Analysis Shows Increased Ovarian Cancer Risk From Hormone Replacement Therapy

Professor Sir Richard Peto

The risk of developing the two most common types of ovarian cancer significantly increases when taking hormone replacement therapy to alleviate symptoms of menopause, according to a meta-analysis of epidemiological studies.

The new analysis, involving 21,488 postmenopausal women with ovarian cancer published in The Lancet, found that women who used hormone replacement therapy (HRT) for at least 5 years are about 40% more likely to develop ovarian cancer than women who have never taken hormone therapy.

"For women who take HRT for 5 years from around age 50, there will be about one extra ovarian cancer for every 1000 users and one extra ovarian cancer death for every 1700 users," study coauthor Professor Sir Richard Peto from the University of Oxford said.

The study was conducted under the auspices of the international Collaborative Group on Epidemiological Studies of Ovarian Cancer, organized by the University of Oxford and involving more than 100 researchers worldwide. The data analysis reported here is based on individual participant data from 52 prospective and retrospective studies, almost all from North America, Europe, and Australia.

More than half of the ovarian cancer cases analyzed were drawn from 17 prospective studies (n = 12,110), of whom 55% (n = 6601) had used HRT.

Researchers found that there was a significantly increased risk of developing ovarian cancer in current or recent HRT users (ie, women who had used HRT within the past 5 years) versus never-users (Relative risk [RR] = 1.37; 95% CI, 1.29-1.46; P = .0001).

Although the risk of ovarian cancer fell over time after stopping treatment, women who had used HRT for at least 5 years still had a somewhat increased risk of ovarian cancer 10 years later (RR = 1.25; 95% CI, 1.07-1.46; P= .005).

The increased risk was seen only for the two most common types of ovarian cancer (serous and endometrioid ovarian cancers), and not for the two less common types (mucinous and clear cell ovarian cancers).

HRT’s effect on the risk of developing ovarian cancer was the same for the two main types of hormone replacement therapy (preparations containing estrogen only, or estrogen together with a progestagen), according to the analysis, which also found that the proportional increase in risk was not materially affected by the age at which the therapy began, body size, past use of oral contraceptives, hysterectomy, alcohol use, tobacco use, or family history of breast or ovarian cancer.

Even though the use of hormone replacement therapy fell rapidly about a decade ago and has leveled off, there are about 6 million women in the United Kingdom and the United States who are still taking the therapy.

While the current World Health Organization, US, and European HRT guidelines do not mention ovarian cancer, the UK guidelines, which are currently being revised, state that the rate of ovarian cancer might increase only with long-term use.

According to study coauthor Professor Dame Valerie Beral, also from the University of Oxford, "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 UK and worldwide guidelines."

Collaborative Group on Epidemiological Studies of Ovarian Cancer. Menopausal hormone use and ovarian cancer risk: individual participant meta-analysis of 52 epidemiological studies [published online February 13, 2015]. Lancet.