Tamoxifen used to be prescribed after you were diagnosed for breast cancer -- and, as with other forms of chemo, you would run a risk for premature menopause as a side effect. But recently doctors have begun prescribing Tamoxifen as a preventative to women with a high risk for breast cancer, since it cuts breast cancer rates by about 45 percent. While the media has focused on the positive aspects of this drug (and there are many), there is an important potential side effect to Tamoxifen that hasn't been played up a great deal: it can send you into premature menopause. This happens because Tamoxifen takes the place that estrogen would and so acts as an estrogen-blocker. Since your body isn't getting the regular amount of estrogen it would naturally get -- and since low estrogen levels signal your body to produce more FSH -- your body ultimately may react by entering menopause prematurely. One important point: Often this is a temporary effect and regular ovarian function returns.
Tamoxifen is an antagonist of the estrogen receptor in breast tissue via its active metabolite, hydroxytamoxifen. In other tissues such as the endometrium, it behaves as an agonist, and thus may be characterized as a mixed agonist/antagonist. Tamoxifen is the usual endocrine (anti-estrogen) therapy for hormone receptor-positive breast cancer in pre-menopausal women, and is also a standard in post-menopausal women although aromatase inhibitors are also frequently used in that setting
Tamoxifen is sold under the trade names Nolvadex, Istubal, and Valodex.
Tamoxifen competitively binds to estrogen receptors on tumor cells and other tissue targets, producing a nuclear complex that decreases DNA synthesis and inhibits estrogen effects. It is a non-steroidal agent with potent antiestrogenic properties which compete with estrogen for binding sites in breast and other tissues.
Tamoxifen and Premature Menopause
Tamoxifen, by itself, does not cause permanent premature menopause in younger women (i.e., women in their thirties). For most young women who take tamoxifen, the ovaries continue to act normally and produce estrogen in the same or slightly increased amounts. In fact, some studies have suggested that tamoxifen may make pre-menopausal women more fertile. Therefore, precautions to avoid pregnancy should be taken if using tamoxifen when sexually active. Tamoxifen should not be taken during pregnancy.
However, for older women, the link between tamoxifen administration and early menopause is more substantial. In one of the studies, Dr. Goodwin, a Professor of Medicine at the University of Toronto, prospectively studied an inception cohort of 183 premenopausal women with locoregional breast cancer who received several forms of tamoxifen therapy or no tamoxifen treatment and followed up their status for 1 year to examine the predictors of the onset of menopause. No treatment was received by 29% of the sample; 12% received tamoxifen therapy alone; 45.3% received either cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) or cyclophosphamide, epirubicin, and 5-fluorouracil (CEF); and 13.6% received either CMF or CEF followed by tamoxifen therapy. It was found, that the use of tamoxifen therapy in addition to either type of chemotherapy resulted in a small but statistically significant increase in the risk of menopause, confirming that beyond the age of 35 years, the risk of menopause is statistically significantly increased when chemotherapy is used as opposed to tamoxifen therapy only or to no adjuvant therapy. These data provide important information for women who may be concerned about the risk of the onset of menopause associated with adjuvant therapy. While there may be some slight increased risk of premature menopause from tamoxifen therapy in the oldest group of premenopausal breast cancer patients, for women younger than 45 years of age, this is not a substantial risk. Even in older menstruating women, this model suggests that the incremental increased risk of menopause from tamoxifen therapy is only about 10% greater than in those women who receive no therapy.
Other possible side effects of tamoxifen
Though the overall occurrence of side effects is relatively low among women who take tamoxifen, the following side effects have been reported. Many women only experience one or two of these side effects and some women do not experience any. Women who are considering tamoxifen should discuss all potential benefits and risks with their physicians prior to treatment. In many cases, the benefit of treating or preventing breast cancer with tamoxifen outweighs the risk of these side effects.
* Hot flashes and other menopausal symptoms: The most commonly reported side effect among women who take tamoxifen is a higher occurrence of hot flashes (approximately 50% of women on tamoxifen experience hot flashes when compared with a placebo, an inactive pill). Hot flashes may be accompanied by sweating, flushing, or heart palpitations. Hot flashes occur when estrogen is blocked in the hypothalamus, the part of the brain that controls the body's thermostat. Some women find that regular exercise can help reduce hot flashes. If the hot flashes are particularly bothersome and do not respond to conservative measures such as exercise, calcium, or other interventions, physicians may prescribe medications such as clonidine (brand name, Duraclon) or Megace (brand name, Megestrol). Physicians may also recommend taking 30 to 60-day "breaks" from tamoxifen to help reduce hot flashes and other menopausal symptoms.
Other reported menopausal symptoms in addition to hot flashes include vaginal dryness, mood changes, headaches, and irregular menstrual cycles. Women who experience vaginal dryness, irritation, or discharge are encouraged to ask their physicians about using vaginal lubricants to help relieve these symptoms. In some cases, vaginal discharge can be an indication of a more serious condition, such as endometrial cancer, and may require further investigation.
* Nausea or vomiting: Some women who take tamoxifen may experience nausea or vomiting while on the medication. Nausea and vomiting usually cease after the first few weeks on tamoxifen. Women who experience severe nausea and vomiting while taking tamoxifen should talk to their physicians about ways to relieve these symptoms.
* Depression or mood changes: A small number of women who take tamoxifen experience sharp mood swings or become severely depressed. Since depression can come on slowly, over a period of several months, some women do not realize that they are depressed. It also may be difficult to determine whether tamoxifen is the source of the patient's depression or if other stress factors (such as coping with breast cancer and/or going through natural menopause) have contributed to the depression. Depending on the individual situation, depression may be treated with counseling or other medications. Some physicians will recommend taking 30 to 60-day "breaks" from tamoxifen to help relieve depression.
* Weight gain: Large studies conducted by the National Surgical Adjuvant Breast and Bowel Project (NSABP) revealed that women who took a placebo (inactive pill) were just as likely to gain weight as women who took tamoxifen. It is difficult to determine whether weight gain is caused by tamoxifen or by other factors, such as prior cancer treatment (especially certain chemotherapy regimens), changes in physical activity, changes in eating habits due to the stress of coping with breast cancer, etc. A few women who take tamoxifen experience weight loss.
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