Transdermal oestrogen and vein clot risk in hormone replacement therapy
Oestrogen absorbed through the skin (transdermal) does not raise the risk of venous thromboembolism (a clot in a vein) at standard doses, whereas oral hormone replacement therapy (HRT) does.
Remember
Women at risk of blood clots who need HRT that works throughout the body are usually offered a patch, gel or spray rather than tablets, because oestrogen absorbed through the skin does not pass through the liver first.
Memory aid
skin skips the liver
Use it to recall that oestrogen absorbed through the skin skips the liver, whereas tablets do not.
With hormone replacement therapy (HRT), the route that oestrogen takes into the body changes the clot risk. Venous thromboembolism (VTE) means a clot in a vein, including a deep vein thrombosis (a clot in a deep leg vein). Such a clot can travel to the lungs.
Oestrogen taken by mouth goes to the liver before it reaches the rest of the body. This step is called first-pass metabolism. The liver responds by making more clotting factors (the proteins that make blood clot), which helps to explain why tablets are linked to a higher risk of VTE. With oral HRT, that risk is proportional to the amount of oestrogen in the tablet.
Transdermal oestrogen (absorbed through the skin from a patch, gel or spray) goes straight into the bloodstream, so it avoids that first pass. In a large UK study, oral HRT carried a clearly higher VTE risk, while transdermal HRT did not. A patch still treats hot flushes and night sweats, because the oestrogen reaches the whole body.
If a woman still has a uterus, a progestogen (a hormone that protects the lining of the uterus) is added to the oestrogen, and a combined patch can supply both. Adding a progestogen does not change the route, so combined tablets still carry a higher clot risk than patches.
A previous clot does not necessarily mean no HRT: the change that helps is the route.
Key facts
- Route
- tablets carry a higher clot risk than a patch, gel or spray.
- Mechanism
- oestrogen absorbed through the skin avoids first-pass metabolism, so the liver is thought to make fewer extra clotting factors.
- Dose
- with oral HRT, the clot risk rises with the amount of oestrogen in the tablet.
- Both tablet types
- oestrogen-only and combined tablets were both linked to a raised VTE risk in the UK study, so a progestogen does not cancel it.
- Previous clot
- it means a change of route, not necessarily no HRT.
- Stopping
- a patch is easy to stop if a problem arises.
Exam traps
- Adding a progestogen does not remove the clot risk of a tablet, because oral combined HRT was still linked to a higher VTE risk.
- Clot risk is higher with oestrogen-only tablets than with patches: taken by mouth, they were still associated with a raised VTE risk.
- A low dose of an oral combined preparation still involves the first liver pass: oral clot risk does rise with the amount of oestrogen, and oral combined preparations were linked to a raised clot risk.
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