February 12, 2015
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Hormone replacement therapy increases risk for ovarian cancer

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Women who used hormone replacement therapy — even only for a few years — demonstrated an increased risk for serous and endometrioid ovarian cancer, according to study results.

“For women who take hormone replacement therapy for 5 years from around age 50, there will be about one extra ovarian cancer for every 1,000 users and one extra ovarian cancer death for every 1,700 users,” Sir Richard Peto, professor of medical statistics and epidemiology at the University of Oxford, said in a press release.

Peto and colleagues from the Collaborative Group on Epidemiological Studies of Ovarian Cancer evaluated data from 21,488 postmenopausal women with ovarian cancer who were enrolled on one of 52 epidemiological studies.

Of the total population, prospective data were available from 12,110 women. The mean year of ovarian cancer diagnosis in this cohort was 2001, and 55% of the women had used hormone therapy for a median of 6 years (interquartile range [IQR], 2-10).

The mean year of ovarian cancer diagnosis of the other 2,702 women enrolled on retrospective studies was 1992. Twenty-nine percent of women in this cohort had used hormone therapy for a median of 4 years (IQR, 1-10).

The prospective studies also included up to four randomly selected matched controls without ovarian cancer per each women with ovarian cancer.

Overall, the risk for ovarian cancer was significantly greater in women who had used hormone replacement therapy compared with those who had never used it in the prospective studies (RR = 1.2; 955% CI, 1.15-1.26) and in all the studies combined (RR = 1.14; 95% CI, 1.1-1.19).

Among women enrolled in the prospective studies for whom duration of therapy data were available, the risk was greatest among women who were current users of hormone therapy (RR = 1.41; 95% CI, 1.32-1.5). This risk persisted even among women who used hormone therapy for fewer than 5 years (median duration, 3 years; RR = 1.43; 95% CI, 1.31-1.56).

Women who were not current users but who used hormone replacement therapy in the prior 5 years also were at increased risk for ovarian cancer (RR = 1.23; 95% CI, 1.09-1.37).

Researchers calculated a 1.37 RR (95% CI, 1.27-1.48) for overall risk for ovarian cancer among current or recent users in prospective studies.

The risk for ovarian cancer was similar among women who were current or recent users of estrogen-only hormone therapy (RR = 1.37; 95% CI, 1.26-1.5) or estrogen-progestogen (RR = 1.37; 95% CI, 1.26-1.48) hormone therapy.

The risk associated with hormone therapy varied significantly according to ovarian tumor type (P ˂ .0001). Prospective data indicated hormone therapy only was associated with an increased risk for serous (RR = 1.53; 95% CI, 1.4-1.66) and endometrioid (RR = 1.42; 95% CI, 1.2-1.67) tumor types.

Although the risk for ovarian cancer generally declined over time, the risk for serous and endometrioid ovarian cancer persisted among women who had not used hormone therapy in the prior 5 years but who were on it for longer than 5 years (RR = 1.25; 95% CI, 1.07-1.46).

“The definitive risk of ovarian cancer even with less than 5 years of hormone replacement therapy is directly relevant to today’s patterns of use — with most women now taking hormone replacement therapy for only a few years — and has implications for current efforts to revise UK and worldwide guidelines,” Dame Valerie Beral, MD, director of the Cancer Epidemiology Unit at the University of Oxford, said in the release.

A limitation to the research is the fact that the researchers were not available to provide data about dosing, Nicolas Wentzensen, MD, PhD, and Britton Trabert, PhD, MS, both of the NCI, wrote in an invited commentary.

“Since the announcement of the Women’s Health Initiative Findings, the use of hormone therapy has dropped substantially, and in the [United States], use of low-dose regimens is more prevalent than use of standard-dose and high-dose regimens,” Wentzensen and Trabert wrote. “The present study did not evaluate dose, and median year of diagnosis was 2001 for the cohort studies — slightly before the widespread change in use patterns occurred. In view of recommendations to use the lowest dose possible for the shortest duration, the study findings did show significant increases in ovarian cancer risk even among current short-term users (median duration 3 years), but a few years after stopping short-term use (after, however, a median of only 1 year of use) the risks were no longer increased. It is unclear to what extent the differences in median duration of use between current and previous users are responsible for these disparate findings.” – by Alexandra Todak

Disclosure: The researchers report no relevant financial disclosures.