Quinestrol and other cyclopentyl ethers of estrogenic steroids: different rates of storage in body fat.
3-cyclopentyl ethers of several estrogens (estradiol, estriol, 17alpha-ethinylestradiol, 17alpha-methylestradiol) are orally more active than the parent steroids. Ethinyl estradiol 3-cyclopentyl ether (Quinestrol) was found to be stored in body fat of animals and humans. This was identified by Meli et al. (Steroids 2: 417, 1968) as the "mechanism by which 3-etherification with cyclopentyl alcohol enhances the oral activity of ethinylestradiol." To establish if storage in body fat is responsible for the enhanced activity of the other mentioned compounds a single dose (4 mg) of them was given orally to adult rats. Autopsies were performed after 24 and 72 hours and the estrogenic activity of the fat extracts was biologically assayed in mice. Different results were observed with the various compounds. The fat of animals killed 24 or 72 hours after treatment with Quinestrol is highly uterotrophic. The fat of rats killed 24 hours after giving 3-cyclopentyl ethers of both estradiol and 17alpha-methylestradiol has only moderate uterotrophic activity, which disappears in rats killed after 72 hours. The fat of rats given 3-cyclopentyl ether of estriol (Quinestradol) does not show such property at either time. These findings shed doubts on fat storage being the mechanism (or the only mechanism) of the enhanced activity of cyclopentyl ethers of estrogenic steroids.(FULL TEXT)