Updated

Women who take hormone replacement therapy (HRT) to ease menopause symptoms such as hot flashes and night sweats may have a lower risk of blood clots if they use estrogens applied vaginally or via skin patches, a Swedish study suggests.

Many women have been reluctant to use HRT to ease menopause symptoms since 2002, when the federally funded Women's Health Initiative (WHI) study linked the treatments containing man-made versions of the female hormones estrogen and progesterone to an increased risk of breast cancer, heart attacks and strokes.

For the current study, researchers found that overall, estrogen-only therapy carries a lower risk of blood clots than treatment with a combination of estrogen and progestin, the synthetic version of progesterone.

But there wasn't a significantly higher clot risk with combination therapy if women got estrogen from patches that deliver medicine through the skin into the bloodstream or from vaginal estrogen creams.

This suggests that estrogen pills may be a bigger problem than alternative formulations, said Dr. JoAnn Pinkerton, executive director of the North American Menopause Society and a researcher at the University of Virginia in Charlottesville.

The risk of having a blood clot may be influenced by the type of estrogen and whether some form of progesterone is added, and if so, what type, Pinkerton, who wasn't involved in the study, said by email.

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Women go through menopause when they stop menstruating, which typically happens between ages 45 and 55. As the ovaries curb production of estrogen and progesterone in the years leading up to menopause, women can experience symptoms ranging from irregular periods and vaginal dryness to mood swings and insomnia.

The Swedish study led by Dr. Annica Bergendal of the Karolinska Institute in Stockholm analyzed data on 838 women who developed blood clots from 2003 to 2009 and a control group of 891 similar women who didn't develop clots.

Women who took combined estrogen and progestin therapy had nearly triple the clot risk of women who didn't use hormones at all, researchers report in the journal Menopause.

When women only used estrogen, their clot risk was 31 percent higher than taking no hormones, though there wasn't any greater risk associated with estrogen delivered vaginally or through the skin.

The study is observational, and can't prove vaginal estrogen or skin patches cause fewer blood clots than alternative treatments, the authors note. Researchers also lacked data to verify the exact timing of menopause, which can influence the blood clot risk associated with HRT.

It's also possible that these results don't directly contradict the WHI findings because of differences between the women in the U.S. and Swedish studies, said Dr. Michael Thomas, a women's health researcher at the University of Cincinnati Academic Health Center who wasn't involved in the study.

Women in the current study were 55 years old on average, while WHI participants were typically around 63.

Age differences between the Swedish and U.S. groups might explain differences in the clot risks found, Thomas said by email. It's also possible women in the U.S. study might have been more prone to obesity or other risk factors for clots that set them apart from their Swedish counterparts.