Even Short-term Hormone Therapy Increases Ovarian Cancer Risk, Meta-study Finds

The thinking had been that taking hormones for a few years to mitigate menopausal symptoms is benign. Not so, says meta-analysis of over 20,000 women

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Operation on a cancer patient.
Operation on a cancer patient.Credit: AP

Even relatively short-term use of hormone replacement therapy to mitigate the effects of menopause significantly increases a woman’s probability of developing ovarian cancer, according to a meta-study of over 20,000 women.

The risk is increased even if the hormone replacement therapy was only used for a few years, according to a meta-analysis of 52 epidemiological studies published today in The Lancet.

“It used to be thought that using hormone replacement therapy for less than five years carries no risk. That’s just not true,” Professor Sir Richard Peto of the University of Oxford told Haaretz.

The No. 1 cause of cancer remains, of course, smoking (“wonderful at killing you,” says Peto,) beside which other causes pale, the professor points out. But based on data from 21,488 women with ovarian cancer, almost all from North America, Europe and Australia, hormone replacement therapy increases the probability of two common types of ovarian cancer by about 40%.

“For women who take hormone replacement therapy 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,” says Peto, co-author of the Lancet paper.

In the American general population, there is a roughly 0.5% risk of getting ovarian cancer in middle age, and a 1% risk of getting it before age 80. Even with hormone therapy, the risks are not enormous — but it’s worth knowing that they increase, Peto points out.

Hormone replacement therapy and oral contraceptives, it bears saying, are completely different animals, and have opposite effects on cancer probabilities.

Birth control

Oral birth control has been around since the early 1960s and, in contrast to scares propagated in the 1990s, “the pill” does not exacerbate the chance of getting cancer of the womb lining or ovaries — it decreases it, Peto says. “Their net effect is to slightly reduce cancer rates, and the decrease in risk stays around for decades,” possibly for life.

Hormone replacement therapy, on the other hand, has been around since the 1970s and increases the risk of certain ovarian cancers – and in contrast to previous thinking, restricting the therapy to a few years does not eliminate that risk.

There are two basic types of hormone replacement therapy. One is estrogen alone, which is suitable for women who underwent hysterectomies.Medical evidence over decades shows that taking that hormone alone significantly increases the probability of endometrial cancer (of the womb lining). The other kind is estrogen and progestagen (E+P,) which has been found to increase the probability of breast cancer.

Therefore, if once hormone replacement therapy had been recommended from the onset of menopause onwards, later thinking was to limit its use to a few years, thereby eliminating cancer risks. Now the meta-study shows the risks are not in fact eliminated.

And if women use hormone replacement therapy for longer than the five year cut-off line of the meta-study, their chances just get worse. As one gets older, one’s chances of contracting cancer increase anyway, Peto says. Add the effect of the hormonal stew and there’s no question that the probability increases. But the pattern of hormone therapy today is to cut it off after overcoming the worst of the menopausal change, not to use the therapy for decades.

Of the four main types of ovarian cancer, the increase in risk was seen only for the two most common types — serous and endometrioid ovarian cancers — but not for the two less common types — mucinous and clear cell ovarian cancers — the scientists say.

They also note that the risk of ovarian cancer falls over time after stopping treatment — but women who had used therapy for at least five years still had a somewhat increased risk of ovarian cancer 10 years later.

In the United States and Ukraine, some six million women use hormone replacement therapy — and the health authorities, including the World Health Organization, will have to change their guidelines, which state only that ovarian cancer might be increased with long-term use.

The 52 studies analyzed by the international Collaborative Group on Epidemiological Studies of Ovarian Cancer, organized by the University of Oxford and with over 100 researchers worldwide, contain virtually all of the epidemiological evidence ever collected on hormone therapy use and ovarian cancer, the authors state.

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