HRT Tablets but Not Patches or Gels Increase Risk of Blood Clots

Headlines the past few years have warned women that hormone replacement therapy (HRT) can be linked to blood clots and stroke. Now, a recent study sheds more light on which types of HRT put them most at risk.
A team from the University of Nottingham published a study this month in the British Medical Journal (BMJ) stating that the blood clot risk was highest in women who take HRT tablets as opposed to other forms of the therapy, such as patches or gels. This risk was also increased in women who took higher doses.
The study found there is no increased risk in other forms of the therapy.
HRT is administered via tablets, patches, and topical creams and gels. Some HRT only contains estrogen (single drug), while other forms of the therapy require women have both estrogen and progesterone (combined drug). HRT can relieve menopause symptoms such as night sweats and hot flushes as well as reduce the risk for certain health conditions in women going through menopause.
Evaluating HRT
The UK researchers hoped their research would give doctors more specifics to help determine the risk of blood clots, known medically as venous thromboembolism, in women who take HRT. They drew data from records of more than 2,000 practices from 1998 to 2017 and examined other health conditions and factors that could impact a woman’s risk for developing blood clots.
When they compared records of all women who developed blood clots with those who had not, they noted that women on HRT tablets were twice as likely to be at risk for blood clots. These women had a 70 percent risk for blood clots compared to those taking other forms of HRT.
The risk of blood clots was 15 percent higher in women on single- and combined-drug treatments for those taking natural estrogen that came from horse urine compared to synthetic estrogen.
Women using HRT in patch, gel, or cream form were not at increased risk for blood clots, even those taking higher doses of the medication. Just 20 percent of HRT prescriptions were for non-oral treatments even though doctors know they pose a lower risk.
“Our findings are particularly important for women who require HRT treatment and are already at increased risk for developing blood clots,” said Yana Vinogradova, PhD, a statistician who conducted the research at the University’s school of medicine.
HRT options explained
JoAnn Pinkerton, executive director of The North American Menopause Society and a professor of obstetrics and gynecology at the University of Virginia Health System, told Healthline that evidence continues to emerge that therapies other than pills, such as through-the-skin (transdermal) HRT, offers less risk of blood clots.
“Oral therapy is metabolized through the liver, which can increase the risk of clotting,” Pinkerton said.
She noted that increased risk of blood clots has not been seen with estrogen that is administered vaginally in different forms such as a cream, suppositories, or a ring.
“By processing estrogen, the liver increases production of blood-clotting factors,” said Dr. Diana Hoppe, an obstetrician and gynecologist based in California. “It’s estrogen, not progesterone, that does this.”
Using HRT creams on the skin or HRT given vaginally can mean less clotting risk, Hoppe said.
Assessing your risk
Whether women are best suited for oral or transdermal therapy can be determined by risk factors for clotting, and personal preference, if there are no risk factors, Pinkerton said.
HRT may not be beneficial in women over the age of 60 and can have negative cardiovascular effects in those over 70, she noted.
“As women age, if they elect to continue low-dose HRT for hot flashes, bone protection, or quality of life, lower doses of transdermal products appear to be safer,” Pinkerton said.
Women at risk for blood clots, or those who have a previous history of blood clots or Factor V Leiden (a blood clotting disorder), should avoid estrogen, she said.
Hoppe said that women can often use a transdermal HRT solution and an oral progesterone if they need combination therapy. Progesterone is better absorbed by the body orally and doesn’t pose increased risk for blood clots because oral progesterone doesn’t increase the risk.
“Most women don’t need to avoid HRT, they just need to know the facts to see if they would benefit from it,” Hoppe said.