The objective of the proposed research is to synthesize new, potent, oral estrogenic and antigonadotropic compounds that are devoid of structural features that contribute to toxic manifestations of the agents currently used. Oxidative metabolism of ethynylestradiol and mestranol at C-2 and the ethynyl side chain have been shown to cause irreversible binding in target and other tissues. The new compounds to be synthesized will be substituted at C-2 with groups that will prevent oxidative metabolism of the aromatic A-ring and substituted at C-7 or C-11 with groups that induce potent oral estrogenic activity to estradiol to the extent that an ethynyl side chain is not necessary for oral activity. The C-7 and C-11 substituents will be carefully chosen to minimize specific and nonspecific serum binding to achieve more efficient delivery of the compounds to target tissues.