A total of 143 subjects was randomized [metformin (MET) = 69; placebo (PL) = 74]. Both groups showed significant improvements in menstrual frequency [median increase (MET = 1, P < 0.001; PL = 1, P < 0.001)] and weight loss [mean (kg) (MET = 2.84; P < 0.001 and PL = 1.46; P = 0.011)]. However, there were no significant differences between the groups. Logistic regression analysis was used to analyse the independent variables (metformin, percentage of weight loss, initial BMI and age) in order to predict the improvement of menses. Only the percentage weight loss correlated with an improvement in menses (regression coefficient = 0.199, P = 0.047, odds ratio = 1.126, 95% CI 1.001, 1.266). There were no significant changes in insulin sensitivity or lipid profiles in either of the groups. Those who received metformin achieved a significant reduction in waist circumference and free androgen index.
                Metformin does not improve weight loss or menstrual frequency in obese patients with PCOS. Weight loss alone through lifestyle changes improves menstrual frequency.
Although statins improve lipid profiles and reduce testosterone levels in women with PCOS, there is no evidence that statins improve resumption of menstrual regularity or spontaneous ovulation, nor is there any improvement of hirsutism or acne. There is a need for further research to be performed with large sample sizes and well-designed RCTs to assess clinical outcomes.