Hormonal Therapy: Managing Side Effects in Women

Hormones are chemicals the body naturally produces to control the growth and activity of normal cells. Hormones can also speed the growth of some types of cancer. For example, the hormones estrogen and progesterone can stimulate the growth of some breast tumors.

Hormonal therapy is used to prevent or block hormones from speeding up the growth of cancer cells. Different forms of hormonal therapy, which is also called hormone therapy or endocrine therapy, are used to treat breast, prostate, and endometrial cancers.

In general, there are two different approaches to hormonal therapy:

• Surgical. Removal of an organ in the body that produces the hormone or hormones that stimulate cancer growth. For example, in men, the testes, which produce testosterone, can be removed with a procedure called an orchiectomy, to slow the growth of some prostate cancers.

• Medical. Agents are used to block the hormones that stimulate cancer growth. For example, the drug tamoxifen helps prevent estrogen from stimulating breast cancer growth.

The female hormones estrogen and progesterone promote the growth of some breast tumors. Hormonal therapy may be given to block these hormones from stimulating tumor growth.

Many breast cancer cells have proteins on their surfaces that can bind to estrogen. These proteins are called estrogen receptors. Tumors may also have progesterone receptors that bind to progesterone. When estrogen or progesterone binds to its receptor on the cancer cell, it signals that cell to grow.

Not all breast cancers have estrogen or progesterone receptors. In general, hormonal therapy appears to be more effective in treating breast tumors that have hormone receptors than in treating tumors that do not have these receptors.

Hormonal therapy is used in women with advanced breast cancer that has spread, or metastasized, to other parts of the body. It is also used on occasion in women who have been recently diagnosed with a large breast tumor to shrink the cancer before surgery (neoadjuvant therapy) or to prevent cancer from returning after surgery or radiation (adjuvant therapy). In some women, who have a high risk for getting breast cancer, hormonal therapy is used to prevent cancer from developing.

Hormonal therapy, like other types of cancer treatment, has side effects. An overview of hormonal therapies and ways to prevent or minimize these side effects are discussed below.

Types of hormonal therapies

There are a variety of hormonal therapies available for breast cancer. Each type works a bit differently, but all have the same goal of starving the tumor of estrogen:

• Selective estrogen receptor modulators (SERMs). SERMs are antiestrogen drugs that bind to the estrogen receptor. This prevents estrogen from binding to the receptor and stimulating cancer cell growth. SERMs include tamoxifen, toremifene, and raloxifene. They are taken as oral tablets.

• Aromatase inhibitors. These drugs are used in older women who have been through menopause. Although the ovaries of these women no longer produce large amounts of estrogen, male hormones (androgens) do circulate in the blood and can be changed into estrogen. An enzyme called aromatase carries out this change. Aromatase inhibitors prevent aromatase from changing androgens into estrogen. Anastrozole, letrozole, and exemestane are examples of aromatase inhibitors. They are taken as oral tablets.

• Estrogen receptor antagonist. A newer class of hormonal therapy drugs is the estrogen receptor (ER) antagonist. One example is fulvestrant, which is given by a monthly injection into the muscle. Like SERMs, ER antagonists bind to the estrogen receptor and block estrogen from binding to it. In addition, they also break down the estrogen receptor, lowering the number of receptors in the cell (a process called downregulation).

• Megestrol acetate. This is a progesterone-like drug that may be used in women with advanced breast cancer who do not benefit from tamoxifen.

• Ovarian ablation. The ovaries are the main source of estrogen in women who have not reached menopause. They may be removed by surgery through a procedure called oophorectomy, or they may be made inactive by radiation therapy. Removing or inactivating the ovaries causes premature menopause and its symptoms, including hot flashes and vaginal dryness. Loss of bone mass also occurs in menopause. When the ovaries are removed, a large amount of bone can be lost in a short time, which can lead to osteoporosis if it is not treated.

Side effects of hormonal therapy and ways to manage them

The side effects of hormonal therapy tend to be less severe than those caused by chemotherapy. In fact, some women experience few symptoms or have side effects that get better with time. But when side effects do arise, it is important for women to report all symptoms, even those that are minor, to a nurse or doctor. Hormonal therapy is often taken for long periods of time and symptoms can last throughout treatment if the symptoms are not treated. Women should also always talk to their doctor about any alternative remedies they might want to try. Some alternative remedies can interfere with treatment.

Below are some ways to cope with some of the side effects of hormonal therapy.

More common side effects

Hot flashes

A hot flash, also called a hot flush, with or without sweating, is a sudden rush of warmth to the face, neck, upper chest, and back that can last for a few seconds to an hour or more. This side effect is quite common with hormonal therapy. Some women experience mild symptoms while others have more severe effects. In many cases, hot flashes stop when hormonal treatment stops. Some women report that hot flashes last for years after treatment is finished. The following are some treatment options for managing hot flashes. Not all have been scientifically tested:

• Megestrol acetate is a form of progesterone called progestin that seems to be effective in lowering hot flash severity, but has some side effects, including breast tenderness, irregular vaginal bleeding, mood changes, and bloating.

• Antidepressants, such as venlafaxine

• Gabapentin

• Clonidine, normally used to lower high blood pressure, may be no better than a placebo, or dummy pill. Side effects include dry mouth, dizziness, drowsiness, and sleep difficulties.

• Phytoestrogens are estrogens that come from plants. Soy products and some herbs contain phytoestrogens. Although raising the amount of phytoestrogens in the diet is commonly recommended to lessen the severity of hot flashes, studies have shown conflicting results about their effectiveness.

• Relaxation training

• Dietary changes. Avoid caffeine, alcohol, and spicy foods.

• Clothing. Wear absorbent cotton clothing in layers that can be easily removed.

• Use sprays or moist wipes to help lower skin temperature.

• Acupuncture

Vaginal dryness and other vaginal issues

Vaginal dryness and/or discharge can be bothersome. Vaginal moisturizers and lubricants can help with this symptom. Vaginal moisturizers, such as Replens, Gyne-Moistrin, and Lubrin, can be used as needed to keep the vagina moist. Water-soluble lubricants, such as KY Jelly and Astroglide or any vaginal moisturizers, can be used before sexual activity.

In addition to vaginal dryness, women may also experience vaginal thinning and difficult or painful intercourse. Lubricants can help with some of these problems, as well.

Vaginal infections may also occur more frequently. Over-the-counter antifungal creams can provide relief for yeast infections, but a woman should contact her gynecologist for symptoms that do not go away.

Fatigue

A common problem in women with cancer is fatigue or a lack of energy. Many things can cause fatigue, such as anemia, depression, pain, poor nutrition, medications, and inadequate sleep. Some ways to prevent fatigue include:

• Go to bed at a regular time

• Take short power naps during the day

• Engage in an exercise routine, with doctor's supervision. For example, walking 10 to 30 minutes a day.

• Eat healthy foods and drink fluids

• If anemia is contributing to fatigue, blood growth stimulators, such as epoetin alfa (Procrit) or blood transfusions, may be prescribed

Nausea and vomiting

This side effect is less common with hormonal therapy than it is with chemotherapy. Nausea often goes away on its own. Women can help manage symptoms by eating bland foods, such as crackers, toast, and cereal, and drinking lots of fluids–6 to 8 glasses of liquids daily, such as water, broth, or Gatorade. The doctor or nurse may recommend antinausea medications or antianxiety medications that prevent or treat nausea or vomiting. If dehydration occurs, intravenous fluids may be needed.

Diarrhea

Diarrhea is a less common side effect of hormone therapy. Dietary measures, such as eating a bland diet and avoiding foods such as dairy products and spicy foods, can help reduce symptoms. Medications, such as loperamide (Imodium) and diphenoxylate (Lomotil), can be used to treat diarrhea.

Constipation

Constipation is a less common side effect of hormone therapy. Daily exercise, eating foods high in fiber (such as uncooked fruits and vegetables and whole grain breads and cereals) and drinking lots of liquids--6 to 8 glasses a day--can help ease symptoms. If these measures do not work, medicines, such as a stool softener or laxative, may be needed.

Weight gain

A daily exercise routine of 20 to 30 minutes per day and a weight management program can be helpful. Eating foods low in fat, such as fruits and vegetables, is a good idea.

Mood swings

Nervousness, depression, and anxiety are some of the symptoms that women may experience. It is natural to experience strong emotions in response to a diagnosis of breast cancer. These may become stronger when a woman receives hormonal therapy. Relaxation, meditation, and yoga may be useful in controlling mood swings. Exercise may help boost mood and relieve anxiety. Support groups and professional counselors may be helpful for some women. Antidepressants may be prescribed.

Pain, including pain in joints, back, and bones

For mild to moderate pain, over-the-counter pain medication can help alleviate pain in various parts of the body, such as the joints or back. Pain felt at an injection site can be treated with warm or cold compresses. A topical anesthetic cream may also be used.

Cough

Certain hormonal therapies, such as the aromatase inhibitor anastrozole, can increase coughing symptoms. Women should try to drink at least 8 glasses of fluid a day to keep the lining of the breathing tube moist. Using a humidifier to increase the moisture in the air is also a good idea. Medicines, such as dextromethorphan, benzonatate, and guaifenesin, may be used to stop or control coughing.

Osteoporosis

Osteoporosis is a disorder in which bones become porous and break more easily. Women who have gone through menopause have a higher risk of bone loss. Some hormone therapies, such as tamoxifen in some case, may lower bone loss in postmenopausal women. Other hormone therapies may not prevent or modify a woman's risk of getting osteoporosis. For this reason, postmenopausal women with breast cancer should have a bone mineral analysis to determine if a preventive therapy should be used.

Women treated with hormonal therapy should have routine screenings (bone density scans) for osteoporosis. The following suggestions are recommended for people at risk:

• Take calcium and vitamin D supplements

• Get regular physical activity, including weight-bearing exercises that put stress on bones, such as jogging, stair climbing, dancing, and resistance exercises, such as weight lifting.

• Quit smoking

• Modify alcohol intake

Medications that prevent bone loss include the bisphosphonates risedronate, zoledronic acid, alendronate, denosumab, and calcitonin. Women should talk to their doctor about which medicines, if any, would be best for them.

Rare but serious side effects

Endometrial cancer

Although most side effects of hormonal therapy are not life-threatening, in very rare cases, tamoxifen can raise a woman's chances of getting endometrial cancer, which occurs in the lining of the uterus. Women taking tamoxifen should report any unusual vaginal discharge, vaginal bleeding, menstrual irregularities, or pain or pressure in the lower abdomen to their doctor or nurse. Annual pelvic examinations to look for signs of cancer are also recommended.

Blood clots

Some hormonal therapies carry a slight risk of blood clots forming in the deep blood vessels of the legs and groin. Clots can break off and spread to the lungs. Blood clots stop the flow of blood and can cause serious medical problems. Signs of a blood clot in the lungs include sudden chest pain, shortness of breath, or coughing up blood. Symptoms of a blood clot in the legs include pain, swelling, or tenderness in the groin or legs. Women should let their doctor know if they have a history of blood clots. They should also report any of these symptoms to the doctor or nurse as soon as possible.

Effects on the eye

Tamoxifen can cause cataracts or changes to the parts of the eye called the cornea and retina. Women should report any vision changes--including an inability to tell the difference between colors--to their health care provider.

Stroke

Tamoxifen increases a woman's chance of having a stroke. Symptoms of stroke include weakness, sudden severe headache, slurred speech, trouble with seeing in one or both eyes, difficulty walking or talking, or numbness of the face, arm, or leg. Women should immediately report these symptoms to their doctor.