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: Women with polycystic ovary syndrome ( PCOS ) are insulin resistant secondary to a postbinding defect in insulin signaling . Sequential euglycemic glucose clamp studies at 40 and 400 mU. m(-2 ) . min(-1 ) insulin doses with serial skeletal muscle biopsies were performed in PCOS and age- , weight- , and ethnicity-matched control women .  Steady-state insulin levels did not differ , but insulin-mediated glucose disposal was significantly decreased in PCOS women ( P < 0.05 ) . Insulin receptor substrate (IRS)-1-associated phosphatidylinositol 3-kinase ( PI 3 K ) activity was significantly decreased in PCOS ( n = 12 ) compared with control skeletal muscle ( n = 8 ; P < 0.05 ) . There was no significant difference in the abundance of IR , IRS-1 , or the p85 regulatory subunit of PI 3 K in PCOS ( n = 14 ) compared with control ( n = 12 ) muscle . The abundance of IRS-2 was significantly increased ( P < 0.05 ) in PCOS skeletal muscle , suggesting a compensatory change . We conclude that there is a physiologically relevant defect in insulin receptor signaling in PCOS that is independent of obesity and type 2 diabetes mellitus We prospect ively estimated the prevalence of the polycystic ovary syndrome ( PCOS ) , as defined by the NIH/NICHHD 1990 endocrine criteria , in a population of 154 Caucasian women of reproductive age reporting spontaneously for blood donation .  Anthropometric data ; the presence of hirsutism , acne , and and rogenic alopecia ; and the menstrual history were recorded by a single investigator . In 145 women , blood sample s were also obtained for measurement of serum and rogen levels .  PCOS was defined by the presence of 1 ) oligomenorrhea , 2 ) clinical and /or biochemical hyper and rogenism , and 3 ) exclusion of hyperprolactinemia , thyroid disorders , and nonclassic 21-hydroxylase deficiency . Hirsutism was defined by a modified Ferriman-Gallwey score of 8 or more , acne was considered as a sign of hyper and rogenism when persistent after the second decade of life , and hyper and rogenemia was defined by an increase in circulating testosterone or dehydroepi and rosterone sulfate or an increase in the free and rogen index above the 95th percentile of the control values derived from the nonhirsute , nonacneic women having regular menses who were not receiving hormonal therapy . PCOS was present in 10(6.5 % ) , hirsutism was present in 11 ( 7.1 % ) , and acne was present in 19 ( 12.3 % ) of the 154 women . Our results demonstrate a 6.5 % prevalence of PCOS , as defined , in a minimally biased population of Caucasian women from Spain . The polycystic ovary syndrome , hirsutism , and acne are common endocrine disorders in women We performed this study to access the changes in glucose tolerance over time in a group of women with polycystic ovary syndrome ( PCOS ) ( n = 71 ) and control women ( n = 23 ) with regular menstrual cycles and baseline normal glucose tolerance . Mean follow-up was between 2 and 3 yr for both groups ( PCOS 2.5 + /- 1.7 yr ; controls 2.9 + /- 2.1 yr ) . Based on World Health Organization glucose tolerance categories , there was no significant difference in the prevalence of glucose intolerance at follow-up in the PCOS group . In the PCOS group , 25 ( 37 % ) had impaired glucose tolerance ( IGT ) and seven ( 10 % ) had type 2 diabetes mellitus at baseline , compared with 30 ( 45 % ) and 10 ( 15 % ) , respectively , at follow-up . There were also no differences within groups ( PCOS or control ) or between groups ( PCOS vs. control ) in the oral glucose tolerance test-derived measure of insulin sensitivity , but in the women with PCOS who converted to either IGT or type 2 diabetes mellitus , there was a significant decrease ( P < 0.0001 ) . At the follow-up visit , the mean glycohemoglobin level was 6.1 + /- 0.9 % in women with PCOS vs. 5.3 + /- 0.7 % in the control women ( P < 0.001 ) . Women with PCOS and baseline IGT had a low conversion risk of 6 % to type 2 diabetes over approximately 3 yr , or 2 % per year . The effect of PCOS , given normal glucose tolerance ( NGT ) at baseline , is more pronounced with 16 % conversion to IGT per year . Our study supports that women with PCOS ( especially with NGT ) should be periodically rescreened for diabetes due to worsening glucose intolerance over time , but this interval may be over several years and not annually BACKGROUND Cross-sectional studies have shown a high frequency of impaired glucose tolerance ( IGT ) and non-insulin dependent diabetes mellitus ( NIDDM ) in women with polycystic ovarian syndrome ( PCOS ) . However , little is known about the change in glucose tolerance that occurs over a period of several years in women with PCOS . METHODS Sixty-seven women with PCOS received a 75 g glucose tolerance test and measurement of lipids at baseline and at follow-up after an average time of 6.2 years . All women followed prospect ively had normal glucose tolerance ( n = 54 ) or IGT ( n = 13 ) at the start of the study . RESULTS Change in glycaemic control from baseline was frequent , with 5/54 ( 9 % ) of normoglycaemic women at baseline developing IGT and a further 4/54 ( 8 % ) moving directly from normoglycaemic to NIDDM . For women with IGT at baseline , 7/13 ( 54 % ) had NIDDM at follow-up . Body mass index ( BMI ) at baseline was an independent significant predictor of adverse change in glycaemic control . CONCLUSIONS Women with PCOS , particularly those with a high BMI , should be review ed regularly with respect to IGT or NIDDM , as the frequency of impaired glycaemic control is high , and that the rate of conversion from normal glucose tolerance to IGT or NIDDM , or from IGT to NIDDM is substantial The role of testosterone on the development of hypertension is controversial , especially in women with polycystic ovary syndrome ( PCOS ) who have higher prevalence of obesity and insulin resistance than women without PCOS . Little is known about the association between serum testosterone level and blood pressure in young women with PCOS . In the 151 young Taiwanese women with PCOS enrolled in this cross-sectional study , we measured the body mass index , waist circumference , blood pressure , fasting glucose , fasting insulin , lipid profile , and hormone profiles .  The  free and rogen index , total testosterone , and sex hormone-binding globulin  , but not the level of dehydroepi and rosterone sulfate  , significantly correlated with both systolic blood pressure ( SBP ) and diastolic blood pressure ( DBP ) . In multiple linear regression models adjusted for age , body mass index , and other anthropometric , metabolic , and hormonal variables , the level of serum free and rogen index  or total testosterone , but not the sex hormone-binding globulin , were independently related to SBP and DBP . The age- and body mass index – adjusted least-square mean of serum-free and rogen index levels were significantly different between the highest quartile and other quartiles of the SBP and DBP levels . The high bioavailable testosterone levels ( free and rogen index : ≥19 % ) in women with PCOS increased the risk of elevated blood pressure ( SBP ≥130 mm Hg and /or DBP ≥85 mm Hg ) with an odds ratio of 3.817 ( P=0.029 ; 95 % CI : 1.14 to 12.74 ) after adjustment for age , anthropometric measures , and metabolic profiles . Our results suggest that the characteristic hyper and rogenemia in young women with PCOS was associated with an elevated SBP and DBP independent of age , insulin resistance , obesity , or dyslipidemia Cross-sectional studies suggest that women who have irregular menstrual cycles and hyper and rogenism may be at increased risk for cardiovascular disease ( CVD ) . However , prospect i ve data are lacking on the relationship between menstrual cycle irregularity and subsequent CVD risk . The objective of this study was to assess prospect ively the risk for coronary heart disease ( CHD )  and stroke associated with a history of irregular menstrual cycles . The study design was a prospect i ve cohort study of 82,439 female nurses who provided information in 1982 on prior menstrual regularity ( at ages 20 - 35 yr ) and were followed through 1996 for cardiovascular events . Incident reports of nonfatal myocardial infa rct ion , fatal CHD , and nonfatal and fatal stroke were made . Medical records were review ed for confirmation . During 14 yr ( 1,155,915 person-yr ) of follow-up , there were 1417 incident cases of CHD and 838 incident cases of stroke , including 471 cases of ischemic stroke . Compared with women reporting a history of very regular menstrual cycles , women reporting usually irregular or very irregular cycles had an increased risk for nonfatal or fatal CHD [ age-adjusted relative risks ( RR ) , 1.25 and 1.67 , respectively ; 95 % confidence intervals ( CI ) , 1.07 - 1.47 and 1.35 - 2.06 , respectively ] . Increased risks for CHD associated with prior cycle irregularity remained significant after adjustment for body mass index and several potential confounders . There was a nonsignificant increase in overall stroke risk ( RR , 1.30 ; 95 % CI = 0.97 - 1.74 ) and in ischemic stroke risk ( RR , 1.40 ; 95 % CI = 0.97 - 2.04 ) associated with very irregular cycles . Menstrual cycle irregularity may be a marker of metabolic abnormalities predisposing to increased risk for CVD The objective of the present study was to estimate the prevalence of the different pathological conditions causing clinical ly evident and rogen excess and to document the degree of long-term success of suppressive and /or anti and rogen hormonal therapy in a large consecutive population of patients . All patients presenting for evaluation of symptoms potentially related to and rogen excess between October 1987 and June 2002 were evaluated , and the data were maintained prospect ively in a computerized data base . For the assessment of therapeutic response , a retrospective review of the medical chart was performed , after the exclusion of those patients seeking fertility therapy only , or with inadequate follow-up or poor compliance . A total of 1281 consecutive patients were seen during the study period . Excluded from analysis were 408 patients in whom we were unable to evaluate hormonal status , determine ovulatory status , or find any evidence of and rogen excess . In the remaining population of 873 patients , the unbiased prevalence of and rogen-secreting neoplasms was 0.2 % , 21-hydroxylase-deficient classic adrenal hyperplasia ( CAH ) was 0.6 % , 21-hydroxylase-deficient nonclassic adrenal hyperplasia ( NCAH ) was 1.6 % , hyper and rogenic insulin-resistant acanthosis nigricans ( HAIRAN ) syndrome was 3.1 % , idiopathic hirsutism was 4.7 % , and polycystic ovary syndrome ( PCOS ) was 82.0 % . Fifty-nine ( 6.75 % ) patients had elevated and rogen levels and hirsutism but normal ovulation . A total of 257 patients were included in the assessment of the response to hormonal therapy . The mean duration of follow-up was 33.5 months ( range , 6 - 155 ) . Hirsutism improved in 86 % , menstrual dysfunction in 80 % , acne in 81 % , and hair loss in 33 % of patients . The major side effects noted were irregular vaginal bleeding ( 16.1 % ) , nausea ( 13.0 % ) , and headaches ( 12.6 % ) ; only 36.6 % of patients never complained of side effects . In this large study of consecutive patients presenting with clinical ly evident and rogen excess , specific identifiable disorders ( NCAH , CAH , HAIRAN syndrome , and and rogen-secreting neoplasms ) were observed in approximately 7 % of subjects , whereas functional and rogen excess , principally PCOS , was observed in the remainder . Hirsutism , menstrual dysfunction , or acne , but not alopecia , improved in the majority of patients treated with a combination suppressive therapy ; although more than 60 % experienced side effects Elevated homocysteine levels are associated with an increased cardiovascular disease ( CVD ) risk , but the underlying mechanism is still unclear . High homocysteine might affect the endothelium , and consequently lead to impaired haemostasis . In a 
    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: Women with polycystic ovary syndrome ( PCOS ) are insulin resistant secondary to a postbinding defect in insulin signaling . Sequential euglycemic glucose clamp studies at 40 and 400 mU. m(-2 ) . min(-1 ) insulin doses with serial skeletal muscle biopsies were performed in PCOS and age- , weight- , and ethnicity-matched control women .  Steady-state insulin levels did not differ , but insulin-mediated glucose disposal was significantly decreased in PCOS women ( P < 0.05 ) . Insulin receptor substrate (IRS)-1-associated phosphatidylinositol 3-kinase ( PI 3 K ) activity was significantly decreased in PCOS ( n = 12 ) compared with control skeletal muscle ( n = 8 ; P < 0.05 ) . There was no significant difference in the abundance of IR , IRS-1 , or the p85 regulatory subunit of PI 3 K in PCOS ( n = 14 ) compared with control ( n = 12 ) muscle . The abundance of IRS-2 was significantly increased ( P < 0.05 ) in PCOS skeletal muscle , suggesting a compensatory change . We conclude that there is a physiologically relevant defect in insulin receptor signaling in PCOS that is independent of obesity and type 2 diabetes mellitus We prospect ively estimated the prevalence of the polycystic ovary syndrome ( PCOS ) , as defined by the NIH/NICHHD 1990 endocrine criteria , in a population of 154 Caucasian women of reproductive age reporting spontaneously for blood donation .  Anthropometric data ; the presence of hirsutism , acne , and and rogenic alopecia ; and the menstrual history were recorded by a single investigator . In 145 women , blood sample s were also obtained for measurement of serum and rogen levels .  PCOS was defined by the presence of 1 ) oligomenorrhea , 2 ) clinical and /or biochemical hyper and rogenism , and 3 ) exclusion of hyperprolactinemia , thyroid disorders , and nonclassic 21-hydroxylase deficiency . Hirsutism was defined by a modified Ferriman-Gallwey score of 8 or more , acne was considered as a sign of hyper and rogenism when persistent after the second decade of life , and hyper and rogenemia was defined by an increase in circulating testosterone or dehydroepi and rosterone sulfate or an increase in the free and rogen index above the 95th percentile of the control values derived from the nonhirsute , nonacneic women having regular menses who were not receiving hormonal therapy . PCOS was present in 10(6.5 % ) , hirsutism was present in 11 ( 7.1 % ) , and acne was present in 19 ( 12.3 % ) of the 154 women . Our results demonstrate a 6.5 % prevalence of PCOS , as defined , in a minimally biased population of Caucasian women from Spain . The polycystic ovary syndrome , hirsutism , and acne are common endocrine disorders in women We performed this study to access the changes in glucose tolerance over time in a group of women with polycystic ovary syndrome ( PCOS ) ( n = 71 ) and control women ( n = 23 ) with regular menstrual cycles and baseline normal glucose tolerance . Mean follow-up was between 2 and 3 yr for both groups ( PCOS 2.5 + /- 1.7 yr ; controls 2.9 + /- 2.1 yr ) . Based on World Health Organization glucose tolerance categories , there was no significant difference in the prevalence of glucose intolerance at follow-up in the PCOS group . In the PCOS group , 25 ( 37 % ) had impaired glucose tolerance ( IGT ) and seven ( 10 % ) had type 2 diabetes mellitus at baseline , compared with 30 ( 45 % ) and 10 ( 15 % ) , respectively , at follow-up . There were also no differences within groups ( PCOS or control ) or between groups ( PCOS vs. control ) in the oral glucose tolerance test-derived measure of insulin sensitivity , but in the women with PCOS who converted to either IGT or type 2 diabetes mellitus , there was a significant decrease ( P < 0.0001 ) . At the follow-up visit , the mean glycohemoglobin level was 6.1 + /- 0.9 % in women with PCOS vs. 5.3 + /- 0.7 % in the control women ( P < 0.001 ) . Women with PCOS and baseline IGT had a low conversion risk of 6 % to type 2 diabetes over approximately 3 yr , or 2 % per year . The effect of PCOS , given normal glucose tolerance ( NGT ) at baseline , is more pronounced with 16 % conversion to IGT per year . Our study supports that women with PCOS ( especially with NGT ) should be periodically rescreened for diabetes due to worsening glucose intolerance over time , but this interval may be over several years and not annually BACKGROUND Cross-sectional studies have shown a high frequency of impaired glucose tolerance ( IGT ) and non-insulin dependent diabetes mellitus ( NIDDM ) in women with polycystic ovarian syndrome ( PCOS ) . However , little is known about the change in glucose tolerance that occurs over a period of several years in women with PCOS . METHODS Sixty-seven women with PCOS received a 75 g glucose tolerance test and measurement of lipids at baseline and at follow-up after an average time of 6.2 years . All women followed prospect ively had normal glucose tolerance ( n = 54 ) or IGT ( n = 13 ) at the start of the study . RESULTS Change in glycaemic control from baseline was frequent , with 5/54 ( 9 % ) of normoglycaemic women at baseline developing IGT and a further 4/54 ( 8 % ) moving directly from normoglycaemic to NIDDM . For women with IGT at baseline , 7/13 ( 54 % ) had NIDDM at follow-up . Body mass index ( BMI ) at baseline was an independent significant predictor of adverse change in glycaemic control . CONCLUSIONS Women with PCOS , particularly those with a high BMI , should be review ed regularly with respect to IGT or NIDDM , as the frequency of impaired glycaemic control is high , and that the rate of conversion from normal glucose tolerance to IGT or NIDDM , or from IGT to NIDDM is substantial The role of testosterone on the development of hypertension is controversial , especially in women with polycystic ovary syndrome ( PCOS ) who have higher prevalence of obesity and insulin resistance than women without PCOS . Little is known about the association between serum testosterone level and blood pressure in young women with PCOS . In the 151 young Taiwanese women with PCOS enrolled in this cross-sectional study , we measured the body mass index , waist circumference , blood pressure , fasting glucose , fasting insulin , lipid profile , and hormone profiles .  The  free and rogen index , total testosterone , and sex hormone-binding globulin  , but not the level of dehydroepi and rosterone sulfate  , significantly correlated with both systolic blood pressure ( SBP ) and diastolic blood pressure ( DBP ) . In multiple linear regression models adjusted for age , body mass index , and other anthropometric , metabolic , and hormonal variables , the level of serum free and rogen index  or total testosterone , but not the sex hormone-binding globulin , were independently related to SBP and DBP . The age- and body mass index – adjusted least-square mean of serum-free and rogen index levels were significantly different between the highest quartile and other quartiles of the SBP and DBP levels . The high bioavailable testosterone levels ( free and rogen index : ≥19 % ) in women with PCOS increased the risk of elevated blood pressure ( SBP ≥130 mm Hg and /or DBP ≥85 mm Hg ) with an odds ratio of 3.817 ( P=0.029 ; 95 % CI : 1.14 to 12.74 ) after adjustment for age , anthropometric measures , and metabolic profiles . Our results suggest that the characteristic hyper and rogenemia in young women with PCOS was associated with an elevated SBP and DBP independent of age , insulin resistance , obesity , or dyslipidemia Cross-sectional studies suggest that women who have irregular menstrual cycles and hyper and rogenism may be at increased risk for cardiovascular disease ( CVD ) . However , prospect i ve data are lacking on the relationship between menstrual cycle irregularity and subsequent CVD risk . The objective of this study was to assess prospect ively the risk for coronary heart disease ( CHD )  and stroke associated with a history of irregular menstrual cycles . The study design was a prospect i ve cohort study of 82,439 female nurses who provided information in 1982 on prior menstrual regularity ( at ages 20 - 35 yr ) and were followed through 1996 for cardiovascular events . Incident reports of nonfatal myocardial infa rct ion , fatal CHD , and nonfatal and fatal stroke were made . Medical records were review ed for confirmation . During 14 yr ( 1,155,915 person-yr ) of follow-up , there were 1417 incident cases of CHD and 838 incident cases of stroke , including 471 cases of ischemic stroke . Compared with women reporting a history of very regular menstrual cycles , women reporting usually irregular or very irregular cycles had an increased risk for nonfatal or fatal CHD [ age-adjusted relative risks ( RR ) , 1.25 and 1.67 , respectively ; 95 % confidence intervals ( CI ) , 1.07 - 1.47 and 1.35 - 2.06 , respectively ] . Increased risks for CHD associated with prior cycle irregularity remained significant after adjustment for body mass index and several potential confounders . There was a nonsignificant increase in overall stroke risk ( RR , 1.30 ; 95 % CI = 0.97 - 1.74 ) and in ischemic stroke risk ( RR , 1.40 ; 95 % CI = 0.97 - 2.04 ) associated with very irregular cycles . Menstrual cycle irregularity may be a marker of metabolic abnormalities predisposing to increased risk for CVD The objective of the present study was to estimate the prevalence of the different pathological conditions causing clinical ly evident and rogen excess and to document the degree of long-term success of suppressive and /or anti and rogen hormonal therapy in a large consecutive population of patients . All patients presenting for evaluation of symptoms potentially related to and rogen excess between October 1987 and June 2002 were evaluated , and the data were maintained prospect ively in a computerized data base . For the assessment of therapeutic response , a retrospective review of the medical chart was performed , after the exclusion of those patients seeking fertility therapy only , or with inadequate follow-up or poor compliance . A total of 1281 consecutive patients were seen during the study period . Excluded from analysis were 408 patients in whom we were unable to evaluate hormonal status , determine ovulatory status , or find any evidence of and rogen excess . In the remaining population of 873 patients , the unbiased prevalence of and rogen-secreting neoplasms was 0.2 % , 21-hydroxylase-deficient classic adrenal hyperplasia ( CAH ) was 0.6 % , 21-hydroxylase-deficient nonclassic adrenal hyperplasia ( NCAH ) was 1.6 % , hyper and rogenic insulin-resistant acanthosis nigricans ( HAIRAN ) syndrome was 3.1 % , idiopathic hirsutism was 4.7 % , and polycystic ovary syndrome ( PCOS ) was 82.0 % . Fifty-nine ( 6.75 % ) patients had elevated and rogen levels and hirsutism but normal ovulation . A total of 257 patients were included in the assessment of the response to hormonal therapy . The mean duration of follow-up was 33.5 months ( range , 6 - 155 ) . Hirsutism improved in 86 % , menstrual dysfunction in 80 % , acne in 81 % , and hair loss in 33 % of patients . The major side effects noted were irregular vaginal bleeding ( 16.1 % ) , nausea ( 13.0 % ) , and headaches ( 12.6 % ) ; only 36.6 % of patients never complained of side effects . In this large study of consecutive patients presenting with clinical ly evident and rogen excess , specific identifiable disorders ( NCAH , CAH , HAIRAN syndrome , and and rogen-secreting neoplasms ) were observed in approximately 7 % of subjects , whereas functional and rogen excess , principally PCOS , was observed in the remainder . Hirsutism , menstrual dysfunction , or acne , but not alopecia , improved in the majority of patients treated with a combination suppressive therapy ; although more than 60 % experienced side effects Elevated homocysteine levels are associated with an increased cardiovascular disease ( CVD ) risk , but the underlying mechanism is still unclear . High homocysteine might affect the endothelium , and consequently lead to impaired haemostasis . In a 
    Output:
    