ANDROGEN LEVEL VARIATIONS, CLINICAL-RESPONSE TO LHRH, AGONISTS AND CHANGES IN THE QUALITY OF THE SUBSCALES IN METASTATIC PROSTATE-CANCER SPECULATIONS ABOUT POSSIBLE ROLE SF THE MONOAMINE SYSTEM

The aim of this study was to investigate the effect of goserelin-aceta t (Zoladex(R) on testosterone suppression, to compare achieved suppres sion with clinical effects in patients with prostate cancer with bone metastases and consequent painful syndrome, to study the behavior of a diol during treatment and to assess life quality with emphases on the physical and psychological domain in relation to clinical and biologic al treatment, effects. Fifteen patients were treated by Zoladex(R) in one dose every 28 days, and followed-up for 12 months. AII patients ha d several metastatic localizations in the bones, initial high prostate specific antigen (PSA), and high acid (AP) and alkaline phosphatase ( ALP). PSA, testosterone, adiol (delta-5-androstenediol), luteinizing h ormone (LH), foliculostimulating hormone (FSH), ALP and AP were also m easured before every cycle. For evaluation of the life quality Rotterd am Symptom Checklist was used. Clinical progression was not registered during follow-up, with drop of PSA, ALP and BE Testosterone and adiol displayed mainly inverse trends during treatment. The complete testos terone suppression was never achieved. It seems that Zoladex(R) has qu ite different influence on LH and FSH, as levels of those hormones hav e Shown opposite trend. Some of the observed hormonal effects could be attributed to stimulation of the monoamine system. Suppression of LH level provoked by administration of LHRH agonists increases level of d opamine in hypothalamus which inhibits releasing of its hormones. By i nhibition of corticotropic releasing factor and ACTH, and by its influ ence on adrenal gland, we could explain drop of adiol levels in the fi rst months of administration of LHRH agonists. Testosterone increase a nd adiol drop in the first months, and adiol increase following testos terone level drop in the fourth to eight month, may be explained by ne gative feed back mechanism between different androgens which could be stimulated or provoked by LHRH therapy. The question of effects which are results of LHRH agonists modulation of the monoamine system and co nsequent activation of other central mechanisms of hormonal regulation is still open. Patients' quality of life under therapy was improved f or about 30% in psychological and functional domains. There were no si gnificant changes on physical subscale, during treatment. It seems tha t the. obtained positive psychological treatment effect is not, only a consequence of pain decrease, but it could be the result of the chang e in the level of monoamines in CNS under Zoladex(R).