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7. Attenuated 21-hydroxylase deficiency, Cushing's syndrome, androgen secreting tumors, and hyperprolactinemia were excluded by appropriate tests. None of the women had acanthosis nigricans. The ratio between LH and follicle-stimulating hormone (FSH) was not used as a selection criterion because gonadotropin release was one of the main parameters to be studied. Obesity was defined as a body mass index (BM!) > 25 kg/m 2. Thirty obese women with PCOS (BMI = 30.5 ± 0.7 kg/m 2) 28 ± 0.7 years of age and 19 nonobese women with PCOS (BMI = 21.4 ± 0.5 kg/m2) 29 ± 0.8 years of age constituted the study group. Seven obese women (BMI = 28.0 ± 0.8 kg/m 2) 31 ± 1.5 years of age and 7 nonobese women (BMI = 22.0 ± 0.9 kg/m2) 31 ± 0.9 years of age with regular 26 to 32-day ovulatory menstrual cycles constituted the control group. Study Design
The women were entered into the study group or the control group in a consecutive fashion. Informed consent was obtained from each woman before study start. The women with PCOS were studied on cycle days 4 to 7, whereas amenorrheic women with PCOS were studied at random. The control women were studied on cycle days 4 to 7. Insulin resistance and glucose tolerance were assessed by means of a continuous infusion of glucose with model assessment (CIGMA) test (12). After an overnight fast, the patients were given a continuous intravenous (IV) infusion of 5 mg of glucose/kg ideal body weight per minute for 60 minutes with measurements of plasma glucose and insulin at 50, 55, and 60 minutes. These concentrations were interpreted using a mathematical model of glucose and insulin homeostasis to assess insulin resistance and glucose tolerance. The insulin resistance measured by CIGMA correlates well with that measured by the euglycemic clamp 488
Dale et al.
peas, B W, and insulin
technique (r = 0.87, P < 0.0001) as shown by Hosker et al. (12). No patient had glucosuria during the CIGMA test. A test value> 4 was considered indicative of insulin resistance. Gonadotrope responsiveness was tested in all women between 8:00A.M. and 12:00A.M. after IV administration of 10 Jlg gonadotropin-releasing hormone (GnRH, Lutrefact, Hoechst, Frankfurt am Main, Germany). Serum samples for LH and FSH were drawn at -30, 0, 15, 30, 60, and 120 minutes. Assays
Plasma glucose was determined using glucose oxidase. Serum levels of LH and FSH were measured using dissociation-enhanced lanthanide fluoroimmunoassay kits obtained from LKB Wallac (SF220101, Turku, Finland). Serum levels of testosterone (T), androstenedione (A), dehydroepiandrosterone sulfate (DHEAS) and sex hormone-binding globulin (SHBG) were measured by radioimmunoassay (RIA) (13). The T/SHBG index is given as T X 100/SHBG. Insulin was determined by RIA with kits from the Radio Chemical Center, Amersham, United Kingdom, (double-antibody method) by the method described by Torjesen et al. (14). Between-assay coefficient of variation for the individual analyses were: LH, 5% to 8%; FSH, 8%; T, 5% to 10%; A, 8%; DHEAS, 5%; SHBG, 10%; insulin, 6% to 9%. Normal serum ranges were as follows: LH, 1 to 12 IU/L; FSH, 1 to 12 IU/L; T, 0.3 to 2.8 nmol/L; A, 3 to 6.6nmol/L; DHEAS, 2 to 8.3 Jlmol/L; SHBG, 30 to 90 nmoljL; fasting insulin,
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7. Attenuated 21-hydroxylase deficiency, Cushing's syndrome, androgen secreting tumors, and hyperprolactinemia were excluded by appropriate tests. None of the women had acanthosis nigricans. The ratio between LH and follicle-stimulating hormone (FSH) was not used as a selection criterion because gonadotropin release was one of the main parameters to be studied. Obesity was defined as a body mass index (BM!) > 25 kg/m 2. Thirty obese women with PCOS (BMI = 30.5 ± 0.7 kg/m 2) 28 ± 0.7 years of age and 19 nonobese women with PCOS (BMI = 21.4 ± 0.5 kg/m2) 29 ± 0.8 years of age constituted the study group. Seven obese women (BMI = 28.0 ± 0.8 kg/m 2) 31 ± 1.5 years of age and 7 nonobese women (BMI = 22.0 ± 0.9 kg/m2) 31 ± 0.9 years of age with regular 26 to 32-day ovulatory menstrual cycles constituted the control group. Study Design
The women were entered into the study group or the control group in a consecutive fashion. Informed consent was obtained from each woman before study start. The women with PCOS were studied on cycle days 4 to 7, whereas amenorrheic women with PCOS were studied at random. The control women were studied on cycle days 4 to 7. Insulin resistance and glucose tolerance were assessed by means of a continuous infusion of glucose with model assessment (CIGMA) test (12). After an overnight fast, the patients were given a continuous intravenous (IV) infusion of 5 mg of glucose/kg ideal body weight per minute for 60 minutes with measurements of plasma glucose and insulin at 50, 55, and 60 minutes. These concentrations were interpreted using a mathematical model of glucose and insulin homeostasis to assess insulin resistance and glucose tolerance. The insulin resistance measured by CIGMA correlates well with that measured by the euglycemic clamp 488
Dale et al.
peas, B W, and insulin
technique (r = 0.87, P < 0.0001) as shown by Hosker et al. (12). No patient had glucosuria during the CIGMA test. A test value> 4 was considered indicative of insulin resistance. Gonadotrope responsiveness was tested in all women between 8:00A.M. and 12:00A.M. after IV administration of 10 Jlg gonadotropin-releasing hormone (GnRH, Lutrefact, Hoechst, Frankfurt am Main, Germany). Serum samples for LH and FSH were drawn at -30, 0, 15, 30, 60, and 120 minutes. Assays
Plasma glucose was determined using glucose oxidase. Serum levels of LH and FSH were measured using dissociation-enhanced lanthanide fluoroimmunoassay kits obtained from LKB Wallac (SF220101, Turku, Finland). Serum levels of testosterone (T), androstenedione (A), dehydroepiandrosterone sulfate (DHEAS) and sex hormone-binding globulin (SHBG) were measured by radioimmunoassay (RIA) (13). The T/SHBG index is given as T X 100/SHBG. Insulin was determined by RIA with kits from the Radio Chemical Center, Amersham, United Kingdom, (double-antibody method) by the method described by Torjesen et al. (14). Between-assay coefficient of variation for the individual analyses were: LH, 5% to 8%; FSH, 8%; T, 5% to 10%; A, 8%; DHEAS, 5%; SHBG, 10%; insulin, 6% to 9%. Normal serum ranges were as follows: LH, 1 to 12 IU/L; FSH, 1 to 12 IU/L; T, 0.3 to 2.8 nmol/L; A, 3 to 6.6nmol/L; DHEAS, 2 to 8.3 Jlmol/L; SHBG, 30 to 90 nmoljL; fasting insulin,
