Oral hormone replacement increases risk of thromboembolism

Replacing hormones after menopause can relieve symptoms that are quite uncomfortable for some women. But certain drugs called hormone replacement therapy (HRT) can increase the risk of blood clots. This is suggested by a study published in the medical journal TheBMJ, 2019.

The research, entitled “Use of hormone replacement therapy and risk of venous thromboembolism: case-control study”, brings important and relevant considerations about the risks and effects of treatment.

Venous thromboembolism (VT) occurs when clots form in the veins – deep vein thrombosis – and there is obstruction of the pulmonary arteries due to the clots – pulmonary embolism .

Considering the general results, the research pointed out that women who take HRT may have up to twice the chance of suffering from VT, when compared to those who do not do therapy, with the use of some medications.

But be warned: not all drugs have these rates and attention is needed to understanding the study, as the results are less alarming than they may appear.

This is because the researchers used a case-control study methodology, which is very effective for making relationships or associations, but not efficient for determining causes.

It is more or less like saying that some HRT medications are likely to increase the risk of clots, but there are several other factors that may also be at fault. There is no way to know precisely.

How was the study done?

Researchers at the University of Nottingham used records from two UK databases, QResearch and Clinical Research Datalink, and identified 80,396 women between 40 and 79 years old who suffered from thromboembolism between 1998 and 2017.

In order to compare control cases – that is, women and without TV – 391,494 women with similar age and health conditions, but who did not suffer from thromboembolism, were selected.

The advantage of this method is that many hypotheses can be raised by looking at what points were common in women who had the disease and those who did not.

Relevant data were collected, such as lifestyle, weight, fat index, alcohol consumption, smoking, use of medications and other risks for thromboembolism.

All of these factors were considered to calculate the chances of patients having suffered a clot if they used other HRT medications or if they did not.

It is necessary to know that there are different means of hormone replacement – gel, patch, pill – and each one still has several possible medications. Therefore, the study is relevant to indicate that not all hormonal replacements increase the risks.

The research found that women who underwent hormone replacement with any type of oral tablet had a 58% increase in the risk of developing clots.

But there are slight differences between each pill.

Those using conjugated equine estrogen combined with medroxyprogesterone acetate had the risks doubled. Those using estrogen estradiol combined with didrogesterone had the lowest risks related to the oral pill.

The research also indicates that the dosages are related to the chances of thromboembolism, and the greater the amount of estradiol, the more occurrences of clots.

That is, among the participants with thromboembolism, 1 in 567 took equine estrogen and medroxyprogesterone, and for the other pills, in every 1,076 patients with thromboembolism, 1 took some other HRT pill.

Read more: Remedies for menopause and risks of hormone replacement

Should I abandon therapy?

The results and surveys of the study show that among those who do not undergo hormone therapy, thromboembolism affects about 16 per 10,000 women annually. Among those taking pills for HRT, the incidence is 9 more cases.

Although it seems a considerable difference, the researchers point out that, in general, this increase is small and the risks do not indicate the need to abandon the treatment, as long as it has been recommended and evaluated by a professional.

It is that good recommendation: all drug therapy needs to be done with trained professionals to indicate the best option for each patient.

But there is yet another relevant aspect that gives relief to the most concerned women: HRT made with gel or patches is not associated with a higher risk of clots.

Although the method is seldom used – about 85% of participants use the pills – the results can encourage choice, as long as it is guided by a health professional.

It is important that there is more space for intradermal options, especially in women who already have other risk factors for developing clots – such as smoking , physical inactivity, obesity or family history.

However, the study should not be a cause for concern, according to the researchers. When necessary and well indicated, HRT brings benefits to health and well-being.

The different types of HRT

Hormone replacement should be evaluated by the doctor according to the patient’s clinical condition. There are women who go through menopause peacefully and others who suffer from changes in the body, so each case needs to be individualized.

There are several options for those who want to relieve symptoms, from the most natural – such as teas and herbal medicines – to hormone replacement therapy.

Read more: Natural remedies to ease menopausal symptoms

The risks and benefits are still much debated, but for those who treat the lack of hormones – whether by menopause or by withdrawal of the uterus, for example -, there is another important aspect: which medicine to choose and which are the associated risks.

In general, there are some more common substances, such as estrogen, progesterone , testosterone, estradiol and tibolone are also used in HRT, which can be used alone or in conjunction with other substances, such as medroxyprogesterone.

But regardless of the choice of the substance, the therapy can be done with pills, cream, gel, adhesive or implants, for example.

The pills are generally the most used by women, but the choice also depends on comfort and convenience, in addition – of course – to consider the risks and benefits of each one.


Research and studies are constantly indicating new options for health. Patients and professionals benefit from the results, which help to measure the impacts of treatments and medications available.

Therefore, the ideal is to always talk to the doctor, clarify doubts and, together with him, choose the therapeutic option that best suits each case.

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