Pharmacokinetics and biotransformation of orally administered oestrone sulphate and oestradiol valerate in post-menopausal women

Abstract

The pharmacokinetic properties and biotransformation of two orally active oestrogens, piperazine oestrone sulphate (PE 1S, 2.5 mg/day) and oestradiol valerate (E 2V, 2.0 mg/day), given alone or in combination with levonorgestrel (LNG, 250 μg/day) were compared in 8 post-menopausal women, using a randomized cross-over design. The end points measured in peripheral plasma included oestrone (E 1), oestradiol (E 2), oestriol (E 3), oestrone sulphate (E 1S), oestradiol sulphate (E 2S) and oestriol sulphate (E 3S). In addition, LNG and sex-hormone-binding globulin SHBG concentrations were also assessed. The plasma levels of E 3 were invariably below the detection limit (220 pmol/1). The levels of all the other oestrogens analyzed were consistently higher and the area under the curve significantly greater (except in the case of E 3S following PE 1S administration than those recorded after E 2V ingestion. The terminal half-lives of the circulating oestrogens measured after PE 1S administration did not differ from those found after E 2V administration. After 21 days of PE 1S administration (in combination with LNG for the the last 10 days), the maximum levels of all the oestrogens (except those of E 2) were significantly higher than those seen after the first dose. No such difference was observed after E 2V administration. There was no difference between the effects of the two treatment regimens with regard to the E 1/ E 2 ratios, but the E 1/E 1S ratios were significantly lower after PE 1S treatment than after E 2V administration. It is concluded that, compared with an equivalent dose of PE 1S, daily repeated oral administration of E 2V yields consistently lower peripheral plasma levels of E 2 and its principal metabolites. However, in contrast to PE 1S therapy, prolonged administration of E 2V does not result in an accumulation of the circulating oestrogens measured.