New Study Shakes Up Thinking on Hormone Replacement Therapy
The ongoing debate about postmenopausal hormone therapy and breast cancer risk may have turned even more muddy: A large, new study suggests that two different types of hormone therapy have opposite effects on women's long-term risk of the disease.
The researchers found that combined hormone replacement therapy (HRT) -- with estrogen and progestin -- increases the risk of breast cancer, with effects that last for years after women discontinue the therapy.
On the other hand, women who take estrogen alone appear to have an equally long-lasting decrease in their breast cancer risk.
The findings come from a long-term follow-up of the Women's Health Initiative (WHI) -- a major U.S. government-funded project begun in the 1990s that tested the health effects of hormone replacement therapy. One trial randomly assigned over 16,000 women aged 50 to 79 to take either combined HRT or placebo pills. The other involved close to 11,000 women the same age who were given either estrogen therapy alone or placebos.
Before the WHI, doctors had thought that menopausal hormone therapy -- which helps control hot flashes -- had other health benefits, including a lower risk of heart disease.
But the initial findings from the WHI made waves when they instead uncovered higher disease risks: Combined HRT raised women's odds of developing heart disease, stroke, blood clots and breast cancer.
The picture was different with estrogen-only therapy: It raised the risk of blood clots and stroke, but did not increase heart risks. In addition, it seemed to lower the odds of developing breast cancer.
But only certain women can take estrogen-only therapy, namely, those who've had a hysterectomy, since using estrogen by itself raises the risk of uterine cancer.
As if that weren't complicated enough, things have gotten murkier over the years. A number of observational studies -- which followed women in the "real world" who opted for hormone therapy or not -- have found that estrogen-only therapy is associated with a higher breast cancer risk.
Enter these latest findings from the WHI. They show that for years after stopping combined HRT, women continue to face an increased risk of breast cancer. Meanwhile, the reduced risk seen with estrogen-only therapy also continued.
"So, who's right? This big clinical trial or those large observational studies?" asked Dr. Rowan Chlebowski, the lead researcher on the new analysis.
Unfortunately, there is no clear answer, according to Chlebowski, chief of medical oncology at Harbor-UCLA Medical Center, in Los Angeles.
He is to present the findings Friday at the annual San Antonio Breast Cancer Symposium. Such research is considered preliminary until published in a peer-reviewed journal.
"Overall," Chlebowski said, "this information suggests that combined HRT is a little worse than we'd thought, and estrogen alone is probably a little safer than we'd thought."
Trial participants on combined HRT typically used it for about five years. Over 18 years of follow-up, those women were 29% more likely to develop breast cancer.
Women on estrogen-only typically used it for seven years. Over 16 years, they were 23% less likely to be diagnosed with breast cancer, the findings showed.
So what does it all mean? Given the overall body of evidence, experts have long advised women against using hormone therapy to prevent any disease.
And that advice still stands, Chlebowski said.
"You should not use hormone therapy to lower chronic disease risks," he said. "If your menopausal hot flashes are bad enough that you want to try hormone therapy, talk with your doctor about the benefits and risks to you."
Susan Brown is senior director of education and patient support at the nonprofit Susan G. Komen. The new findings give women another piece of information "to make informed decisions about their health," she agreed.
"Large population studies are needed to understand the complex impact menopausal hormone therapy has on breast cancer risk and incidence," Brown said. "We're encouraged to see the results of research like this."
The U.S. National Cancer Institute has more on menopausal hormone therapy and cancer.
SOURCES: Rowan Chlebowski, M.D., chief, medical oncology and hematology, Harbor-UCLA Medical Center, Los Angeles; Susan Brown, M.S., R.N., senior director, education and patient support, Susan G. Komen, Dallas; Dec. 13, 2019 presentation, San Antonio Breast Cancer Symposium, San Antonio, Texas