EFFECT OF RALOXIFENE ON SALIVARY STEROIDS

描述：（申请人的描述） 雷洛昔芬，他莫昔芬的化学表亲，目前正在测试作为一个 三苯氧胺和雷洛昔芬（星星）在乳腺癌预防中的研究 绝经后高危女性雷洛昔芬是一种被批准用于预防 骨质疏松症，尚未在绝经前女性中进行过测试。显然，如果 发现雷洛昔芬对预防绝经后妇女乳腺癌有价值， 妇女将有必要使用该药物在绝经前妇女。NCI已经 启动了一项安全性研究，以评估雷洛昔芬对骨密度的影响 高危绝经前妇女的死亡率雷洛昔芬是一种雌激素性较低的抗雌激素药 比他莫昔芬更有可能 损失此外，预计雷洛昔芬将对 月经周期这是通过大量抽血来监测的。 然而，这对于任何临床研究都是极其不便的。这项建议 监测雷洛昔芬对循环类固醇的作用， 唾液中的雌二醇和孕酮。我们已经开发并验证了 敏感的检测唾液类固醇的方法。临床工作正在进行中， 具体目标是：1.）以确定雌二醇的唾液变化， 孕激素在整个月经周期，2.）来确定 通过比较，以雷洛昔芬的两种剂量（每日60 mg和300 mg）启动 无治疗周期，和3.）以确定唾液皮质醇的变化 由雷洛昔芬生产。完成安全性研究将确定 雷洛昔芬对绝经前妇女的内分泌影响。最重要的是， 这项研究的完成将证实一种重要的新方法， 任何新的化学预防剂对卵巢的影响， 绝经前妇女

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.