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: BACKGROUND In an observational study of 13 women with polycystic ovary syndrome ( PCOS ) not optimally responsive to metformin diet  , we assessed the efficacy and safety of addition of pioglitazone . We also compared these 13 women to 26 women with PCOS , who were responsive to metformin diet , matched by age and by pre- treatment menstrual history and not different by obesity categories . METHODS Prospect ively , as out patients , with diet constant [ 1500 - 2000 calorie ( depending on entry body mass index ) , 26 % protein , 44 % carbohydrate , 30 % fat ] , metformin ( 2.55 g/day ) was given for 12 months to 39 women , 13 not optimally responsive , 26 responsive to metformin diet  , followed by addition of pioglitazone ( 45 mg/day ) for 10 months in the 13 non-responders . Outcome measures included changes in sex hormones , insulin , insulin resistance ( IR ) , insulin secretion , high density lipoprotein cholesterol , weight , and menstrual status . RESULTS In 13 non-responders , on metformin diet , median serum insulin fell ( 21 to 16 microIU/ml , P<0.05 ) and insulin secretion fell from 251 to 200 ( P<0.01 ) ; weight , dehydroepi and rosterone sulphate ( DHEAS ) , testosterone and IR were unchanged ( P > or = 0.07 ) . Compared with 14 % pre- treatment , on metformin diet , expected menses occurred 46 % of the time at 3 months ( P=0.05 ) , 38 % at 6 months ( P=0.07 ) , 27 % at 9 months , and 24 % at 12 months . In 26 responders , on metformin diet , median weight fell ( 93 to 87 kg ) , testosterone fell ( 50 to 32 ng/dl ) , insulin fell ( 26 to 16 microIU/ml ) , IR fell ( 5.32 to 3.45 ) and insulin secretion fell ( 351 to 271 ) ( P < or = 0.017 for all ) . The occurrence of expected menses in the 26 responders was 2.5-fold higher than in the 13 non-responders ( P<0.0001 ) . In 11 non-responders , on pioglitazone + metformin diet over 10 months versus antecedent metformin diet , DHEAS fell ( 211 to 171 microg/dl , P=0.02 ) , insulin fell ( 16 to 10 microIU/ml , P= 0.001 ) , IR fell ( 3.37 to 1.73 , P=0.002 ) , insulin secretion fell ( 217 to 124 , P=0.004 ) , sex hormone-binding globulin rose ( 31 to 43 nmol/l , P=0.006 ) , and HDL cholesterol rose ( 38 to 42 mg/dl , P=0.003 ) . On pioglitazone + metformin diet , the occurrence of expected menses was 2-fold higher than on metformin diet ( P<0.0001 ) . CONCLUSIONS In women with PCOS who failed to respond optimally to metformin , when pioglitazone was added , insulin , glucose , IR , insulin secretion , and DHEAS fell , HDL cholesterol and sex hormone-binding globulin rose , and menstrual regularity improved , without adverse side-effects 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 BACKGROUND Obese women with the polycystic ovary syndrome are relatively unresponsive to the induction of ovulation by clomiphene . We hypothesized that reducing insulin secretion by administering metformin would increase the ovulatory response to clomiphene . METHODS We performed oral glucose-tolerance tests before and after the administration of 500 mg of metformin or placebo three times daily for 35 days in 61 obese women with the polycystic ovary syndrome . Women who did not ovulate spontaneously were then given 50 mg of clomiphene daily for five days while continuing to take metformin or placebo .  Serum progesterone was measured on days 14 , 28 , 35 , 44 , and 53 , and ovulation was presumed to have occurred if the concentration exceeded 8 ng per milliliter ( 26 nmol per liter ) on any of these days . RESULTS Twenty-one women in the metformin group and 25 women in the placebo group were given clomiphene because they did not ovulate spontaneously during the first phase of the study . Among the 21 women given metformin plus clomiphene , the mean ( + /-SE ) area under the serum insulin curve after oral glucose administration decreased from 6745+/-2021 to 3479+/-455 microU per milliliter per minute ( 40.5+/-12.1 to 20.9+/-2.7 nmol per liter per minute , P=0.03 ) , but it did not change significantly in the 25 women given placebo plus clomiphene . Nineteen of the 21 women ( 90 percent ) who received metformin plus clomiphene  ovulated ( mean peak serum progesterone concentration , 23.8+/-3.4 ng per milliliter [ 7.6+/-10.9 nmol per liter ] ) . Two of the 25 women ( 8 percent ) who received placebo plus clomiphene  ovulated ( P<0.001 ) . Overall , 31 of the 35 women ( 89 percent ) treated with metformin  ovulated spontaneously or in response to clomiphene  , as compared with 3 of the 26 women ( 12 percent ) treated with placebo . CONCLUSIONS The ovulatory response to clomiphene can be increased in obese women with the polycystic ovary syndrome by decreasing insulin secretion with metformin background Hyper and rogenism , hyperinsulinaemia and obesity play a key and coordinating roles in the pathogenesis of polycystic ovary syndrome ( PCOS ) , contributing in different ways to the clinical expression of the syndrome . Weight loss is beneficial , but the additional administration of insulin‐lowering drugs , such as metformin , and anti and rogens may produce further benefits , due to their different spectrum of action . The effects of long‐term metformin and flutamide , an anti and rogen drug , added alone or in combination with a low‐calorie diet , on body weight and fat distribution , and rogens , metabolic parameters and clinical status in obese women with PCOS were investigated 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 BACKGROUND Recognition of the importance of insulin resistance in clomiphene-resistant women with polycystic ovary syndrome ( PCOS ) has led to the use of insulin sensitizers . METHODS A r and omized , controlled trial was conducted to compare efficacy of sequential treatment with metformin and clomiphene citrate with conventional gonadotrophins .  Sixty clomiphene-resistant women with PCOS were r and omized to two groups ( n = 30 each ) , using computer-generated tables . Group I received metformin for 6 months , followed by ovulation induction with clomiphene citrate ; group II received hMG for ovulation induction . Hormonal profiles were evaluated at the onset and after completion of treatment . RESULTS There was no significant difference in pregnancy rates between the two groups ( 16.7 versus 23.3 % ) . In group I , there was a significant improvement in menstrual function and ovulation after treatment ( 40 % , P < 0.001 ; and 46.7 % , P < 0.001 ) , with a significant decrease in fasting insulin levels ( P < 0.05 ) . There were no changes in other biochemical parameters . The ovulation rate in group II was 43.3 % , with a high drop-out rate . The cost-effective analysis for medications per pregnancy in group I was US$ 71 + /- 3 versus US$ 277 + /- 171 in group II . CONCLUSIONS Sequential treatment with metformin and clomiphene citrate 
    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: BACKGROUND In an observational study of 13 women with polycystic ovary syndrome ( PCOS ) not optimally responsive to metformin diet  , we assessed the efficacy and safety of addition of pioglitazone . We also compared these 13 women to 26 women with PCOS , who were responsive to metformin diet , matched by age and by pre- treatment menstrual history and not different by obesity categories . METHODS Prospect ively , as out patients , with diet constant [ 1500 - 2000 calorie ( depending on entry body mass index ) , 26 % protein , 44 % carbohydrate , 30 % fat ] , metformin ( 2.55 g/day ) was given for 12 months to 39 women , 13 not optimally responsive , 26 responsive to metformin diet  , followed by addition of pioglitazone ( 45 mg/day ) for 10 months in the 13 non-responders . Outcome measures included changes in sex hormones , insulin , insulin resistance ( IR ) , insulin secretion , high density lipoprotein cholesterol , weight , and menstrual status . RESULTS In 13 non-responders , on metformin diet , median serum insulin fell ( 21 to 16 microIU/ml , P<0.05 ) and insulin secretion fell from 251 to 200 ( P<0.01 ) ; weight , dehydroepi and rosterone sulphate ( DHEAS ) , testosterone and IR were unchanged ( P > or = 0.07 ) . Compared with 14 % pre- treatment , on metformin diet , expected menses occurred 46 % of the time at 3 months ( P=0.05 ) , 38 % at 6 months ( P=0.07 ) , 27 % at 9 months , and 24 % at 12 months . In 26 responders , on metformin diet , median weight fell ( 93 to 87 kg ) , testosterone fell ( 50 to 32 ng/dl ) , insulin fell ( 26 to 16 microIU/ml ) , IR fell ( 5.32 to 3.45 ) and insulin secretion fell ( 351 to 271 ) ( P < or = 0.017 for all ) . The occurrence of expected menses in the 26 responders was 2.5-fold higher than in the 13 non-responders ( P<0.0001 ) . In 11 non-responders , on pioglitazone + metformin diet over 10 months versus antecedent metformin diet , DHEAS fell ( 211 to 171 microg/dl , P=0.02 ) , insulin fell ( 16 to 10 microIU/ml , P= 0.001 ) , IR fell ( 3.37 to 1.73 , P=0.002 ) , insulin secretion fell ( 217 to 124 , P=0.004 ) , sex hormone-binding globulin rose ( 31 to 43 nmol/l , P=0.006 ) , and HDL cholesterol rose ( 38 to 42 mg/dl , P=0.003 ) . On pioglitazone + metformin diet , the occurrence of expected menses was 2-fold higher than on metformin diet ( P<0.0001 ) . CONCLUSIONS In women with PCOS who failed to respond optimally to metformin , when pioglitazone was added , insulin , glucose , IR , insulin secretion , and DHEAS fell , HDL cholesterol and sex hormone-binding globulin rose , and menstrual regularity improved , without adverse side-effects 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 BACKGROUND Obese women with the polycystic ovary syndrome are relatively unresponsive to the induction of ovulation by clomiphene . We hypothesized that reducing insulin secretion by administering metformin would increase the ovulatory response to clomiphene . METHODS We performed oral glucose-tolerance tests before and after the administration of 500 mg of metformin or placebo three times daily for 35 days in 61 obese women with the polycystic ovary syndrome . Women who did not ovulate spontaneously were then given 50 mg of clomiphene daily for five days while continuing to take metformin or placebo .  Serum progesterone was measured on days 14 , 28 , 35 , 44 , and 53 , and ovulation was presumed to have occurred if the concentration exceeded 8 ng per milliliter ( 26 nmol per liter ) on any of these days . RESULTS Twenty-one women in the metformin group and 25 women in the placebo group were given clomiphene because they did not ovulate spontaneously during the first phase of the study . Among the 21 women given metformin plus clomiphene , the mean ( + /-SE ) area under the serum insulin curve after oral glucose administration decreased from 6745+/-2021 to 3479+/-455 microU per milliliter per minute ( 40.5+/-12.1 to 20.9+/-2.7 nmol per liter per minute , P=0.03 ) , but it did not change significantly in the 25 women given placebo plus clomiphene . Nineteen of the 21 women ( 90 percent ) who received metformin plus clomiphene  ovulated ( mean peak serum progesterone concentration , 23.8+/-3.4 ng per milliliter [ 7.6+/-10.9 nmol per liter ] ) . Two of the 25 women ( 8 percent ) who received placebo plus clomiphene  ovulated ( P<0.001 ) . Overall , 31 of the 35 women ( 89 percent ) treated with metformin  ovulated spontaneously or in response to clomiphene  , as compared with 3 of the 26 women ( 12 percent ) treated with placebo . CONCLUSIONS The ovulatory response to clomiphene can be increased in obese women with the polycystic ovary syndrome by decreasing insulin secretion with metformin background Hyper and rogenism , hyperinsulinaemia and obesity play a key and coordinating roles in the pathogenesis of polycystic ovary syndrome ( PCOS ) , contributing in different ways to the clinical expression of the syndrome . Weight loss is beneficial , but the additional administration of insulin‐lowering drugs , such as metformin , and anti and rogens may produce further benefits , due to their different spectrum of action . The effects of long‐term metformin and flutamide , an anti and rogen drug , added alone or in combination with a low‐calorie diet , on body weight and fat distribution , and rogens , metabolic parameters and clinical status in obese women with PCOS were investigated 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 BACKGROUND Recognition of the importance of insulin resistance in clomiphene-resistant women with polycystic ovary syndrome ( PCOS ) has led to the use of insulin sensitizers . METHODS A r and omized , controlled trial was conducted to compare efficacy of sequential treatment with metformin and clomiphene citrate with conventional gonadotrophins .  Sixty clomiphene-resistant women with PCOS were r and omized to two groups ( n = 30 each ) , using computer-generated tables . Group I received metformin for 6 months , followed by ovulation induction with clomiphene citrate ; group II received hMG for ovulation induction . Hormonal profiles were evaluated at the onset and after completion of treatment . RESULTS There was no significant difference in pregnancy rates between the two groups ( 16.7 versus 23.3 % ) . In group I , there was a significant improvement in menstrual function and ovulation after treatment ( 40 % , P < 0.001 ; and 46.7 % , P < 0.001 ) , with a significant decrease in fasting insulin levels ( P < 0.05 ) . There were no changes in other biochemical parameters . The ovulation rate in group II was 43.3 % , with a high drop-out rate . The cost-effective analysis for medications per pregnancy in group I was US$ 71 + /- 3 versus US$ 277 + /- 171 in group II . CONCLUSIONS Sequential treatment with metformin and clomiphene citrate 
    Output:
    