Effects of protein versus simple sugar intake on weight loss in polycystic ovary syndrome (according to the National Institutes of Health criteria). The impact of metformin, oral contraceptives, and lifestyle modification on polycystic ovary syndrome in obese adolescent women in two randomized, placebo-controlled clinical trials. Efficacy of metformin in obese and non-obese women with polycystic ovary syndrome: a randomized, double-blinded, placebo-controlled cross-over trial. Effects of metformin and rosiglitazone, alone and in combination, in nonobese women with polycystic ovary syndrome and normal indices of insulin sensitivity. 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. Obesity, weight loss, and the polycystic ovary syndrome: effect of treatment with diet and orlistat for 24 weeks on insulin resistance and androgen levels. An observational study of reduction of insulin resistance and prevention of development of type 2 diabetes mellitus in women with polycystic ovary syndrome treated with metformin and diet. Decreases in ovarian cytochrome P450c17 alpha activity and serum free testosterone after reduction of insulin secretion in polycystic ovary syndrome. Co-administration of metformin during rFSH treatment in patients with clomiphene citrate-resistant polycystic ovarian syndrome: a prospective randomized trial. Uses and misuses of the STROBE statement: bibliographic study Metformin therapy improves ovulatory rates, cervical scores, and pregnancy rates in clomiphene citrate-resistant women with polycystic ovary syndrome. Role of diet in the treatment of polycystic ovary syndrome. Metformin reduces serum C-reactive protein levels in women with polycystic ovary syndrome. Metformin and weight loss in obese women with polycystic ovary syndrome: comparison of doses. 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. Clomiphene, metformin, or both for infertility in the polycystic ovary syndrome. A randomized trial of the effects of two types of short-term hypocaloric diets on weight loss in women with polycystic ovary syndrome. Structured exercise training programme versus hypocaloric hyperproteic diet in obese polycystic ovary syndrome patients with anovulatory infertility: a 24-week pilot study. Orlistat is as beneficial as metformin in the treatment of polycystic ovarian syndrome. Effect of the insulin sensitizer pioglitazone on insulin resistance, hyperandrogenism, and ovulatory dysfunction in women with polycystic ovary syndrome.
OBJECTIVE To compare the effects of protein vs. simple sugars on weight loss , body composition , and metabolic and endocrine parameters in polycystic ovary syndrome ( PCOS ) . DESIGN A 2-month , free-living , r and omized , single-blinded study . SETTING University PCOS clinic . PATIENT(S ) Thirty-three patients with PCOS . INTERVENTION(S ) To achieve a final energy reduction of 450 kcal/day , first the daily energy intake was reduced by 700 kcal ; then a 240-kcal supplement containing either whey protein or simple sugars was added . MAIN OUTCOME MEASURE(S ) Changes in weight , fat mass , fasting glucose and insulin , plasma lipoproteins , and sex steroids . RESULT ( S ) Twenty-four subjects ( 13 in the simple sugars group and 11 in the protein group ) completed the study . The protein group lost more weight ( -3.3 + /- 0.8 kg vs. -1.1 + /- 0.6 kg ) and more fat mass ( -3.1 + /- 0.9 kg vs. -0.5 + /- 0.6 kg ) and had larger decreases in serum cholesterol ( -33.0 + /- 8.4 mg/dL vs. -2.3 + /- 6.8 mg/dL ) , high-density lipoprotein cholesterol ( -4.5 + /- 1.3 mg/dL vs. -0.4 + /- 1.3 mg/dL ) , and apoprotein B ( -20 + /- 5 mg/dL vs. 3 + /- 5 mg/dL ) . CONCLUSION ( S ) In patients with PCOS , a hypocaloric diet supplemented with protein reduced body weight , fat mass , serum cholesterol , and apoprotein B more than the diet supplemented with simple sugars 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 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 r and omized , controlled , double-blinded 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 ( p=0.009 and 0.047 , respectively ) , while high-density lipoprotein ( HDL ) increased ( p=0.001 ) . On placebo , weight and FPG increased ( p<0.05 ) . Post-hoc subgrouping according to BMI revealed reductions in testosterone ( p=0.013 ) , FPG ( p=0.018 ) , insulin ( p=0.045 ) and HOMA-index ( p=0.022 ) 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 , p=0.041 ) , insulin ( -4.17 ( -8.10 , -0.23 ) mIU/l , p=0.039 ) and HOMA index ( -1.50 ( -2.53 , -0.47 ) mIU/l*mmol/l , p=0.006 ) . 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 OBJECTIVE To determine whether insulin-sensitizing drugs would improve ovulation and T levels in women with polycystic ovary syndrome ( PCOS ) , without clinical or biochemical criteria indicating insulin resistance and whether the combination of two distinct insulin-sensitizing drugs would be of any benefit over either drug alone . DESIGN R and omized controlled double-blind trial . SETTING A referral center in Caracas , Venezuela . PATIENT(S ) One hundred twenty-eight nonobese PCOS women with normal indices of insulin sensitivity-that is , normal glucose tolerance , fasting insulin , peak insulin during an oral glucose tolerance test ( OGTT ) , and fasting glucose-to-insulin ratio . Twenty-eight women were lost to follow-up initially and did not receive any intervention . INTERVENTION(S ) One hundred women received twice daily one of the following for 6 months : metformin ( 850 mg ) , rosiglitazone ( 4 mg ) , combination of both drugs , or at least one placebo . MAIN OUTCOME MEASURE(S ) Frequencies of ovulation and serum free T after 6 months . RESULT ( S ) Frequencies of ovulation were higher after treatment with an insulin-sensitizing drug ( ovulations per subject in 6 months : metformin , 3.3 ; rosiglitazone , 2.4 ; and combination , 3.4 ) than with placebo ( 0.4 ) . Ovulatory frequencies increased significantly more with metformin than rosiglitazone , and the combination was not more potent . After treatment , serum free-T levels were comparable among all active treatment groups ( metformin : 2.34 pg/mL , rosiglitazone : 3.06 pg/mL , and combination : 2.39 pg/mL ) and were significantly lower than in the placebo group ( 7.26 pg/mL ) . Compared with placebo , fasting insulin levels , area under the insulin curve during OGTT , the homeostatic model assessment of insulin sensitivity , and OGTT-derived insulin sensitivity index improved significantly after metformin or combination therapies but not after rosiglitazone . CONCLUSION ( S ) These findings suggest that insulin-sensitizing drugs increase ovulatory frequency and ameliorate hyper and rogenemia , even in nonobese women with PCOS who appear to have normal insulin sensitivity 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 OBJECTIVE To investigate the combined effect of diet and orlistat , for 24 weeks , on anthropometric features , hormonal parameters , and indices of insulin resistance in obese women with polycystic ovary syndrome ( PCOS ) and in obese women without the syndrome . DESIGN Prospect i ve clinical study . SETTING Department of obstetrics and gynecology in a major university in Greece . PATIENT(S ) Eighteen selected women with PCOS were matched for age and body mass index with 14 obese control women . INTERVENTION(S ) Subjects were prescribed an energy-restricted diet , and orlistat ( 120 mg , 3 times per d ) was administered to all subjects for 24 weeks . MAIN OUTCOME MEASURE(S ) At baseline , week 12 , and week 24 , after an overnight fast , blood sample s were collected , and serum levels of FSH , LH , PRL , T , Delta(4)A , DHEAS , 17 alpha-hydroxyprogesterone , sex hormone-binding globulin , glucose , and insulin were measured . RESULT ( S ) Testosterone levels were significantly decreased with treatment in women with PCOS ; this decrease was attributed to the first trimester , whereas T levels did not change during the second 12-week period . In women with PCOS , insulin levels and HOMA-IR values were decreased during the first 12 weeks , whereas no significant change was observed during the second trimester . CONCLUSION ( S ) Orlistat administration , combined with diet , for 24 weeks , result ed in significant weight loss and improvement of insulin resistance in obese women , with or without PCOS . Moreover , T levels were significantly decreased in women with PCOS . There appears to be a trend during the first 12-week period for greater improvement of metabolic and hormonal parameters in women with PCOS Our first specific aim in an observational study of 431 nondiabetic women with polycystic ovary syndrome ( PCOS ) , aged > or=20 years and with > or=11 months follow-up on metformin diet  , was to prospect ively assess relationships between pretreatment glucose and insulin resistance ( IR ) and the development of type 2 diabetes mellitus ( T2DM ) or gestational diabetes ( GD ) . Our second specific aim was to determine whether development of T2DM and GD was independently associated with lesser reduction of IR on metformin diet when compared with women who remained free of T2DM and GD . Women with body mass index < 25 kg/m(2 ) and those with body mass index > or=25 kg/m(2 ) were , respectively , instructed in a 2000- or 1500-cal/d , high-protein ( 26 % of calories ) , low-carbohydrate ( 44 % ) diet , with 30 % of calories as fat and a polyunsaturate-saturate ratio of 2:1 . Three groups of women with PCOS were categorized : ( a ) 17 with no previous GD , who developed T2DM on metformin diet ( mean + /- SD follow-up , 49 + /- 33 months ) , ( b ) 401 with no previous GD and free of T2DM on metformin diet ( follow-up , 38 + /- 25 months ) , and ( c ) 13 with either previous GD or GD on metformin diet ( follow-up , 38 + /- 25 months ) . On metformin diet , women who developed T2DM vs those who remained free of T2DM had higher pretreatment glucose ( odds ratio [ OR ] , 1.09 ; 95 % confidence interval [ CI ] , 1.03 - 1.16 ; P = .003 ) and homeostasis model assessment of insulin resistance ( HOMA-IR ) ( OR , 1.22 ; 95 % CI , 1.04 - 1.42 ; P = .01 ) , and less reduction of HOMA-IR ( OR , 0.82 ; 95 % CI , 0.72 - 0.92 ; P = .0008 ) . On metformin diet , women either with previous GD or who developed GD vs those who remained free of T2DM had less reduction of HOMA-IR ( OR , 0.88 ; 95 % CI , 0.78 - 0.99 ; P = .03 ) . By repeated- measures analysis , on metformin diet , women who did not develop T2DM had reduction in HOMA-IR ( P < .0001 ) , with the slope of this curve different ( P = .002 ) from the unchanged IR exhibited by women who developed T2DM and different ( P = .017 ) from an increased IR slope ( P = .049 ) in women who had GD . In women with PCOS , pretreatment glucose and IR , and lesser reduction in IR on metformin diet were associated with T2DM and GD BACKGROUND Insulin resistance and increased ovarian cytochrome P450c17 alpha activity are both features of the polycystic ovary syndrome . P450c17 alpha , which is involved in and rogen bio synthesis , has both 17 alpha-hydroxylase and 17,20-lyase activities . Increased activity of this enzyme results in exaggerated conversion of progesterone to 17 alpha-hydroxyprogesterone in response to stimulation by gonadotrophin . We hypothesized that hyperinsulinemia stimulates ovarian P450c17 alpha activity . METHODS We measured fasting serum steroid concentrations and the response of serum 17 alpha-hydroxyprogesterone to leuprolide , a gonadotrophin-releasing hormone agonist , and performed oral glucose-tolerance tests before and after oral administration of either metformin ( 500 mg three times daily ) or placebo for four to eight weeks in 24 obese women with the polycystic ovary syndrome . RESULTS In the 11 women given metformin , the mean ( + /- SE ) area under the serum insulin curve after oral glucose administration decreased from 9303 + /- 1603 to 4982 + /- 911 microU per milliliter per minute ( 56 + /- 10 to 30 + /- 6 nmol per liter per minute ) ( P = 0.004 ) . This decrease was associated with a reduction in the basal serum 17 alpha-hydroxyprogesterone concentration from 135 + /- 21 to 66 + /- 7 ng per deciliter ( 4.1 + /- 0.6 to 2.0 + /- 0.2 nmol per liter ) ( P = 0.01 ) and a reduction in the leuprolide-stimulated peak serum 17 alpha-hydroxyprogesterone concentration from 455 + /- 54 to 281 + /- 52 ng per deciliter ( 13.7 + /- 1.6 to 8.5 + /- 1.6 nmol per liter ) ( P = 0.01 ) . The serum 17 alpha-hydroxyprogesterone values increased slightly in the placebo group . In the metformin group , the basal serum luteinizing hormone concentration decreased from 8.5 + /- 2.2 to 2.8 + /- 0.5 mlU per milliliter ( P = 0.01 ) , the serum free testosterone concentration decreased from 0.34 + /- 0.07 to 0.19 + /- 0.05 ng per deciliter ( 12 + /- 3 to 7 + /- 2 pmol per liter ) ( P = 0.009 ) , and the serum sex hormone-binding globulin concentration increased from 0.8 + /- 0.2 to 2.3 + /- 0.6 microgram per deciliter ( 29 + /- 7 to 80 + /- 21 nmol per liter ) ( P < 0.001 ) . None of these values changed significantly in the placebo group . CONCLUSIONS In obese women with the polycystic ovary syndrome , decreasing serum insulin concentrations with metformin reduces ovarian cytochrome P450c17 alpha activity and ameliorates hyper and rogenism BACKGROUND This study aims to evaluate the impact of metformin on ovarian response when co-administered during recombinant (r)FSH using the low-dose step-up protocol in clomiphene citrate-resistant polycystic ovarian syndrome ( PCOS ) patients with normal glucose tolerance . METHODS AND RESULTS Thirty-two patients were r and omized to metformin  ( n = 16 ) and placebo  ( n = 16 ) groups . Hormonal assessment , a 75 g oral glucose tolerance test ( OGTT ) and a frequently sample d i.v . glucose tolerance test ( FSIGTT ) were performed before and after oral administration of metformin ( 850 mg twice daily ) or placebo for 6 weeks . Recombinant FSH treatment was undertaken , thereafter , in women who did not ovulate on metformin ( n = 10 ) or placebo ( n = 15 ) . There was no significant change in all insulin sensitivity indices in both groups . The only change noted was a decline in mean serum free testosterone concentration in the metformin group ( P = 0.049 ) . One patient on placebo and six patients on metformin  ovulated spontaneously ( P < 0.05 ) . All parameters of ovarian response were comparable between the two groups during rFSH treatment . Combining the 6 week placebo or metformin-only period with a single rFSH treatment cycle , the overall ovulation rates were 75 and 94 % in the placebo and metformin groups respectively ( P > 0.05 ) . The respective figures for pregnancy were 6.3 and 31.3 % ( P > 0.05 ) . CONCLUSIONS Metformin may restore ovulation with no improvement on insulin resistance in clomiphene citrate-resistant PCOS patients with normal glucose tolerance , but has no significant effect on ovarian response during rFSH treatment Objectives Appropriate reporting is central to the application of findings from research to clinical practice . The Strengthening the Reporting of Observational Studies in Epidemiology ( STROBE ) recommendations consist of a checklist of 22 items that provide guidance on the reporting of cohort , case – control and cross-sectional studies , in order to facilitate critical appraisal and interpretation of results . STROBE was published in October 2007 in several journals including The Lancet , BMJ , Annals of Internal Medicine and PLoS Medicine . Within the framework of the revision of the STROBE recommendations , the authors examined the context and circumstances in which the STROBE statement was used in the past . Design The authors search ed the Web of Science data base in August 2010 for articles which cited STROBE and examined a r and om sample of 100 articles using a st and ardised , piloted data extraction form . The use of STROBE in observational studies and systematic review s ( including meta-analyses ) was classified as appropriate or inappropriate . The use of STROBE to guide the reporting of observational studies was considered appropriate . Inappropriate uses included the use of STROBE as a tool to assess the method ological quality of studies or as a guideline on how to design and conduct studies . Results The authors identified 640 articles that cited STROBE . In the r and om sample of 100 articles , about half were observational studies ( 32 % ) or systematic review s ( 19 % ) . Comments , editorials and letters accounted for 15 % , method ological articles for 8 % , and recommendations and narrative review s for 26 % of articles . Of the 32 observational studies , 26 ( 81 % ) made appropriate use of STROBE , and three uses ( 10 % ) were considered inappropriate . Among 19 systematic review s , 10 ( 53 % ) used STROBE inappropriately as a tool to assess study quality . Conclusions The STROBE reporting recommendations are frequently used inappropriately in systematic review s and meta-analyses as an instrument to assess the method ological quality of observational studies OBJECTIVE To evaluate the effect of metformin therapy on hyper and rogenism , insulin resistance , cervical scores , ovulation , and pregnancy rates in clomiphene citrate-resistant women with polycystic ovary syndrome ( PCOS ) . DESIGN Prospect i ve , r and omized , double-blind , placebo-controlled study . SETTING Infertility clinic of a tertiary referral center . PATIENT(S ) Fifty-six women with clomiphene citrate-resistant PCOS . INTERVENTION(S ) Two cycles of oral metformin therapy ( 850 mg , twice daily ) in group I and placebo therapy ( twice daily ) in group II . Clomiphene citrate ( 100 mg/day ) on cycle days 3 - 7 of the second cycle in both groups . MAIN OUTCOME MEASURE(S ) Insulin , T , DHEAS , FSH , LH , body mass index ( BMI ) , waist-to-hip ratio , endometrial thickness , cervical score , ovulation , and pregnancy rates in clomiphene-induced cycles after metformin therapy . RESULT ( S ) Metformin therapy result ed in a significant decrease in total T , LH level , LH/FSH ratio , insulin resistance , and mean BMI . No difference in waist-to-hip ratio , DHEAS level , and fasting insulin level was observed . Clomiphene citrate induction result ed in higher ovulation rates and thicker endometrium in the metformin group than in the placebo group . There was higher cumulative pregnancy rate in the metformin group ; however , there was no significant difference in the pregnancy rate between the two groups . CONCLUSION ( S ) Metformin therapy not only decreases hyper and rogenism and insulin resistance but also improves ovulation rates , cervical scores , and pregnancy rates in clomiphene citrate-resistant women with PCOS OBJECTIVE To determine whether eucaloric diets either enriched with monounsaturated fatty acids ( MUFA ; 17 % energy ) or low in carbohydrates ( Low CHO ; 43 % energy ) would increase insulin sensitivity ( Si ) and decrease circulating insulin concentrations , relative to a st and ard diet ( STD ; 56 % CHO , 31 % fat , 16 % protein ) , among women with polycystic ovary syndrome ( PCOS ) . DESIGN Crossover . SETTING Academic research environment . PATIENT(S ) Healthy women with PCOS not on hormonal or insulin-sensitizing therapy . INTERVENTION(S ) Subjects consumed three , 16-day , eucaloric diets , each separated by a 3-week washout period . A frequently sample d , intravenous , glucose tolerance test was administered at baseline and following each diet . MAIN OUTCOME MEASURE(S ) Fasting glucose , insulin , the acute insulin response to glucose ( AIRg ) , Si , sex hormone-binding globulin ( SHBG ) , dehydroepi and rosterone sulfate ( DHEAS ) , total testosterone ( T ) , free T , A4 , total cholesterol , high-density lipoprotein cholesterol ( HDL-C ) , tryglycerides ( TG ) , and free fatty acids ( FFA ) . RESULT ( S ) Fasting insulin was lower following the Low CHO diet relative to the STD diet ; AIRg was lower following the Low CHO diet relative to the MUFA diet . Fasting glucose , Si , and the circulating concentrations of reproductive hormones were not significantly affected by the intervention . CONCLUSION ( S ) A moderate reduction in dietary carbohydrate reduced the fasting and postchallenge insulin concentrations among women with PCOS , which , over time , may improve reproductive/endocrine outcomes Low- grade chronic inflammation , reflected in elevated levels of serum C-reactive protein ( CRP ) , has recently been linked to obesity , insulin resistance syndromes such as polycystic ovary syndrome ( PCOS ) , and an increased risk of cardiovascular disease . Because the insulin sensitizer metformin has been shown to improve metabolic disturbances in PCOS , it was of particular interest to examine serum CRP levels during metformin therapy .  Twenty nonobese women [ body mass index ( BMI ) < /= 25 kg/m(2 ) ] and 32 obese women ( BMI > /== " BORDER="0 " > 27 kg/m(2 ) ) with PCOS were r and omized to receive either metformin ( 500 mg twice daily for 3 months , then 1000 mg twice daily for 3 months ) or ethinyl estradiol ( 35 micro g)-cyproterone acetate ( 2 mg ) oral contraceptive pills . The serum concentrations of CRP were significantly higher in obese than in nonobese subjects at baseline [ 4.08 + /- 0.53 ( SE ) vs. 1.31 + /- 0.28 mg/liter ; P < 0.001 ] and correlated to BMI and to a lesser extent waist-hip ratio , suggesting that the elevated CRP levels may be related to obesity and not only to PCOS itself . During metformin treatment , serum CRP levels decreased significantly from 3.08 + /- 0.7 mg/liter to 1.52 + /- 0.26 mg/liter at 6 months in the whole study population ( P = 0.006 ) and especially in obese subjects . In contrast , the treatment with ethinyl estradiol-cyproterone acetate increased serum CRP levels from 2.91 + /- 0.68 mg/liter to 4.58 + /- 0.84 mg/liter ( P < 0.001 ) . Whether this effect is related to estrogen action in the liver or whether it reflects increased inflammation process and possible risks for cardiovascular disease remains unclear . The decrease of serum CRP levels during metformin therapy is in accordance with the known beneficial metabolic effects of this drug and suggests that CRP or other inflammation parameters could be used as markers of treatment efficiency in women with PCOS CONTEXT Metformin treatment of women with polycystic ovary syndrome ( PCOS ) is widespread , as determined by studies with diverse patient population s. No comparative examination of weight changes or metabolite responses to different doses has been reported . OBJECTIVE The aim of this study was to determine whether different doses of metformin ( 1500 or 2550 mg/d ) would have different effects on body weight , circulating hormones , markers of inflammation , and lipid profiles . DESIGN The study included prospect i ve cohorts r and omized to two doses of metformin . SETTING The study was performed at a university teaching hospital with patients from gynecology/endocrinology clinics . PATIENTS The patients studied were obese ( body mass index , 30 to < 37 kg/m2 ; n = 42 ) and morbidly obese ( body mass index , > or = 37 kg/m2 ; n = 41 ) women with PCOS . INTERVENTION Patients were r and omized to two doses of metformin , and parameters were assessed after 4 and 8 months . MAIN OUTCOME MEASURES The main outcome measures were changes in body mass , circulating hormones , markers of inflammation , and lipid profiles . RESULTS Intention to treat analyses showed significant weight loss in both dose groups . Only the obese subgroup showed a dose relationship ( 1.5 and 3.6 kg in 1500- and 2550-mg groups , respectively ; P = 0.04 ) . The morbidly obese group showed similar reductions ( 3.9 and 3.8 kg ) in both groups . Suppression of and rostenedione was significant with both metformin doses , but there was no clear dose relationship . Generally , beneficial changes in lipid profiles were not related to dose . CONCLUSION Weight loss is a feature of protracted metformin therapy in obese women with PCOS , with greater weight reduction potentially achievable with higher doses . Additional studies are required to determine whether other aspects of the disorder may benefit from the higher dose of metformin 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 The polycystic ovary syndrome is a common cause of infertility . Clomiphene and insulin sensitizers are used alone and in combination to induce ovulation , but it is unknown whether one approach is superior . METHODS We r and omly assigned 626 infertile women with the polycystic ovary syndrome to receive clomiphene citrate plus placebo , extended-release metformin plus placebo , or a combination of metformin and clomiphene for up to 6 months . Medication was discontinued when pregnancy was confirmed , and subjects were followed until delivery . RESULTS The live-birth rate was 22.5 % ( 47 of 209 subjects ) in the clomiphene group , 7.2 % ( 15 of 208 ) in the metformin group , and 26.8 % ( 56 of 209 ) in the combination-therapy group ( P<0.001 for metformin vs. both clomiphene and combination therapy ; P=0.31 for clomiphene vs. combination therapy ) . Among pregnancies , the rate of multiple pregnancy was 6.0 % in the clomiphene group , 0 % in the metformin group , and 3.1 % in the combination-therapy group . The rates of first-trimester pregnancy loss did not differ significantly among the groups . However , the conception rate among subjects who ovulated was significantly lower in the metformin group ( 21.7 % ) than in either the clomiphene group ( 39.5 % , P=0.002 ) or the combination-therapy group ( 46.0 % , P<0.001 ) . With the exception of pregnancy complications , adverse-event rates were similar in all groups , though gastrointestinal side effects were more frequent , and vasomotor and ovulatory symptoms less frequent , in the metformin group than in the clomiphene group . CONCLUSIONS Clomiphene is superior to metformin in achieving live birth in infertile women with the polycystic ovary syndrome , although multiple birth is a complication . ( Clinical Trials.gov number , NCT00068861 [ Clinical Trials.gov ] . ) OBJECTIVE We performed this study as a pilot experiment to investigate the short term effects of two diets of varying composition on weight loss as the primary outcome in obese women with polycystic ovary syndrome ( PCOS ) seeking fertility . DESIGN R and omized clinical trial . SETTING Academic medical center . PATIENT(S ) Thirty-five obese women with PCOS . INTERVENTION(S ) We examined the effects of a 1-month dietary intervention on the PCOS phenotype . Participants were r and omized to one of two energy-restricted diets ; high protein ( HP : 30 % protein , 40 % carbohydrate , and 30 % fat ) or high carbohydrate ( HC : 15 % protein , 55 % carbohydrate , and 30 % fat ) . The fat content was held constant in both diets . MAIN OUTCOME MEASURE(S ) Primary - change in body weight ; Secondary - biometric , hormonal , lipid and lipoprotein , and markers of glucose homeostasis and energy metabolism . RESULT ( S ) Twenty-six women completed the study . Both the HP ( -3.7 + /- 1.9 kg ) and HC ( -4.4 + /- 1.5 kg ) diets result ed in significant weight loss , but there was no significant difference in mean weight loss between the two groups . There were also no differences between diets on a variety of measures including circulating and rogens , measures of glucose metabolism , and leptin . However , the effects of a hypocaloric diet per se on improving metabolic and reproductive abnormalities in a group of PCOS women were marked by a decline in circulating and rogens ( P=.03 ) , fasting and area under the curve ( AUC ) insulins ( P<.05 ) on a 3-hour oral glucose tolerance test ( OGTT ) , and fasting and AUC leptin levels ( P<.0001 ) . There was a high prevalence of menstrual bleeding during the trial ( 14 out of 26 patients ) . CONCLUSION ( S ) Those who completed the short-term hypocaloric diet had a significant weight loss and a significant improvement in their reproductive and metabolic abnormalities . There was no increased benefit to a high-protein diet . Future diet studies evaluating the ideal composition of a hypocaloric diet in women with PCOS will require a large study population , and will most likely require a multicenter trial BACKGROUND Lifestyle modifications are successfully employed to treat obese and overweight women with polycystic ovary syndrome ( PCOS ) . The aims of the current pilot study were ( i ) to compare the efficacy on reproductive functions of a structured exercise training ( SET ) programme with a diet programme in obese PCOS patients and ( ii ) to study their clinical , hormonal and metabolic effects to eluci date potentially different mechanisms of action . METHODS Forty obese PCOS patients with anovulatory infertility underwent a  SET programme ( SET group , n = 20 ) and a hypocaloric hyperproteic diet ( diet group , n = 20 ) . Clinical , hormonal and metabolic data were assessed at baseline , and at 12- and 24-week follow-ups . Primary endpoint was cumulative pregnancy rate . RESULTS The two groups had similar demographic , anthropometric and biochemical parameters . After intervention , a significant improvement in menstrual cycles and fertility was noted in both groups , with no differences between groups . The frequency of menses and the ovulation rate were significantly ( P < 0.05 ) higher in the SET group than in diet group but the increased cumulative pregnancy rate was not significant . Body weight , body mass index , waist circumference , insulin resistance indexes and serum levels of sex hormone-binding globulin , and rostenedione and dehydroepi and rosterone sulphate changed significantly ( P < 0.05 ) from baseline and were significantly different ( P < 0.05 ) between the two groups . CONCLUSIONS Both SET and diet interventions  improve fertility in obese PCOS patients with anovulatory infertility . We hypothesize that in both interventions an improvement in insulin sensitivity is the pivotal factor involved in the restoration of ovarian function but potentially acting through different mechanisms The objective of this study was to evaluate and compare the effect of treatment with orlistat vs. metformin on the hormonal and biochemical features of patients with polycystic ovarian syndrome ( PCOS ) . Twenty-one Caucasian women with PCOS [ mean ( + /-SEM ) age 27 + /- 0.9 yr and body mass index 36.7 + /- 3.3 kg/m(2 ) ] participated in this prospect i ve , r and omized , open-labeled study . All subjects had an 8-wk run-in period of dietary modification and then r and omized to receive either metformin ( 500 mg three times daily ) or orlistat ( 120 mg three times daily ) for 3 months . Weight , blood pressure , and fasting blood sample s were taken at screening , r and omization , and on completion . Insulin resistance ( IR ) was calculated using the homeostasis model of assessment (HOMA)-IR method [ HOMA-IR = ( insulin x glucose)/22.5 ] . The results are expressed as mean + /- SEM . When compared with baseline , treatment with both orlistat [ 93.5 + /- 11.5 ng/dl ( 3.24 + /- 0.4 nmol/liter ) vs. 114.5 + /- 11.5 ng/dl ( 3.97 + /- 0.4 nmol/liter ) , P = 0.039 ] and metformin [ 97.2 + /- 11.5 ng/dl ( 3.37 + /- 0.4 nmol/liter ) vs. 120.0 + /- 8.7 ng/dl ( 4.16 + /- 0.3 nmol/liter ) , P = 0.048 ] produced a significant reduction in total testosterone . Treatment with orlistat produced a 4.69 % reduction in weight ( 99.0 + /- 6.0 vs. 94.6 + /- 6.1 kg , P = 0.002 ) , and this reduction was more significant than the reduction produced by metformin ( 4.69 vs. 1.02 % , P = 0.006 ) . There was no significant reduction seen after either treatment group for fasting insulin , HOMA-IR , SHBG , or any of the lipid parameters studied . In this study , orlistat produced a significant reduction in weight and total testosterone . The reduction in total testosterone was similar to that seen after treatment with metformin . Therefore , orlistat may prove to be a useful adjunct in the treatment of PCOS Polycystic ovary syndrome ( PCOS ) is characterized by hyper and rogenism , chronic anovulation , and insulin resistance ; long-term consequences include diabetes mellitus type 2 . The aim of this r and omized , double-blind , controlled trial was to investigate whether the thiazolidinedione derivative pioglitazone diminishes insulin resistance and hyper and rogenism and enhances ovulation rates in women with PCOS . Forty premenopausal women with PCOS were r and omly allocated to treatment with either pioglitazone ( 30 mg/d ) or placebo for periods of 3 months . Administration of pioglitazone result ed in a remarkable decline in both fasting serum insulin levels ( P < 0.02 ) and the area under the insulin response curve after an oral glucose load ( P < 0.02 ) . This represented an increase in insulin sensitivity and a decrease in insulin secretion ( P < 0.05 ) . Furthermore , pioglitazone increased serum SHBG ( P < 0.05 ) , result ing in a significant decrease in the free and rogen index ( P < 0.05 compared with placebo ) . Treatment with pioglitazone was also associated with higher ovulation rates ( P < 0.02 ) . Thus , pioglitazone significantly improved insulin sensitivity , hyper and rogenism , and ovulation rates in women with PCOS , thereby providing both metabolic and reproductive benefits
Objective : Polycystic ovarian syndrome ( PCOS ) is a common condition amongst women of reproductive age that can result in increased mortality and morbidity in women due to increased risk of diabetes mellitus and cardiovascular diseases .
The aim of this systematic review was to assess the effectiveness of common treatments of PCOS on the predictors of diabetes in non-diabetic PCOS women .