Background. Insulin resistance is probably the key factor in the pathogenesis of polycystic ovary Syndrome, and thus insulin sensitization can be a beneficial treatment. We tried to investigate effects of Long-term therapy with metformin in polycystic ovary Syndrome on steroid Levels, ovarian steroidogenesis and on insulin resistance and secretion. We also tried to find predictors of the successful therapy (in terms of improvement of menstrual cyclicity). Methods and Results. 24 oligo/amenorhoeic women with polycystic ovary syndrome were included roto the study. Basal blond samples were taken for the deterrnination of testosterone, estradiol, androstenedione, dehydroepiandrosterone, dehydroepiandrosterone-sulphate, 170H progesterone, 170H pregnenonole, sex-hormone binding globulin and cortisol. Gonadoliberin (GnRH) analogue test was perfonned with estimation of the same steroids and LH. Oral glucose tolerance test was done with dextrose, and with estimation of glucose, insulin, and C peptide. HOMA model assessment was used for calculation of insulin resistance and insulin secretion. All examinations were done before and after 27±4 weeks (average ± standard deviation) of therapy with metformin 1000 mg/day. Significant improvement in menstrual cyclicity was observed in 58 % of women. No Significant change in basal steroid Levels was found. A trend towards dechne in insulin resistance and secretion was detected. Significant decrease in the mean stimulated testosterone level (from 1.74 to 1.54 nmoUl, 95% CI l .42-2.08 and 1.21-1.87; p<0.05), 170H progesterone level (from 3.32 to 2.37, 95%o CI 1.42-2.08 and 1.21-1.87; p<0.05), LH (from 9.1 to 4.8 IU/I, 95%o CI 6.4-12.8 and 3.4-6.8; p<0.05), and estradiol level (from 0.91 to 0.43 nmol/I, 95% CI 0.69-1.19 and 0.38-0.65; p<0.01) were detected. The best prediction of the improvement in menstrual cyclicity after metformin was achieved with the combination of basal 170H progesterone, androstendione, testosterone and SHBG. This model correctly classified 86.7% of subjects. Conclusions. Long-term therapy with metformin led to the improvementin menstrual cyclicity, without Significant change in basal steroid Levels or parameters of insulin resistance.

        Key words: polycystic ovary syndrome, insulin resistance, metformin.