Postmenopausal women who take hormone replacement therapy (HRT) for less than five years have a significantly increased risk of two of the most common types of ovarian cancer, according to a meta-analysis of 52 epidemiological studies that was published February 12 online ahead of print in The Lancet.

The Collaborative Group on Epidemiological Studies of Ovarian Cancer, which includes more than 100 researchers around the world, evaluated data on 21,488 women with ovarian cancer, mainly from North America, Europe, and Australia. They found that women who used HRT for five years were approximately 40% more likely to develop ovarian cancer than were women who had never been on HRT.

“The increased risk may well be largely or wholly causal,” the authors wrote. “If it is, women who use hormone therapy for five years from around age 50 years have about one extra ovarian cancer per 1,000 users and, if its prognosis is typical, about one extra ovarian cancer death per 1,700 users.”

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Although the risk of ovarian cancer decreased over time after discontinuing HRT, the investigators found that women who had used HRT for five years or more still had an increased risk of ovarian cancer 10 years later. The increase in risk of developing ovarian cancer was the same for the two main types of HRT (i.e., preparations containing estrogen only or a combination of estrogen and progestogen). 

Of the four main types of ovarian cancer, it was in the two most common types (serous and endometrioid), and not in the two less common types (mucinous and clear cell), that HRT was associated with an increased risk.