Estrogen Lowers Breast Cancer and Heart Attack Risk in Some

By TARA PARKER-POPE

Ron Wurzer for The New York Times Andrea LaCroix of the Fred Hutchinson Cancer Center in Seattle found that estrogen lowers breast cancer risk in some women.

In a finding that challenges the conventional wisdom about the risks of some hormones used in menopause, a major government study has found that years after using estrogen-only therapy, certain women had a markedly reduced risk of breast cancer and heart attack.

The research, part of the landmark Women’s Health Initiative study, is likely to surprise women and their doctors, who for years have heard frightening news about the risks of hormone therapy. But most of those fears are related to the use of a combination of two hormones, estrogen and progestin, which are prescribed to relieve hot flashes and other symptoms of menopause, and have been shown to increase a woman’s risk of breast cancer.

The new findings, reported Tuesday in The Journal of the American Medical Association, come from 10,739 women in the Women’s Health Initiative study who had previously had a hysterectomy, the surgical removal of the uterus. Nationwide, about one-third of women in their 50s have had a hysterectomy.

While other women in the study were taking combination hormone therapy, women without a uterus took estrogen alone or a placebo for about six years and were followed for nearly 11 years. The estrogen-only group was not given progestin, which is prescribed only to protect the uterus from the harmful effects of estrogen. Although all the women in the estrogen study stopped using the treatment in 2004, the investigators have continued to monitor their health, as is typical in large clinical trials.

The most surprising new finding relates to breast cancer. The women with hysterectomies who used estrogen alone had a 23 percent lower risk for breast cancer compared with those who had taken a placebo. This is in stark contrast to the higher risk of breast cancer shown in the estrogen-progestin part of the trial.

“The decreased risk of breast cancer in this group is something we totally didn’t expect when we started the W.H.I. hormone therapy trials,” said Andrea Z. LaCroix, the study’s lead author and a professor of epidemiology at the Fred Hutchinson Cancer Research Center in Seattle. “This study differentiates estrogen alone from estrogen and progestin in a very big way. I hope it gets across to women, because we are not reversing ourselves.”

Indeed, the investigators emphasized that the results do not change recommendations concerning combination hormone therapy for the two-thirds of menopausal women who still have a uterus. The Women’s Health Initiative data have consistently shown that the combination of estrogen and progestin raises breast cancer risk, and the treatment should be used only to relieve severe menopause symptoms, using the lowest dose for the shortest possible time.

An accompanying editorial in the journal was skeptical about the results, arguing that the design of the Women’s Health Initiative, which is skewed toward older women and stopped all forms of hormone treatment after several years of use, does not match the way doctors typically prescribe treatment to women in their 50s at the onset of menopause.

Dr. Graham Colditz, an author of the editorial and professor of surgery at Washington University School of Medicine in St. Louis, said he thought data collected from observational studies that show a higher risk of breast cancer associated with estrogen use were more reliable than the data gathered from the Women’s Health Initiative clinical trial.

“The finding doesn’t reflect how hormones are used in the U.S. at the moment,” Dr. Colditz said.

The trial has, however, been held up for years as the gold standard for medical research, and its findings linking combination hormones to breast cancer and heart problems led to significant changes in the way doctors around the world treated menopause.

A major caveat in interpreting the new estrogen data is that the study used conjugated equine estrogens, which are estrogen compounds derived from the urine of pregnant mares and marketed by Wyeth Pharmaceuticals under the brand Premarin. The brand has fallen out of favor with many women who are choosing treatments that contain estradiol, which is chemically similar to a woman’s natural estrogen. It is not known whether the benefits of estrogen shown in the Women’s Health Initiative would be replicated using a different type of estrogen.

Nobody knows why estrogen treatment alone appeared to lower breast cancer risk in the study, but one explanation may be that in menopausal women with low levels of natural estrogen, the effects of estrogen drugs induce cell death in existing tumors. Nobody is suggesting that women start using estrogen to prevent breast cancer, but the finding opens a potentially new avenue of research in the prevention of the disease.

“We need to look closely at these findings to see if we can learn more about ways to prevent breast cancer in women,” said Dr. JoAnn Manson, a Women’s Health Initiative investigator and an author of the study who is chief of preventive medicine at Brigham and Women’s Hospital in Boston.

In the estrogen-only group in the trial, use of the hormone was not associated with any significant risks or benefits pertaining to blood clots, stroke, hip fracture, colon cancer or overall death rates.

But there were surprising differences in the risks and benefits of estrogen use on heart risk when comparing the youngest and oldest women in the study. Women who were in their 50s when they first started using estrogen also had significantly fewer heart risks, including almost 50 percent fewer heart attacks, compared with those assigned to the placebo group.

The data indicate that for every 10,000 women in their 50s, those using estrogen would experience 12 fewer heart attacks, 13 fewer deaths and 18 fewer adverse events like blood clots or stroke in a given year, compared with those taking a placebo.

But the risks of estrogen use were pronounced in older women. For every 10,000 women in their 70s, using estrogen would cause 16 extra heart attacks, 19 extra deaths and 48 serious adverse events.

“The big message there is that the data look much more favorable for younger women and much riskier for older women,” said Dr. LaCroix.

Dr. Rowan Chlebowski, another author of the study and a medical oncologist at Los Angeles Biomedical Research Institute, said the findings underscore the fact that the risks and benefits of menopause hormones change depending on a woman’s health status, her age and the type of hormone used.

Dr. Chlebowski previously led research that showed cancer risks associated with combination hormone therapy, but he says the new data on estrogen alone show that in certain women, estrogen use to relieve menopausal symptoms is a “good choice.”

“When you look at the debate, people are saying hormones are good or not good – it’s been all or nothing. This calls attention to the fact that there are differences,” said Dr. Chlebowski. “I hope that separation will become clearer now.”

Comments

  1. Finally some major help so women can let go of breast cancer fears taking estrogen in menopause! Huge value in this research data set! This article provides important confirmation of our basic biology and healthy hormone effects in early menopause.

    It has been known for a long time that menopausal women who took estrogen did much better with regard to breast cancer that those who did not. The power of this information, from the largest menopausal randomized,controlled, double- blinded prospective trial of ever, is a reassuring 23% decrease in observed breast cancer cases in estrogen users compared to those women who took the placebo (dummy) pills. Note that these women had hysterectomies, took estrogen not paired with MPA, or Medroxy Progesterone Acetate, a synthetic progestin also called Provera. Not that the data for the combination are scary, just not as clearly positive as estrogen alone.
    As women let’s keep our level heads. We must demand our care providers present evidence-based, not fear generating, information to guide the hormone decision (see Tara Parker Pope’s book, The Hormone Decision, 2007, Rodale Press). Logical, plausible, coherent information that integrates principles of basic physiology, observed clinical outcomes and wise hormonal relief of menopausal symptoms is available to every woman. Women have to look for it and be confident of the good well-documented information that exists.

    Estrogen is a powerful antioxidant in breast tissue, blood vessels and acts favorably throughout the body. So it makes sense that the larger effect of estrogen will be health-enhancing in many organ systems, including the breast and cardiovascular systems.

    It is also well known that “bad things happen” with respect to heart disease risk factors in women once estrogen levels fall. And heart-health enhancing effects of estrogen have been clearly shown for over 25 years in monkey models of menopause (Clarkson T Ref). All sorts of clinical studies have pointed to this important heart disease risk reducing power of early estrogen administration in menopause (called the timing hypothesis, (Hodis H ref).

    The fact that some professional disagreement exists is not hard to explain, kind of like the two party system of government. Study design can be misleading and experts get invested in defending one trial over another. But the fact that reputable doctors still cling to old misconceptions is mystifying and disappointing. Starting hormones early in menopause (at least within the first ten years)allow us optimal disease risk reduction for virtually all systems examined closely. The facts are quite clear: women who do not take estrogen, as a group, suffer acceleration of disease risks (heart, bones, diabetes, loss of muscle mass, brain-neuron loss) after menopause. This the brutal biologic truth. Outliving natural evolutionary life spans places women at greater risk for diseases as we age as compared to men. (see “The Evolutionary Origin and Significance of Menopause,” in the journal, Menopause, Vol 18,number 3, pages 336-342, March 2011, by Pollycove R, Naftolin F, Simon, JA.) Men continue to produce ample amounts of estrogen (and testosterone, of course) well into their 80’s and 90’s! We are living longer and so now have the diseases of aging afflicting millions of women each year. Estrogen is not the fountain of youth. It won’t turn back the clock entirely. But it slows down the harmful effects of sustained low estrogen levels that accelerate aging processes of every organ system. For those women who have had a hysterectomy, as in this study, post menopausal estrogen is safe and can be easily tailored to meet each woman’s personal needs. And for those who still have their uterus, natural progesterone (often prescribed as Prometrium brand of micronized bioidentical FDA approved progesterone) or progesterone-like opposing progestin (such as Aygesten brand or Norethindrone generic)on a periodic basis, can be adjusted to each woman’s life style and estrogen dose required to feel her best and avoid menopausal symptoms.
    For more comprehensive information, see Dr. Pollycove’s book, The Pocket Guide to Bioidentical Hormones, Alpha Press, 2010. Each organ system and symptom complex is addressed chapter by chapter, paying attention to your unique menopausal experience and goals for optimal health and quality of life. The better the information the greater will your confidence in making the right health-enhancing choice.

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