A sweeping new analysis adds to the evidence that many women who take hormone therapy during menopause are more likely to develop breast cancer—and remain at higher risk of cancer for more than a decade after they stop taking the drugs.

The study, published Thursday in the Lancet, looked at data from dozens of studies, including long-term data on more than 100,000 women who developed breast cancer after menopause. Half of those women had used what’s known as menopausal hormone therapy, or MHT. The longer women took the medicine, the more likely they were to develop breast cancer. Experts say the findings could shape how women and their health care providers decide how to manage symptoms of menopause.

“This is a consensus of many researchers and many studies all around the world. These are important new results,” said said Valerie Beral, a cancer epidemiologist at the University of Oxford and one of the lead authors of the new study.

Women have long been prescribed synthetic versions to replace the hormones that decline during menopause. The medications—usually delivered in a pill, but sometimes in a patch, gel, or injection—provide women either estrogen or a combination of estrogen and progesterone. For many women, they help to tamp down symptoms of menopause, including osteoporosis.

For years, research has suggested a potential link between MHT and an increased risk of breast cancer. In 2002 and 2004, the Women’s Health Initiative released reports that showed women who used combination MHT were more likely to develop breast cancer. MHT use fell after the reports received widespread coverage. That was followed by a decline in breast cancer rates.

But there wasn’t much information on whether that risk persisted, or how it differed based on the type of MHT a woman took. So an international group of researchers pulled together data from dozens of studies—published and unpublished—to examine the issue more closely. They took a woman’s age at first use of MHT, how long she used the medication, and the time elapsed since she last used it into account. The mean age of women starting menopause was 50, which was also the mean age at which women started using MHT.

The researchers found that compared with women who never used MHT, women who did had a significantly higher risk of developing invasive breast cancer. They estimated that 6.3% of women who never used MHT developed breast cancer, compared to 8.3% of women who used the combination drug continually for five years. That’s roughly one extra cancer diagnosis for every 50 users.

The longer women used MHT, the greater their risk of breast cancer. Women who were no longer using MHT had a lower relative risk than women who were currently using it—but they remained at an elevated risk for more than a decade after they stopped taking the drug. The level of risk was dependent on how long a woman took MHT. The study also found that women who took the combination drug were more likely to develop cancer than women who took the estrogen-only drug.

“The findings are significant,” said Joanne Kotsopoulos, a breast cancer researcher at Women’s College Research Institute in Toronto. “The longer you use it, the higher the risk,” added Kotsopoulos, who wasn’t involved in the research but wrote a commentary on the study, also published in the Lancet.

The new analysis doesn’t show that MHT directly causes breast cancer. But researchers suspect the association has to do with the hormonal changes of menopause. The level of hormones produced by the ovaries dramatically drops during menopause. Going into menopause early is thought to lower the risk of breast cancer. But using MHT might keep women in something like a pre-menopausal state, keeping them from getting the protective benefits of menopause on cancer risk.

“Estrogens stimulate activity in the breast and increase the risk of breast cancer. [MHT] is just putting that stimulus, which had gone after menopause, back,” said Beral.

The caveat: The findings, broadly speaking, apply to women of average weight in developed countries. The researchers found that MHT didn’t have a significant adverse effect on women who were obese, though obesity is also a risk factor for breast cancer after menopause.

For now, experts say patients and providers should carefully consider when the potential benefit of using MHT outweighs the risks. Alternatives to MHT—like taking vitamin D and calcium supplements or keeping rooms cooler—should be a part of that conversation, experts said. It’s also critical for doctors to check in with women on MHT about whether the medication is actually easing their symptoms—and if it isn’t, clinicians should consider taking them off the drugs.

“It’s a balance. Every woman is different,” said Kotsopoulos. “But the risk is high for breast cancer, so they need to take a very serious approach.”

Republished with permission from STAT. This article originally appeared on August 29, 2019