EFFECT OF RALOXIFENE ON SALIVARY STEROIDS

描述：(申请人描述) 雷洛昔芬是他莫昔芬的化学表亲，目前正在接受测试，作为一种 三苯氧胺和雷洛昔芬预防乳腺癌的研究 绝经后的高危女性。雷洛昔芬是一种被批准用于预防 骨质疏松症，尚未在绝经前妇女身上进行测试。显然，如果 雷洛昔芬被发现对预防绝经后乳腺癌有价值 有必要对绝经前妇女使用该药。国家情报局已经 启动了一项安全性研究，以评估雷洛昔芬对骨密度的影响 在高危绝经前妇女中。雷洛昔芬是一种雌激素活性较低的抗雌激素 而不是他莫昔芬，有可能有重要的骨骼 损失。此外，预计雷洛昔芬将对 月经周期。这一情况正在通过大量抽血进行监测。 然而，这对任何临床研究都是极其不便的。这项建议 通过测量监测雷洛昔芬对循环类固醇的作用 唾液中的雌二醇和黄体酮。我们已经开发并验证了 唾液类固醇的灵敏测定法。临床工作正在进行中， 具体目标是1.)测定唾液中雌二醇和 黄体酮贯穿月经周期，2。)要建立这些变化 比较两种剂量(每天60毫克和300毫克)的雷洛昔芬 非治疗周期，3)测定唾液皮质醇的变化 由雷洛昔芬生产。安全研究完成后，将确立 雷洛昔芬对绝经前妇女的内分泌影响。最重要的是， 该研究的完成将验证一种重要的新监测方法 任何一种新的化学预防药物对卵巢的影响 绝经前的女性。

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.