Tubal Ligation Cuts Ovarian Ca Risk

OB/GYN News, June 15, 2001 by Kate Johnson

Women with BRCA1 mutations who have undergone a tubal ligation have a 60% lower risk of developing invasive ovarian cancer than those who haven't had the procedure, results of a matched case-control study indicate.

And women who used oral contraceptives before having a tubal ligation had an even greater benefit; their risk dropped by 72%. "Up until now, I have been advising high-risk women to have their ovaries removed at age 35, but that comes with all the side effects of surgical menopause," the study's lead author, Dr. Steven Narod, said in an interview.

Because of these side effects, few women choose to have oophorectomy before age 35. Offering tubal ligation as soon as childbearing is complete is a reasonable alternative and should be followed by an oophorectomy at a later date, said Dr. Narod, a medical geneticist at Sunnybrook and Women's College Hospital, Toronto.

Previous studies have suggested that tubal ligation reduces ovarian cancer risk, but this is the first study to look specifically at its effects in carriers of BRCA1 or BRCA2 mutations, who are at high risk for the disease.

Aside from prophylactic oophorectomy, other strategies for reducing the risk of ovarian cancer in high-risk women include chemoprevention with oral contraceptives and regular ultrasound screening. But the effectiveness of ultrasound screening has not been established, and there are concerns that oral contraceptive use could be associated with an increased risk of breast cancer.

Women are considered to be at high risk for ovarian cancer if they have a mutation in either the BRCA1 or BRCA2 gene. The risk of developing ovarian cancer is about 40% in BRCA1 carriers and about 25% in BRCA2 carriers. In the study, the protective effect of tubal ligation was apparent only in carriers of BRCA1 mutations. "We don't fully understand why this is, but because of this we cannot yet make specific recommendations for carriers of BRCA2" mutations, he said.

The study compared women from the United States, Canada, and the United Kingdom who carried a pathogenic mutation in their BRCA1 or BRCA2 genes. A total of 232 women who had a history of invasive ovarian cancer were matched with 232 controls who had the same genetic mutation but did not have the cancer and had not undergone bilateral oophorectomy (Lancet 357[9267]:1467-70, 2001).

The women were matched for year of birth, country of residence, and BRCA1 or BRCA2 mutation.

Among the 173 patients and their matched controls who had the BRCA1 mutation, tubal ligation was much less common among the women with ovarian cancer (18%), compared with those who did not have the disease (35%).

After adjustment for possible confounding variables such as history of breast cancer, parity, and ethnic group, the investigators found a 60% decrease in the relative risk of ovarian cancer in women who'd had a tubal ligation and a 72% reduction in those who had a tubal ligation plus a history of oral contraceptive use. Tubal ligation conveyed the greatest protection when the procedure was done before age 30.

"This is very practical information that we can give patients. They come in for their genetic testing on Monday, get their tubal ligation on Tuesday, and their risk of ovarian cancer is reduced by 60% on Wednesday" he said.

Dr. Narod said he would still recommend that women at high risk for ovarian cancer also have an oophorectomy at a later date. Not only does this strategy offer women further protection against ovarian cancer, but it also reduces their already increased breast cancer risk. "Having the ovaries removed dramatically reduces breast cancer risk by 80%, and tubal ligations don't offer any breast cancer protection," he said.

There are several theories concerning how tubal ligation might protect ovaries from cancer, but none of them are very convincing, Dr. Narod said.

In some studies, tubal ligation has been associated with changes in local or circulating hormones, possibly as a result of a compromised blood supply to the ovary. It also has been noted that there is a slight increase in menstrual irregularities following tubal ligation. Other studies suggest that tubal ligation reduces the potential for inflammatory processes.