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Endometrial cancer

Related Terms

Adenocarcinoma, benign, bilateral salpingo-oophorectomy, cervical cancer, cervical dysplasia, cervix, chemotherapy, D & C, DES, diethylstilbestrol, dilatation and curettage, endometrial biopsy, endometrial cancer, endometriosis, endometrium, estrogen, fallopian tubes, fundus, gynecological cancers, hereditary nonpolyposis colorectal cancer, HNPCC, hormone therapy, HPV, human papillomaviruses, lichen sclerosis, malignant, melanoma, menstruation, myometrium, ovaries, PCOS, perimenopause, polycystic ovary syndrome, progesterone, radiation, squamous cell cancer, uterine cancer, uterus, VIN, vulvar cancer, vulvar intraepithelial neoplasia.

Background

Gynecologic cancer is cancer originating in the female reproductive organs. Gynecological cancers include cancer of the cervix, fallopian tubes, ovaries, uterus, vagina, and vulva.

Gynecologic cancer affects many women, with about 80,000 new cases diagnosed in the United States each year. About half of those cases are uterine cancer. The risk of getting cancer increases with age, and inherited gene mutations or a family history of cancer may increase the risk.

Gynecological cancers can be benign (non-cancerous) or malignant (cancerous).

Ovarian cancer, with more than 22,000 new cases estimated per year, is the second most common gynecologic cancer, and it accounts for more than 16,000 deaths annually.

Gynecologic cancer is a serious disease but in the majority of cases, it can be treated and cured. Gynecologic cancer may be treated by specialized surgical procedures, radiation therapy, and/or chemotherapy.

For more information on ovarian and cervical cancers, see the respective condition monographs.

Signs and symptoms

Cervical cancer: Early cervical cancer generally produces no signs or symptoms. Early signs may include abnormal vaginal bleeding, especially irregular heavy bleeding, bleeding after menopause, bleeding or spotting between periods, bleeding after sexual intercourse, pelvic (lower abdominal) pain, pain or pressure on the bladder or rectum, unexplained bladder irritation, and unexplained vaginal discharge (particularly when it is thick or foul-smelling). As the cancer progresses, symptoms may include vaginal bleeding following intercourse, between periods, or after menopause; watery, bloody vaginal discharge that may be heavy and foul smelling; and pelvic pain or pain during intercourse.

It is extremely important for women to have routine Pap tests to detect early, precancerous cellular changes. The American Cancer Society recommends that all women have a yearly Pap test starting at the age of 18 or the age they become sexually active. Some clinicians think that if the results are normal for three consecutive tests, then Pap tests can be performed every two to three years rather than annually. Older women should continue to have Pap tests because a large percentage of deaths from cervical cancer occur in women aged 65 and older.

Endometrial cancer: Endometrial cancer often develops over a period of years. Abnormal vaginal bleeding may be one of the first signs of endometrial cancer. Most cases of endometrial cancer develop in postmenopausal women whose periods have stopped. However, a small percentage of cases affects women younger than 40.

Signs and symptoms of endometrial cancer may include prolonged periods or bleeding between periods; more frequent vaginal bleeding or spotting during the years leading up to menopause (termed perimenopause); any bleeding after the time of menopause; a pink, watery, or white discharge from the vagina; pelvic pain, especially late in the disease; pain during intercourse; and weight loss.

Rarely does endometrial cancer reach an advanced stage before any signs and symptoms are present.

Ovarian cancer: Symptoms of ovarian cancer may mimic those of many other more common conditions, including digestive and bladder disorders. Symptoms include sensation of abdominal pressure, fullness, swelling or bloating, urinary urgency, and pelvic discomfort or pain. These symptoms during ovarian cancer do not tend to subside. Additional signs and symptoms that women with ovarian cancer may experience include persistent indigestion, gas or nausea, unexplained changes in bowel habits, including diarrhea or constipation, changes in bladder habits, including a frequent need to urinate, loss of appetite, unexplained weight loss or gain, increased abdominal girth or clothes fitting tighter around the waist, pain during intercourse (dyspareunia), lack of energy, and low back pain.

Vaginal cancer: Signs and symptoms of vaginal cancer include: vaginal bleeding after menopause; vaginal bleeding after intercourse; abnormal vaginal discharge; a mass in the vagina that can be felt; pain during sex; pain when urinating; constipation; and constant pain in the pelvis.

Vulvar cancer: Signs and symptoms of vulvar cancer include: vulvar itching that does not improve; a change in skin color around the vulva; a change in the feel of the skin around the vulva; and wart-like bump/bumps, cauliflower-like growths, or ulcers/sores on the vulva or clitoral area - the lump or sore can be red, gray, or white.

Other symptoms include: pain when urinating; burning or bleeding and discharge not related to the menstrual cycle; enlarged glands in the groin; a new mole on the vulva or a change in a mole that has been present for years; and an abnormal mole.

Diagnosis

A gynecologist (a doctor who specializes in conditions affecting the female reproductive system) will conduct a complete medical history and perform a physical and pelvic examination. During the pelvic examination, the doctor feels for any lumps or changes in the shape of the uterus that may indicate a problem.

Diagnosis of gynecological cancers may or may not involve these diagnostic tests:

Pap test: Pap test, or Pap smear, involves the doctor taking a sample of cells from the cervix, the lower, narrower portion of the uterus that opens into the vagina. Doctors mainly use the Pap test to detect changes in cervical cells and to detect cervical cancer.

Endometrial biopsy: Endometrial biopsy is usually performed in a doctor's office. Endometrial biopsy involves inserting a narrow tube into the uterus through the vagina and removing a small amount of tissue from the uterine wall. This tissue is tested in a lab for cancerous or precancerous cells. The procedure usually takes just a few minutes and is painless.

Dilatation and curettage (D & C): A dilatation and curettage (D & C) involves dilating (widening) the cervix (the opening of the uterus) and inserting an instrument to scrape or suction the uterine wall and collect tissue. D & C is also an outpatient procedure. It takes about an hour and usually requires general anesthesia.

Imaging tests: Imaging tests are used in patients with certain medical conditions such as severe high blood pressure, obesity, diabetes, or cancer. These patients may not be able to safely have anesthesia. In these patients, imaging tests such as a magnetic resonance imagine (MRI) scan, computerized tomography (CT) scan, or ultrasound may help diagnose cancer of the uterus.

If gynecological cancer is found, more tests to determine if the cancer has spread (metastasized) to other parts of the body will be performed (termed "staging"). These tests may include a chest X-ray, a computerized tomography (CT) scan, and a blood test to measure cancer antigen 125 (CA 125), a substance that's released in the bloodstream by some endometrial and ovarian cancers.

Complications

Complications of gynecological cancers include metastasis (spreading) to other organs, including the pelvic and abdominal lymph nodes, the abdominal cavity (causing fluid buildup), the lungs and sac surrounding the lungs (pleura), bones, liver, and brain. Pain may be present, especially in the pelvic region and lower gastrointestinal system.

Women with certain gynecological cancers (such as endometrial cancer) may lose enough blood from vaginal bleeding to cause anemia - a condition in which the blood is low in red blood cells. Anemia causes fatigue and shortness of breath.

Treatment

The treatment of gynecological cancers is based on the stage of the disease, specifically, the extent to which the cancer has spread to other parts of the body. Treatments include surgery, chemotherapy, radiation, and biological therapy.

Chemotherapy: Chemotherapy uses a combination of drugs to slow tumor growth and destroy cancer cells. Chemotherapy may be used in addition to surgery to treat gynecological cancer and to prevent recurrent disease. Drugs may be administered by mouth or intravenously (IV, or into the veins). Side effects of chemotherapy may be severe and include: fatigue; fever; hair loss (alopecia); infection; low blood cell count (such as anemia, neutropenia, thrombocytopenia); and nausea.

Hormone therapy: Some gynecological tumors, such as uterine tumors, contain certain proteins, called hormone receptors, which attract and bind to estrogen and use this hormone to grow. Hormone therapy is a treatment that uses progesterone to balance the effect of estrogen and slow tumor growth.

Hormone therapy usually involves a synthetic type of progesterone (progestin) in pill form. Side effects include increased appetite, fluid retention, weight gain, and, in premenopausal women, changes in the menstrual cycle.

Radiation therapy: Radiation uses high-energy X-rays to destroy cancer cells and shrink tumors. This treatment may be used prior to surgery (called neoadjuvant therapy) or after surgery to destroy remaining cancer cells. Radiation also may be used in patients who are unable to undergo surgery.

External beam radiation is an outpatient treatment delivered by a machine outside the body. This treatment usually is administered five days a week for several weeks. Most individuals refrain from sexual intercourse during and for several weeks following radiation therapy because contact with the genitals and vagina may be painful.

Internal beam radiation may be administered for four to six weeks after surgery. In this procedure, which is usually performed in the radiation department of a hospital, a special applicator is used to insert pellets of radioactive material into the upper vagina. In some cases, both external and internal radiation therapies are used.

Side effects of radiation include: diarrhea; dryness, itching, tightening, and burning in the skin of the vagina; fatigue; frequent, painful urination; hair loss; and changes in tastes and loss of appetite.

Surgery: Treatment for many gynecological cancers usually involves removal of the uterus, including the cervix (called total hysterectomy), and removal of the fallopian tubes and ovaries (called bilateral salpingo-oophorectomy). Surgery may be performed through an incision in the abdomen or through the vagina (called transvaginal hysterectomy).

Postoperative pain, nausea, vomiting, and fatigue are common side effects of surgery. Individuals may remain hospitalized for a few days to one week and usually can resume normal activities in four to eight weeks. Complications include the following: adverse reaction to anesthesia; hemorrhage (bleeding) caused by injury to surrounding blood vessels; injury to surrounding organs (such as the large intestine); and thromboembolism (blockage of an artery or vein by a blood clot).

Other therapies: Biological therapies involve treatments to help improve the immune system. It uses such agents as interleukin-2 (IL-2), vaccine therapy, and anti-HER-2. Anti-angiogenesis (the growth of new blood vessels to tumors) therapy decreases the amount of blood a tumor can get, thereby possibly killing or decreasing the tumor.

Some drugs treat the side effects of chemotherapy. Anemia (low number of red blood cells) is a frequent side effect of chemotherapy and may cause symptoms such as extreme tiredness, dizziness, or shortness of breath. Epoetin alfa (Procrit?, Epogen?) is a synthetic hormone that is used for the treatment of chemotherapy-related anemia by stimulating red blood cell production. Immune system problems caused by chemotherapy may be treated with filgrastim (Neupogen?), a human granulocyte colony-stimulating factor (G-CSF). G-CSF helps stimulate the production of cells of the immune system, including granulocytes, macrophages, and stem cells.

Integrative therapies

Good scientific evidence:

Greater celandine: UkrainT, a semisynthetic drug derived from greater celandine (Chelidonium majus), has been studied in clinical trials of various types of cancer with consistently positive outcomes. However, the quality of the research performed to date is inadequate, and higher quality studies are needed.

Use cautiously in patients taking amphetamines, morphine, hexobarbital, MAOIs, or dopaminergic or serotonergic drugs, or in patients undergoing radiation therapy. Avoid in patients with liver disease or in pregnant and lactating women.

Guided imagery: Early research suggests that guided imagery may help reduce cancer pain. Further research is needed to confirm these results.

Guided imagery is usually intended to supplement medical care, not to replace it, and guided imagery should not be relied on as the sole therapy for a medical problem. Contact a qualified health care provider if mental or physical health is unstable or fragile. Never use guided imagery techniques while driving or doing any other activity that requires strict attention. Use cautiously with physical symptoms that can be brought about by stress, anxiety or emotional upset because imagery may trigger these symptoms. If feeling unusually anxious while practicing guided imagery, or with a history of trauma or abuse, speak with a qualified health care provider before practicing guided imagery.

Meditation: There is good evidence that various types of meditation may help improve quality of life in cancer patients. Studies have shown benefits for mood, sleep quality, and the stresses of treatment. The specific effects of meditation are not fully understood. Additional research is needed in this area.

Use cautiously with underlying mental illnesses. People with psychiatric disorders should consult with their primary mental healthcare professional(s) before starting a program of meditation, and should explore how meditation may or may not fit in with their current treatment plan. Avoid with risk of seizures. The practice of meditation should not delay the time to diagnosis or treatment with more proven techniques or therapies, and should not be used as the sole approach to illnesses.

Psychotherapy: Psychotherapy is an interactive process between a person and a qualified mental health care professional (psychiatrist, psychologist, clinical social worker, licensed counselor, or other trained practitioner). There is good evidence that psychotherapy may enhance quality of life in cancer patients by reducing emotional distress and aiding in coping with the stresses and challenges of cancer. Therapy may be supportive-expressive therapy, cognitive therapy or group therapy. While some patients seek psychotherapy in hopes of extending survival, there conclusive evidence of effects on medical prognosis is currently lacking. Psychotherapy may help people come to terms with the fact that they may die of cancer, which is the 4th stage of dealing with a terminal illness, including denial, anger, bargaining, and acceptance.

Psychotherapy is not always sufficient to resolve mental or emotional conditions. Psychiatric medication is sometimes needed. The reluctance to seek and use appropriate medication may contribute to worsening of symptoms or increased risk for poor outcomes. In order to be successful, psychotherapy requires considerable personal motivation and investment in the process. This includes consistent attendance and attention to treatment recommendations provided by the practitioner. Not all therapists are sufficiently qualified to work with all problems. The client or patient should seek referrals from trusted sources and should also inquire of the practitioner's training and background before committing to work with a particular therapist. Some forms of psychotherapy evoke strong emotional feelings and expression. This can be disturbing for people with serious mental illness or some medical conditions. Psychotherapy may help with post-partum depression, but is not a substitute for medication, which may be needed in severe cases.

Yoga: Yoga is an ancient system of relaxation, exercise, and healing with origins in Indian philosophy. Several studies report enhanced quality of life in cancer, lower sleep disturbance, decreased stress symptoms and changes in cancer-related immune cells after patients received relaxation, meditation and gentle yoga therapy. Yoga is not recommended as a sole treatment for cancer but may be helpful as an adjunct therapy.

Yoga is generally considered to be safe in healthy individuals when practiced appropriately. Avoid some inverted poses with disc disease of the spine, fragile or atherosclerotic neck arteries, risk for blood clots, extremely high or low blood pressure, glaucoma, detachment of the retina, ear problems, severe osteoporosis, or cervical spondylitis. Certain yoga breathing techniques should be avoided in people with heart or lung disease. Use cautiously with a history of psychotic disorders. Yoga techniques are believed to be safe during pregnancy and breastfeeding when practiced under the guidance of expert instruction (the popular Lamaze techniques are based on yogic breathing). However, poses that put pressure on the uterus, such as abdominal twists, should be avoided in pregnancy.

Unclear or conflicting scientific evidence:

Acupuncture: Acupuncture, or the use of needles to manipulate the "chi" or body energy, originated in China over 5,000 years ago. There has been limited research on acupuncture for cancer pain, and the research that was done was shown to have mixed results. More studies are needed to determine potential benefits. Evidence from several small studies supports use of acupuncture at a specific point on the wrist (P6) to help chemotherapy patients reduce nausea and vomiting. Acupuncture may also reduce the pain associated with cancer.

Needles must be sterile in order to avoid disease transmission. Avoid with valvular heart disease, infections, bleeding disorders or with drugs that increase the risk of bleeding (anticoagulants), medical conditions of unknown origin, or neurological disorders. Avoid on areas that have received radiation therapy and during pregnancy. Use cautiously with pulmonary disease (like asthma or emphysema). Use cautiously in elderly or medically compromised patients, diabetics or with history of seizures. Avoid electroacupuncture with arrhythmia (irregular heartbeat) or in patients with pacemakers.

Aloe: Transparent gel from the pulp of the meaty leaves of Aloe vera has been used on the skin for thousands of years to treat wounds, skin infections, burns, and numerous other skin conditions. Dried latex from the inner lining of the leaf has traditionally been used as an oral laxative. Preliminary research suggests that aloe may help in the area of cancer prevention or may aid in the regression of cancerous tumors. Additional research is needed in this area.

Caution is advised when taking aloe supplements as numerous adverse effects including a laxative effect, cramping, dehydration and drug interactions are possible. Aloe should not be used if pregnant or breast-feeding, unless otherwise directed by a doctor.

American pawpaw: Evidence supporting the use of the American pawpaw (Asimina triloba) tree for cancer treatment in humans is largely anecdotal and subjective. However, use in humans has reported minimal side effects, and evidence from animal and test tube studies suggest that American pawpaw extract does have some anticancer activity. Pawpaw standardized extract has been used for 18 months in patients with various forms of cancer. Well-designed studies on the long-term effects of pawpaw extracts are currently lacking. Pawpaw should not be used if pregnant or breast-feeding, unless otherwise directed by a doctor.

Antineoplastons: Antineoplastons are a group of naturally occurring peptide fractions, which were observed by Stanislaw Burzynski, MD, PhD in the late 1970s to be absent in the urine of cancer patients. There is inconclusive scientific evidence regarding the effectiveness of antineoplastons in the treatment of cancer. Several preliminary human studies (case series, phase I/II trials) have examined antineoplaston types A2, A5, A10, AS2-1, and AS2-5 for a variety of cancer types. It remains unclear if antineoplastons are effective, or what doses may be safe. Until better research is available, no clear conclusion can be drawn.

Avoid if allergic or hypersensitive to antineoplastons. Use cautiously with high medical or psychiatric risk, an active infection due to a possible decrease in white blood cells, high blood pressure, heart conditions, chronic obstructive pulmonary disease, liver disease or damage, or kidney disease or damage. Avoid if pregnant or breastfeeding.

Arabinoxylan: Arabinoxylan is made by altering the outer shell of rice bran using enzymes from Hyphomycetes mycelia mushroom extract. Arabinoxylan has been found to improve immune reactions in patients with diabetes and cancer of various types. Arabinoxylan products may contain high calcium and phosphorus levels, which may be harmful for patients with compromised renal (kidney) function. Caution is advised when taking arabinoxylan supplements, as numerous adverse effects including drug interactions are possible. Arabinoxylan should not be used if pregnant or breast-feeding, unless otherwise directed by a doctor.

Aromatherapy: Healing with fragrant oils has been used for thousands of years. Aromatherapy is often used in people with chronic illnesses (frequently in combination with massage), with the intention to improve quality of life or well-being. There is currently not enough scientific evidence to form a firm conclusion about the effectiveness of aromatherapy for quality of life in cancer.

Essential oils should only be used on the skin in areas without irritation. Essential oils should be administered in a carrier oil to avoid toxicity. Avoid with a history of allergic dermatitis. Use cautiously if driving or operating heavy machinery. Avoid consuming essential oils. Avoid direct contact of undiluted oils with mucous membranes. Use cautiously if pregnant.

Art therapy: Art therapy involves the application of a variety of art modalities including drawing, painting, clay and sculpture. Art therapy enables the expression of inner thoughts or feelings when verbalization is difficult or not possible. Limited evidence suggests that art therapy may be of benefit in cancer caregiving for families of cancer patients. Possible benefits include reduced stress, lowered anxiety, increased positive emotions and increased positive communication with cancer patients and health care professionals. Art therapy may also reduce pain and other symptoms in cancer patients. More studies are needed to determine how best to use this form of intervention with this population. Art therapy may also benefit children hospitalized with leukemia during and after painful procedures. Limited available study suggests that art therapy improves cooperation with treatment. Children requested art therapy again when procedures were repeated, and parents reported that children were more manageable after art therapy.

Art therapy may evoke distressing thoughts or feelings. Use under the guidance of a qualified art therapist or other mental health professional. Some forms of art therapy use potentially harmful materials. Only materials known to be safe should be used. Related clean-up materials (like turpentine or mineral spirits) that release potentially toxic fumes should only be used with good ventilation.

Astragalus: Astragalus (Astragalus membranaceus) has been used in Chinese medicine for centuries for its immune enhancing properties. Although early laboratory and animal studies report immune stimulation and reduced cancer cell growth associated with the use of astragalus, reliable human evidence in these areas is currently lacking. In Chinese medicine, astragalus-containing herbal mixtures are also sometimes used with the intention to reduce side effects of chemotherapy and other cancer treatments. Astragalus-containing herbal combination formulas may also have beneficial effects in aplastic anemia. Due to a lack of well-designed research, a firm conclusion cannot be drawn.

Caution is advised when taking astragalus supplements, as numerous adverse effects including drug interactions are possible. Astragalus should not be used if pregnant or breast-feeding, unless otherwise directed by a doctor.

Baikal skullcap: Although the outcomes of early studies using baikal skullcap for cancer are promising, high-quality clinical studies are needed in this area before a conclusion can be made. Avoid if allergic or hypersensitive to Baikal skullcap (Scutellaria barbata), its constituents, or members of the Lamiaceae family. Use cautiously if taking sedatives and/or operating heavy machinery. Use cautiously if taking antineoplastic (anticancer) agents or agents metabolized by cytochrome P450 enzymes. Avoid if pregnant or breastfeeding. Baikal skullcap is an ingredient in PC-SPES, a product that has been recalled from the U.S. market and should not be used.

Bee pollen: Bee pollen is considered a highly nutritious food because it contains a balance of vitamins, minerals, proteins, carbohydrates, fats, enzymes, and essential amino acids. Research has found that bee pollen may reduce some adverse effects of cancer treatment side effects. Additional study is needed before a firm recommendation can be made. Caution is advised when taking bee pollen supplements as allergic reactions may occur in sensitive individuals. Bee pollen should not be used if pregnant or breast-feeding, unless otherwise directed by a doctor.

Beta-glucan: Treatment with a beta-glucan, called lentinan, plus chemotherapy (S-1) may help prolong the lives of patients with cancer that has returned or cannot be operated on. More research is needed in this area. Avoid if allergic or hypersensitive to beta-glucan. When taken by mouth, beta-glucan is generally considered safe. Use cautiously with AIDS or AIDS-related complex (ARC). Avoid using particulate beta-glucan. Avoid if pregnant or breastfeeding.

Bitter melon: Bitter melon (Momordica charantia) is used in Avurvedic medicine from India to lower blood sugar levels. Research has also found that bitter melon extracts may be beneficial in cancer therapies. MAP30, a protein isolated from bitter melon extract, is reported to possess anti-cancer effects in laboratory studies. Potential anti-cancer effects have not been studied appropriately in humans. Caution is advised when taking bitter melon supplements, as numerous adverse effects including blood sugar lowering and drug interactions are possible. Bitter melon should not be used if pregnant or breast-feeding, unless otherwise directed by a doctor.

Black tea: Black tea (Camellia sinensis) is from the same plant as green tea, but the leaves are processed differently. Black tea usually contains more caffeine than green tea. Several studies have explored a possible association between regular consumption of black tea and rates of cancer in several populations. This research has yielded conflicting results, with some studies suggesting benefits, and others reporting no effects. Laboratory and animal studies report that components of tea, such as polyphenols, have antioxidant properties and effects against tumors. However, effects in humans remain unclear, and these components may be more common in green tea rather than in black tea. Some animal and laboratory research suggests that components of black tea may actually be carcinogenic, or cancer causing, although effects in humans are not clear. Overall, the relationship of black tea consumption and human cancer prevention remains undetermined.

Avoid if allergic or hypersensitive to caffeine or tannins. Skin rash and hives have been reported with caffeine ingestion. Use caution with diabetes. Use cautiously if pregnant. Heavy caffeine intake during pregnancy may increase the risk of SIDS (sudden infant death syndrome). Very high doses of caffeine have been linked with birth defects. Caffeine is transferred into breast milk. Caffeine ingestion by infants can lead to sleep disturbances/insomnia. Infants nursing from mothers consuming greater than 500 milligrams of caffeine daily have been reported to experience tremors and heart rhythm abnormalities. Tea consumption by infants has been linked to anemia, decreased iron metabolism, and irritability.

Bovine cartilage: In early study, bovine tracheal cartilage (preparations such as Catrix? and VitaCarte?) has been studied for the treatment of cancer with encouraging results. High quality clinical research is needed to better determine the effectiveness of bovine tracheal cartilage preparations for cancer treatment.

Avoid if allergic or hypersensitive to bovine cartilage or any of its constituents. Use cautiously with cancer, renal (kidney) failure, or hepatic (liver) failure. Avoid if pregnant or breastfeeding.

Bromelain: Bromelain is a sulfur-containing digestive enzyme (proteins which help with digestion) that is extracted from the stem and the fruit of the pineapple plant (Ananas comosus). There is not enough information to recommend for or against the use of bromelain in the treatment of cancer, either alone or in addition to other therapies. One small study found that a bromelain supplement decreased tumor size in 12 breast cancer patients. Patients took the supplements for different periods of time, lasting from months to years. Caution is advised when taking bromelain supplements, as numerous adverse effects including blood thinning and drug interactions are possible. Bromelain should not be used if pregnant or breast-feeding, unless otherwise directed by a doctor.

Cat's claw: Originally found in Peru, the use of cat's claw (Uncaria tomentosa) has been said to date back to the Inca civilization, possibly as far back as 2,000 years. Cat's claw has anti-inflammatory properties, and several low-quality studies suggest that cat's claw may slow tumor growth. However, this research is early and has not identified specific types of cancer that may benefit; thus, the results are not clear. A few studies suggest that cat's claw may also boost the immune system. Caution is advised when taking cat's claw supplements, as numerous adverse effects including blood thinning and drug interactions are possible. Cat's claw should not be used if pregnant or breast-feeding, unless otherwise directed by a doctor.

Chaparral: Chaparral was used by the Native Americans for various health conditions. The chaparral component nordihydroguaiaretic acid (NDGA) has been evaluated as a treatment for cancer but due to risk of toxicity is considered unsafe and not recommended for use. Chaparral and NDGA have been associated with cases of kidney and liver failure, liver cirrhosis, kidney cysts, and kidney cancer in humans. In response to these reports, the U.S. Food and Drug Administration (FDA) removed chaparral from its "generally recognized as safe" (GRAS) list in 1970. Chaparral and NDGA are generally considered unsafe and are not recommended for use.

Avoid if allergic to chaparral or any of its components, including nordihydroguaiaretic acid. Use cautiously if taking blood thinners (anticoagulants), blood sugar medication, or drugs that are broken down by the liver (like amiodarone, phenobarbital, valproic acid). Stop use two weeks before surgery/dental/diagnostic procedures with bleeding risk, and do not use immediately after these procedures. Use cautiously if driving or operating heavy machinery. Avoid if pregnant or breastfeeding.

Chelation therapy: Early evidence shows that the chemical ethylene diamine tetraacetic acid (EDTA) may be beneficial as a chemotherapy adjunct for ovarian cancer. However, further studies are needed before a conclusion can be made.

Chelation therapy may cause serious side effects, such as dangerously low calcium levels in the blood, bone marrow damage that leads to low levels of blood cells, kidney damage (with elevated creatinine levels), very low blood pressure, fast heart rate, increased risk of bleeding or blood clots (including interference with the effects of the blood thinning drug warfarin [Coumadin?]), bacterial blood infections, seizures, allergic or immune system reactions, heart rhythm abnormalities, and unstable blood sugar levels. Other side effects may include fever, nausea, vomiting, gastrointestinal upset, excessive thirst, increased sweating, headache, decreased thyroid function, fatigue, low white blood cell count (leukopenia), low blood platelet count (thrombocytopenia), or inflammation of the uvea (uveitis). Severe reactions have occurred causing people to stop breathing. Although deaths have been reported in people receiving chelation, it is unclear if chelation therapy was the direct cause. One possible cause may be due to the loss of calcium. Chelation may be dangerous in people with heart, kidney, or liver disease or with conditions affecting blood cells or the immune system. Use during pregnancy, breastfeeding, or in children may also be dangerous due to potential toxic effects.

Chlorophyll: Preliminary evidence in suggest that chlorophyll may aid in the reduction of side effects associated with photodynamic therapies, such as those used in management of malignant tumors. Further research is required to support the use of chlorophyll as a laser therapy adjunct for cancer treatment.

Avoid if allergic or hypersensitive to chlorophyll or any of its metabolites. Use cautiously with photosensitivity, compromised liver function, diabetes or gastrointestinal conditions or obstructions. Use cautiously if taking immunosuppressant agents or antidiabetes agents. Avoid if pregnant or breastfeeding.

Chrysanthemum: Early study indicates that hua-sheng-ping (includes Chrysanthemum morifolium, Glycyrrhiza uralensis, and Panax notoginseng) may be beneficial for patients with precancerous lesions. However, more research is needed.

Avoid if allergic or hypersensitive to Chrysanthemum, its constituents, or members of the Asteraceae/Compositae family, such as dandelion, goldenrod, ragweed, sunflower, and daisies. Use cautiously if taking medication for gout, cancer, or HIV. Use cautiously with compromised immune systems or if taking immunomodulators. Avoid with photosensitivity or if taking photosensitizers. Avoid large acute or chronic doses of ingested pyrethrin. Avoid pyrethrin with compromised liver function, epilepsy, or asthma. Avoid ocular exposure to pyrethrin. Avoid if pregnant or breastfeeding.

Coenzyme Q10: Further research is needed to determine if coenzyme Q10 (CoQ10) may be of benefit for cancer when used with other therapies.

Allergy associated with Coenzyme Q10 supplements has not been reported, although rash and itching have been reported rarely. Stop use two weeks before surgery/dental/diagnostic procedures with bleeding risk and do not use immediately after these procedures. Use caution with a history of blood clots, diabetes, high blood pressure, heart attack, or stroke, or with anticoagulants (blood thinners) or antiplatelet drugs (like aspirin, warfarin, clopidogrel (like Plavix?), or blood pressure, blood sugar, cholesterol or thyroid drugs. Avoid if pregnant or breastfeeding.

Copper: Copper is a mineral that occurs naturally in many foods, including vegetables, legumes, nuts, grains and fruits, as well as shellfish, avocado, and beef (organs such as liver). Preliminary research reports that lowering copper levels theoretically may arrest the progression of cancer by inhibiting blood vessel growth (angiogenesis). Copper intake has not been identified as a risk factor for the development or progression of cancer. Copper is potentially unsafe when used orally in higher doses than the RDA. Copper supplements should not be used if pregnant or breast-feeding, unless otherwise directed by a doctor.

Cranberry: Several laboratory studies have reported positive effects of proanthocyanidins, flavonoid components of cranberry (Vaccinium macrocarpon) and other fruits such as blueberries, grape seed, and pomegranate, on health. Based on early laboratory research, cranberry has been proposed for cancer prevention. Additional study is needed in humans before a conclusion can be made.

Avoid if allergic to cranberries, blueberries or other plants of the Vaccinium species. Sweetened cranberry juice may effect blood sugar levels. Use cautiously with a history of kidney stones. Avoid more than the amount usually found in foods if pregnant or breastfeeding.

Dandelion: Limited animal research does not provide a clear assessment of the effects of dandelion on tumor growth. Well-conducted human studies are needed to better determine dandelion's effects on cancer.

Avoid if allergic to chamomile, feverfew, honey, yarrow, or any related plants such as aster, daisies, sunflower, chrysanthemum, mugwort, ragweed, or ragwort. Use cautiously with diabetes or bleeding disorders, gastroesophageal reflux disease (GERD), kidney or liver diseases, or a history of stroke or electrolyte disorders. Monitor potassium blood levels. Stop use two weeks before surgery/dental/diagnostic procedures with bleeding risk and do not use immediately after these procedures. Avoid if pregnant or breastfeeding.

DHEA (dehydroepiandrosterone): Initial research reports that the use of intravaginal DHEA may be safe, and may promote regression of low-grade cervical cancer lesions. However, further study is necessary in this area before a firm conclusion can be drawn. Patients should not substitute the use of DHEA for more established therapies, and should discuss management options and follow-up with a primary healthcare professional or gynecologist.

Avoid if allergic to DHEA. Avoid with a history of seizures. Use with caution in adrenal or thyroid disorders or with use of anticoagulants, or drugs, herbs or supplements for diabetes, heart disease, seizure or stroke. Stop use two weeks before surgery/dental/diagnostic procedures with bleeding risk, and do not use immediately after these procedures. Avoid if pregnant or breastfeeding.

Echinacea: There is currently a lack of clear human evidence that echinacea affects any type of cancer. The evidence from a small number of clinical trials evaluating efficacy of echinacea in the treatment of radiation-induced leukopenia (decrease in white blood cells) is equivocal. Studies have used the combination product Esberitox?, which includes extracts of echinacea (Echinacea purpurea and pallida) root, white cedar (Thuja occidentalis) leaf, and wild indigo (Baptisia tinctoria)root. Additional clinical studies are needed to make a conclusion.

Caution is advised when taking echinacea supplements, as numerous adverse effects including drug interactions are possible. Echinacea should not be used if pregnant or breast-feeding, unless otherwise directed by a doctor.

Essiac?: Essiac? contains a combination of herbs, including burdock root (Arctium lappa), sheep sorrel (Rumex acetosella), slippery elm inner bark (Ulmus fulva), and Turkish rhubarb (Rheum palmatum). The original formula was developed by the Canadian nurse Rene Caisse (1888-1978) and is thought to be effective in cancer therapies, although currently there is not enough evidence to recommend for or against the use of this herbal mixture as a therapy for any type of cancer. Different brands may contain variable ingredients, and the comparative effectiveness of these formulas is not known. None of the individual herbs used in Essiac? has been tested in rigorous human cancer trials, although some components have anti-tumor activity in laboratory studies. Numerous individual patient testimonials and reports from manufacturers are available on the Internet, although these cannot be considered scientifically viable as evidence. Individuals with cancer are advised not to delay treatment with more proven therapies. Caution is advised when taking Essiac? supplements, as numerous adverse effects including drug interactions are possible. Essiac? should not be used if pregnant or breast-feeding, unless otherwise directed by a doctor.

Focusing: Focusing (experiential therapy) is a method of psychotherapy that involves being aware of one's feelings surrounding a particular issue and understanding the meaning behind words or images conveyed by those feelings. Early evidence suggests focusing may improve mood and attitude in cancer patients. Firm recommendations cannot be made until well-designed clinical trials are available.

Side effect reporting is rare, but patients should consult with a qualified healthcare practitioner before making decisions about medical conditions and practices. Individuals with severe emotional difficulties should not abandon proven medical and psychological therapies but rather choose focusing as a possible adjunct.

Folic acid: Folic acid or folate is a form of a water-soluble B vitamin needed for human health. Preliminary evidence suggests that folate may decrease the risk of several types of cancer. Additional research is needed to make a conclusion. Folic acid supplementation may mask the symptoms of pernicious, aplastic, or normocytic anemias caused by vitamin B12 deficiency and may lead to neurological damage.

Avoid if allergic or hypersensitive to folate or any folate product ingredients. Use cautiously if receiving coronary stents and with anemia and seizure disorders. It is recommended that pregnant women consume 400 micrograms daily in order to reduce the risk of fetal defects. Folate is likely safe if breastfeeding.

Gamma linolenic acid (GLA): GLA is an omega-6 essential fatty acid. Some laboratory and human studies indicate that GLA may have anti-tumor activity and may be used as a cancer treatment adjunct. Additional research is needed in this area.

Caution is advised when taking GLA supplements, as numerous adverse effects including an increased risk of bleeding and drug interactions are possible. GLA should not be used if pregnant or breast-feeding, unless otherwise directed by a doctor.

Garlic: Preliminary human studies suggest that regular consumption of garlic (Allium sativum) supplements may reduce the risk of developing several types of cancer. Some studies use multi-ingredient products so it is difficult to determine if garlic alone may play a beneficial role in cancer prevention. Further well-designed human clinical trials are needed to conclude whether eating garlic or taking garlic supplements may prevent or treat cancer.

Caution is advised when taking garlic supplements, as numerous adverse effects including an increased risk of bleeding and drug interactions are possible. Garlic should not be used if pregnant or breast-feeding, unless otherwise directed by a doctor.

Ginseng: Early studies report that ginseng taken by mouth may be of benefit in cancer prevention, especially if ginseng powder or extract is used. Weak studies suggest that ginseng in combination with other herbs may improve cell activity, immune function, and red and white blood cell counts in patients with aplastic anemia; however, other studies have found decreases in blood cell counts. Early studies suggest that ginseng may decrease radiation therapy side effects and may be used as a chemotherapy adjunct to improve body weight, quality of life, and the immune response. There is currently not enough evidence to recommend the use of Panax ginseng or American ginseng for these indications. Study results are unclear, and more research is needed before a clear conclusion can be reached.

Caution is advised when taking ginseng supplements, as numerous adverse effects including an increased risk of drug interactions are possible. Ginseng should not be used if pregnant or breast-feeding, unless otherwise directed by a doctor.

Goji: Polysaccharide constituents, such as alpha- and beta-glucans from a variety of plants, are reported to have immune system enhancing properties. In clinical study, Lycium barbarum polysaccharides (LBP) demonstrated a synergistic effect in various cancer treatments, when administered in conjunction with powerful immune stimulating drugs.

Use cautiously in patients who are taking blood-thinning medications, such as warfarin. Use cautiously in asthma patients and in patients with sulfite sensitivities. The New York Department of Agriculture has detected the presence of undeclared sulfites, a food additive, in two dried goji berry products from China. Avoid in patients who are allergic to goji, any of its constituents, or to members of the Solanaceae family.

Grape seed: There is currently little information available on the use of grape seed extract in the treatment of human cancer. Further research is needed before a recommendation can be made.

Avoid if allergic or hypersensitive to grapes or other grape compounds. Use cautiously with bleeding disorders or if taking blood thinners such as warfarin, aspirin, non-steroidal anti-inflammatory drugs (NSAIDS), or anti-platelet agents. Use cautiously with drugs processed using the liver's cytochrome P450 enzyme system. Use cautiously with blood pressure disorders or if taking ACE inhibitors. Avoid if pregnant or breastfeeding.

Green tea: Green tea is made from the dried leaves of Camellia sinensis, a perennial evergreen shrub. Green tea has a long history of use in health and longevity, dating back to China approximately 5,000 years ago. Although used for centuries to help prevent diseases, the relationship of green tea consumption and human cancer in general remains inconclusive. Evidence from well-designed clinical trials is needed before a firm conclusion can be made in this area.

Caution is advised when taking green tea supplements, as numerous adverse effects including an increased risk of drug interactions are possible. Green tea should not be used if pregnant or breast-feeding, unless otherwise directed by a doctor.

Healing touch: Preliminary data suggests that healing touch (HT) may increase quality of life in cancer. However, due to weaknesses in design and the small number of studies, data are insufficient to make definitive recommendations. Studies with stronger designs are needed. HT should not be regarded as a substitute for established medical treatments. Use cautiously if pregnant or breastfeeding.

Hoxsey formula: "Hoxsey formula" is a misleading name, because it is not a single formula, but rather is a therapeutic regimen consisting of an oral tonic, topical (on the skin) preparations, and supportive therapy. The tonic is individualized for cancer patients based on general condition, location of cancer, and previous history of treatment. An ingredient that usually remains constant for every patient is potassium iodide. Other ingredients are then added and may include licorice, red clover, burdock, stillingia root, berberis root, pokeroot, cascara, Aromatic USP 14, prickly ash bark, and buckthorn bark. A red paste may be used, which tends to be caustic (irritating), and contains antimony trisulfide, zinc chloride, and bloodroot. A topical yellow powder may be used, and contains arsenic sulfide, talc, sulfur, and a "yellow precipitate." A clear solution may also be administered, and contains trichloroacetic acid.

Well-designed human studies available evaluating the safety or effectiveness of Hoxsey formula are currently lacking. Caution is advised when taking the Hoxsey formula supplements, as numerous adverse effects including an increased risk of drug interactions are possible. Hoxsey formula should not be used if pregnant or breast-feeding, unless otherwise directed by a doctor.

Hydrazine sulfate: Hydrazine is an industrial chemical marketed as having the potential to repress weight loss and cachexia (muscle wasting) associated with cancer, and to improve general appetite status. However, in large randomized controlled trials, hydrazine has not been proven effective for improving appetite, reducing weight loss, or improving survival in adults. The National Cancer Institute (NCI) sponsored studies of hydrazine sulfate that claimed efficacy in improving survival for some patients with advanced cancer. Trial results found that hydrazine sulfate did not prolong survival for cancer patients. The U.S. Food and Drug Administration (FDA) has received requests from individual physicians for approval to use hydrazine sulfate on a case-by-case "compassionate use" basis on the chance that patients with no other available effective cancer treatment options might benefit from this therapy. The overall controversy in the use of hydrazine sulfate is ongoing, and relevance to clinical practice is unknown. The use of hydrazine sulfate needs to be evaluated further before any recommendations can be made.

Hydrazine sulfate may cause cancer. Avoid if allergic or hypersensitive to hydrazine sulfate or any of its constituents. Use cautiously with liver or kidney problems, psychosis, diabetes or seizure disorders. Avoid if pregnant or breastfeeding. Side effects have been reported, including dizziness, nausea, and vomiting.

Iodine: Iodine is an element (atomic number 53), which is required by humans for the synthesis of thyroid hormones (triiodothyronine/T3 and thyroxine/T4). The potential role of non-radioactive iodine in cancer care remains unknown. Antioxidant and anti-tumor effects have been proposed based on laboratory research. In contrast, some scientists have asserted that tumors may uptake more iodine than normal tissues. It has been suggested that high rates of gastric (stomach) cancer or low rates of breast cancer in coastal Japan may be due to high iodine intake, although this has not been demonstrated scientifically. Povidone-iodine solutions have been used as a part of alternative cancer regimens, such as the Hoxsey formula. Preliminary study has also indicated povidone-iodone solution as a potential rectal washout for rectal cancer. Overall, no clear conclusion can be drawn based on the currently available evidence.

Reactions can be severe, and deaths have occurred with exposure to iodine. Avoid iodine-based products if allergic or hypersensitive to iodine. Do no use for more than 14 days. Avoid Lugol solution and saturated solution of potassium iodide (SSKI, PIMA) with hyperkalemia (high amounts of potassium in the blood), pulmonary edema (fluid in the lungs), bronchitis, or tuberculosis. Use cautiously when applying to the skin because it may irritate/burn tissues. Use sodium iodide cautiously with kidney failure. Avoid sodium iodide with gastrointestinal obstruction. Iodine is safe in recommended doses for pregnant or breastfeeding women. Avoid povidone-iodine for perianal preparation during delivery or postpartum antisepsis.

Jiaogulan: Preliminary evidence indicates that gypenosides extracted from Gynostemma pentaphyllum may decrease cancer cell viability, arrest the cell cycle, and induce apoptosis (cell death) in human cancer cells. Immune function in cancer patients has also been studied. Additional study is needed in this area.

Avoid if allergic or hypersensitive to jiaogulan (Gynostemma pentaphyllum), its constituents, or members of the Cucurbitaceae family. Use cautiously with blood disorders or taking anticoagulants or anti-platelet drugs (blood thinners). Use cautiously with diabetes. Avoid if pregnant or breastfeeding.

Lavender: Perillyl alcohol (POH), derived from lavender (Lavendula officinalis), may be beneficial in the treatment of some types of cancer. Preliminary small studies in humans, involving the use of POH suggest safety and tolerability, but effectiveness has not been established.

Avoid if allergic or hypersensitive to lavender. Avoid with a history of seizures, bleeding disorders, eating disorders (anorexia, bulimia), or anemia (low levels of iron). Avoid if pregnant or breastfeeding.

Lutein: Currently, there is insufficient available evidence to recommend for or against the use of lutein for cancer. Available evidence in humans is conflicting.

Avoid if allergic or hypersensitive to lutein or zeaxanthin. Use cautiously if at risk for cardiovascular disease or cancer. Avoid if pregnant or breastfeeding.

Lycopene: High levels of lycopene are found in tomatoes and in tomato-based products. Tomatoes are also sources of other nutrients such as vitamin C, folate, and potassium. Several laboratory and human studies examining tomato-based products and blood lycopene levels suggest that lycopene may be associated with a lower risk of developing cancer and may help stimulate the immune system. However, due to a lack of well-designed human research using lycopene supplements, its effectiveness for cancer prevention remains unclear. Based on population studies, lycopene intake in food seems to decrease the risk for ovarian cancer. However, research that specifically examines lycopene supplementation and ovarian cancer prevention is currently lacking. Observations of large human populations suggest possible benefits of tomato product intake in preventing cervical cancer. However, other studies report no benefits for cervical cancer prevention. Research that specifically studies lycopene supplements is lacking. Additional research is needed to make a conclusion.

Avoid if allergic to tomatoes or to lycopene. Due to a lack of conclusive data, avoid if pregnant or breastfeeding.

Maitake mushroom: Maitake is the Japanese name for the edible mushroom Grifola frondosa. Maitake has been used traditionally both as a food and for medicinal purposes. Early studies in the laboratory as well as in humans suggest that beta-glucan extracts from maitake may increase the body's ability to fight cancer. However, these studies have not been well designed, and better research is needed before the use of maitake for cancer can be recommended.

Caution is advised when taking maitake supplements, as numerous adverse effects including an increased risk of bleeding and drug interactions are possible. Maitake should not be used if pregnant or breast-feeding, unless otherwise directed by a doctor.

Meditation: Not enough research has shown meditation to be of benefit in cancer prevention. More studies are needed.

Melatonin: There are several early-phase and controlled human trials of melatonin in patients with various advanced stage malignancies. There is currently not enough definitive scientific evidence to discern if melatonin is beneficial as a cancer treatment, whether it increases (or decreases) the effectiveness of other cancer therapies, or if it safely reduces chemotherapy side effects.

Melatonin is not to be used for extended periods of time. Caution is advised when taking melatonin supplements, as numerous adverse effects including drug interactions are possible. Melatonin is not recommended during pregnancy or breastfeeding unless otherwise advised by a doctor.

Milk thistle: Milk thistle (Silybum marianum) has been used medicinally in China for over 2,000 years, most commonly for the treatment of liver and gallbladder disorders. There are early reports from laboratory experiments that the components silymarin and silibinin found in milk thistle may reduce the growth of human cancer cells. However, effects have not been shown in high-quality human trials.

Caution is advised when taking milk thistle supplements, as numerous adverse effects including an increased risk of bleeding and drug interactions are possible. Milk thistle should not be used if pregnant or breast-feeding, unless otherwise directed by a doctor.

Mistletoe: Mistletoe is one of the most widely used unconventional cancer treatments in Europe. Mistletoe extracts have been studied for a variety of human cancers as well as melanoma and leukemia. However, efficacy has not been conclusively proven for any one condition. In fact, some studies have shown lack of efficacy of certain preparations for a variety of cancers. Larger, well-designed clinical trials are needed.

Caution is advised when taking mistletoe supplements, as numerous adverse effects including nausea, vomiting, and drug interactions are possible. Mistletoe should not be used if pregnant or breast-feeding, unless otherwise directed by a doctor.

Moxibustion: Moxibustion is a healing technique employed across the diverse traditions of acupuncture and oriental medicine for over 2,000 years. Moxibustion uses the principle of heat to stimulate circulation and break up congestion or stagnation of blood and chi. Moxibustion is closely related to acupuncture as it is applied to specific acupuncture points. Preliminary evidence suggests that moxibustion may reduce side effects of chemotherapy or radiation therapy. More studies are needed.

Use cautiously over large blood vessels and thin or weak skin. Avoid with aneurysms, any kind of "heat syndrome," cardiac disease, convulsions or cramps, diabetic neuropathy, extreme fatigue and/or anemia, fever, inflammatory conditions, over allergic skin conditions or ulcerated sores, or skin adhesions. Avoid if pregnant or breastfeeding. Avoid areas with an inflamed organ, contraindicated acupuncture points, face, genitals, head, inflamed areas in general, nipples, and skin adhesions. Avoid in patients who have just finished exercising or taking a hot bath or shower. Use cautiously with elderly people with large vessels. It is considered not advisable to bathe or shower for up to 24 hours after a moxibustion treatment.

Oleander: Laboratory studies of oleander (Nerium oleander) suggest possible anti-cancer effects, although reliable research in humans is not currently available. There are reports that long-term use of oleander may have positive effects in patients several types of cancer. More research is needed.

Caution is advised when taking oleander supplements, as numerous adverse effects including drug interactions are possible. Oleander should not be used if pregnant or breast-feeding, unless otherwise directed by a doctor.

Omega-3 fatty acids: Omega-3 fatty acids are essential fatty acids found in some plants and fish. A balance of omega-6 and omega-3 fatty acids is advised for health. Several population studies report that dietary omega-3 fatty acids or fish oil may reduce the risk of developing several different types of cancer. Well conducted clinical trials are necessary before a clear conclusion can be drawn regarding the use of omega-3 fatty acids for cancer prevention.

Caution is advised when taking omega-3 fatty acid supplements, as numerous adverse effects including an increase in bleeding and drug interactions are possible. Omega-3 fatty acid supplements should not be used if pregnant or breast-feeding, unless otherwise directed by a doctor.

Para-aminobenzoic acid: N-butyl-p-aminobenzoate (BAB) has been shown to be a lipid-soluble local anesthetic. Early study found significant pain relief in patients with intractable cancer pain after an epidural injection of BAB suspension. Larger scale clinical study is needed to confirm these findings.

Avoid with known hypersensitivity to PABA or its derivatives. Avoid oral use in children and pregnant or nursing women. Use cautiously in patients with renal disease, bleeding disorders or taking anticoagulants, diabetics or patients at risk for hypoglycemia. Discontinue use if rash, nausea, or anorexia occurs. Pharmaceutical doses of PABA and its derivatives should only be taken under appropriate medical supervision. PABA should not be given concurrently with sulfonamides.

Perillyl alcohol: Perillyl alcohol has been used to treat cancer. However, high quality scientific studies are lacking. Further research is required before recommendations can be made.

Avoid if allergic/hypersensitive to perillyl alcohol. Avoid use in the absence of medical supervision. Use cautiously in patients under medical supervision. Avoid if pregnant or breastfeeding.

Podophyllum: Preliminary evidence suggests that podophyllum may inhibit the growth of cancer cells, and may be beneficial as an adjunct to radiation for uterine cancer. Further research is needed before a strong recommendation can be made.

Avoid if allergic/hypersensitive to podophyllum or to members of the Berberidaceae family. Podophyllum, when applied topically, may be absorbed through the skin and cause irritation of the stomach and intestines. Podophyllum toxicity may cause heart palpitations and blood pressure changes, muscle paralysis, difficulty walking, confusion, and convulsions. Using podophyllum and laxatives may result in dehydration and electrolyte depletion. Use cautiously with arrhythmia, Crohn's disease, cardiovascular problems, gallbladder disease or gallstones, high blood pressure, irritable bowel syndrome, liver insufficiency, muscular, and neurologic disorders, psychosis, kidney insufficiency. Use cautiously if taking antimiotic agents like vincristine, anti-psychotic agents, or laxatives. Avoid if pregnant or breastfeeding.

Prayer: Initial studies of prayer in patients with cancer (such as leukemia) report variable effects on disease progression or death rates when intercessory prayer is used. Better quality research is necessary before a firm conclusion can be drawn.

Prayer is not recommended as the sole treatment approach for potentially serious medical conditions, and should not delay the time it takes to consult with a healthcare professional or receive established therapies. Sometimes religious beliefs come into conflict with standard medical approaches, and require an open dialog between patients and caregivers. In clinical study, patients certain that they were receiving intercessory prayer had a higher incidence of complications following cardiac bypass surgery than those who did not know they were being prayed for.

Reiki: Reiki may contribute to reduced perception of pain, improved quality of life, and reduced fatigue in cancer patients. More studies are needed.

Reiki is not recommended as the sole treatment approach for potentially serious medical conditions, and should not delay the time it takes to consult with a healthcare professional or receive established therapies. Use cautiously with psychiatric illnesses.

Reishi mushroom: Reishi (Ganoderma lucidum) has been shown to have antineoplastic and immunomodulatory effects in animal studies. Human studies exist of advanced cancer patients using Ganopoly?, a Ganoderma lucidum polysaccharide extract. Results show improved quality of life and enhanced immune responses, which are typically reduced or damaged in cancer patients receiving chemotherapy and/or radiation therapy. Well-designed long-term studies are needed confirm these results and to determine potential side effects.

Caution is advised when taking reishi supplements, as numerous adverse effects including an increased risk of bleeding and drug interactions are possible. Reishi should not be used if pregnant or breast-feeding, unless otherwise directed by a doctor.

Resveratrol: The effects of resveratrol cannot be adequately assessed from trials using foods, wine, or combination products containing resveratrol and other substances. Well-designed clinical trials of resveratrol alone are needed before a recommendation can be made in regards to cancer prevention and/or treatment.

Avoid if allergic or hypersensitive to resveratrol, grapes, red wine or polyphenols. Resveratrol is generally considered safe and is commonly found in food and beverages. Use cautiously with bleeding disorders, abnormal blood pressure. Use cautiously with drugs that are broken down by the body's cytochrome P450 system or digoxin (or digoxin-like drugs). Avoid if pregnant or breastfeeding.

Seaweed: Bladderwrack (Fucus vesiculosus) is a brown seaweed that grows on the northern coasts of the Atlantic and Pacific oceans, and the North and Baltic seas. Bladderwrack appears to suppress the growth of various cancer cells in animal and laboratory studies. However, reliable human studies to support a recommendation for use in cancer are currently lacking.

Caution is advised when taking bladderwrack supplements, as numerous adverse effects including an increased risk of drug interactions are possible. Bladderwrack should not be used if pregnant or breast-feeding, unless otherwise directed by a doctor.

Selenium: Selenium is a trace mineral found in soil, water, and some foods. It is an essential element in several metabolic pathways. Several studies suggest that low levels of selenium (measured in the blood or in tissues such as toenail clippings), may be a risk factor for developing cancer. Population studies suggest that people with cancer are more likely to have low selenium levels than healthy matched individuals, but in most cases it is not clear if the low selenium levels are a cause or merely a consequence of disease. It currently remains unclear if selenium is beneficial for cancer prevention or cancer treatment.

Avoid if allergic or sensitive to products containing selenium. Avoid with a history of nonmelanoma skin cancer. Selenium is generally regarded as safe for pregnant or breastfeeding women. However, animal research reports that large doses of selenium may lead to birth defects.

Shark cartilage: For several decades, shark cartilage has been proposed as a cancer treatment. Studies have shown shark cartilage or the shark cartilage product AE-941 (Neovastat?) to block the growth of new blood vessels, a process called "anti-angiogenesis," which is believed to play a role in controlling growth of some tumors. There have also been several reports of successful treatments of end-stage cancer patients with shark cartilage, but these have not been well-designed and have not included reliable comparisons to accepted treatments. Many studies have been supported by shark cartilage product manufacturers, which may influence the results. In the United States, shark cartilage products cannot claim to cure cancer, and the U.S. Food and Drug Administration (FDA) has sent warning letters to companies not to promote products in this way. Without further evidence from well-designed human trials, it remains unclear if shark cartilage is of any benefit in cancer and patients are advised to check with their doctor and pharmacist before taking shark cartilage.

Shark cartilage available in Asian grocery stores and restaurants should not be eaten due to declining populations of sharks. Caution is advised when taking shark cartilage supplements, as numerous adverse effects including an increased risk of drug interactions are possible. Shark cartilage should not be used by patients who are pregnant or breast-feeding, unless otherwise directed by a doctor.

Shiitake mushroom: Shiitake (Lentinus edodes) has been taken by mouth for boosting the immune system, decreasing cholesterol levels, and for anti-aging. Lentinan, derived from shiitake, has been injected as an adjunct treatment for cancer and HIV infection. Laboratory, animal and human studies of lentinan have shown positive results in cancer patients when used as a chemotherapy adjunct. Further well-designed clinical trials on all types of cancer are required to confirm these results.

Caution is advised when taking shiitake supplements, as numerous adverse effects including an increased risk of bleeding and drug interactions are possible. Shiitake should not be used if pregnant or breast-feeding, unless otherwise directed by a doctor.

Slippery elm: Slippery elm is found as a common ingredient in a purported herbal anticancer product called Essiac? and a number of Essiac-like products. These products contain other herbs such as rhubarb, sorrel, and burdock root. Currently, there is not enough evidence to recommend for or against the use of this herbal mixture as a therapy for any type of cancer. Avoid if allergic or hypersensitive to slippery elm. Avoid if pregnant or breastfeeding.

Sorrel: Early evidence suggests that herbal formulations containing sorrel, such as Essiac?, do not shrink tumor size or increase life expectancy in patients with cancer. However, currently there is a lack of studies evaluating sorrel as the sole treatment for cancer. A conclusion cannot be made without further research.

Avoid with a known allergy or hypersensitivity to sorrel. Avoid large doses due to reports of toxicity and death, possibly because of the oxalate found in sorrel. Many tinctures contain high levels of alcohol and should be avoided when driving or operating heavy machinery. Sorrel formulations may cause nausea or vomiting when taken with the prescription drugs metronidazole (Flagyl?) or disulfiram (Antabuse?). Avoid if pregnant or breastfeeding.

Soy: Soy (Glycine max) contains compounds which have been reported to be effective as a cancer treatment. Genistein, an isoflavone found in soy, has been found in laboratory and animal studies to possess anti-cancer effects, such as blocking new blood vessel growth (anti-angiogenesis), acting as a tyrosine kinase inhibitor (a mechanism of many new cancer treatments), or causing cancer cell death (apoptosis). In contrast, genistein has also been reported to increase the growth of pancreas tumor cells in laboratory research. Until reliable human research is available, it remains unclear if dietary soy or soy isoflavone supplements are beneficial, harmful, or neutral in people with various types of cancer. There is also currently insufficient available evidence to determine the effectiveness of soy for endometrial cancer prevention.

Caution is advised when taking soy supplements, as numerous adverse effects including an increased risk of drug interactions are possible. Soy should not be used if pregnant or breast-feeding, unless otherwise directed by a doctor.

Spiritual healing: Cancer patients, especially those who fear recurrence or are unhappy with their physicians, commonly use prayer and spiritual healing. More research is needed to address the effects of spiritual healing on anxiety, depression, and quality of life in patients with cancer.

Spiritual healing should not be used as the only treatment approach for medical or psychiatric conditions, and should not delay the time it takes to consider more proven therapies.

Sweet annie: Certain constituents found in sweet annie show promise for use in cancer when used in combination with standard chemotherapy. However, currently there is not enough scientific evidence in humans to make a strong recommendation for this use.

Avoid if allergic or hypersensitive to sweet annie (Artemisia annua), its constituents, or members of the Asteraceae/Compositae family such dandelion, goldenrod, ragweed, sunflower, and daisies. Use cautiously in patients who are pregnant, taking angiogenic agents, or recovering from surgery or other wounds. Use cautiously if taking cardiotoxic or neurotoxic agents or with compromised cardiac or neural function. Use cautiously if taking immunostimulants or quinolines. Avoid if pregnant or breastfeeding.

Transcutaneous electrical nerve stimulation (TENS): Transcutaneous electrical nerve stimulation (TENS) is a non-invasive technique in which a low-voltage electrical current is delivered through wires from a small power unit to electrodes located on the skin. Although TENS has been used with some success in cancer pain, there is not enough reliable evidence to draw a firm conclusion in this area. TENS is often used in combination with acupuncture.

Avoid with implantable devices, like defibrillators, pacemakers, intravenous infusion pumps, or hepatic artery infusion pumps. Use cautiously with decreased sensation, like neuropathy, and with seizure disorders. Avoid if pregnant or breastfeeding.

Thiamin (Vitamin B1): Thiamin deficiency has been observed in some cancer patients, possibly due to increased metabolic needs. It is not clear if lowered levels of thiamin in such patients may actually be beneficial. Currently, it remains unclear if thiamin supplementation plays a role in the management of any particular type(s) of cancer.

Thiamin is generally considered safe and relatively nontoxic. Avoid if allergic or hypersensitive to thiamin. Rare hypersensitivity/allergic reactions have occurred with thiamin supplementation. Skin irritation, burning, or itching may rarely occur at injection sites. Large doses may cause drowsiness or muscle relaxation. Use cautiously if pregnant or breastfeeding.

Thymus extract: Preliminary evidence suggests that thymus extract may increase disease-free survival and immunological improvement in several types of cancer. Additional study is needed in this area.

Avoid if allergic or hypersensitive to thymus extracts. Use bovine thymus extract supplements cautiously due to potential for exposure to the virus that causes "mad cow disease." Avoid with an organ transplant or other forms of allografts or xenografts. Avoid if receiving immunosuppressive therapy, with thymic tumors, myasthenia gravis (neuromuscular disorder), untreated hypothyroidism, or if taking hormonal therapy. Avoid if pregnant or breastfeeding.

Traditional Chinese Medicine (TCM): The ancient Chinese philosophy of Taoism provided the basis for the development of Chinese medical theory. TCM uses over 120 different herbs in cancer treatment, depending on the type of cancer and its cause according to Chinese medical theory. Studies have reported significant benefits include reducing tumors, reducing treatment side effects and improved response to treatment. More studies of stronger design are needed before TCM can be recommended with confidence as an adjunct to cancer treatment, although centuries of traditional use in cancer cannot be discounted.

Chinese herbs can be potent and may interact with other herbs, foods or drugs. Consult a qualified healthcare professional before taking. There have been reports of manufactured or processed Chinese herbal products being tainted with toxins or heavy metal or not containing the listed ingredients. Herbal products should be purchased from reliable sources. Avoid ma huang, which is the active ingredient in ephedra. Avoid ginseng if pregnant or breastfeeding.

Turmeric: Turmeric (Curcuma longa) is commonly used for its anti-inflammatory properties. Several early animal and laboratory studies report anti-cancer (colon, skin, breast) properties of curcumin. Many mechanisms have been considered, including antioxidant activity, anti-angiogenesis (prevention of new blood vessel growth), and direct effects on cancer cells. Currently it remains unclear if turmeric or curcumin has a role in preventing or treating human cancer. There are several ongoing studies in this area.

Caution is advised when taking turmeric supplements, as numerous adverse effects including an increased risk of bleeding and drug interactions are possible. Turmeric should not be used if pregnant or breast-feeding, unless otherwise directed by a doctor.

Vitamin C (ascorbic acid): Dietary intake of fruits and vegetables high in vitamin C has been associated with a reduced risk of various types of cancer in population studies (particularly cancers of the mouth, esophagus, stomach, colon, or lung). However, it is not clear that it is specifically the vitamin C in these foods that is beneficial, and vitamin C supplements have not been found to be associated with this protective effect. Experts have recommended increasing dietary consumption of fruits and vegetables high in vitamin C, such as apples, asparagus, berries, broccoli, cabbage, melon (cantaloupe, honeydew, watermelon), cauliflower, citrus fruits (lemons, oranges), fortified breads/grains/cereal, kale, kiwi, potatoes, spinach, and tomatoes. Vitamin C has a long history of adjunctive use in cancer therapy, and although there have not been any definitive studies using intravenous (or oral) vitamin C, there is evidence that it has benefit in some cases. Better-designed studies are needed to better determine the role of vitamin C in cancer prevention and cancer treatment.

Avoid if allergic or sensitive to vitamin C product ingredients. Vitamin C is generally considered safe in amounts found in foods. Vitamin C supplements are also generally considered safe in most individuals if taken in recommended doses. Large doses (greater than 2 grams) may cause diarrhea and gastrointestinal upset. Avoid high doses of vitamin C with glucose 6-phosphate dehydrogenase deficiency, kidney disorders or stones, cirrhosis (inflammation of the liver), gout, or paroxysmal nocturnal hemoglobinuria (bleeding disorder). Vitamin C intake from food is generally considered safe if pregnant or breastfeeding. It is not clear if vitamin C supplements in doses higher than Dietary Reference Intake recommendations are safe for pregnant or breastfeeding women. Vitamin C is naturally found in breast milk.

Vitamin D: Limited research suggests that synthetic vitamin D analogs may play a role in the treatment of human cancers. However, it remains unclear if vitamin D deficiency raises cancer risk, or if an increased intake of vitamin D is protective against some cancers. Until additional trials are conducted, it is premature to advise the use of regular vitamin D supplementation for cancer prevention.

Avoid if allergic or hypersensitive to vitamin D or any of its components. Vitamin D is generally well-tolerated in recommended doses; doses higher than recommended may cause toxic effects. Use cautiously with hyperparathyroidism (overactive thyroid), kidney disease, sarcoidosis, tuberculosis, and histoplasmosis. Vitamin D is safe in pregnant and breastfeeding women when taken in recommended doses.

Vitamin E: Reliable scientific evidence that vitamin E is effective as a cancer treatment is currently lacking.

Caution is merited in people undergoing chemotherapy or radiation, because it has been proposed that the use of high-dose antioxidants may actually reduce the anti-cancer effects of these therapies. This remains an area of controversy and studies have produced variable results. Patients interested in using high-dose antioxidants such as vitamin E during chemotherapy or radiation should discuss this decision with their medical oncologist or radiation oncologist. Caution is advised when taking vitamin E supplements, as numerous adverse effects including an increased risk of bleeding and drug interactions are possible. Avoid if allergic or hypersensitive to vitamin E. Avoid with retinitis pigmentosa (loss of peripheral vision). Use cautiously with bleeding disorders or if taking blood thinners. Avoid above the recommended daily level in pregnant women and breastfeeding women.

Fair negative scientific evidence:

Apricot: Available clinical trials on the use of whole apricots for cancer are currently lacking. However, some research has been conducted on "LaetrileT," an alternative cancer drug marketed in Mexico and other countries outside of the U.S. LaetrileT is derived from amygdalin found in apricot pits and nuts such as bitter almond. There are multiple animal studies and initial human evidence to suggest that LaetrileT is not beneficial in the treatment of cancer. Based on a phase II trial in 1982, the U.S. National Cancer Institute concluded that LaetrileT is not an effective chemotherapeutic agent. Nonetheless, many people still travel to use this therapy outside the U.S.

Multiple cases of cyanide poisoning, including deaths, have been associated with LaetrileT therapy. Avoid if allergic to apricot, its constituents or members of the Rosaceae family, especially the Prunoideae subfamily of plants. Avoid eating excessive amounts of apricot kernels (about 7 grams daily, or more than ten kernels daily). Use cautiously with diabetes. Use cautiously when taking supplements containing beta-carotene, iron, niacin, potassium, thiamine or vitamin C. Use cautiously when taking products that may lower blood pressure. Avoid if pregnant or breastfeeding.

Beta-carotene: While diets high in fruits and vegetables rich in beta-carotene have been shown to potentially reduce certain cancer incidences, results from randomized controlled trials with oral supplements do not support this claim.

There is some concern that beta-carotene metabolites with pharmacological activity can accumulate and potentially have cancer-causing (carcinogenic) effects. A higher, statistically significant incidence of lung cancer in male smokers who took beta-carotene supplements has been discovered. Beta-carotene/vitamin A supplements may have an adverse effect on the incidence of lung cancer and on the risk of death in smokers and asbestos exposed people or in those who ingest significant amounts of alcohol. In addition, high-dose antioxidants theoretically may interfere with the activity of some chemotherapy drugs or radiation therapy. Therefore, individuals undergoing cancer treatment should speak with their oncologist if they are taking or considering the use of high dose antioxidants. Beta-carotene in the amounts normally found in food does not appear to have this adverse effect. Avoid if sensitive to beta-carotene, vitamin A or any other ingredients in beta-carotene products.

Bitter almond: "Laetrile" is an alternative cancer drug marketed in Mexico and other countries outside of the United States. Laetrile is derived from amygdalin, found in the pits of fruits and nuts such as the bitter almond. Early evidence suggests that laetrile is not beneficial in the treatment of cancer. In 1982, the U.S. National Cancer Institute concluded that laetrile was not effective for cancer therapy. Nonetheless, many people still travel to use this therapy outside the United States.

Multiple cases of cyanide poisoning, including deaths, have been associated with laetrile therapy. Avoid if allergic to almonds or other nuts. Use cautiously if driving or operating machinery. Avoid if pregnant or breastfeeding because of the risk of birth defects.

Hypnotherapy, hypnosis: Hypnosis did not reduce radiotherapy side effects such as anxiety and did not improve quality of life in patients undergoing curative radiotherapy in early high-quality studies.

Use cautiously with mental illnesses like psychosis/schizophrenia, manic depression, multiple personality disorder or dissociative disorders, or with seizure disorders.

Iridology: There is currently limited available data supporting iridology as a tool for cancer diagnosis. Additional study is needed.

Iridology should not be used alone to diagnose disease. Studies of iridology have reported incorrect diagnoses, and thus, potentially severe medical problems may go undiagnosed. In addition, research suggests that iridology may lead to inappropriate treatment. Iridology is therefore not recommended as a sole method of diagnosis or treatment for any condition.

Vitamin E: Recent evidence from well-conducted clinical study reports no reduction in the development of cancer with the use of natural-source vitamin E taken daily. Previously, there have been laboratory, population, and other human trials examining whether vitamin E is beneficial in general cancer prevention, including that for prostate, colon, or stomach cancer. Results of these prior studies have been variable. At this time, based on the best available scientific evidence, and recent concerns about the safety of vitamin E supplementation, vitamin E cannot be recommended for cancer prevention.

Avoid if allergic or hypersensitive to vitamin E. Avoid with retinitis pigmentosa (loss of peripheral vision). Use cautiously with bleeding disorders or if taking blood thinners. Avoid above the recommended daily level in pregnant women and breastfeeding women.

Prevention

Screening: Recently, the U.S. Food and Drug Administration (FDA) approved Gardasil? to protect against the Human papillomavirus (HPV) in females nine to 26 years of age to prevent cervical cancer. The Centers for Disease Controls' (CDC's) National Immunization Program (NIP) and the federal Advisory Committee on Immunization Practices (ACIP) have recommended the use of the HPV vaccine. Although the vaccine could prevent up to 70% of cervical cancer cases, it can't prevent infection with every virus that causes cervical cancer. Routine Pap tests to screen for cervical cancer remain very important. Another vaccine against HPV is in clinical trials (Cervarix?), and its results are unknown at this time.

Recommendations for prevention of cervical cancer include regular cervical cancer screening (Pap tests) for all women (within three years of when a woman begins sexual activity or at age 21) or HPV vaccination for girls and women aged nine to 26. The HPV vaccination for women aged 27 or older is not supported. All women receiving the HPV vaccine should continue to receive regular cervical cancer screenings (Pap tests) according to established screening recommendations.

Other prevention factors: Other factors recommended by healthcare professionals to prevent gynecological cancers include limiting the number of sexual partners, getting screened regularly with a Pap test, and following up any abnormal Pap test results as recommended by a healthcare provider.

Dietary factors: Dietary factors that significantly reduce the risk of gynecological cancer include eating more antioxidant-containing fresh fruits and vegetables and decreasing the intake of red meats and foods high in animal fat (such as dairy products - milk, cheese, sour cream). A study found the strongest link between dietary risk factors and ovarian cancer was meat and cheese intake. The same study found significantly reduced risk of all ovarian cancer with higher tomato consumption. Other studies have found no link between preventing ovarian cancer and dietary factors.

Exercise: An increase in physical activity has been reported to decrease the chances of developing cancer. High levels of sedentary behavior may increase the risk of ovarian cancer. A doctor can advise the patient as to what type of exercise would be best for that individual.

Oral contraception (OC, birth control pills): Studies have found a correlation between birth control pill use and a reduced risk of ovarian cancer. However, other studies have shown that oral contraception increases a woman's risk for breast cancer as well liver and cervical cancer.

Pregnancy and breastfeeding: Having at least one child lowers the risk of developing ovarian cancer. Breastfeeding a child for a year or longer also may reduce the risk of ovarian cancer.

Tubal ligation or hysterectomy: The Nurses' Health Study, which followed thousands of women for 20 years, found a substantial reduction in ovarian cancer risk in women who had had tubal ligations. The procedure also has been shown to reduce ovarian cancer risk among women with mutations in the BRCA1 gene, although how the procedure helps is uncertain. The Nurses' Health Study also indicated that having a hysterectomy may reduce ovarian cancer risk, but not by as much as tubal ligation. However, there are risks associated with tubal ligation and hysterectomy that should be discussed with a qualified healthcare professional. Studies conducted at the Alan Guttmacher Institute found that, depending on the sterilization technique used, up to two percent of women can expect a major complication at the time of operation. Patients may suffer from such complications as infection, injury to the bladder or bleeding from a major blood vessel, and burning of the bowel or other structures. A study in Britain followed 374 post-tubal patients and found that 43% had subsequent gynecological treatment for such conditions as heavy menstrual bleeding, menstrual disturbances requiring hormonal treatments, cervical erosion, ovarian tumors, and recanalization of the fallopian tubes requiring a second operation.The risk of cervical cancer among a study of 489 post-tubal women was 3.5 times the normal rate.

Weight control: The incidence of obesity is increasing in the developed world such that it now contributes as much as smoking to overall cancer deaths. Women with a body mass index (BMI) >40 have a 60% higher risk of dying from all cancers than women of normal weight. They are also at increased risk for gynecological cancer.

Author information

This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

Bibliography

American Cancer Society. .

Hanna L, Adams M. Prevention of ovarian cancer. Best Pract Res Clin Obstet Gynaecol. 2006;20(2):339-62.

Hargrove JT, Abraham GE. Endocrine profile of patients with post-tubal-ligation syndrome. J Reprod Med. 1981 Jul;26(7):359-62.

Harlap S, Kost K, Forrest JD. Preventing Pregnancy, Protecting Health: A New Look at Birth Control Choices in the United States. New York: Alan Guttmacher Institute, 1991.

Koushik A, Hunter DJ, Spiegelman D, et al. Fruits and vegetables and ovarian cancer risk in a pooled analysis of 12 cohort studies. Cancer Epidemiol Biomarkers Prev. 2005;14(9):2160-7.

National Cancer Institute (NCI). .

Natural Standard: The Authority on Integrative Medicine. .

Navarro Silvera SA, Jain M, Howe GR, Miller AB, Rohan TE. Dietary folate consumption and risk of ovarian cancer: a prospective cohort study. Eur J Cancer Prev. 2006;15(6):511-5.

No authors listed. Gynaecological illness after sterilization. Br Med J. 1972 Mar 18;1(5802):748-9.

Rieck G, Fiander A. The effect of lifestyle factors on gynaecological cancer. Best Pract Res Clin Obstet Gynaecol. 2006;20(2):227-51.

Thompson R, Bandera E, Burley V, et al. Reproducibility of systematic literature reviews on food, nutrition, physical activity and endometrial cancer. Public Health Nutr. 2007:1-9.

Causes and risk factors

Cervical cancer:

HPV (human papilloma virus): For cervical cancer, the most important risk factor is infection with HPV (human papilloma virus). HPV is a group of more than 100 types of viruses that may cause genital warts or cancers of the cervix. If the viruses cause cervical cancer, they are known as high risk HPVs. HPV is contracted during sexual intercourse. Having unprotected sex increases the risk of acquiring an HPV infection, and this occurs more often in the younger population. Women who have many sexual partners (or who have sex with men who have had many partners) have a greater chance of getting HPV and thereby developing cervical cancer.

Smoking: Women who smoke are twice as likely as to contract cervical cancer. Tobacco smoke can produce chemicals that may damage DNA in cells of the cervix, which makes the cancer more likely to occur.

HIV infection (human immunodeficiency virus): HIV is the virus that causes AIDS, and may also be a risk factor for cervical cancer. Being HIV positive makes a woman's immune system less able to fight both HPV and early cancers.

Many sexual partners: The larger the number of sexual partners, the greater the chances of acquiring HPV and possibly cervical cancer.

Early sexual activity: Having sex before the age of 18 may increase the risk of HPV infection. Immature cells are found in younger aged women, and seem to be more susceptible to the precancerous changes that HPV can cause.

Chlamydiainfection: Chlamydia is a form of bacteria that can infect women's sex organs and spread during sexual intercourse. Many women are unaware that they have it unless samples are taken at the time of their Pap test. Some studies suggest that women who have this infection (or have had it in the past) are at greater risk for cervical cancer. While further studies are needed to determine if this is true, there are good reasons to avoid this infection or to have it treated. Long-term infections can cause other serious problems.

Dietary choices: Diet can play a role in its development as well. Diets low in fruits and vegetables are linked to an increased risk of cancers including cervical cancer. Women who are overweight have been reported to be at a higher risk.

Birth control pills: The long-term use of birth control pills increases the risk of cervical cancer. Some studies have shown a higher risk after five or more years of use.

Multiple pregnancies: Women who have had more than one full-term pregnancy have an increased risk of cervical cancer. The cause is not well understood, but has been proven to be true in large studies.

Low income: Women who are poor are at greater risk for contracting cancer of the cervix. This may be due to their inability to afford good healthcare, such as Pap tests.

DES (diethylstilbestrol): This drug is a hormone that was used between 1940 and 1971 for women who were in danger of miscarriages. Daughters of women who took this drug have been reported to have a slightly higher risk of vaginal and cervical cancer.

Family history: Studies suggest that women whose family members have had cervical cancer are at an increased risk of getting the disease themselves. This may be because they are less able to fight HPV or a number of other factors could be involved.

Age: Because full-blown cervical cancer typically takes years to develop, women between the ages of 35 and 50 years are the ones who are most frequently diagnosed. However, women older than 50 or who are postmenopausal are not protected from cervical cancer. Women aged 65 years and older account for 25% of cervical cancer cases and 41% of deaths.

Endometrial cancer:

When the balance of the hormones estrogen and progesterone shifts toward more estrogen (which stimulates growth of the endometrium), a woman's risk of developing endometrial cancer increases. Factors that increase levels of estrogen in the body include:

Long-term menstruation: Individuals who begin menstruating at an early age, such as before age 12, and continue to have periods into their 50s, are at greater risk of endometrial cancer than a woman who has menstruated for fewer years. The more years the individual has had periods, the more exposure the endometrium has to estrogen.

Never being pregnant: Pregnancy seems to protect against endometrial cancer. The body produces more estrogen during pregnancy, but also produces more progesterone. Increased progesterone production offsets the effects of the rise in estrogen levels. Women with excess exposure to estrogen that is not balanced by progesterone tend to be at an increased risk of endometrial cancer.

Irregular ovulation: Ovulation, the monthly release of an egg from an ovary in menstruating women, is regulated by estrogen. Irregular ovulation or failure to ovulate can increase the individual's lifetime exposure to estrogen. Ovulation irregularities have many causes, including obesity and a condition known as polycystic ovary syndrome (PCOS). PCOS is a condition in which hormonal imbalances prevent ovulation and menstruation. Treating obesity and PCOS can help restore monthly ovulation and menstruation cycle, decreasing the risk of endometrial cancer.

Obesity: Fat tissue can alter estrogen levels. Being obese can increase levels of estrogen in the body by altering the metabolism of estrogen, putting the individual at a higher risk of endometrial cancer and other cancers. A high-fat diet and lack of exercise can also add to the risk by promoting obesity. Fatty foods (especially trans fats found in snacks and fried foods) may also directly affect estrogen metabolism, further increasing a woman's risk of endometrial cancer. Obesity may lead to diabetes and metabolic syndrome (including high cholesterol levels, blood sugar regulation problems, and inflammation).

Estrogen-only replacement therapy (ERT): Replacing estrogen alone after menopause by using estrogen drug therapy may increase the risk of developing endometrial cancer. Taking synthetic progestin, a form of the hormone progesterone, with estrogen (combination hormone replacement therapy or HRT) causes the lining of the uterus to shed and may actually lower the risk of endometrial cancer. Shedding is important because if the uterine lining becomes too thick and the endometrial glands too crowded, endometrial hyperplasia may occur allowing for the development of cellular atypia and then possibly cancer. However, the combination of estrogen and progestin therapy may increase the risk of developing other health conditions, such as cardiovascular disease, breast cancer, and ovarian cancer.

Ovarian tumors: Tumors in the ovaries may themselves be a source of estrogen, increasing estrogen levels.

Age: Most endometrial cancers develop over many years. Therefore, the older the individual, the greater their risk of developing gynecological cancers. Approximately 95% of endometrial cancer occurs in women older than 40.

History of breast cancer or ovarian cancer: A history of breast cancer or ovarian cancer can also increase the risk of endometrial cancer.

Tamoxifen therapy: One in every 500 women whose breast cancer was treated with tamoxifen (Nolvadex?) will develop endometrial cancer. Although tamoxifen acts mostly as an estrogen blocker, it does have some estrogen-like effects and can cause the uterine lining to grow. If the individual is being treated with tamoxifen, a doctor will recommend an annual pelvic examination and ask the individual to report any unusual vaginal bleeding.

Race: Caucasian women are more likely to develop endometrial cancer, but African American women are much more likely to die of the disease. Although the reasons are not known for this increase in death rates among African American women, socioeconomic, biologic, and cultural factors increase their risks of death.

Hereditary nonpolyposis colorectal cancer (HNPCC): Hereditary nonpolyposis colorectal cancer (HNPCC) is an inherited disease caused by an abnormality in a gene important for DNA repair. Women with HNPCC also have a significantly higher risk of endometrial cancer as well as colon and other cancers.

Ovarian cancer:

Women who started menstruating at an early age (before age 12), have no children, had their first child after age 30, and/or experienced menopause after age 50 are at high risk of developing ovarian cancer. Women with a history of breast cancer also are at high risk for developing ovarian cancer. Menopause also increases the risk of developing ovarian cancer, especially if hormonal replacement therapy (HRT) is being used.

Inherited gene mutations: The most significant risk factor for ovarian cancer is having an inherited mutation in one of two genes called breast cancer gene 1 (BRCA1) and breast cancer gene 2 (BRCA2). These genes were originally identified in families with multiple cases of breast cancer, but they are also responsible for about five to 10% of ovarian cancers. An individual is at particularly high risk of carrying these types of mutations if they're of Ashkenazi Jewish descent. Another known genetic link involves an inherited syndrome called hereditary nonpolyposis colorectal cancer (HNPCC). Individuals in HNPCC families are at an increased risk of cancers of the uterine lining (endometrium), colon, ovary, stomach, and small intestine. Risk of ovarian cancer associated with HNPCC is lower than is that of ovarian cancer associated with BRCA mutations. Other hereditary risk factors include basal cell nevus syndrome, Lynch II Syndrome (also known as hereditary nonpolyposis colorectal cancer), multiple endocrine neoplasia I, and Peutz-Jeghers Syndrome.

Family history: Ovarian cancer may occur in more than one family member, although it can occur in individuals who have no family members with the disease. If the individual has one first-degree relative (a mother, daughter or sister) with ovarian cancer, the risk of developing the disease is five percent over a lifetime.

Age: Ovarian cancer most often develops after menopause. The risk of developing ovarian cancer increases with age through a woman's late 70s. Although most cases of ovarian cancer are diagnosed in postmenopausal women, the disease may also occur in premenopausal women.

Childbearing status: Women who have had at least one pregnancy appear to have a lower risk of developing ovarian cancer, unless the pregnancy was not carried to term.

Infertility: Studies indicate that infertility may increase the risk of ovarian cancer, even without the use of fertility drugs. The risk appears to be highest for women with unexplained infertility and for women with infertility who never conceive. In some studies, researchers have found that prolonged use of the fertility drug clomiphene citrate (Clomid?), especially without achieving pregnancy, may increase the risk for developing ovarian tumors.

Ovarian cysts: Cyst formation is a normal part of ovulation in premenopausal women. However, cysts that form after menopause have a greater chance of being cancerous. The likelihood of cancer increases with the size of the growth and with age. Polycystic ovary syndrome (PCOS) is a disorder where many fluid-filled cysts (sacs) are present and male hormones (androgens) are excessively high. PCOS can increase the risk of developing ovarian cancer.

Hormone replacement therapy (HRT): Some research suggests that long-term use of HRT (10 years or more) increases the risk of ovarian cancer. In a study of more than 200,000 women, researchers from the American Cancer Society found that using estrogen replacement therapy (estrogen without progestin) for 10 or more years increases the risk of death from ovarian cancer. While the chances of developing ovarian cancer doubles with prolonged estrogen use, the risk still appears to be small, estimated at approximately two percent over a lifetime. However, the study did not include data from women who used combination hormone replacement therapy (estrogen and progesterone), which is the most common regimen prescribed today. While researchers are not certain why estrogen therapy increases the risk of ovarian cancer, they do know that estrogen causes ovarian cells to produce at faster than normal rates.

Obesity in early adulthood: Studies have suggested that women who are obese at age 18 are at increased risk of developing ovarian cancer before menopause. Obesity may also be linked to more aggressive ovarian cancers, which can result in a shorter time to disease relapse and a decrease in the overall survival rate.

Talcum powder: Some studies have shown a slight increase in the risk of ovarian cancer among women who used talcum powder (baby powder) on the genital area. Asbestos in the powder may explain the link, but these products have been free of asbestos for more than 20 years.

Smoking and alcohol use: Some studies have found smoking and alcohol use may increase the risk for developing one type of ovarian cancer, called mucinous ovarian cancer.

Vaginal cancer:

Risk factors for developing vaginal cancer include: being aged 60 or older and being exposed to diethylstilbestrol (DES) while in the mother's womb. In the 1950s, the hormonal drug DES was given to some pregnant women to prevent miscarriage. Women who were exposed to DES before birth have an increased risk of developing vaginal cancer. Some of these women develop a rare form of cancer called clear cell adenocarcinoma. Having human papilloma virus (HPV) infection and having a history of abnormal cells in the cervix or cervical cancer may also increase the risk of developing vaginal cancer.

Vulvar cancer:

Diabetes: Diabetes may be a risk factor for vulvar cancer. The reasons are not clear.

Age: Advancing age increases the risk for developing squamous cell carcinoma, the most common type of vulvar cancer. Many women diagnosed with this cancer are in their 70s or older.

Human papillomavirus (HPV): Human papillomaviruses can cause genital warts or precancer of the cervix without visible warts. HPV may also increase the risk for vulvar cancer.

Smoking: Smoking increases the risk for vulvar cancer. If the individual smokes and also has genital warts or human papillomavirus (HPV) infection in the genital tract, the risk is even greater for vulvar cancer.

Vulvar intraepithelial neoplasia (VIN): Vulvar intraepithelial neoplasia (VIN) is a precancerous condition that causes a change in the cells on the surface of the vulva. VIN may or may not be visible, but having it may increase the individual's risk for the most common type of vulvar cancer, squamous cell carcinoma.

Lichen sclerosis: Lichen sclerosis, a condition that makes the vulvar skin itchy and thin, slightly increases the risk of developing vulvar cancer.

Melanoma: If a parent or sibling has had melanoma or atypical moles, an individual may have a higher risk of getting a melanoma of the vulva. Melanoma is a rare kind of vulvar cancer but one that can be quite aggressive. There is no known hereditary risk for other types of vulvar cancer. Any new mole, freckle, or dark spot on the vulva should be checked by a doctor.

Chronic vulvar infections or irritations: Chronic infections or irritations of the skin of the vulva may also be a risk factor for vulvar cancer. Improving hygiene or managing infections will help to decrease the risk.

Human immunodeficiency virus (HIV): Human immunodeficiency virus increases the individual's risk for vulvar cancer due to a decrease in immunity.

Types of gynecological cancers

Cervical cancer: Cervical cancer develops in the lining of the cervix, which is the lower part of the uterus (womb) entering the vagina (birth canal). Cells usually change from normal to pre-cancer and then to cancer over a number of years, although some cases can happen more quickly. These changes are referred to by several terms, including cervical dysplasia (also known as cervical intraepithelial neoplasia or CIN). For some women, these changes may go away without any treatment, but more often they need to be treated to prevent them from becoming true cancers.

Cervical cancer is the focus of intense screening efforts using the Pap smear (also known as Pap test). The Pap smear is a diagnostic procedure that checks for changes in the cells of the cervix. In developed countries, the widespread use of cervical screening programs, such as Pap smear testing, has reduced the incidence of invasive cervical cancer by 50% or more.

The causes of cervical cancer include the human papilloma virus (HPV).

The American Cancer Society predicts that there will be about 11,150 new cases of invasive cervical cancer in the United States in 2007. About 3,670 women will die from this disease that same year, and it most commonly develops in women aged 40 years or older. Currently, 11% of U.S. women report that they do not have regular cervical cancer screenings.

See the Cervical Cancer condition monograph for more details.

Endometrial cancer:Endometrial cancer, carcinoma of the lining of the uterus, is the most common gynecologic malignancy, comprising approximately 95% of all uterine cancers diagnosed. Approximately 40,000 American women receive a diagnosis of endometrial cancer each year, making it the fourth most common cancer found in women, after breast cancer, lung cancer, and colon cancer. Endometrial cancer is most common after the reproductive years, between the ages of 60 and 70.

The uterus is part of a woman's reproductive system. It is the hollow, upside down, pear-shaped organ (womb) in which a baby grows. The uterus is in the pelvis between the bladder and the rectum. The narrow, lower portion of the uterus is the cervix. The broad, middle part of the uterus is the body or corpus. The dome-shaped top of the uterus is the fundus. The fallopian tubes extend from either side of the top of the uterus to the ovaries. The wall of the uterus has two layers of tissue. The inner layer, or lining, is the endometrium. The outer layer is muscle tissue called the myometrium. Uterine cancer originates in the myometrium and accounts for less than 10% of uterine cancer cases.

In women of childbearing age, the lining of the uterus grows and thickens each month to prepare for pregnancy. If a woman does not become pregnant, the thick, bloody lining flows out of the body through the vagina. This flow is called menstruation.

Endometrial cancer is often detected at an early stage because it frequently produces vaginal bleeding between menstrual periods or after menopause. If discovered early, this slow-growing cancer is likely to be confined to the uterus. Removing the uterus surgically often eliminates all of the cancer (see Treatment: hysterectomy). Unfortunately, not all endometrial cancer can be successfully treated. In these cases, the cancer has spread beyond the uterus by the time it is detected. The National Cancer Institute estimates that about 7,000 American women die each year of endometrial cancer.

Ovarian cancer: Women have two ovaries, one on each side of the uterus. The ovaries, each about the size of an almond, produce eggs (ova) as well as the female sex hormones estrogen and progesterone. Ovarian cancer is a disease in which normal ovarian cells begin to grow in an uncontrolled, abnormal manner and produce tumors in one or both ovaries.

According to the American Cancer Society, ovarian cancer ranks fifth in cancer deaths among women. Approximately 20,000 women in the United States develop ovarian cancer annually. About 15,000 deaths from ovarian cancer will occur in American women during that same time frame.

The chances of surviving ovarian cancer are better if the cancer is found early. But because the disease is difficult to detect in its early stage, only about 20 percent of ovarian cancers are found before tumor growth has spread into adjacent tissues and organs beyond the ovaries. Most of the time, the disease has already advanced before it's diagnosed.

Until recently, doctors thought that early-stage ovarian cancer rarely produced any symptoms. But new evidence has shown that most women may have signs and symptoms even in the early stages of the disease. Being aware of them may lead to earlier detection.

See the Ovarian Cancer condition monograph for more details.

Vaginal cancer: Cancer of the vagina, a rare type of gynecological cancer in women, is a disease in which cancer cells are found in the tissues of the vagina. The vagina is the passageway through which fluid passes out of the body during menstrual periods and through which a woman gives birth. It is also called the "birth canal." The vagina connects the cervix (the opening of the womb or uterus) and the vulva (the folds of skin around the opening to the vagina).

There are two types of cancer of the vagina - squamous cell cancer (squamous carcinoma) and adenocarcinoma. Squamous carcinoma is usually found in women between the ages of 60 and 80. Adenocarcinoma is more often found in women between the ages of 12 and 30.

Individuals infected with human papillomaviruses (HPV) or certain subtypes of HPV may be also be at risk for vaginal cancer.

Vulvar cancer: Cancer of the vulva, a rare kind of cancer in women, is a disease in which cancer cells are found in the vulva. The vulva is the outer part of a woman's vagina. The vagina is the passage between the uterus (the hollow, pear-shaped organ where a fetus grows) and the outside of the body.

Approximately 4,000 women in the United States are diagnosed with vulvar cancer annually. Most women with cancer of the vulva are over age 50. However, it is becoming more common in women under age 40. Women who have constant itching and changes in the color and the way the vulva looks are at a high risk to get cancer of the vulva. A clinician should be seen if there is bleeding or discharge not related to menstruation (periods), severe burning/itching or pain in the vulva, or if the skin of the vulva looks white and feels rough. The chance of recovery and choice of treatment depend on the whether the cancer in the vulva has spread to other places as well as the individual's general state of health.

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