Risk Factors and Prevention:

Ovarian cancer is the eighth most common cancer in women, and the fifth leading cause of female cancer death. Each year in the United States, about 22,000 women are diagnosed with ovarian cancer. About 15,000 American women die each year from the disease.

Certain factors increase the risk for ovarian cancer, while other factors reduce risk. Many of the preventive factors are related to the number of times a woman ovulates during her lifetime, which is indicated by the number of menstrual periods she has. Fewer menstrual periods and ovulations appear to be associated with reduced risk for ovarian cancer.

Some research suggests that ovarian cancer develops in women with a higher number of ovulations because of persistent damage to the epithelial cells as the egg passes through during ovulation. Researchers think that the recurring cell division needed to heal these tiny wounds to the ovaries, month after month and year after year, creates opportunities for errors in cell reproduction that lead to the formation of cancerous cells. Therefore, the more ovulations, the more risk of ovarian cancer.

Factors That Increase the Risk for Ovarian Cancer

The main risk factors for ovarian cancer are:

• Age
• Family history of ovarian, breast, or colorectal cancer
• Genetic mutations
• Obesity
• Hormone replacement therapy use
• Menstrual and reproductive history

Age. Ovarian cancer risk increases with age. About two-thirds of women are diagnosed with ovarian cancer at age 55 or older. The average age for the onset of ovarian cancer is about age 63, although ovarian cancer can develop in women of all ages.

Family History. A family history of breast or ovarian cancer is one of the strongest risk factors for ovarian cancer. Women are also at high risk for ovarian cancer if they have a family history of a hereditary form of colorectal cancer, along with endometrial cancer and other types of colorectal cancer.

In general, women are considered at high risk for ovarian cancer if they have:

• A first-degree relative (mother, sister, or daughter) with ovarian cancer at any age. The risk increases with the number of affected first-degree relatives.
• A first-degree relative (or two second-degree relatives on the same side) with early onset breast cancer (occurring before age 50)
• A family member with both breast and ovarian cancer
• A family history of male breast cancer
• A family history of hereditary nonpolyposis colorectal cancer
• Ashkenazi (Eastern European) Jewish ancestry

When a woman describes her family history to her doctor, she should include the history of cancer in women on both the mother's and the father's side. Both are significant.

Genetic Mutations. The main genetic mutations associated with increased ovarian cancer risk are:

• BRCA1 and BRCA2 genes. Inherited mutations in the genes called BRCA1 and BRCA2 increase the risk for ovarian and breast cancers. While these mutations are more common among women of Ashkenazi Jewish ancestry, they are not restricted to this population and and occur in women of any ethnicity, including women of Asian and African descent. Women with a BRCA1 mutation have about a 40% lifetime risk for ovarian cancer. Women with a BRCA2 mutation have about a 10 - 20% lifetime risk for ovarian cancer. (By contrast, the lifetime ovarian cancer risk for women in the general public is about 1.4%.)
• HNPCC. Women who have genetic mutations associated with hereditary nonpolyposis colorectal cancer (HNPCC) have about a 12% lifetime risk of developing ovarian cancer

Obesity. Many studies have found an association between obesity and increased risk for ovarian cancer.

Hormone Replacement Therapy (HRT). Hormone replacement therapy (HRT) appears to increase the risk for ovarian cancer. A study of nearly 1 million women found that women who used HRT for more than 5 years were 20% more likely to develop and die from ovarian cancer than women who had never taken HRT. Another important study, from the U.S. National Cancer Institute, indicated that 5 or more years of combination HRT (estrogen and progestin) increases the risk of ovarian cancer for women who have not had a hysterectomy.

Menstrual and Reproductive History. Women are at increased risk for ovarian cancer if they began menstruating at an early age (before age 12), have not had any children, had their first child after age 30, or experienced early menopause (before age 50).

Risk Factors with Less Conclusive Evidence. Dietary fats have been under scrutiny for some time as possibly putting some women at higher risk for ovarian cancer. While some reviews have reported an association between a high intake in animal fats and a greater risk, other studies have found no correlation between fat intake and increased risk for ovarian cancer.

Some studies, but not all, have indicated that use of the fertility drug clomiphene (Clomid) may increase the risk for ovarian cancer. However, infertility itself is a risk factor for ovarian cancer, so it is not definite whether fertility drugs play an additional role in affecting risk.

There is inconclusive evidence as to whether environmental factors increase the risk for ovarian cancer. Possible carcinogens studied have included radiation exposure, talcum powder, and asbestos.

Factors That Reduce the Risk for Ovarian Cancer

In general, factors or behaviors that limit stimulation of the ovaries or inhibit ovulation appear to be protective. These preventive factors include:

• Oral contraceptive use
• Pregnancy and childbirth
• Tubal ligation and hysterectomy

Oral Contraceptives. Birth control pills definitely reduce the risk of ovarian cancer. Studies suggest that routine use of birth control pills that contain the female hormones estrogen and progestin, even low-dose forms, reduces a woman's risk of ovarian cancer by about 50% when compared to women who have never taken oral contraceptives. The longer a woman takes oral contraceptives the greater the protection and the longer protection lasts after stopping oral contraceptives. However, birth control pills are not safe or appropriate for all women. [For more information, see In-Depth Report #91: Birth control options for women.]

Pregnancy and Childbirth. The more times a woman gives birth, the less likely she is to develop ovarian cancer. Breast-feeding for a year or more may also decrease ovarian cancer risk.

Tubal Ligation and Hysterectomy. Tubal ligation, a method of sterilization that ties off the fallopian tubes, has been associated with a decreased risk for ovarian cancer when it is performed after a women has completed childbearing. Similarly, hysterectomy, the surgical removal of the uterus, is also associated with decreased risk. However, these procedures should not be performed solely for ovarian cancer risk reduction.

Preventive Factors with Less Conclusive Evidence. Some studies, but not all, have suggested that tea consumption is associated with reduced risk of ovarian cancer.

Preventive Strategies for High-Risk Women

Women with a strong family history of ovarian cancer may wish to discuss these preventive strategies with their doctors.

Genetic Counseling and Screening for BRCA Genes. The latest guidelines from the U.S. Preventive Services Task Force (USPSTF) recommend BRCA testing for women at high risk for ovarian cancer. The USPSTF does not recommend routine genetic counseling or testing for BRCA genes in low-risk women (no family history of BRCA1 or BRCA2 genetic mutations).

Removal of Ovaries (Oophorectomy). Surgical removal of the ovaries, called oophorectomy, significantly reduces the risk for ovarian cancer. When it is used to specifically prevent ovarian cancer in high-risk women, the procedure is called a prophylactic oophorectomy. Prophylactic oophorectomy is approximately 95% protective against ovarian cancer. It is sometimes recommended for women at high risk for ovarian cancer. These women generally have the BRCA1 or BRCA2 genetic mutation, or have two or more first-degree relatives who have had ovarian cancer.

Bilateral oophorectomy is the removal of both ovaries. Bilateral salpingo-oophorectomy is the removal of both fallopian tubes plus both ovaries. Several recent studies indicate that salpingo-oophorectomy is very effective in reducing risk for ovarian cancer in women who carry the BRCA1 or BRCA2 mutation.

Even after oophorectomy, women in high-risk groups for ovarian cancer still have a risk for the development of cancer in the peritoneum (the sac inside the abdomen that holds the intestines, uterus, and ovaries).

Premenopausal women should be aware that oophorectomy causes immediate menopause, which poses a risk for several health problems, including osteoporosis, heart disease, and reduction in muscle tone. Estrogen replacement can help offset these problems. Women who have a bilateral oophorectomy and do not receive hormone replacement therapy may experience more severe hot flashes than women who naturally enter menopause.