If you ask most health care providers this question, they will probably say “yes.” And, they wouldn’t necessarily be wrong. But the answer is not straightforward. That’s because estrogen can increase the risk of a blood clot, but it depends on the particular estrogen being taken. Before explaining this in greater detail, let’s review what we mean by blood clots.
In discussing blood clots, we generally are referring to those that develop in the veins in the legs. We call this deep vein thrombosis, or DVT. These clots block the flow of blood in the veins and this leads to leg swelling and pain. The more serious consequence of having a DVT is that part of the clot can break loose and travel through the blood stream into the lungs. This causes a blockage of blood flow to a section of lung creating a pulmonary embolism (PE). Symptoms of a PE include pain and shortness of breath. A PE causes lung damage and can be fatal if the clot is a large one. In my book, The Estrogen Question, I describe in greater detail the nature and consequences of blood clots.
It became apparent many years ago that women taking hormonal birth control pills (BCPs) had higher rates of DVTs and PEs. Although the pills used in the past were prescribed in higher doses, even the low-dose pills available today are associated with a three-to-four-fold increased risk of causing a clot. And, while oral contraceptives contain synthetic hormones, it has been shown that the more natural estrogens used in hormone replacement therapy also increase the risk of a clot. In addition, the fact that pregnant women have a high risk of DVT made everyone assume that it must be something about estrogen that puts women at higher risk for clotting.
However, what we know now is that estrogen per se is not the culprit. Studies are indicating that it is only oral estrogen, meaning estrogen taken in pill form by mouth, that appears to have an adverse effect on the clotting system. Applying estrogen into the vagina or onto the skin in the form of patches, creams, or gels does not appear to increase the risk of clots.
The reason for this is because pills taken orally are absorbed from the stomach and then go directly to the liver before circulating widely in the system. The liver processes the estrogen in ways that lead to an increased production of proteins that accelerate the clotting system. This phenomenon is referred to as the first-pass effect, which impacts the way a number of drugs behave in the body. The reason why estrogen applied to the skin or vagina escapes this phenomenon is that after applied it goes directly into the circulation and doesn’t make that first major stop at the liver.
Numerous studies analyzing thousands of women have convinced most menopause experts that transdermal estrogen products, such as estrogen patches, do not put women at any higher risks for clotting than normal. A recent study assessing over 80,000 women in England confirmed the observation that women on transdermal estrogen were not at an increased risk for clots. As expected, this same analysis showed that women on oral estrogen were at an increased risk for clots and, interestingly, women taking horse-derived estrogens had a higher risk than women on oral estradiol.
One final issue to address is whether a progestogen has any effect on clotting. Women who have a uterus are advised to take a progestogen drug along with their estrogen as part of an HRT regimen because this protects the uterus from any negative effects. Studies have indicated that synthetic progestogens, such as the ones in birth control pills, may play a role in increasing the tendency for a blood clot. However, natural progesterone does not appear to have a negative effect on the clotting system.
This information on how the type and mode of administration of hormone replacement products affects blood clots has led many menopause experts to believe that the ideal choices for HRT are transdermal estrogen and natural progesterone, and I agree.
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