Abstract:
:Estrogen inhibits postmenopausal bone loss and decreases fracture risk. Unfortunately, estrogen replacement therapy has many undesirable side effects, the majority of which are due to stimulation of reproductive tissues. Tissue specific estrogen agonists provide a promising new alternative to natural estrogens for hormone replacement. Clomiphene (CLO) is a substituted triphenylethylene antiestrogen based on its ability to antagonize estrogen-mediated uterine growth in rodents. CLO is used clinically for the treatment of disorders of ovulation in patients wishing to become pregnant. In order to determine whether CLO has tissue selective actions, we performed a dose-response study in adult (6-month-old) ovariectomized (OVX'd) rats. The rats received daily (gavage) doses of either 17 alpha-ethynyl estradiol (E) (0.1 mg/kg) or CLO (0.01-10 mg/kg) daily for 5 weeks. Long-term loss of ovarian function had no effect on serum cholesterol, greatly decreased uterine weight, cancellous bone area and trabecular number, and increased bone formation rate (BFR) and osteoblast and osteoclast perimeters. E treatment of OVX'd rats prevented uterine atrophy, greatly lowered cholesterol, and prevented many of the bone changes. CLO was a very weak estrogen agonist in supporting uterine weight, a partial agonist in reducing serum cholesterol, and an excellent agonist in maintaining normal bone mass and indices of bone turnover. We conclude from these studies that CLO exhibits pronounced tissue selective estrogen agonism in the rat. Specifically, CLO is effective in preventing cancellous bone loss in the OVX'd rats and has minimal uterotrophic activity.
journal_name
Endocrinologyjournal_title
Endocrinologyauthors
Jimenez MA,Magee DE,Bryant HU,Turner RTdoi
10.1210/endo.138.5.5109subject
Has Abstractpub_date
1997-05-01 00:00:00pages
1794-800issue
5eissn
0013-7227issn
1945-7170journal_volume
138pub_type
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