Estrogen Replacement Therapy and Ovarian Cancer Mortality in a Large Prospective Study of US Women.

Estrogen Replacement Therapy and Ovarian Cancer Mortality in a Large Prospective Study of US Women Rodriguez C, Patel AV, Calle EE, et al (Department of Epidemiology and Surveillance Research, American Cancer Society, Atlanta, Ga), JAMA. 2001; 285:1460-1465.

This prospective study examined the relationship between oral estrogen replacement therapy (ERT) and the incidence of ovarian cancer. It was a follow-up and a more extensive study than an earlier one previously reported by the same researchers. This study used data collected over 14 years with a sample population of 211,581 women.

The women were volunteers who agreed to fill out a health questionnaire in 1982 and who did not have a history of cancer, hysterectomy, or ovarian surgery at the start of the study. Follow-ups through personal inquiries by volunteers from the American Cancer Society were made in 1984, 1986, 1988, and 1996. The results indicated that 22% of this sample had received ERT. In the women who had received ERT, 76% had used estrogen prior to their enrollment in this study, and 24% were still receiving ERT when they enrolled in the study. From the entire sample (211,581 women), the authors reported 944 ovarian cancer deaths. After adjusting for possible confounding factors, the authors determined that the risk of fatal ovarian cancer was significantly increased in the cohort that had received ERT (fully adjusted rate ratio [RR]=1.23; 95% confidence interval [CI]=1.06-1.43). The increased risk of ovarian cancer mortality was observed primarily in women who were still using estrogen when they enrolled in the study (RR=1.51, 95% CI=1.16-1.96). A slight, nonsignificant increase in risk was observed in the women who used estrogen prior to their enrollment (RR=1.16, 95% CI=0.99-1.37). Further analysis indicated that duration of estrogen use and how recently estrogen was last used were also predictors of increased risk.

Based on their reading of the literature, the authors suggested that estrogen use only contributes to the development of non-mucinous types of ovarian cancer. The authors proposed reasons why this finding might be true. First, the authors argued that estrogen therapy decreases the secretion of gonadotrophins and previous studies have linked decreased levels of gonadotrophin to ovarian cancer. Second, the authors also suggested, based on the literature, that estrogen might directly promote the proliferation and malignant transformation of ovarian cells.

The authors, however, pointed out that the combined use of estrogen and progesterone is currently the prevalent form of estrogen replacement therapy; therefore, the findings in this study may not be as relevant if the addition of progesterone influences or protects against ovarian cancer. They recommended further study to determine the incidence of ovarian cancer with combined progesterone-estrogen therapy.

Carolyn Galleher, PT, MHS Gannon University Erie, Pa