Novel compounds inhibit estrogen formation and action.

Estrogens are well known to play a predominant role in human breast cancer. The current endocrine therapy of breast cancer consists in administering an antiestrogen which blocks the action of estrogens at the receptor level. However, the currently available antiestrogens possess mixed estrogenic and antiestrogenic activity, thus limiting their potential therapeutic efficacy. The present data show that a series of new estrogen derivatives demonstrate not only pure antiestrogenic activity in the sensitive in vivo mouse uterus assay, but simultaneously exert potent inhibitory effects on 17 beta-hydroxysteroid dehydrogenase activity, the enzyme responsible for the formation of 17 beta-estradiol from estrone, the last step in estrogen formation. Such compounds having a dual site of inhibitory action, namely on estrogen formation and on the estrogen receptor, could well lead to an improved endocrine therapy of breast and other estrogen-sensitive cancers as well as other nonmalignant estrogen-sensitive diseases.