Selective Estrogen Receptor Modulators - SERMs
Selective Estrogen Receptor Modulators (SERMs) are chemical compounds that act on the estrogen receptors in the body. They have different effects on different tissue so they may block estrogen’s action in breast cells and activate estrogen’s action in other cells such as uterine or bone cells. Physiologically SERMs can act as either estorgen agonists or estogran antagoists. As drugs, SERMs are used to treat cancer, osteoporosis, menopause symptoms and halted ovulation among other things. They can prevent the growth of estrogen-sensitive cancer cells by taking the place of the estrogen in the receptors so the estrogen cannot enter.
In bone, estrogen receptors ERα and ERβ are present in the cells - osteoblastes, osteocytes, and condrocytes - of the growth plate cartilage.
The first SERM in wide clinical use was tamoxifen. It was originally developed as a contraceptive because of its anti-estrogen effects, but proved not useful for birth control. In 1977 the Federal Drug Administration (FDA) approved its use for advanced breast cancer, because in tests and clinical trials it proved to deprive the cancer cells of estrogen. It was also successful in prolonging the survival rate for women who had had breast cancer surgery as well as lymph cancer that was less advanced. Tamoxifen was approved for both breast cancer surgery adjuvant chemotherapy and for lymph cancer in 1980.
A newer SERM, raloxifene, was approved by the FDA in 2007 for women with osteoporosis or considered to have a good possibility for invasive breast cancer. The FDA approval was based on tests of almost 20,000 women to measure the difference between raloxifene and tamoxifen in reducing the probability of breast cancer. Raloxifene reduced by 50% the incidence of invasive breast cancer compared to tamoxifen, blood clots by 29% and cancer of the uterus by 36%. Raloxifene (sold under the name Evista) has been shown to reduce bone turnover in postmenopausal women. Its activity in fighting both breast cancer and osteoporosis make it an attractive drug.
Raloxifene is the only SERM available in the US, and has been a big money-maker for its manufacturer, the drug company Eli Lilly. The patent protection on this medicine will expire in 2014, and afterwards less expensive generic equivalents should be available.
Arzoxifene is another SERM which has anti-estrogen activity. Eli Lilly developed it as an osteoporosis treatment, but clinical trials showed poor results - it did not reduce nonspinal fractures and it increased the risk of blood clots - and Lilly dropped development efforts on arzoxifene. Toremifene is another estrogen blocker that started being used in 2008 for metastatic breast cancer and is being considered for prostate cancer prevention.
Bazedoxifene (http://www.ncbi.nlm.nih.gov/pubmed/21187592) has been approved for osteoporosis treatment in Europe and Japan. It is expected to be approved in the US and will be sold as a daily pill under the brand name Viviant. Tests show it is relatively safe. The SERM Lasofoxifene is also used in Europe by not approved in the US and its maker, Pfizer, does not appear to be pushing for approval any more. Tests had shown it was as effective as raloxifene in firming up bones as well as reducing the risk of breat cancer and vaginal atrophy.
There have been comparative studies of aromatase inhibitors and tamoxifen. Aromatase inhibitors are enzymes that block the synthesis of estrogen. A lower estrogen level slows the growth of cancers that depend on estrogen to grow. They are considered the best kind of hormonal therapy to begin with for post-menopausal women. The studies found that a combination of tamoxifen for two to three years then changing to an aromatase inhibitor for an additional two years is more beneficial than five years of tamoxifen. Also, taking each for five years further reduces the risk of the cancer returning.
The possible side effects of SERMs include blood clots, endometrial cancer and stroke. If there is any history of stroke or blood clots or if the patient smokes, the doctor should be informed immediately. The side effects most often seen are hot flashes, vaginal discharge, fatigue, mood swings, low libido and night sweats, but there are other less common side effects including endometrial thickening (or hyperplasia), risk of uterine cancer, dizziness, severe headaches and chest pain.
There have also been several studies comparing raloxifene to alendronate . The bisphosphonate alendronate increased bone density more than raloxifene did. Results were inconclusive as to whether alendronate or raloxifene was better for reducing the risk of fractures.
Journal abstracts: SERMs in the prevention and treatment of postmenopausal osteoporosis
Last updated: June 6, 2013