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

The pharmacokinetic properties and biotransformation of two orally active oestrogens, piperazine oestrone sulphate (PE₁S, 2.5 mg/day) and oestradiol valerate (E₂V, 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 (E₁), oestradiol (E₂), oestriol (E₃), oestrone sulphate (E₁S), oestradiol sulphate (E₂S) and oestriol sulphate (E₃S). In addition, LNG and sex-hormone-binding globulin SHBG concentrations were also assessed.

The plasma levels of E₃ 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 E₃S following PE₁S administration than those recorded after E₂V ingestion.

The terminal half-lives of the circulating oestrogens measured after PE₁S administration did not differ from those found after E₂V administration.

After 21 days of PE₁S administration (in combination with LNG for the the last 10 days), the maximum levels of all the oestrogens (except those of E₂) were significantly higher than those seen after the first dose. No such difference was observed after E₂V administration.

There was no difference between the effects of the two treatment regimens with regard to the E₁/ E₂ ratios, but the E₁/E₁S ratios were significantly lower after PE₁S treatment than after E₂V administration.

It is concluded that, compared with an equivalent dose of PE₁S, daily repeated oral administration of E₂V yields consistently lower peripheral plasma levels of E₂ and its principal metabolites. However, in contrast to PE₁S therapy, prolonged administration of E₂V does not result in an accumulation of the circulating oestrogens measured.