Oestrogenic Activity of Oestradiol-Decanoate After Oral Administration to Rodents

Abstract

Oestradiol-decanoate, dissolved in arachis oil and orally administered to rodents, produces oestrogenic effects. Compared on a molecular basis the ester has 0.1\p=n-\1.0 times the activity of ethinyl oestradiol, dependent on the species and the parameter studied.The effects of oestradiol-decanoate are less or absent when the oil is omitted. It is likely that absorption of the steroid ester takes place via the intestinal lymphatics in conjunction with the oil. The principal oestrogen, naturally produced by the human ovaries, oestradiol-17/?, is not very effective in bringing about therapeutic oestrogenic effects if it is administered orally.For this reason oestradiol derivatives, such as ethinyl oestradiol and mestranol, are commonly used if substitution therapy with an orally active oestro¬ genic steroid is required, e. g. after ovariectomy or in the post-menopause.However, concern about possible unwanted side effects of such compounds has developed and a preparation which acts, after oral administration, by increasing the level of the natural hormone, oestradiol, in the plasma would be of advantage.The demonstration of the oral androgenic activity of testosterone-undecanoate dissolved in oil, which results from an increase of natural androgens in the plasma ), induced us to study a similar lipophilic ester, oestradiol decanoate, for its oestrogenic effects.In this report the results of this study in rodents are described. 422Endocrinological R&D Laboratories,

Effects of Orally Administered Oestradiol Decanoate on Plasma Oestradiol, Oestrone and Gonadotrophin Levels, Vaginal Cytology, Cervical Mucus and Endometrium in Ovariectomized Women

“…In one recent study, however, it has been demonstrated that after an intravenous injection of tritiated oestradiol into postmenopausal patients with cancer, the most prevalent oestrogen in the unconjugated oestrogen fraction in the plasma was oestrone (Vaughn et al, 1976). As oestradiol decanoate* had been found in rats to be a potent orally active ester when administered in oily solution (de Visser & van der Vies, 1976), it was of interest to investigate the bioavailability of oestradiol after oral administration of oestradiol decanoate in women. The present study was undertaken to assess effects of oral oestradiol decanoate dissolved in oil, given in a daily dose of 0.5 mg, on plasma levels of oestradiol, oestrone, FSH and LH, as well as on vaginal cytology, cervical mucus and endometrial proliferation.…”