Sachynska O. Functional state of the rat prostate and antitumor effects of hormonal and antihormonal preparations under their combined use

Object of the study: functional state of the prostate and its regulation in normal and pathologic conditions. Aim of the study: to examine experimentally and to prove the possibility of new combinations of hormonal and antihormonal preparations use in the therapy of androgen-dependent prostate cancer. Methods of the study and facilities: biological, biochemical, radioimmunological and statistic methods; spectrophotometer SF-26, gamma- and beta-counters (5500-B and LS-5000). Theoretical and practical results: it was established that under the separate or combined use of the antiandrogen preparations with different mechanisms of action the most pronounced inhibitory effect on the rat prostate was caused by the combination of medicines decreasing testosterone production (hexestrol, LH-RH agonists) with antiandrogen flutamide or steroid 5-alpha-reductase inhibitor (finasteride). The reduction of prostate weight and decrease of DNA, RNA, protein and fructose content in it close to postcastrational levels were observed. The significant "antiprostatic" effect caused by prolonged hexestrol administration in a dose of 1 mcg/kg may be taken into account in the schemes of prostate cancer estrogen therapy with reduced doses of the preparations. Novelty: first the capability of hexestrol in microdoses (1-2 mcg/kg) to depress the functional state of prostate was demonstrated. The reciprocal potentiation of flutamide and hexestrol actions on the depression of morpho-functional state of androgen-dependent reproductive organs of male rats was revealed. The marked antitumor action of hexestrol (2 mcg/kg) combinations with flutamide or finasteride, realised in pronouced inhibition of prostate human adenocarcinoma xenografts, was proved. Degree of application: on the basis of investigation the patent of Ukraine "The method of the prostate cancer treatment" was received. Fields of application: endocrinology, oncourology.