Part of “CHAPTER 100 – MENOPAUSE“

Postmenopausal estrogen use may protect against osteoporosis and heart disease, but may increase the risks of breast and endometrial cancers. Many women discontinue hormone treatment because of lingering concerns they have about these long-term hazards, or because of unacceptable side effects such as vaginal bleeding and breast tenderness.

Because estrogen is not an ideal treatment, drugs have been sought that have an estrogenic effect in some tissues, such as bone and the cardiovascular system, but not in others, such as the breast and endometrium. Drugs that have these tissue-specific effects have been termed selective estrogen receptor modulators (SERMs).81,81a Potentially, the benefits of estrogen could be derived without the accompanying risks. This tissue selectivity is biologically possible, because the conformation of a drug-estradiol receptor complex determines the particular DNA response elements to which it can bind. Raloxifene, a benzo-thiophene that binds to the estrogen receptor,81 is a SERM. The raloxifene-estrogen receptor complex does not bind to the estrogen-response element. Instead, it binds to a unique area of DNA, the raloxifene response element. The drug has an estrogen-antagonist effect on breast and endometrium and an estrogen-agonist effect on bone and cholesterol.

Raloxifene was first evaluated as a possible treatment for metastatic breast cancer. Large-scale clinical trials have been initiated to assess its efficacy in the prevention and treatment of osteoporosis in otherwise healthy postmenopausal women. To date, more than 14,000 women have been enrolled in raloxifene studies, of whom 8000 women were assigned treatment with raloxifene. Although most of these studies are ongoing, interim and short-term results indicate the following.