Higher endogenous estradiol linked to increased stroke risk

But newer estrogen-mediating drugs may aid stroke prevention in older women with high endogenous estradiol levels.

Older women with high levels of endogenous serum estradiol may have an increased risk of stroke, according to findings presented at the American Stroke Association’s International Stroke Conference 2006, held in Kissimmee, Fla.

The Multiple Outcomes of Raloxifene Evaluation (MORE) trial, led by Jennifer Lee, MD, from the California Pacific Medical Center Research Institute in San Francisco, also indicated that treatment with raloxifene (Evista, Eli Lilly) may reduce the risk of stroke in women with high levels of endogenous estradiol.

Although the MORE trial results need to be confirmed, Lee said her findings indicate that raloxifene – which is currently not labeled for use in stroke prevention – could offer potential treatment for older women who may be at an increased risk for stroke.

Lee noted that this study was important because it suggests that doctors may be able to assess the risk of stroke in older women by measuring endogenous serum estradiol levels. Furthermore, the study results also indicate that newer estrogen-mediating drugs may aid stroke prevention in older women with higher endogenous serum estradiol levels.

In women, the risk of stroke increases after age 55, doubling every 10 years. Lee noted that also during this time, a women’s estradiol production decreases and serum levels typically decline from about > 185 pmol/L to about < 75 pmol/L.

Although the MORE trial was originally designed to determine the effect of raloxifene on bone mineral density and fractures in postmenopausal women, the researchers were also able to assess raloxifene’s effect on stroke risk in this patient population.

About 7,700 postmenopausal women were recruited at 80 sites in 25 countries. All women were osteoporotic, at least two years postmenopausal, age < 80, and had no history of stroke during the past decade. The average age of the patients was 67; the average BMI was 25; the average woman was 19 years postmenopausal.

The women were randomized to treatment with placebo or raloxifene. At baseline, blood samples were taken to measure the women’s levels of naturally occurring estradiol.

After a four-year follow-up, Lee and colleagues found that women who had higher baseline estradiol levels and were treated with placebo had the highest risk of stoke. A similar risk was not seen in women with high baseline estradiol levels who received treatment with raloxifene. For women with baseline estradiol levels < 16 pmol/L, the risk of stroke was 0.82% in those treated with placebo and 0.83% in those treated with raloxifene. For women with estradiol levels > 16 pmol/L, the risk of stroke was 2.42% for those treated with placebo and 1.13% for those treated with raloxifene. This reduced risk in the women treated with raloxifene was seen even after adjusting for other CVD risk factors, including diabetes, cholesterol levels, hypertension or smoking status.

Lee said she was somewhat surprised at the protective effects that seemed to be associated with raloxifene status. “We hypothesized that endogenous estradiol levels would be associated with the risk of stroke in postmenopausal women,” Lee told Today in Cardiology. “This was based on prior studies that endogenous estradiol levels are associated with certain types of breast cancer risk and osteoporotic fractures in postmenopausal women. However, we did not anticipate the mediating relationship between endogenous estradiol and raloxifene and its effect on stroke risk.” – by Jay Lewis

For more information:

• Lee J. Low endogenous estradiol decreases risk of stroke and estradiol mediates the effect of raloxifene on stroke in older women. #LB2. Presented at the American Stroke Association’s International Stroke Conference 2006. Feb. 16-18, 2006. Kissimmee, Fla