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Study Confirms Hormone Replacement Therapy Increases Cardiovascular Disease Risk

En Español (Spanish Version)

Hormone replacement therapy (HRT) replaces the hormones (estrogen alone or estrogen plus progesterone) that decline during menopause . Early studies suggested that long-term HRT use might reduce the risk of heart disease and osteoporosis -related fractures in postmenopausal women. But in 2002, the US Women’s Health Initiative (WHI) trial showed that postmenopausal women taking HRT had an increased risk of stroke , heart attack , blood clots, and breast cancer .

The Women’s International Study of Long Duration Oestrogen After Menopause (WISDOM) trial started recruiting volunteers in 1999. WISDOM was designed to compare the long-term risks and benefits of combined (estrogen and progesterone) HRT, estrogen-only HRT, and placebo over 10 years of treatment and five years of follow-up. The trial stopped early, after less than a year, following publication of the WHI trial results.

In a study published in the July 11, 2007 online issue of the British Medical Journal , researchers published results from the abbreviated WISDOM trial. WISDOM found that women who started taking combined HRT several years after menopause had a significantly increased risk of cardiovascular disease and blood clots, compared to those taking placebo.

About the Study

5,692 postmenopausal women, aged 50-69 years, were assigned to one of three treatments: 0.625 mg estrogen daily; 0.625 mg estrogen plus 2.5 mg progesterone daily; or placebo. The researchers noted all cardiovascular events (including unstable angina and heart attack), osteoporosis-related fractures, breast and other cancers, death from all causes, venous thromboembolism (blood clots in the leg or lung), and strokes, that occurred during the study. They compared the risks of combined HRT versus placebo, and of combined HRT versus estrogen-only HRT. The women were followed for an average of 11.9 months.

The study participants’ average age was 62.8 years, and the women had started or restarted HRT an average of 14 years after menopause. In this population, women taking combined HRT had a significantly increased risk of cardiovascular disease and venous thromboembolism compared to women taking placebo. There were no statistically significant differences between the two groups in the numbers of breast or other cancers, stroke, fractures, or overall deaths. There were no significant differences between combined HRT and estrogen-only HRT.

This study is limited by its short follow-up time, which makes it difficult to determine whether adverse events drop off over time and whether HRT affects the risk of cancer, which may take longer than one year to appear.

How Does This Affect You?

This study found that in older women who started or restarted HRT several years after menopause, hormone replacement increased the risk of cardiovascular disease and blood clots, compared to placebo. The study reinforces the notion that older women should not take HRT to prevent heart disease.

For now, most doctors only prescribe HRT at the lowest effective dose, for the shortest possible time, to treat moderate to severe menopausal symptoms, such as hot flashes and vaginal dryness. This seems prudent given the findings of this and numerous other studies.




  • Vickers MR et al. Main morbidities recorded in the women’s international study of long duration oestrogen after menopause (WISDOM): a randomized controlled trial of hormone replacement therapy in postmenopausal women. Br Med J [serial online]. July 11, 2007;doi:10.1136/bmj.39266.425069.AD.

Last reviewed August 2007 by Richard Glickman-Simon, MD

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