Side Effects of Tamoxifen

Side effects of tamoxifen include:

  • blood clots (thrombosis)
  • endometrial cancer (cancer of the uterine lining)
  • abnormal growth of uterine tissue (endometriosis)
  • stroke
  • fertility issues
  • hair and nail thinning

Blood clots (thrombosis)

The most common place for a blood clot to form is in the leg veins. These clots are dangerous because they can break loose, travel to the lung, and clog a vital blood vessel. This is called a pulmonary embolism. If you have had any history of blood clots, tamoxifen will probably not be an option for you. If anyone in your family has had blood clots, be sure to tell your doctor about this as well.

The possibility of pulmonary embolism is less than 1%, meaning that it's likely to affect less than one woman in a hundred taking tamoxifen. If you are taking tamoxifen, call your doctor if you notice any new swelling, redness, discomfort, or warmth in your legs, which might be the first sign of a clot forming there. If you have a tendency to form clots, extra care in choosing a hormonal therapy is important. Sometimes you may need to take a blood-thinning medication (such as baby aspirin) along with hormonal therapy.

Endometrial cancer

Tamoxifen has been shown to increase the risk of endometrial cancer in post-menopausal women who still have a uterus (who have not had a hysterectomy). The lining of the uterus is called the "endometrium." Tamoxifen stimulates the growth of endometrial cells. Over time, the risk of cancer cells developing in this lining is higher for women on tamoxifen.

If you have had breast cancer, you have an increased risk of endometrial cancer. Tamoxifen makes the risk of endometrial cancer a bit higher. The longer you take tamoxifen, the higher your risk of developing a tamoxifen-related endometrial cancer. (But the risk is still low, less than 1%, even if you take tamoxifen for 10 years.) If you are diagnosed with endometrial cancer within the first two years of taking tamoxifen, the cancer was most likely there before you started taking the drug.

Whether or not it is related to tamoxifen use, endometrial cancer can usually be detected in the early stages, and cured with surgery. There are often (but not always) clear early warning signs. Unexpected vaginal bleeding is generally the first sign of trouble, and should be reported to your doctor immediately.

Professional societies of gynecologists and oncologists recommend that you see your gynecologist each year for an exam. Of course, if you have any unusual vaginal bleeding or other disturbing symptoms, you should see your doctor immediately.

A Pap smear, always part of your routine yearly exam, can't detect endometrial cancer. This test only evaluates the health of the cervix. The cervix is the mouth of the uterus, not the inner lining (endometrium).

There are two ways to check out the endometrium:

  • In trans-vaginal ultrasound, an ultrasound probe is placed inside the vagina to measure the thickness and evenness of the endometrium lining.
  • A sample of uterine tissue can be taken so it can be tested. Taking the sample is a quick procedure that can usually be done in the doctor's office and doesn't usually require any anesthesia.

Endometrial ultrasounds and biopsies are not routinely recommended unless you have irregular vaginal bleeding or other related symptoms. Discuss this issue with your doctor.

If you have had a hysterectomy (removal of the uterus) because of endometrial cancer, you may not be able to take tamoxifen to treat breast cancer. But if you have had a hysterectomy for a non-cancerous problem, such as fibroids, endometrial hyperplasia (an overgrowth of normal endometrial cells), or endometrial polyps (fingerlike projections made up of normal cells), you don't have to worry about endometrial cancer.

If you are still menstruating every month, then your risk of endometrial cancer is practically zero.

Other uterine effects of tamoxifen

If you have a history of endometriosis—a non-cancerous condition in which endometrial (uterine lining) cells grow outside the uterus in the belly cavity, on the ovaries, or on the bladder—tamoxifen can make this condition worse.

Tamoxifen can also affect the uterine wall, which can lead to uneven thickening of the muscle and supportive tissues within the wall of the uterus. The result can be fibroids (ball-like overgrowths of the tissues in the wall of the uterus), or there can be bumpy irregularities in one area or throughout the uterine wall. These changes can make it difficult for your doctor to examine the endometrium by ultrasound. This is because the ultrasound study may show a thickened or uneven endometrium, when the change is really in the underlying uterine wall.

In June 2002, a new warning was added to the prescribing information, or PI, for tamoxifen. The PI is the leaflet that comes with the medication. According to this warning, women who take tamoxifen have a slightly higher risk than other women for developing cancer of the muscle wall of the uterus, also called uterine sarcoma. The risk of uterine sarcoma with tamoxifen is less than 1%.

For most women who are considered good candidates for tamoxifen, its anti–breast cancer benefits usually outweigh the risks that it could contribute to development of an endometrial cancer or uterine sarcoma.

Stroke

A comparison of six different studies found that tamoxifen may slightly increase (by less than 1%) the risk of having a stroke.

Fertility issues

If you are taking tamoxifen and you were pre-menopausal before your breast cancer treatment began, you may still be fertile. That's true even if your periods stopped or became irregular during treatment. Your ovaries may recover and might start developing eggs again. If you do not want to get pregnant, you must use a barrier form of birth control, such as condoms or a diaphragm with contraceptive gel (the gel also serves as a lubricant). Do not take birth control pills. They contain estrogens, which are not considered safe for women who have had breast cancer. Also, both birth control pills and tamoxifen have each been shown to increase the risk of blood clots. Therefore, taking them together may result in an extra-high risk of blood clots, which could be dangerous.

It's also especially important, if you are fertile, to stick to your daily dose schedule of tamoxifen. That's because if tamoxifen is taken on and off, it can actually stimulate the ovaries, like a fertility drug. If you want to get pregnant, stop taking tamoxifen before you start trying to conceive, because the drug should not be taken during any stage of pregnancy.

If you do get pregnant while you are taking tamoxifen and you want to keep the pregnancy, stop the tamoxifen. But don't drive yourself crazy worrying about the effect that a month or so of tamoxifen might have had on the baby. Tamoxifen has not been shown to produce birth defects in humans.

Hair and nail thinning

Hair thinning is unlikely to happen to you, but it's distressing if it does—especially if your hair has just grown back after you've lost it from chemotherapy. Hair thinning or loss associated with tamoxifen is much like hair loss related to low estrogen during menopause. In both cases, it tends to level off with time.

Hair thinning may respond to the prescription medication Rogaine (chemical name: minoxidil), but taking this drug is expensive and time-consuming. In addition, it can cause side effects, such as skin rash or itchy skin. If you have heart disease, you should not take Rogaine because it has been shown increase heart rate and decrease blood pressure.

For nail thinning, use moisturizing cream on your hands and avoid vigorous manicures. Nail polish can strengthen your nails and decrease their risk of breaking and peeling. Watch for any signs of infection and follow the do's and don'ts of caring for arm swelling (lymphedema) for the affected side. You may also want to talk to your cancer doctor or nurse about this problem.

Memory loss

Many women on tamoxifen feel that they are growing more forgetful. This is not surprising, since changes in memory often start around the time of a breast cancer diagnosis or during treatment. You're dealing with anxiety, lower estrogen levels, stress, and sleep loss, which all can make it harder for you to remember things. In addition, depression, medication (including chemotherapy), or other medical problems may increase memory loss.

Most women take tamoxifen for two to five years. During those years, the aging process may take away a few cells that help you remember. On the other hand, time can also help in some ways. The trauma of a breast cancer diagnosis will not be as fresh. Your body will grow more able to adjust to new medicines in its system.

Still, many women believe that their hormonal therapy is affecting their memory and thinking ability. So far, few studies have looked at a possible link between memory loss and tamoxifen. One small 2003 study did provide support for the claim that hormone therapy for breast cancer may affect memory.

Any sign of memory loss can be unnerving. If you believe you have tamoxifen-related memory loss, discuss it with your doctor. More studies are needed on this important question.

Rare or unproven side effects of tamoxifen

Vision changes: Eye problems are a rare but possible side effect of tamoxifen. Years ago, when the doses of tamoxifen given were twice what they are today, a few women suffered minor eye damage in the cornea and retina (areas of the eye). A small study of women on today's doses showed an extremely low risk of such eye changes, and those changes went away when the women stopped taking tamoxifen.

There are no strict guidelines on follow-up eye exams for women taking tamoxifen. Some, but not all, cancer doctors recommend eye examinations every year. If you notice any change of vision while taking tamoxifen, have it evaluated by an ophthalmologist or optometrist (eye doctors who treat diseases of the eye) immediately. Your eye doctor will give you eye drops to dilate (fully open) your pupils during the exam in order to get a good view of any early, small changes. If changes are noted, you can discuss them with your cancer doctor to weigh the risks and benefits of continuing to take tamoxifen.

Liver cancer: Studies so far show that tamoxifen does not increase your chance of getting liver cancer. Liver cancer starts in liver cells. It is not the same thing as breast cancer that starts in the breast and spreads to the liver. Liver cancer has been associated with high doses of tamoxifen in rats, but this effect may be specific to the biology of rats—even laboratory MICE do not get liver cancer from tamoxifen.

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