Menopausal women who take hormone-replacement therapy pills more than double their risk of developing a potentially fatal blood clot, French researchers said on Friday.
The review of 17 studies suggested that the risk was also significantly higher during the first year of treatment, they reported in the British Medical Journal.
Blood clots in the arteries are a common cause of heart attacks and strokes. Vein blood clots can kill if they move through the body to the lungs.
"This meta-analysis ... showed that current use of oral estrogen increases the risk of (blood clots) by two-fold to three-fold," Pierre-Yves Scarabin and Marianne Canonico of the Paul Brousse Hospital in France wrote.
Hormone-replacement therapy relieves serious menopause symptoms such as hot flashes and was popular until a 2002 study suggested it could raise the risk of breast and ovarian cancer along with strokes and other serious conditions.
The findings spurred millions of women to abandon the drugs, hitting shares in makers of hormone therapies such as Wyeth.
Other experts, however, see that study as flawed and earlier this week issued a statement saying their review of dozens of studies found HRT is safe for early menopause and does not raise the risk of heart disease for women aged 50 to 59.
Earlier trials had also linked the drugs to blood clots but the French review marks the first systematic meta-analysis — a look at what many different studies have found — to assess how big the increased risk actually is.
"Although this relative risk is raised in hormone users when compared to non-users, the absolute risk is indeed very small as blood clots do not often occur in this age group in healthy women on no treatment," said David Sturdee, president of the International Menopause Society.
"This very slightly increased risk of a blood clot should not discourage healthy women from using HRT if it is needed."
The analysis of eight observational studies and nine randomized controlled trials found that hormone-replacement therapy given as a patch showed no significant increased risk, unlike the pills.
A reason for the difference might be due to the different way estrogen is absorbed, they added. Further research was needed to confirm the findings, they said.
When taken orally, estrogen enters through the digestive system and is processed by the liver. This might impair the balance between clotting and anti-clotting factors in the blood, the researchers said.