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Breast cancer risk from menopausal hormone therapy is larger than once thought, study finds

menopausal hormone therapy
Photo by Brett Jordan on Unsplash
For average-weight women who have never taken menopausal hormone therapy, the risk of developing breast cancer by age 69 is about 6.3 percent, the researchers point out.

The use of menopausal hormone therapy (MHT) has long been linked to an increased risk of developing breast cancer. But a major new study suggests the risk may be twice what was previously thought.

The study, published in The Lancet, also found that women are at risk even if they take MHT for two to five years — a period of time that physicians used to think was safe — and that the risk persists for more than 10 years after the drugs are stopped.

Nor does it matter at what age women start MHT. Taking the drugs at any age was associated in the study with an increased risk of breast cancer.

The breast cancer risk associated with MHT has been “widely misrepresented” as being lower than it really is, said Richard Peto, a medical statistician at the University of Oxford and one of the team of researchers who worked on the study, in an interview with the Financial Times.


“We don’t want to be unduly alarming. Nor do we want to be unduly reassuring,” he added.

The ups and downs of MHT

For decades, menopause has been looked on by some members of the medical community — and marketed by pharmaceutical companies — as a disease that needs treatment rather than as a natural passage through life. As a result, women are often prescribed synthetic hormones, either estrogen alone or estrogen plus progesterone, to make up for the drop in hormones that their bodies experience after menopause.

There is some evidence that taking hormones at menopause helps reduce hot flashes and slows bone loss. It may also reduce the risk of colon cancer. But, as a major study — the Women’s Health Initiative — demonstrated more than a decade ago, the health risks associated with MHT, which include a higher risk of breast cancer, blood clots, gallstones and urinary incontinence, outweigh the benefits for most women. (Despite claims to the contrary, the increased risks are the same for “bioidentical,” or “natural” [derived from plants], hormone medications as they are for synthetic ones.)

After the Women’s Health Initiative reported its findings, prescriptions for MHT fell precipitously. Soon, breast cancer rates also began to fall. As the National Women’s Health Network points out on its website, “In 2013, there were about 8 percent fewer cases of breast cancer than in 1990, which translates to 18,000 fewer women being diagnosed with the disease each year.”

Although it’s now well accepted that MHT increases the risk of breast cancer, the research has been less clear about the effects that different types of MHT have on that risk or about how long women remain at risk after the therapy is stopped. The current study set out to examine those issues.

How the study was done

For the study, Peto and his colleagues conducted a meta-analysis of data from 58 previous studies involving more than 100,000 women in the United States and other developed countries who were diagnosed with breast cancer after menopause. About half of those women had taken MHT. The average age at which they started using the drugs was 50, and the average length of time they took them was 10 years for current users and seven years for past users.

By pooling the data from these studies, the researchers were able to look at a large number of cases, thus increasing the statistical significance of their findings.


For average-weight women who have never taken MHT, the risk of developing breast cancer by age 69 is about 6.3 percent, the researchers point out. In other words, about 63 in every 1,000 average-weight women who have never taken MHT will develop breast cancer between 50 and 69.

Using the pooled data collected from the 58 studies, the researchers then calculated the 20-year risk of developing breast cancer for average-weight women who had taken the three main types of MHT for five years starting at age 50. They found the following:

  • The risk for women taking estrogen plus daily progesterone was 8.3 percent. That means 83 in every 1,000 women would develop breast cancer by age 69 — an absolute increase of one woman for every 50 users of the hormones.
  • The risk for women taking estrogen plus intermittent progesterone was 7.7 percent (77 in every 1,000) — an absolute risk of one woman for every 70 users. (Intermittent progesterone is prescribed for only 10 to 14 days per month.)
  • The risk for women taking estrogen alone was 6.8 percent (69 in every 1,000) — an absolute risk of one woman for every 200 users. (Women are seldom given estrogen without progesterone unless they have already had a hysterectomy because of the increased risk of endometrial cancer. More than 80 percent of the women in the study who were taking estrogen-only MHT had undergone a hysterectomy.)

Other findings

Although the meta-analysis discovered no excess risk of breast cancer among women on MHT for less than 12 months, the risks began to show up after one year of use and increased progressively after that.

Indeed, the risk of developing breast cancer was twice as great for women who used MHT for 10 years than for those who used it for five years, the meta-analysis found.


Also troubling was the finding that even after the therapy was stopped, “some excess risk persisted for more than 10 years.”

The researchers also looked at the breast cancer risk for women who started MHT earlier than age 50. They found the risks to be similar to those for women who began the hormones at a later age.

Risks and benefits

The meta-analysis’ findings apply to women of average weight. Obese women who took MHT were not found to be at significantly increased risk of breast cancer, although obesity is itself a risk factor for the disease, the researchers point out.

It’s also important to note that the findings show only an association between MHT and breast cancer. They don’t prove a causal relationship.

Still, as Peto and his colleagues note in their paper, if the findings are causal, it would mean that about 1 million of the 20 million breast cancers diagnosed in developed countries since 1990 were caused by MHT.

“For 18 years now I have been trying to convince women that they don’t want to start postmenopausal estrogens, and I’ve been encouraging women who have hot flashes to try to resolve those hot flashes through other medical means,” said Dr. Otis Brawley, a professor of oncology and epidemiology at Johns Hopkins University, in an interview with CNN. Brawley, who served for 10 years as the chief medical and scientific officer of the American Cancer Society, was not involved with the new research.

“Now there’s some women who have hot flashes that are so significant that giving them estrogen actually is worth the risk,” he added. “Virtually everything we do in medicine has a risk and a benefit to it, and when the benefit starts getting to be clearly higher than the risk then perhaps you ought to do it, but when the benefit is not clearly higher than the risk, I try to avoid using it.”

FMI: You will find the study on The Lancet’s website.

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