Polycystic ovary syndrome : A study on factors of potential impact on body fat and carbohydrate metabolism

Sammanfattning: The aim of the present thesis was to investigate some factors underlying the metabolic, anthropometric, and endocrine abnormalities of women with the polycystic ovary syndrome (PCOS).An iv insulin tolerance test (0.15 IU bolus) showed substantially preserved glucose counterregulation in women with PCOS (n=18). Signs suggesting symptomatic adaptation to hypoglycaemia were found in obese hyperinsulinaemic women with PCOS, together with lesser activation of the sympathetic nervous system, assessed by measurements of the noradrenaline and neuropeptide Y responses. The molar ratio between the increments of cortisol and ACTH was higher, and cortisol levels fell more rapidly in women with PCOS compared with controls (n=17). The responses of intermediate adrenal steroids revealed no signs ofdysregulation of single enzymes in the women with PCOS.Serum levels of leptin were similar in women with PCOS (n=49) and controls (n=32). The percentage of body fat was the single independent predictor of the variability in leptin concentrations in both groups.A high prevalence (41%) of polycystic ovaries, according to ultrasonography, was found in a group of women with gestational diabetes mellitus (GDM) 3-5 years prior to the investigation (n=34), compared with only 3% among women with previous uncomplicated pregnancies (n=36). When comparing the women with previous GDM and polycystic ovaries to those with previous GDM and normal ovaries, the former were younger, had greater accumulation of truncal-abdominal fat, higher concentrations of androgens and a higher LH/FSH ratio, more abnormal serum lipid profile, lower insulin sensitivity, all independent of age and BMI, and a higher prevalence of pregnancy induced hypertension during the index pregnancy.Three prediction models of insulin resistance (measured by the euglycaemic hyperinsulinaemic clamp) in PCOS were derived from stepwise regression analyses of anthropometric, hormonal, and metabolic variables in 72 women with PCOS, each one containing waist girth in combination with concentrations of fasting serum insulin (R2=0.77), triglycerides (R2=0.65), or subscapularis skinfolds (R2=0.64).Main conclusions: Although the counterregulatory response to hypoglycaemia was intact in women with PCOS, those characterised by obesity and hyperinsulinaemia showed signs indicative of adaptation to hypoglycaemia, suggesting that repeated episodes of low blood glucose may occur in these women. Women with PCOS showed signs of enhanced adrenal sensitivity and increased cortisol turn-over, factors of putative importance for the. accumulation of truncal-abdominal fat. According to these cross-sectional results. it seems unlikely that leptin plays an important role in the metabolic aberrations in PCOS. Although clinical and hormonal features of the PCO syndrome were scarce in the women with previous GDM and polycystic ovaries, they showed several features of the insulin resistance syndrome, suggesting thatpolycystic ovaries could be a marker of increased risk for later metabolic dysregulation.