There's been a lot of conflicting information about the risks and benefits of hormone replacement therapy (HRT) published in the last ten years. Before 2002, menopausal women were told that hormone replacement therapy was associated with a decreased risk of cardiovascular disease, colon cancer, and osteoporosis, based on the findings from observational studies.

Then in 2002, the Women’s Health Initiative Study linked HRT to an increased risk of breast cancer and cardiovascular disease. This contradictory evidence led to what has been called the "timing hypothesis" – the idea that the results of previous studies and the WHI were conflicting because the women in the WHI study were older and had been menopausal for several years, compared to the women in the other studies.

Even after the discontinuation of therapy, the women who took HRT for 10 years had a significantly reduced risk of death, heart failure, and heart attack without any increased risk of breast cancer, deep vein thrombosis, or stroke. So what should you believe?

A team of doctors in Denmark conducted a study of 1,006 women enrolled in the Danish Osteoporosis Prevention Study to determine if HRT begun soon after the onset of menopausal symptoms could reduce the risk of cardiovascular events such as heart failure, heart attack, or death. Among the study participants, 502 women were randomly assigned to receive HRT and 504 were assigned to receive no treatment.

Those randomized to receive HRT began taking it within two years of beginning menopause. They had been taking HRT for about 10 or 11 years when they were asked to stop because of the findings of the WHI study. They were then followed for about another five years.

Even after the discontinuation of therapy, the women who took HRT for 10 years had a significantly reduced risk of death, heart failure, and heart attack without any increased risk of breast cancer, deep vein thrombosis, or stroke. They attributed this benefit to the fact that the women began HRT soon after menopause, and possibly to the different HRT preparations used in the Danish study compared to those used in the WHI study.

A Matter of Timing and Preparation

The women in the WHI study received conjugated equine estrogens and medroxyprogesterone, and those in the Danish study received 17-β-estradiol and norethisterone. “The compounds used in the Danish study were more similar [compared to those used in the WHI] to the estrogens in our bodies,” Nieca Goldberg, medical director of the Joan H. Tisch Center for Women’s Health at NYU Langone Medical Center in New York City, told TheDoctor.

Goldberg went on to say that based on the findings of the current study, she would recommend HRT for menopausal symptoms. However, more work is needed. “Only 1,006 women were enrolled in this study, and only 502 got HRT, and you cannot base therapeutic recommendations for millions of women on the findings of a study enrolling only 502 women in the treatment group,” she said.

The study findings help doctors better define the differences in women taking HRT when they are younger versus when they are older, said Goldberg. The data suggest that the increase in heart disease risk seen in the WHI study could be attributed to the age of the women in that study; they were older and perhaps they had heart disease that was not yet diagnosed. Somehow taking HRT made those problems worse, because hormone-based therapies, both HRT and oral contraceptives, increase the risk for blood clots.

“I think the study is exciting,” Goldberg said. “I am really glad that we are continuing to refine our knowledge about HRT and its risks and benefits to women.” The study was published online in The British Medical Journal.