PROFOUND DECREASE OF IN-VIVO FORMATION OF THROMBOXANE DURING ESTROGENTHERAPY

Oestrogen has been proposed to influence platelet activity and formati on of the vasoactive eicosanoids thromboxane and prostacyclin. Previou s studies have been based on ex vivo techniques with well-known artifa cts during blood sampling and ex vivo conditions. The present study is the first to assess in vivo formation through gas chromatographic/mas s spectrometric analysis of the major urinary metabolites 2,3-dinor-th romboxane B-2 and 2,3-dinor-6-keto-PGF(1 alpha). Ten consecutive male patients with prostatic carcinoma participating in a randomized study comparing the effects of parenteral oestrogen therapy (n = 5) with orc hidectomy (n = 5) were included. Oestrogen was given as polyestradiol phosphate 240 mg i.m. every month. 2,3-dinor thromboxane B-2 and 2,3-d inor-6-keto-PGF(1 alpha) were analysed with the help of tetradeuterate d internal carriers/standards, We found a consistent decrease of in vi vo formation of thromboxane by approximate to 40% during parenteral oe strogen therapy (P = 0.008) and a doubling after surgical castration. The ratio of prostacyclin to thromboxane increased by approximate to 5 0% (P = 0.023) during oestrogen therapy. In conclusion, oestrogen indu ced a marked decrease of in vivo formation of thromboxane and a marked increase in the ratio of prostacyclin to thromboxane formation in all patients. According to current knowledge this should be beneficial fo r the cardiovascular system. Furthermore, thromboxane formation increa sed after surgical castration. The latter fact should direct attention to the influence of androgens on thromboxane synthesis. Our findings discloses a marked sex-hormone sensitivity of the thromboxane-forming system.