Short-term intervention with liraglutide improved eating behavior in obese women with polycystic ovary syndrome Metformin reduces pregnancy complications without affecting androgen levels in pregnant polycystic ovary syndrome women: results of a randomized 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. Prevention of diabetes in women with a history of gestational diabetes: effects of metformin and lifestyle interventions. Effect of long-term treatment with metformin added to hypocaloric diet on body composition, fat distribution, and androgen and insulin levels in abdominally obese women with and without the polycystic ovary syndrome. Women with polycystic ovary syndrome have intrinsic insulin resistance on euglycaemic-hyperinsulaemic clamp. Diet, physical exercise and Orlistat administration increase serum Anti-Müllerian Hormone (AMH) levels in women with polycystic ovary syndrome (PCOS) Metformin versus lifestyle changes in treating women with polycystic ovary syndrome Long-Term Safety, Tolerability, and Weight Loss Associated With Metformin in the Diabetes Prevention Program Outcomes Study The potential implications of a PCOS diagnosis on a woman's long-term health using data linkage. The Indian Diabetes Prevention Programme shows that lifestyle modification and metformin prevent type 2 diabetes in Asian Indian subjects with impaired glucose tolerance (IDPP-1) Longitudinal weight gain in women identified with polycystic ovary syndrome: results of an observational study in young women. Treatment with flutamide, metformin, and their combination added to a hypocaloric diet in overweight-obese women with polycystic ovary syndrome: a randomized, 12-month, placebo-controlled study. A randomized, 48-week, placebo-controlled trial of intensive lifestyle modification and/or metformin therapy in overweight women with polycystic ovary syndrome: a pilot study. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. The effects of metformin with lifestyle therapy in polycystic ovary syndrome: a randomized double-blind study. Effect of metformin compared with hypocaloric diet on serum C-reactive protein level and insulin resistance in obese and overweight women with polycystic ovary syndrome. An assessment of lifestyle modification versus medical treatment with clomiphene citrate, metformin, and clomiphene citrate-metformin in patients with polycystic ovary syndrome.
Abstract Aim : Glucagon-like peptide 1 receptor agonists ( GLP-1 RA ) stimulate satiety leading to reductions in food intake and body weight . The effects of long- acting GLP-1 RA liraglutide on eating behavior of women with PCOS have not been investigated yet . Methods : Thirty-six obese women with PCOS ( mean ± SD , aged 31.2 ± 7.8 years , with BMI 38.7 ± 0.1 kg/m2 ) , pretreated with metformin ( 1000 mg BID ) were switched to liraglutide 1.2 mg QD sc for 12 weeks . Adiposity parameters and eating behavior as assessed by Three-Factor Eating Question naire ( TFEQ-R18 ) were examined at baseline and after 12 weeks . Results : Subjects treated with liraglutide lost on average 3.8 ± 0.1 kg ( p < 0.001 ) . Significant reductions of waist circumference and visceral adipose tissue ( VAT ) mass , volume and area were demonstrated from liraglutide induction to the end of the study . TFEQ-R18 scores were significantly different pre- and post-liraglutide intervention . After treatment with liraglutide  the uncontrolled eating ( UE ) score decreased from 36.8 ± 24.5 to 19.6 ± 18.4 ( p < 0.001 ) and emotional eating ( EE ) score decreased from 49.9 ± 33.3 to 28.5 ± 26.9 ( p < 0.001 ) . Scores for cognitive restraint ( CR ) were not changed . Conclusions : Short-term liraglutide treatment was associated with weight loss and significantly improved eating behavior in obese women with PCOS BACKGROUND Investigation of a possible effect of metformin on and rogen levels in pregnant women with polycystic ovary syndrome ( PCOS ) . METHODS A prospect i ve , r and omized , double-blind , placebo-controlled pilot study was conducted . Forty pregnant women with PCOS received diet and lifestyle counselling  and were r and omized to either metformin 850 mg twice daily or placebo . Primary outcome measures were changes in serum levels of dehydroepi and rosterone sulphate , and rostenedione , testosterone , sex hormone-binding globulin , and free testosterone index . Secondary outcome measures were pregnancy complications and outcome . Two-tailed t-tests and chi2-tests were used . RESULTS Maternal and rogen levels were unaffected by metformin treatment in pregnant women with PCOS . While none of the 18 women in the metformin group experienced a severe pregnancy or post-partum complication , seven of the 22 ( 32 % ) women experienced severe complications in the placebo group ( P = 0.01 ) . CONCLUSIONS Metformin treatment did not reduce maternal and rogen levels in pregnant women with PCOS . In the metformin-treated group we observed a reduction of severe , pregnancy and post-partum complications .  Metformin treatment of pregnant PCOS women may reduce complications during pregnancy and in the post-partum period CONTEXT 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 . OBJECTIVE We investigated the effects of metformin , oral contraceptives ( OCs ) , and /or lifestyle modification in obese adolescent women with PCOS . DESIGN Two small , r and omized , placebo-controlled clinical trials were performed . PATIENTS AND PARTICIPANTS A total of 79 obese adolescent women with PCOS participated . INTERVENTIONS In the single treatment trial , subjects were r and omized to metformin , placebo , a lifestyle modification program , or OC . In the combined treatment trial , all subjects received lifestyle modification and OC and were r and omized to metformin or placebo . MAIN OUTCOME MEASURES Serum concentrations of and rogens and lipids were measured . RESULTS Lifestyle modification alone result ed in a 59 % reduction in free and rogen index with a 122 % increase in SHBG . OC result ed in a significant decrease in total testosterone ( 44 % ) and free and rogen index ( 86 % ) but also result ed in an increase in C-reactive protein ( 39.7 % ) and cholesterol ( 14 % ) . The combination of lifestyle modification , OC , and metformin result ed 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 % ) . CONCLUSIONS In these preliminary trials , both lifestyle modification and OCs significantly reduce and rogens 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 CONTEXT A past history of gestational diabetes mellitus ( GDM ) confers a very high risk of postpartum development of diabetes , particularly type 2 diabetes . OBJECTIVE The Diabetes Prevention Program ( DPP ) sought to identify individuals with impaired glucose tolerance ( IGT ) and intervene in an effort to prevent or delay their progression to diabetes . This analysis examined the differences between women enrolled in DPP with and without a reported history of GDM . DESIGN The DPP was a r and omized , controlled clinical trial . SETTING The study was a multicenter , National Institutes of Health-sponsored trial carried out at 27 centers including academic and Indian Health Services sites . PATIENTS A total of 2190 women were r and omized into the DPP and provided information for past history of GDM . This analysis addressed the differences between those 350 women providing a past history of GDM and those 1416 women with a previous live birth but no history of GDM . INTERVENTIONS Subjects were r and omized to either st and ard lifestyle and placebo or metformin therapy or to an intensive lifestyle intervention . MAIN OUTCOMES The primary outcome was the time to development of diabetes ascertained by semiannual fasting plasma glucose and annual oral glucose tolerance testing . Assessment s of insulin secretion and insulin sensitivity were also performed . RESULTS Whereas entering the study with similar glucose levels , women with a history of GDM r and omized to placebo had a crude incidence rate of diabetes 71 % higher than that of women without such a history . Among women reporting a history of GDM , both intensive lifestyle and metformin therapy reduced the incidence of diabetes by approximately 50 % compared with the placebo group , whereas this reduction was 49 and 14 % , respectively in parous women without GDM . These data suggest that metformin may be more effective in women with a GDM history as compared with those without . CONCLUSIONS Progression to diabetes is more common in women with a history of GDM compared with those without GDM history despite equivalent degrees of IGT at baseline . Both intensive lifestyle and metformin are highly effective in delaying or preventing diabetes in women with IGT and a history of GDM Abdominal obesity and hyperinsulinemia play a key role in the development of the polycystic ovary syndrome ( PCOS ) . Dietary-induced weight loss and the administration of insulin-lowering drugs , such as metformin , are usually followed by improved hyper and rogenism and related clinical abnormalities . This study was carried out to evaluate the effects of combined hypocaloric diet and metformin on body weight , fat distribution , the glucose-insulin system , and hormones in a group of 20 obese PCOS women [ body mass index ( BMI ) > 28 kg/m2 ] with the abdominal phenotype ( waist to hip ratio > 0.80 ) , and an appropriate control group of 20 obese women who were comparable for age and pattern of body fat distribution but without PCOS . At baseline , we measured sex hormone , sex hormone-binding globulin ( SHBG ) , and leptin blood concentrations and performed an oral glucose tolerance test and computerized tomography ( CT ) at the L4-L5 level , to measure sc adipose tissue area ( SAT ) and visceral adipose tissue area . All women were then given a low-calorie diet ( 1,200 - 1,400 kcal/day ) alone for one month , after which anthropometric parameters and CT scan were newly measured . While continuing dietary treatment , PCOS women and obese controls were subsequently placed , in a r and om order , on metformin ( 850 mg/os , twice daily ) ( 12 and 8 , respectively ) or placebo ( 8 and 12 , respectively ) , according to a double-blind design , for the following 6 months . Blood tests and the CT scan were performed in each woman at the end of the study while they were still on treatment . During the treatment period , 3 women of the control group ( all treated with placebo ) were excluded because of noncompliance ; and 2 PCOS women , both treated with metformin , were also excluded because they became pregnant . Therefore , the women cohort available for final statistical analysis included 18 PCOS ( 10 treated with metformin and 8 with placebo ) and 17 control women ( 8 treated with metformin and 9 with placebo )  . The treatment was well tolerated . In the PCOS group , metformin therapy improved hirsutism and menstrual cycles significantly more than placebo .  Baseline anthropometric and CT parameters were similar in all groups . Hypocaloric dieting for 1 month similarly reduced BMI values and the waist circumference in both PCOS and control groups , without any significant effect on CT scan parameters . In both PCOS and control women , however , metformin treatment reduced body weight and BMI significantly more than placebo . Changes in the waist-to-hip ratio values were similar in PCOS women and controls , regardless of pharmacological treatment . Metformin treatment significantly decreased SAT values in both PCOS and control groups , although only in the latter group were SAT changes significantly greater than those observed during the placebo treatment . On the contrary , visceral adipose tissue area values significantly decreased during metformin treatment in both PCOS and control groups , but only in the former was the effect of metformin treatment significantly higher than that of placebo .  Fasting insulin significantly decreased in both PCOS women and controls , regardless of treatment , whereas glucose-stimulated insulin significantly decreased only in PCOS women and controls treated with metformin . Neither metformin or placebo significantly modified the levels of LH , FSH , dehydroepi and rosterone sulphate , and progesterone in any group , whereas testosterone concentrations decreased only in PCOS women treated with metformin .  SHBG concentrations remained unchanged in all PCOS women ; whereas in the control group , they significantly increased after both metformin and placebo .  Leptin levels decreased only during metformin treatment in both PCOS and control groups . ( ABSTRACT TRUNCATED STUDY QUESTION What is the prevalence of insulin resistance ( IR ) and the contributions of intrinsic and extrinsic IR in women diagnosed with polycystic ovary syndrome ( PCOS ) according to the Rotterdam criteria ? SUMMARY ANSWER We report novel clamp data in Rotterdam diagnosed PCOS women , using World Health Organization criteria for IR showing that women with PCOS have a high prevalence of IR , strengthening the evidence for an aetiological role of IR in both National Institutes of Health ( NIH ) and Rotterdam diagnosed PCOS in lean and overweight women . WHAT IS KNOWN ALREADY PCOS is a complex endocrine condition with a significant increased risk of gestational diabetes and type 2 diabetes . STUDY DESIGN , SIZE , DURATION Using a cross-sectional study design , 20 overweight and 20 lean PCOS ( Rotterdam criteria ) , 14 overweight and 19 lean body mass index ( BMI ) -matched control non-PCOS women underwent clinical measures of IR after a 3-month withdrawal of insulin sensitizers and the oral contraceptive pill . MATERIAL S , SETTING , METHODS In an academic clinic setting ,  glucose infusion rate ( GIR )  on euglycaemic-hyperinsulinaemic clamp was investigated as a marker of insulin sensitivity . MAIN RESULTS AND THE ROLE OF CHANCE PCOS women were more IR than BMI -matched controls ( main effect for BMI and PCOS ; P < 0.001 ) . IR was present in 75 % of lean PCOS , 62 % of overweight controls and 95 % of overweight PCOS . Lean controls ( mean ± SD ; GIR 339 ± 76 mg min⁻¹ m⁻² ) were less IR than lean PCOS ( 270 ± 66 mg min⁻¹ m⁻² ) , overweight controls ( 264 ± 66 mg min⁻¹ m⁻² ) and overweight PCOS ( 175 ± 96 mg min⁻¹ m⁻² ) . The negative relationship between BMI and IR reflected by GIR was more marked in PCOS ( y = 445.1 - 7.7x , R² = 0.42 ( P < 0.0001 ) than controls ( y = 435.5 - 4.6x , R² = 0.04 ( P < 0.01 ) ) . LIMITATIONS , REASONS FOR CAUTION The study did not use glucose tracer techniques to completely characterize the IR , as well as the lack of matching for body composition and age . WIDER IMPLICATION S OF THE FINDINGS IR is exacerbated by increased BMI , supporting intrinsic IR in PCOS . BMI impact on IR is greater in PCOS , than in controls , irrespective of visceral fat , prioritizing lifestyle intervention and the need for effective therapeutic interventions to address intrinsic IR and prevent diabetes in this high-risk population . STUDY FUNDING /COMPETING INTEREST(S ) This investigator-initiated trial was supported by grants from the National Health & Medical Research Council ( NHMRC ) Grant number 606553 ( H.J.T. , N.K.S. and S.K.H. ) as well as Monash University and The Jean Hailes Foundation . H.J.T. is an NHMRC Research Fellow . N.K.S. is supported through the Australian Government 's Collaborative Research Networks ( CRN ) programme . A.E.J. is a Jean Hailes and NHMRC scholarship holder . The authors declare that there is no conflict of interest associated with this manuscript The present study investigates the combined effect of diet , physical exercise and Orlistat for 24 weeks , on serum Anti-Müllerian Hormone ( AMH ) levels in overweight and obese women with polycystic ovary syndrome ( PCOS ) and in overweight and obese controls . Sixty-one ( 61 ) selected women with PCOS and 20 overweight and obese controls followed an energy-restricted diet , physical exercise plus Orlistat administration ( 120 mg , 3 times per day ) for 24 weeks . At baseline , week 12 and week 24 , serum levels of AMH , FSH , LH , PRL , and rogens , sex hormone – binding globulin ( SHBG ) , glucose , and insulin were measured and Free And rogen Index ( FAI ) and Insulin Resistance ( IR ) indices were calculated . In PCOS women , serum AMH levels increased after 12 and 24 weeks of treatment . After 12 weeks LH and SHBG were increased , while Testosterone decreased . After 12 and 24 weeks , FAI was decreased and all indices of IR were significantly improved . We concluded that in overweight and obese women with PCOS Orlistat administration , combined with diet and physical exercise , for 24 weeks , result ed in significant weight loss , improvement of hyper and rogenism and insulin sensitivity , and increased serum AMH levels Objective : To compare the efficacy of metformin with that of lifestyle changes in patients with polycystic ovary syndrome ( PCOS ) . Design : Prospect i ve , r and omized clinical trial of 40 women with PCOS to analyze the effects of metformin and lifestyle intervention treatments on menstrual pattern and hormone and metabolic profile . The duration of treatment was 6 months . Statistical analysis was done using Student ’s t-test . Results : Fifteen women in the metformin group and 12 in the lifestyle changes group completed the study . The menstrual pattern improved by ~67 % in both groups . There was a significant decrease in waist circumference in the lifestyle changes group ( 101.8 ± 3.9 and 95.1 ± 3.6 , at baseline and at 6 months of treatment , respectively ; p < 0.001 ) and in body mass index ( BMI ) in both groups . The predictor of menstrual pattern improvement was BMI . Conclusions : Both metformin and lifestyle changes may increase the number of menstrual cycles in PCOS . This effect was related to a decrease in BMI OBJECTIVE  Metformin produced weight loss and delayed or prevented diabetes in the Diabetes Prevention Program ( DPP ) . We examined its long-term safety and tolerability along with weight loss , and change in waist circumference during the DPP and its long-term follow-up . RESEARCH DESIGN AND METHODS The r and omized double-blind clinical trial of metformin or placebo followed by a 7–8-year open-label extension and analysis of adverse events , tolerability , and the effect of adherence on change in weight and waist circumference . RESULTS No significant safety issues were identified . Gastrointestinal symptoms were more common in metformin than placebo participants and declined over time . During the DPP , average hemoglobin and hematocrit levels were slightly lower in the  metformin  group than in the placebo group . Decreases in hemoglobin and hematocrit in the metformin group occurred during the first year following r and omization , with no further changes observed over time . During the DPP , metformin participants had reduced body weight and waist circumference compared with placebo ( weight by 2.06 ± 5.65 % vs. 0.02 ± 5.52 % , P < 0.001 , and waist circumference by 2.13 ± 7.06 cm vs. 0.79 ± 6.54 cm , P < 0.001 in metformin vs. placebo , respectively ) . The magnitude of weight loss during the 2-year double-blind period was directly related to adherence ( P < 0.001 ) . Throughout the unblinded follow-up , weight loss remained significantly greater in the metformin group than in the placebo group ( 2.0 vs. 0.2 % , P < 0.001 ) , and this was related to the degree of continuing metformin adherence ( P < 0.001 ) . CONCLUSIONS Metformin used for diabetes prevention is safe and well tolerated . Weight loss is related to adherence to metformin and is durable for at least 10 years of treatment CONTEXT The polycystic ovary syndrome ( PCOS ) is the commonest endocrine abnormality in women of reproductive age . OBJECTIVE To determine the rate of hospital admissions for women with PCOS in Western Australian population in comparison to women without PCOS . DESIGN A population -based retrospective cohort study using data linkage in a statewide hospital morbidity data base system . SETTING All hospitals within Western Australia . PARTICIPANTS A total of 2566 women with PCOS hospitalized from 1997 - 2011 and 25 660 r and omly selected age-matched women without a PCOS diagnosis derived from the electoral roll . MAIN OUTCOME MEASURES Hospitalizations by ICD-10-M diagnoses from 15 years were compared . RESULTS Hospitalizations were followed until a median age of 35.8 years ( interquartile range , 31.0 - 39.9 ) . PCOS was associated with more nonobstetric and non-injury-related hospital admissions ( median , 5 vs 2 ; P < .001 ) , a diagnosis of adult-onset diabetes ( 12.5 vs 3.8 % ) , obesity ( 16.0 vs 3.7 % ) , hypertensive disorder ( 3.8 vs 0.7 % ) , ischemic heart disease ( 0.8 vs 0.2 % ) , cerebrovascular disease ( 0.6 vs 0.2 % ) , arterial and venous disease ( 0.5 vs 0.2 % and 10.4 vs 5.6 % , respectively ) , asthma ( 10.6 vs 4.5 % ) , stress/anxiety ( 14.0 vs 5.9 % ) , depression ( 9.8 vs 4.3 % ) , licit/illicit drug-related admissions ( 8.8 vs 4.5 % ) , self-harm ( 7.2 vs 2.9 % ) , l and transport accidents ( 5.2 vs 3.8 % ) , and mortality ( 0.7 vs 0.4 % ) ( all P < .001 ) . Women with PCOS had a higher rate of admissions for menorrhagia ( 14.1 vs 3.6 % ) , treatment of infertility ( 40.9 vs 4.6 % ) , and miscarriage ( 11.1 vs 6.1 % ) and were more likely to require in vitro fertilization ( 17.2 vs 2.0 % ) . CONCLUSION PCOS has profound medical implication s for the health of women , and health care re sources should be directed accordingly Aims /hypothesisLifestyle modification helps in the primary prevention of diabetes in multiethnic American , Finnish and Chinese population s. In a prospect i ve community-based study , we tested whether the progression to diabetes could be influenced by interventions in native Asian Indians with IGT who were younger , leaner and more insulin resistant than the above population s. Methods We r and omised 531 ( 421 men 110 women ) subjects with IGT ( mean age 45.9±5.7 years , BMI 25.8±3.5 kg/m2 ) into four groups . Group 1 was the control , Group 2 was given advice on lifestyle modification ( LSM ) , Group 3 was treated with metformin ( MET ) and Group 4 was given LSM plus MET . The primary outcome measure was type 2 diabetes as diagnosed using World Health Organization criteria . Results The median follow-up period was 30 months , and the 3-year cumulative incidences of diabetes were 55.0 % , 39.3 % , 40.5 % and 39.5 % in Groups 1–4 , respectively . The relative risk reduction was 28.5 % with LSM ( 95 % CI 20.5–37.3 , p=0.018 ) , 26.4 % with MET ( 95 % CI 19.1–35.1 , p=0.029 ) and 28.2 % with LSM + MET ( 95 % CI 20.3–37.0 , p=0.022 ) , as compared with the control group . The number needed to treat to prevent one incident case of diabetes was 6.4 for LSM , 6.9 for MET and 6.5 for LSM + MET . Conclusions /interpretationProgression of IGT to diabetes is high in native Asian Indians .  Both LSM and MET significantly reduced the incidence of diabetes  in Asian Indians with IGT ; there was no added benefit from combining them OBJECTIVE Polycystic ovary syndrome ( PCOS ) affects 6 - 18 % of women . The natural history of weight gain in women with PCOS has not been well described . Here we aim ed to examine longitudinal weight gain in women with and without PCOS and to assess the association between obesity and PCOS prevalence . DESIGN AND METHODS The observational study was set in the general community . Participants were women r and omly selected from the national health insurance scheme ( Medicare ) data base .  Mailed survey data were collected by the Australian Longitudinal Study on Women 's Health . Data from respondents to survey 4 , aged 28 - 33 years ( 2006 , n = 9,145 ) were analyzed . The main outcome measures were PCOS prevalence and body mass index ( BMI ) . RESULTS Self-reported PCOS prevalence was 5.8 % ( 95 % CI : 5.3%-6.4 % ) . Women reporting PCOS had higher weight , mean BMI [ 2.5 kg/m(2 ) ( 95 % CI : 1.9 - 3.1 ) ] , and greater 10-year weight gain [ 2.6 kg ( 95 % CI : 1.2 - 4.0 ) ] . BMI was the strongest correlate of PCOS status with every BMI increment increasing the risk of reporting PCOS by 9.2 % ( 95 % CI : 6%-12 % ) . CONCLUSIONS This community based observational study with longitudinal reporting of weight shows that weight , BMI , and 10-year weight gain were higher in PCOS . We report the novel finding that obesity and greater weight gain are significantly associated with PCOS status . Considering the prevalence , major health and economic burden of PCOS , the increasing weight gain in young women , and established benefits of weight loss , these results have major public health implication CONTEXT The few controlled trials performed so far indicate that the addition of metformin and /or flutamide to a hypocaloric diet in obese women with polycystic ovary syndrome ( PCOS ) effectively influences different phenotypic aspects of the syndrome . All these studies are , however , characterized by a short to medium period of treatment . OBJECTIVE Our objective was to investigate the long-term effects of these therapies . DESIGN AND SETTING We conducted a prospect i ve , r and omized , placebo-controlled trial at a medical center . PATIENTS Of 80 overweight-obese women with PCOS , 76 completed the study . INTERVENTIONS Patients were placed on a hypocaloric diet for the first month and then on a hypocaloric diet plus placebo , metformin ( 850 mg , orally , twice a day ) , flutamide ( 250 mg , orally , twice a day ) , or metformin plus flutamide for the subsequent 12 months ( 20 subjects in each group ) . MAIN OUTCOME MEASURES We assessed clinical features , computerized tomography measurement of fat distribution , and rogens , lipids , and fasting and glucose-stimulated glucose and insulin levels at baseline and after 6 and 12 months of treatment . RESULTS After 6 months , compared with placebo , flutamide further decreased visceral/sc fat mass ( P = 0.044 ) , and rostenedione ( P < 0.001 ) , dehydroepi and rosterone sulfate ( P < 0.001 ) , and hirsutism score ( P < 0.001 ) , whereas metformin further increased frequency of menstruation ( P = 0.039 ) . After 12 months , flutamide maintained the effects observed after 6 months on visceral/sc fat mass ( P = 0.033 ) and and rostenedione ( P < 0.001 ) , whereas it produced an additional decrease in dehydroepi and rosterone sulfate ( P = 0.020 ) and hirsutism score ( P = 0.019 ) ; metformin further improved the menstrual pattern ( P = 0.013 ) . Moreover , after 12 months , flutamide improved more than placebo the menstrual pattern ( P = 0.008 ) , glucose-stimulated glucose levels ( P = 0.041 ) , insulin sensitivity ( P < 0.001 ) , and low-density lipoprotein cholesterol levels ( P = 0.003 ) , whereas metformin  decreased glucose-stimulated insulin levels ( P = 0.014 ) . The combination of the two drugs maintained the specific effect of each of the compounds , without any additive or synergistic effect . CONCLUSIONS These findings add relevance to the usefulness of metformin and flutamide in the treatment of dieting overweight-obese PCOS women and provide a rationale for targeting different therapeutic options according to the required outcomes in the long term OBJECTIVE To obtain data from a pilot r and omized trial on the effect of metformin therapy and lifestyle modification on ovulation and and rogen concentrations in women with polycystic ovary syndrome ( PCOS ) . DESIGN Prospect i ve , r and omized , placebo-controlled pilot trial . SETTING Academic medical center . PATIENT(S ) Thirty-eight overweight or obese women with PCOS . INTERVENTION(S ) All subjects were r and omized to one of four 48-week interventions : metformin 850 mg two times per day , lifestyle modification plus metformin 850 mg two times per day , lifestyle modification plus placebo , or placebo alone . MAIN OUTCOME MEASURE(S ) Recruitment , dropout , and compliance with a long-term lifestyle intervention in PCOS ; preliminary estimates of treatment effect on ovulation , as measured by weekly urinary pregnanediol glucuronide , and on total T and free and rogen index . RESULT ( S ) It was necessary to screen seven women to have one subject r and omized . The dropout rate was 39 % , with the majority of dropouts occurring within the first 24 weeks . Mean body mass index was > 39 mg/kg(2 ) . Modest weight reduction was found in all treatment groups , with the most significant reduction occurring with the combination of metformin and lifestyle intervention .  Significant and rogen reduction occurred in the combination group only . Ovulation rates did not differ significantly between groups . However , when data were analyzed by presence or absence of weight reduction in subjects , independent of treatment group , the estimated odds ratio for weight loss was 9.0 ( 95 % confidence interval 1.2 - 64.7 ) with respect to regular ovulation . If weight loss occurred during metformin therapy , the odds ratio for regular ovulation was 16.2 ( 95 % confidence interval 4.4 - 60.2 ) . CONCLUSION ( S ) Key method ologic issues for a large-scale , r and omized trial of lifestyle intervention in PCOS include minimizing early dropout from the lifestyle intervention and including a range of body mass index that is not skewed toward severe obesity . Weight reduction might play the most significant role in restoration of ovulation in obese women with PCOS BACKGROUND Type 2 diabetes affects approximately 8 percent of adults in the United States . Some risk factors -- elevated plasma glucose concentrations in the fasting state and after an oral glucose load , overweight , and a sedentary lifestyle -- are potentially reversible . We hypothesized that modifying these factors with a lifestyle-intervention program or the administration of metformin would prevent or delay the development of diabetes . METHODS We r and omly assigned 3234 nondiabetic persons with elevated fasting and post-load plasma glucose concentrations to placebo , metformin ( 850 mg twice daily ) , or a lifestyle-modification program  with the goals of at least a 7 percent weight loss and at least 150 minutes of physical activity per week . The mean age of the participants was 51 years , and the mean body-mass index ( the weight in kilograms divided by the square of the height in meters ) was 34.0 ; 68 percent were women , and 45 percent were members of minority groups . RESULTS The average follow-up was 2.8 years . The incidence of diabetes was 11.0 , 7.8 , and 4.8 cases per 100 person-years in the placebo , metformin , and lifestyle groups , respectively . The lifestyle intervention reduced the incidence by 58 percent ( 95 percent confidence interval , 48 to 66 percent ) and metformin by 31 percent ( 95 percent confidence interval , 17 to 43 percent ) , as compared with placebo ; the lifestyle intervention was significantly more effective than metformin . To prevent one case of diabetes during a period of three years , 6.9 persons would have to participate in the lifestyle-intervention program , and 13.9 would have to receive metformin . CONCLUSIONS Lifestyle changes and treatment with metformin both reduced the incidence of diabetes in persons at high risk . The lifestyle intervention was more effective than metformin OBJECTIVE To determine if the combination of lifestyle ( caloric restriction and exercise ) and metformin ( MET ) would be superior to lifestyle and placebo ( PBO ) in improving the polycystic ovary syndrome ( PCOS ) phenotype . DESIGN Double-blind r and omized 6-month trial of MET versus PBO . SETTING Two academic medical centers . PATIENT(S ) One hundred fourteen subjects with PCOS were r and omized to MET  ( N = 55 ) or PBO ( N = 59 ) . INTERVENTION(S ) Subjects collected urine daily for ovulation monitoring , had monthly monitoring of hormones and weight and determination of body composition by dual-energy x-ray absorptiometry , glucose tolerance , and were evaluated for quality of life at baseline and completion . MAIN OUTCOME MEASURE(S ) Ovulation rates and testosterone levels . RESULT ( S ) Dropout rates were high . There was no significant difference in ovulation rates . Testosterone levels were significantly lower compared with baseline in the MET group at 3 mos but not at 6 mos . There were no differences in weight loss between groups , but MET showed a significant decline at 6 months compared with baseline ( -3.4 kg , 95 % confidence interval -5.3 to -1.5 kg ) . We noted divergent effects of MET versus PBO on oral glucose tolerance test indices of insulin sensitivity ( increased ) and secretion ( worsened ) . Total bone mineral density increased significantly in MET . There were no differences in quality of life measures between the groups . The MET group had increased diarrhea and headache , but fewer bladder infections and musculoskeletal complaints . CONCLUSION ( S ) The addition of metformin to lifestyle therapy produced little reproductive or glycemic benefit in women with PCOS , although our study had limited power owing to a high dropout rate . It is not possible at baseline to identify women likely to drop out AIM The aim of the present study was to investigate the efficacy of Metformin compared with a hypocaloric diet on C-reactive protein ( CRP ) level and markers of insulin resistance in obese and overweight women with polycystic ovary syndrome ( PCOS ) . MATERIAL AND METHODS Forty women with body mass index ≥ 27 and PCOS were r and omly allocated to receive either Metformin or hypocaloric diet and were assessed before and after a treatment period of 12 weeks . High-sensitivity CRP ( hs-CRP ) and markers of insulin resistance ( IR ) , homeostasis model assessment -IR , quantitative insulin-sensitivity check index and fasting glucose to insulin ratio were evaluated in each patient . RESULTS A total of 10 subjects did not complete the trial ( three patients in the Metformin group and seven patients in the diet group ) and a total of 30 subjects completed the trial ( 17 subjects in the Metformin group and 13 subjects in the diet group ) . Serum concentration of hs-CRP significantly decreased in both the Metformin ( 5.29 ± 2.50 vs 3.81 ± 1.99 , P = 0.008 ) and diet groups ( 6.08 ± 2.14 vs 4.27 ± 1.60 , P = 0.004 ) . There were no significant differences in mean hs-CRP decrement between the two groups . Decrease in hs-CRP levels was significantly correlated with waist circumference in the diet group ( r = 0.8 , P < 0.001 ) . The effect of a hypocaloric diet with 5 - 10 % weight reduction on markers of insulin resistance ( homeostasis model assessment -IR , fasting glucose to insulin ratio , quantitative insulin-sensitivity check index ) was better than Metformin therapy ( P = 0.001 ) . CONCLUSIONS Although weight reduction has equal efficacy with Metformin in decreasing serum hs-CRP levels , it was significantly more effective in improving insulin resistance in obese and overweight PCOS women OBJECTIVE To compare the effect of clomiphene citrate , metformin , and lifestyle modification on treatment of patients with polycystic ovary syndrome ( PCOS ) . DESIGN Prospect i ve r and omized double-blind study . SETTING University-based infertility clinic and research center . PATIENT(S ) Three hundred forty-three overweight infertile women with PCOS . INTERVENTION(S ) The participating women were assigned to four groups : clomiphene ( n = 90 ) , metformin ( n = 90 ) , clomiphene + metformin ( n = 88 ) , and lifestyle modification ( n = 75 ) . The patients in each group received st and ardized dietary and exercise advice from a dietitian . MAIN OUTCOME MEASURE(S ) The primary outcome variables were change in menstrual cycle , waist circumference measurements , endocrine parameters , and lipid profile . The main secondary outcome variable was clinical pregnancy rate . RESULT ( S ) The clinical pregnancy rate was 12.2 % in clomiphene group , 14.4 % in metformin group , 14.8 % in clomiphene + metformin group , and 20 % in lifestyle modification group . Lifestyle modification group achieved a significant reduction in waist circumference , total and rogen , and lipid profile . CONCLUSION ( S ) Lifestyle modification improves the lipid profile in PCOS patients . Therefore , lifestyle modification may be used as the first line of ovulation induction in PCOS patients
BACKGROUND : Polycystic ovary syndrome ( PCOS ) is a common endocrine disorder with diverse reproductive and metabolic features .
It is underpinned by insulin resistance that is exacerbated by obesity .
Lifestyle modification is the first line treatment in PCOS , but it is associated with low adherence and sustainability .
In small studies , metformin improves outcomes such as hyperinsulinaemia , ovulation and menstrual cyclicity .
We conducted a systematic review and meta- analysis to compare the effect of lifestyle modification + metformin with lifestyle modification ± placebo , and of metformin alone with lifestyle modification ± placebo in PCOS on anthropometric , metabolic , reproductive and psychological outcomes .