Profound decrease of in vivo formation of thromboxane during oestrogen therapy

Oestrogen has been proposed to influence platelet activity and formation of the vasoactive eicosanoids thromboxane and prostacyclin. Previous studies have been based on ex vivo techniques with well-known artifacts during blood sampling and ex vivo conditions. The present study is the first to assess in vivo formation through gas chromatographic/mass spectrometric analysis of the major urinary metabolites 2,3-dinor-thromboxane B2 and 2,3-dinor-6-keto-PGF1 alpha. Ten consecutive male patients with prostatic carcinoma participating in a randomized study comparing the effects of parenteral oestrogen therapy (n = 5) with orchidectomy (n = 5) were included. Oestrogen was given as polyestradiol phosphate 240 mg i.m. every month, 2,3-dinor thromboxane B2 and 2,3-dinor-6-keto-PGF1 alpha were analysed with the help of tetradeuterated internal carriers/standards. We found a consistent decrease of in vivo formation of thromboxane by approximately 40% during parenteral oestrogen therapy (P = 0.008) and a doubling after surgical castration. The ratio of prostacyclin to thromboxane increased by approximately 50% (P = 0.023) during oestrogen therapy. In conclusion, oestrogen induced 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 for the cardiovascular system. Furthermore, thromboxane formation increased 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.