***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 An RCT among newly diagnosed , therapy naive women with polycystic ovary syndrome ( PCOS ) showed no significant differences in ovulation rate , ongoing pregnancy rate or spontaneous abortion rate in favour of clomifene citrate plus metformin compared with clomifene citrate . We wanted to assess whether there are specific subgroups of women with PCOS in whom clomifene citrate plus metformin leads to higher pregnancy rates . METHODS Subgroup analysis based on clinical and biochemical parameters of 111 women r and omized to clomifene citrate plus metformin compared with 114 women r and omized to clomifene citrate plus placebo .  The data for age , BMI , waist – hip ratio ( WHR ) and plasma testosterone were available in all women , 2 h glucose in 80 % of women and homeostatic model assessment for assessing insulin sensitivity ( HOMA ) in 50 % of women . RESULTS Of the women who were allocated to the metformin group , 44 women ( 40 % ) reached an ongoing pregnancy . In the placebo group , 52 women ( 46 % ) reached an ongoing pregnancy . There was a significantly different chance of an ongoing pregnancy  for metformin versus placebo between subgroups based on age and WHR ( P = 0.014 ) . There was a positive effect of metformin versus placebo  on pregnancy rate in older women ( ≥28 years ) with a high WHR , a negative effect of metformin versus placebo in young women ( < 28 years ) regardless of their WHR and no effect in older , not viscerally obese women . No significant differences in effect of treatment were found for groups based on BMI , 2 h glucose , HOMA or plasma testosterone . CONCLUSIONS Metformin may be an effective addition to clomifene citrate in infertile women with PCOS , especially in older and viscerally obese patients OBJECTIVE To evaluate the effect of ultra-short ( 12 days ) metformin pretreatment in clomiphene-citrate ( CC ) resistant polycystic ovary syndrome ( PCOS ) . METHOD Eighty women with CC-resistant PCOS were r and omly allocated to metformin pretreatment or usual treatment . Forty women received 1500 mg metformin daily for 12 days , followed by clomiphene 150 mg daily for 5 days along with metformin . Forty women ( control group ) received the same dose of clomiphene but no metformin pretreatment . RESULTS In the metformin group , 17 ( 42.5 % ) women ovulated , and 6 ( 15 % ) conceived . In the control group , 5 ( 12.5 % ) women ovulated but none conceived . Compared with the control group , the metformin group had significantly higher ovulation ( P = 0.03 ) and pregnancy rates ( P = 0.026 ) . CONCLUSION Twelve days of metformin pretreatment improves ovulation and pregnancy rates in women with CC-resistant PCOS 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 Estimates of the prevalence of the polycystic ovary syndrome ( PCOS )  in the general population have ranged from 2 - 20 % . The vast majority of these reports have studied White population s in Europe , used limited definitions of the disorder , and /or used bias population s , such as those seeking medical care . To estimate the prevalence of this disorder in the United States and address these limitations , we prospect ively determined the prevalence of PCOS in a reproductive-aged population of 369 consecutive women ( 174 White and 195 Black ; aged 18 - 45 yr ) , examined at the time of their preemployment physical .  Body measures  were obtained , and body hair was quantified by a modified Ferriman-Gallwey ( F-G ) method . All exams were initially performed by 2 trained nurses , and any subject with an F-G score above 3 was reexamined by a physician , the same for all patients . Of the 369 women , 277 ( 75.1 % ) also agreed to complete a question naire and have additional blood drawn . Subjects were studied regardless of current estrogen/progestin hormonal use ( 28.5 % ) . PCOS was defined as 1 ) oligoovulation , 2 ) clinical hyper and rogenism ( i.e. hirsutism ) and /or hyper and rogenemia , and 3 ) exclusion of other related disorders , such as hyperprolactinemia , thyroid abnormalities , and non-classic adrenal hyperplasia . Hirsutism was defined by a F-G score of 6 or more , and hyper and rogenemia was defined as a total or free testosterone , and rostenedione , and /or dehydroepi and rosterone sulfate level above the 95th percentile of control values [ i.e. all eumenorrheic women in the study , who had no hirsutism ( F-G < or = 5 ) or acne and were receiving no hormonal therapy ; n = 98 ] . Considering all 369 women studied , White and Black women had similar mean ages ( 29.4 + /- 7.1 and 31.1 + /- 7.8 yr , respectively ) , although White women had a lesser body mass than Black women ( 24.9 + /- 6.1 vs. 29.2 + /- 8.1 kg/m2 , respectively ; P < 0.001 ) . Of these 7.6 % , 4.6 % , and 1.9 % demonstrated a F-G score of 6 or more , 8 or 10 , respectively , and there was no significant racial difference , with hirsutism prevalences of 8.0 % , 2.8 % , and 1.6 % in Whites , and 7.1 % , 6.1 % , and 2.1 % in Blacks , respectively . Of the 277 women consenting to a history and hormonal evaluation , 4.0 % had PCOS as defined , 4.7 % ( 6 of 129 ) of Whites and 3.4 % ( 5 of 148 ) of Blacks . In conclusion , in our consecutive population of unselected women the prevalence of hirsutism varied from 2 - 8 % depending on the chosen cut-off F-G score , with no significant difference between White and Black women . Using an F-G score of 6 or more as indicative of hirsutism , 3.4 % of Blacks and 4.7 % of Whites had PCOS as defined . These data suggest that PCOS may be one of most common reproductive endocrinological disorders of women 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 Objective To assess the effect of insulin-lowering treatment on menstrual cyclicity in polycystic ovary syndrome ( PCOS ) . Methods Forty oligoamenorrheic women with PCOS were recruited in a prospect i ve clinical study to receive metformin for a minimum period of 6 months . Twenty-two women completed the study .  Serum LH , FSH , free testosterone , and glucose and insulin response to oral glucose load were measured both before and after 8 weeks of metformin treatment .  Menstrual cyclicity and serum progesterone levels at the midluteal phase were assessed at the 30th week of metformin treatment . Results Twenty-one of 22 women had restoration of menstrual cyclicity ( 95.7 % ) . Four of these women ( 19 % ) became pregnant within the 6th and 7th months of treatment . All four of the pregnant women delivered , and the infants were healthy . Thirteen of 15 women who had regular menses demonstrated a serum progesterone level within the ovulatory range ( 3.1–28 ng/mL ) . Fasting ( P < .001 ) and the integrated insulin response to the glucose load decreased ( P 
    Output:
    
Benefits , Harms , and Costs : Benefits include weight reduction and improvements in ovulation , pregnancy , and live birth rates .
Potential harms include medication side effects and multiple pregnancies .