FAT‐SOLUBLE 17β‐ESTRADIOL: A WAY OF REDUCING DOSAGE IN STEROID HORMONAL SUBSTITUTION?

Abstract

Eight ovariectomized women were given 0.5 mg 17β-estradiol cyclo-octyl acetate (E₂COA) dissolved in arachis oil+0.15 mg desogestrel, and 2 mg micronized 17β-estradiol (mE₂) + 0.15 mg desogestrel orally in a crossover fashion for 20 days each. The preparations were taken on 10 days together with a meal, on 10 days 3 hours after a meal. Blood samplings were performed 3 h after capsule ingestion for analysis of serum estradiol (S-E₂), estrone (S-E₁) and sex hormone binding globulin (SHBG). Before treatment, all women had climacteric complaints. During treatment these symtoms were alleviated and no discomfort was reported. No differences in serum levels of estrogens were found in either of the preparations when capsules were taken with or without food. However, serum levels of E₂ were found to be 100% higher per mg substance given after E₂COA vis-à-vis mE₂. This indicates either a delayed breakdown and/or a better resorption. The E₁/E₂ ratio after E₂COA was only half that after mE₂ intake. This hints at another route of resorption. SHBG concentrations were somewhat elevated following mE₂ administration, whereas a slight decrease was found after E₂COA. The resulting post-treatment difference was significant, suggesting a less estrogenic liver effect by E₂COA. No accumulation of E₂ or E₁ was seen after either of the preparations. Our findings support the hypothesis that E₂COA. being fat soluble, is resorbed via the lymphatic system. By avoiding the first liver pass the dosage of estrogen can be halved.