The first drug, clomifene (2-[4-(2-chloro-1,2-diphenylethenyl)phenoxy]-N,N-diethylethanamine;2-hydroxy-1,2,3-propanetricarboxylate; see figure 6) has a chloro-substituent on the ethylene side chain which produces similar binding affinities as the later discovered drug tamoxifen. Clomifene is a mixture of estrogenic (cis-form) and antiestrogenic isomers (trans-form). Cis and trans are defined in terms of the geometric relationships of the two unsubstituted phenyl rings. The two isomers of clomifene have different profiles, where the trans-form has activity more similar to tamoxifen while the cis-form behaves more like 17β-estradiol. Cis is approximately ten times more potent than trans. However, trans isomer is the most potent stimulator of epithelial cell hypertrophy since clomifene is antagonistic at low doses and agonistic at high doses. The antagonist isomers may cause inhibitory estrogenic effects in the uterus and mammary cancers, but the estrogenic isomer could combine with novel receptors to produce estrogen-like effects in bone.