Hormonal and clinical effects of chronic gonadotropin-releasing hormone agonist treatment in polycystic ovary syndrome.

The aim of the study was to evaluate the hormonal (focusing on the urinary steroid profile) and clinical effects of chronic gonadotropin-releasing hormone (GnRH) agonist treatment in patients with polycystic ovary syndrome (PCOS) suffering from hirsutism. A long-acting GnRH agonist was administered for 6 months in eight PCOS patients. Hormonal effects were measured by determining serum luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin, testosterone and estradiol concentrations, and by profiling urinary steroids using capillary gas chromatography of 24-hour urine samples. To evaluate 5 alpha-reductase enzyme activity, the ratios of androsterone to etiocholanolone and 5 alpha-tetrahydrocortisol to tetrahydrocortisol were calculated in urine samples. The ratio of androgen to cortisol metabolites was also determined before, and 3 and 6 months after therapy. LH and estradiol levels were suppressed significantly after the first injection and testosterone after the second injection of the GnRH agonist. Thus, serum testosterone was normalized. Ratios of urinary steroids reflecting 5 alpha-reductase enzyme activity (androsterone to etiocholanolone and 5 alpha-tetrahydrocortisol to tetrahydrocortisol) and the ratio of androgen to cortisol metabolites decreased significantly after 3 months of treatment. Degree of hirsutism, assessed by Ferriman-Gallwey score, diminished after 6 months, but not significantly. In conclusion, our data show that long-acting GnRH agonist treatment of PCOS patients is effective in reducing serum and urinary androgen levels, but it is not accompanied by an effective reduction in hirsutism during a 6-month treatment period. A longer or a combined treatment would be needed to achieve significant improvement in hirsutism. Gas chromatographic profiling of urinary steroids and the use of specific ratios of the excreted metabolites seems to be a sensitive tool both in the diagnosis of PCOS and in monitoring ovarian suppression.