WOMEN'S HEALTH
January 30, 2019

The Most Dangerous Form of Hormone Therapy

Hormone replacement therapy helps millions of women transition to menopause. But patches, pills and creams carry different risks.

Hormone replacement therapy, HRT, provides welcome relief for women experiencing severe hot flashes and other symptoms as they enter menopause. But it also carries several risks.

Tablets are the most common way hormone replacement therapy is delivered; but it is also administered using skin patches, gels and creams. Unfortunately, a recent study finds that taking HRT in pills raises women's risk of venous thromboembolisms (VTE), a form of severe blood clot.

Women who took hormone replacement therapy orally had a significantly increased risk of blood clots compared to women who did not take oral HRT.

British researchers looked at the prescription records of over 80,000 women on HRT from two primary care databases in the United Kingdom. They compared women diagnosed with venous thromboembolism (VTE) with those of a control group of nearly 400,000 women not diagnosed with VTE.

Almost 6,000 women in the VTE group had used some form of hormone replacement therapy, and almost 22,000 women in the control group used HRT. Almost 5,000 women in the VTE group and 17,000 controls took an oral HRT preparation.

The study made clear that most women with menopausal symptoms are prescribed the oral form of hormone replacement therapy. It also showed that women who took hormone replacement therapy orally had a significantly increased risk of blood clots compared to women who did not take oral HRT. Conjugated equine estrogens, made from the urine of pregnant mares, both alone or combined with progesterone, were associated with greater VTE risk than the synthetic estrogen estradiol.

The dose of estrogen was directly associated with VTE risk: the higher the dose of estrogen, the greater the risk of VTE. Transdermal HRT preparations did not affect VTE risk. Compared to women who did not take HRT, women taking hormones made from equine estrogens combined with medroxyprogesterone had the highest VTE risk, and those taking estradiol and dydrogesterone had the lowest risk.

The risk of VTE in women who don’t take HRT is very low, so the small risk increase in healthy women who do take HRT should not be of concern, Yana Vinogradova, co-lead author of the study, told TheDoctor in an email.

Women already at increased risk for VTE — because of cancer, cardiovascular disease, recent surgery or injury, smoking, obesity or because they take drugs that increase VTE risk may want to discuss the risks and benefits of different HRT formulations with their doctor, said Vinogradova, a research statistician at the University of Nottingham. But generally, she adds, the study underscores the fact that “…there is no increased risk when HRT is used by means of patches or gels.” Hopefully, women's doctors will get the message and shift their prescribing to safer hormone delivery methods.

The study is published in the British Medical Journal.
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