Induction of ovulation by nonsteroidal antiestrogens

The clinical finding that the rodent antifertility agent nonsteroidal antiestrogen clomiphene (a mixture of geometric isomers) was actually a profertility agent in subfertile women created the first practical method for enhancing fertility in women. A related compound, ICI 46,474, the pure trans isomer of a substituted triphenylethylene, was also a product of an industry fertility control program in the 1960s and it too was tested and then marketed in the United Kingdom as an inducer of ovulation in subfertile women, at the same time as an orphan drug for the treatment of metastatic breast cancer in postmenopausal women. Clomiphene has, however, remained the clinical gold standard for the induction of ovulation worldwide for 40 years. However, the fact that tamoxifen is a potent inducer of ovulation in premenopausal women remains an important consideration in breast cancer patients made infertile by combination cytotoxic chemotherapy. This chapter will trace the genesis of agents for the induction of ovulation and the current potential applications of tamoxifen for women with breast cancer who choose to preserve fertility.