Hormone Replacement Therapy May Up Ovarian Cancer Risk

New Study May Pave Way for Detecting Ovarian Cancer Earlier
New Study May Pave Way for Detecting Ovarian Cancer Earlier
Even a few years of use increases cancer risk.

Use of hormone replacement therapy (HRT) for menopause, even for a few years, has been linked to a significantly increased risk for developing the two most common types of ovarian cancer, according to a new meta-analysis of available data published in The Lancet.

“For women who take HRT 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,” study co-author Professor Sir Richard Peto, FRS, from the University of Oxford in the United Kingdom, said in a press release.

The meta-analysis, which was conducted by the international Collaborative Group on Epidemiological Studies of Ovarian Cancer, included 52 epidemiological studies, involving 21,488 women with ovarian cancer, mostly from North America, Europe and Australia.  

During prospective follow-up, 12,110 women developed ovarian cancer. Of these women, more than half (55%) had used HRT.

The findings indicated that women who used HRT, even for less than 5 years, are about 40% more likely to develop ovarian cancer than those who have never taken HRT (RR for current users=1.43; P<.0001).

Further, combining current or recent use for any duration but stopped less than 5 years before diagnosis, also resulted in an increased risk for ovarian cancer (RR=1.37; P<.0001), which was similar in European and American prospective studies as well as for estrogen-only and estrogen-progestogen preparations.

Risk for the disease did, however, differ across the four main tumor types, with risk being definitely increased only for the two most common types: serous (RR=1.53; P<.0001) and endometrioid (RR=1.42; P<.0001).

Results also showed that, while the risk for ovarian cancer decreased over time after stopping treatment, women who had used HRT for at least 5 years still had a somewhat increased risk for the disease 10 years later.

“The definite risk of ovarian cancer even with less than 5 years of HRT is directly relevant to today’s patterns of use — with most women now taking HRT for only a few years — and has implications for current efforts to revise U.K. and worldwide guidelines,” study co-author Professor Dame Valerie Beral, also from the University of Oxford, said in the release.

In an accompanying comment, Nicolas Wentzensen, MD, PhD, and Britton Trabert, PhD, MS, both from the National Cancer Institute of the National Institutes of Health in Bethesda, Maryland, placed the findings in clinical context.

“In the context of the observational data presented in this study, it is still not clear whether the current recommendation to use hormone therapy for the shortest duration possible is appropriate for women who are concerned about an increased risk of ovarian cancer,” they wrote.

“The current report underlines the importance and limitations of observational data for rare and long-term outcomes, especially for the complex associations between regimen, dose, duration, route of administration, and timing of hormone therapy use with ovarian, breast, and endometrial cancers.”


  1. Collaborative Group on Epidemiological Studies of Ovarian Cancer. Lancet. 2015;doi: 10.1016/S0140-6736(14)61687-1.
  2. Wentzensen N, Trabert B. Lancet. 2015;doi:10.1016/S0140-6736(14)62458-2.