科研之友
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摘要
The steroidal hormone estrogen is an intracellular key mediator of diverse processes regulating skeletal, muscular, cardiovascular, neuronal and. reproductive functions. The aim of developing selective estrogen receptor modulators (SERM) was to use the physiological estrogen pathway to obtain tissue specific estrogen agonist effects on bone and estrogen antagonist effects on the breast and uterus. The first selective estrogen receptor modulator that was introduced in the adjuvant treatment of hormone receptor positive breast cancer was tamoxifen. In addition to the positive effects on the recurrence rates of breast cancer, tamoxifen also showed positive effects on bone metabolism and bone mineral density as well as on lipid profiles in postmenopausal women. Raloxifene was the first SERM, which was introduced in 1998, for the therapy and the prevention of postmenopausal osteoporosis. In bone, raloxifene leads to an inhibition of osteoclast function, which is reflected in a reduction of bone resorption markers (CTX and NIX) to the pre-menopausal range. Bone mineral density at the lumbar spine and the hip increases and the risk of vertebral fracture is significantly reduced. In breast tissue,. the estrogen antagonistic effects lead to a significant reduction in the risk of breast cancer in osteoporotic patients and women at a high risk; of breast cancer, without having any relevant, effects on the endometrium. The two major clinically relevant side effects are the increased risk for hot flushes and thromboembolic events. In summary, raloxifene comprises a positive risk benefit ratio and is therefore an effective treatment for postmenopausal osteoporosis. Further : third generation SERM, such as lasofoxifene and arzoxifene etc. are currently being investigated in large clinical trials. Recently, lasofoxifene and bazedoxifene received approval for the treatment of postmenopausal osteoporosis (February and April 2009, respectively) but are not yet available. A new, promising approach using the combination of bazedoxifene and conjugated estrogen for the treatment of hot. flushes as well as postmenopausal osteoporosis is currently being investigated.
- 出版日期2010
