EFFECT OF RALOXIFENE ON SALIVARY STEROIDS

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DESCRIPTION: (Applicant's Description) Raloxifene, a chemical cousin of tamoxifen, is currently being tested as a breast cancer preventive in Study of Tamoxifen and Raloxifene (STAR) in postmenopausal, high-risk women. Raloxifene is a drug approved to prevent osteoporosis and has not been tested in premenopausal women. Clearly, if raloxifene is found to be of value to prevent breast cancer in postmenopausal women there will be a need to use the drug in premenopausal women. The NCI has initiated a safety study to evaluate the effect of raloxifene on bone density in high-risk premenopausal women. Raloxifene is a less estrogenic antiestrogen than tamoxifen and there is a possibility there could be significant bone loss. Additionally, it is anticipated that raloxifene will have an effect on the menstrual cycle. This is being monitored by extensive blood drawings. However, this is extremely inconvenient for any clinical study. This proposal monitors the actions of raloxifene on circulating steroids by measuring estradiol and progesterone in saliva. We have developed and validated a sensitive assay to measure salivary steroids. The clinical work is ongoing and the specific aims are 1.) to determine the salivary changes in estradiol and progesterone throughout the menstrual cycle, 2.) to establish the changes initiated by two doses (60mg and 300 mg daily) of raloxifene by comparison with nontreatment cycles, and 3.) to determine changes in salivary cortisol produced by raloxifene. Completion of the safety study will establish the endocrine effects of raloxifene in pre-menopausal women. Most importantly, completion of the study will validate an important new methodology to monitor the ovarian effects of any new chemopreventive that can be used in premenopausal women.