Ovarian cancer risk goes up by 40% in menopausal women who take hormone replacement therapy (HRT), even if they take the treatment only for a few years, revealed a study.
The probe marks the widest-ever analysis of the risk of ovarian cancer from HRT, a treatment whose use declined when its safety was questioned a dozen years ago.
Researchers publishing in The Lancet carried out an overview of 52 published studies, covering nearly 21,500 women in North America, Europe and Australia who had been diagnosed with ovarian cancer.
The disease has been dubbed a "silent killer," as it is often spotted too late.
"For women who take HRT for five 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," said Richard Peto, a University of Oxford professor who co-authored the study.
HRT uses the female hormones oestrogen or progestogen, sometimes combined, to ease menopausal symptoms such as hot flushes, vaginal dryness and lack of sex drive.
The increased risk was the same in both types of treatment.
It was also seen in the two most common types of cancer -- known as serious and endometrial ovarian cancers -- but not in the rarest kinds, mucinous and clear-cell cancers.
The risk fell back over time after women stopped taking HRT.
But women who had used the drug for at least five years still had a noticeable increased risk of ovarian cancer 10 years later.
An outside commentator, Rod Baber, a professor of gynaecology at Australia's University of Sydney and president of the International Menopause Society, said the study had brought much-needed clarity.
Previous studies have found either a significant increase in cancer probability -- or none at all.
In absolute terms, though, the risk for women using HRT "is very very low," Baber cautioned.
HRT sparked a storm in 2003, when the so-called Million Women Study, an investigation among 1.3 million Britons, found its use was linked to a rise in breast cancer incidence.
A debate has raged backwards and forwards over whether that study, based on questionnaires returned by post-menopausal women, used flawed methods.
In 2007, the same study found a 20-percent increased risk of ovarian cancer among women who took HRT compared to those who had never taken it.
After the controversy erupted, use of the drug declined, but has now stabilized, according to the new probe.
It said around six million women worldwide were on HRT today, and most tend to take it for only a few years.
"The definite risk of ovarian cancer with even with less than five years of HRT is directly relevant to today's patterns of use," said Peto's university colleague and co-author, Valerie Beral.
"(It) has implications for current efforts to revise UK and worldwide guidelines."