A potential role for analogues of gonadotropin hormone-releasing hormone (GnRH) to prevent cancers of the breast, ovary, and endometrium was first suggested by Pike et al.1 The rationale for considering GnRH analogues is their ability to suppress ovulation and sex-steroid production. The suppression of ovulation should prevent ovarian cancer, and the suppression of sex steroids should prevent cancers of the breast and endometrium. However, the GnRH analogue-induced hypo-estrogenic state will have associated symptoms (hot flashes) and morbidity (urogenital atrophy and osteoporotic fractures). To minimize the deleterious effects of hypoestrogenemia, addition of other agents, including bisphosphonates, selective estrogen receptor modulators (SERMS), and low-dose add-back sex steroids, is under consideration for study. In this chapter, the epidemiological basis for considering GnRH analogues to prevent breast cancer and available preclinical and clinical data will be reviewed.
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