Two small groups of steroids in the estrane series—here designated as impeded estrogens,—represent a class of compounds which differ from the majority of estrogenic substances in exerting certain unusual influences on growth of the uterus. The induction of these effects previously was considered to be peculiar to estriol. The unusual growth properties common to impeded estrogens are twofold: (a) after the threshold dosage required to initiate growth has been reached, the slope of the curve of increment of uterine weight in response to increased steroid dosage is very gradual rather than steep; (b) these compounds possess the ability to inhibit to a limited extent the uterine growth induced by estrone administered concurrently.
The partial inhibition of estrone-induced growth of the uterus is confined to a critical dosage of the impeded estrogen and is overcome by increased dosage of the inhibitor. Estrone-induced growth of the vagina is not inhibited by impeded estrogens. Furthermore the simultaneous administration of impeded estrogens and testosterone does not lessen the amount of uterine growth evoked by the latter.
The impeded estrogens so far encountered are 3-hydroxyestratriene derivatives possessing either a ketone group at position 6 or a hydroxyl group at position 16. Oxygenated functions at these positions in phenolic estrogens have special significance in the excitation and restraint of uterine growth unshared by similar groups at certain other sites of the estrane molecule.