human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 
    Output:
    
agent
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 
    Output:
    