History of endometriosis places women at high risk of ovarian cancer, but pill use remains protective.

Women who have had endometriosis have an increased likelihood of developing ovarian cancer, but some of the same reproductive factors that lower the odds of cancer for women in general also appear to be protective for this high-risk group. (1) In an analysis based on pooled data from four population-based U.S. studies, the odds of ovarian cancer were 30% higher for women with a history of endometriosis (a condition marked by the presence of endometrial tissue outside the uterine lining) than for others. Regardless of whether women had had endometriosis, the risk of ovarian cancer was reduced among those who had ever used oral contraceptives, and it declined as a woman's number of live births increased.

The analysts pooled data from case-control studies conducted in different regions of the United States between 1993 and 2001. They used chi-square analyses and t-tests to compare characteristics of 2,098 women with ovarian cancer and 2,953 controls, and unconditional logistic regression to examine the factors associated with ovarian cancer. The multivariate analyses were conducted for all women and separately for women with and without endometriosis.

About half of both women with ovarian cancer and controls were in their 40s or 50s, and three-quarters were white; nine in 10 in each group had at least a high school education. Lower proportions of women with cancer than of controls had had a live birth (71% vs. 86%), had been sterilized (16% vs. 28%) and had used oral contraceptives (52% vs. 63%). Most pill users in both groups had taken oral contraceptives for less than 10 years. Four percent of women with ovarian cancer reported a family history of the disease, compared with 2% of controls; 9% and 6%, respectively, had a history of endometriosis.

Regardless of women's cancer status, the proportion who had ever used the pill was higher among those who had had endometriosis than among those with no history of the condition. However, the proportions who had used the pill for 10 or more years did not differ by whether women had had endometriosis.

Analyses controlling for study site, duration of pill use, parity, age, sterilization and family history of ovarian cancer confirmed that women with a history of endometriosis had a higher risk of ovarian cancer than women with no such history (odds ratio, 1.3). The differential was even greater for women who had never given birth (1.8). According to the analysts, the elevated risk among nulliparous women suggests an effect of endometriosis itself, rather than fertility problems caused by the condition.

When all relevant factors were controlled for, women who had ever used oral contraceptives had a reduced risk of ovarian cancer, and the benefit increased with duration of use: Compared with women who had never taken the pill, those who had used it for less than 10 years had 31% lower odds of developing cancer, and longer-term users had 55% lower odds. Similarly, reductions in the odds of ovarian cancer grew with parity (54% for women who had had 1-2 births and 64% for those who had had three or more). Women who had been sterilized had a lower risk than those who had not (odds ratio, 0.6).

Findings generally were similar for women with a history of endometriosis and those who had never had it; the exception was that women who had been sterilized had a reduced risk of ovarian cancer only if they had never had endometriosis. Notably, among women who had had endometriosis, long-term users of oral contraceptives had a markedly lower risk of ovarian cancer than never-users (odds ratio, 0.2); high parity (three or more live births) was associated with a similarly sharp reduction (0.2).

The analysts stress that strategies to reduce the likelihood of ovarian cancer are "critical in all women, but especially in women at an identifiably increased risk," such as those who have had endometriosis. Oral contraceptives are often prescribed as treatment for endometriosis; results of these analyses suggest that women with endometriosis are given the pill at first, but are then switched to other regimens. The analysts observe that such a change could reduce the pill's potential protection against ovarian cancer for these women. They conclude that "when women with endometriosis are being treated, the use of [oral contraceptives,] especially long-term use, should be encouraged."

REFERENCE

(1.) Modugno F et al., Oral contraceptive use, reproductive history, and risk of epithelial ovarian cancer in women with and without endometriosis, American Journal of Obstetrics and Gynecology, 2004, 191(3):733-740.