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Stopping a Zombie: The Truth about Estrogen and Heart Disease

October 30, 2015
by Rick Harrison

In 2002, The National Heart, Lung, and Blood Institute stopped a major clinical study testing the health benefits of combined estrogen and progestin therapy in menopausal women three years early after discovering an increased risk of breast cancer.

More than a decade later, women are still suffering from the fallout of that study, known as the Women’s Health Initiative (WHI). But not in the way many people might imagine.

“Women are dying because they are not using estrogen,” said Dr. Phillip M. Sarrel, Emeritus Professor of Obstetrics, Gynecology and Psychiatry at Yale School of Medicine, describing the confusion following the WHI report as “a muddle.”

“The age of muddle is where we are now,” he said. “And we’re hoping to get out of that.”

Dr. Sarrel joined a panel of experts for a continuing medical education seminar last month at Yale School of Medicine, urging practitioners and the public to re-think the role of estrogens in the primary prevention of cardiovascular disease in women.

“Re-thinking means re-searching,” said Dr. Lawrence S. Cohen, a cardiologist and the Ebenezer K. Hunt Professor of Medicine Emeritus at Yale School of Medicine. “We must look again at old concepts as science moves ahead and we learn more about the topics.”

More than 290,000 women die of cardiovascular disease in the United States each year, making it the number one killer of women and responsible for one of every four female deaths. From 2002-2012, a study led by Sarrel found that the declining use of estrogen-only therapy after a hysterectomy contributed to the premature deaths of a minimum of 18,601 and as many as 91,610 postmenopausal women.

The WHI involved two separate studies. One enrolled women who still have a uterus taking a combination of equine estrogens and a progestogen. Women who had their uterus removed in a hysterectomy took only estrogen.

The women with an intact uterus had increased risks of cardiovascular disease, breast cancer, blood clots and stroke. News headlines following the study’s cancellation in 2002 stressed this threat to women’s health. And people took notice.

In July 2002, doctors were prescribing estrogen therapy to 90 percent of women without a uterus to treat symptoms such as hot flashes, night sweats, sleep problems, mood changes, and vaginal dryness and to prevent diseases such as osteoporosis, which leaves bones brittle and weak. By two years later, half of the women who had been using estrogen had stopped. Today, medical practitioners offer estrogen therapy to only 40 percent of women after a hysterectomy. And 10 months after surgery, only 25 percent are still on it.

“The way it was reported was very frightening,” Sarrel said.

But lost in the reporting of the negative outcomes associated with the combined therapy for women with a uterus were results for the estrogen-only therapy in women without a uterus that told a far more beneficial story.

While those women did experience an increased risk of blood clots, they had no increase in cardiovascular disease or breast cancer. And they had no increase in stroke if they started estrogen therapy between the ages of 50 and 59.

More importantly, follow-up studies of estrogen-only therapy in women without a uterus who started treatment in their 50s actually showed a reduced risk for cardiovascular disease and death. And researchers found that all women taking estrogen-only therapy were less likely to develop breast cancer, no matter how old they were at the start of treatment.

Dr. Howard Hodis, Director of the Atherosclerosis Research Unit at the University of Southern California’s Keck School of Medicine, presented evidence that the best time for women without a uterus to begin estrogen-only therapy is immediately after the onset of menopause and no later than six years. He said that when women begin hormone replacement therapy in their 50s and continue it for 15-30 years, they gain 1.5 quality-adjusted life-years, a measure of disease-free life following specific health care interventions.

Hodis concluded that the risks associated with estrogen-only therapy in women without a uterus compared with a placebo are not statistically significant.

In the United States, 15 million women have had a hysterectomy by the time they reach their 60th birthday. That’s 40 percent of 60-year-old women who could benefit from estrogen-only therapy. A 2011 study led by Dr. Andrea Z. LaCroix of the Fred Hutchinson Cancer Research Center found that a group of 10,000 women in their 50s who received estrogen-only therapy after a hysterectomy could expect to have 12 fewer heart attacks and 13 fewer deaths after almost 11 years.

Sarrel called the report “the most important paper in the last decade,” definitively establishing estrogen as the only menopause treatment that controls symptoms, reduces disease risk and saves lives.

And he lamented the persistence of the idea that estrogen is harmful for everyone even when rigorous data proves otherwise.

“In spite of a mountain of evidence to the contrary, the idea persists,” Sarrel said. “It walks among us like a zombie, resistant to our best efforts.”


Changing Concepts: Re-Thinking the Role of Estrogens in the Primary Prevention of Cardiovascular Disease in Women — View videos of the conference lectures here.


To reduce your chances of getting heart disease it's important to:

  • Know your blood pressure. Having uncontrolled blood pressure can result in heart disease. High blood pressure has no symptoms so it’s important to have your blood pressure checked regularly.
  • Talk to your healthcare provider about whether you should be tested for diabetes. Having uncontrolled diabetes raises your chances of heart disease.
  • Quit smoking.
  • Discuss checking your cholesterol and triglycerides with your healthcare provider.
  • Make healthy food choices. Being overweight and obese raises your risk of heart disease.
  • Limit alcohol intake to one drink a day.
  • Lower your stress level and find healthy ways to cope with stress.

Source: U.S. Centers for Disease Control and Prevention


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For questions, please contact Rick Harrison, Communications Officer, at 203-764-6610 or rick.harrison@yale.edu.

Submitted by Carissa R Violante on October 30, 2015