Effects of estradiol decanoate in ovariectomized women

Abstract

Estradiol decanoate (E₂D) dissolved in ethyl oleate was given orally for 14 days in a daily dose of 0.25 mg to 6 ovariectomized women with the uterus left in situ. Effects on plasma estrone (E₁), estradiol (E₂), FSH, LH and prolactin (PRL), as well as on vaginal smears, cervical mucus Ferning and Spinnbarkeit, and endometrial proliferation were studied. Circulating plasma E₁, E₂, FSH, LH and PRL were measured by specific radioimmunoassays on days 0, 1, 2, 4, 7, 10, 15, 16 and 17 at 08:00 h. Plasma E₁ and E₂ were also frequently assayed on days 1 and 14. Determination of plasma estrogens was always done after isolation of the individual steroids by chromatography on Sephadex LH-20. For the statistical evaluation paired t-test was applied. After a single dose of E₂D mean plasma E₂ rose from 21.3 to 40.8 pg/ml (p <0.05) and to 57.7 pg/ml (p < 0.001) within 30 minutes and 1 hour, respectively. There was a further rise to 88.7 pg/ml after 10 hours. Mean plasma E₁ rose slowly from 18.5 to a maximum of 57.3 pg/ml after a single dose of E₂D. On repeated daily administration of E₂D mean plasma E₂ and E₁, measured at 08:00 h, rose to 116.2 and 58.2 pg/ml, respectively. Frequent plasma sampling on day 14 revealed similar proportional increases of E₂ and E₁ levels, with mean peak values of 140.3 and 76.8 pg/ml, respectively. During treatment mean plasma E₁:E₂ ratio remained between 0,5 and 0.6. After discontinuation of E₂D therapy plasma estrogen levels fell progressively within 48 hours. Suppression of plasma FSH and LH was weak, while mean PRL level increased 3-fold, although remaining within the range of normal menstruating women. Marked effects on vaginal epithelium and cervical mucus were recorded in all cases. Endometrial specimens showed moderate proliferative changes. No side-effects were reported. It was concluded that therapy with oral E₂D dissolved in oil offers new possibilities for estrogen supplementation therapy.