Menstrual, Reproductive And Other Risk Factors For Cance

Environmental Health Sciences

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Abstract

Although use of oral contraceptives and history of hysterectomy or tubal ligation are associated with reduced risks of ovarian cancer, little is known about specific environmental or hormonal influences on this disease. Phenolphthalein, the active ingredient in many laxatives, was recently found to be a carcinogen in rats and mice. In the female mice, one of the affected sites was the ovary, and the ovarian lesions (stromal cell hyperplasia and stromal cell tumor) were seen at the lowest dose of phenolphthalein used (3,000 ppm in feed, administered continuously for 2 years). This dose is similar to the dose in humans consuming two or more phenolphthalein-containing laxative pills per day. The purpose of this study was to examine the risk of ovarian cancer in relation to use of phenolphthalein-containing laxatives. In a separate analysis, we examined the relationship between age at natural menopause and risk of developing epithelial ovarian cancer. We examined the association between epithelial ovarian cancer and use of phenolphthalein-containing laxatives in 356 epithelial ovarian cancer cases (256 invasive, 100 borderline) and 424 controls. Cases were identified through a population-based registry in Los Angeles County in 1992-1998, and controls were matched to cases by age, race/ethnicity, and neighborhood. Data on laxative use (specific brands, frequency of use, usual dose) were obtained by structured in-person interview. Using data from six population-based, case-control studies conducted in the United States, we analyzed age at natural menopause among 1,411 women with epithelial ovarian cancer and 6,380 control subjects (age 18-81 years) using survival analysis methods, including Kaplan-Meier and proportional hazards models. Compared to women who never used a laxative, ever use of a phenolphthalein-containing laxative was not associated with an increased risk of invasive ovarian cancer (odds ratio, OR, 1.1, 95% confidence interval, CI, 0.74, 1.5) or of borderline ovarian cancer (OR 0.74, 95% CI 0.37, 1.5). Total days used, mean number of pills per day, and cumulative dose were also unrelated to risk. We observed a weak association between ovarian cancer risk and age at natural menopause and, among women with early onset disease, there was little evidence to suggest that early menopause is related to ovarian cancer. The median age at natural menopause was 50 years among cases compared with 51 years among controls, a difference of borderline statistical significance (P = 0.06). The hazard ratio for the relationship between case-control status and age at natural menopause was 1.09 (95% confidence interval = 0.99 , 1.20).