HAE and the Estrogen Connection: A Guide to Hormonal Triggers
Hereditary angioedema (HAE) is a rare disease that causes painful and sudden swelling in the body. Many factors can lead to these attacks. One major factor for many people is estrogen. Estrogen is a natural hormone in the body. However, it can act as a biological trigger for HAE swelling.1,2
How estrogen triggers swelling
Estrogen changes the way certain proteins work in your blood. It increases the activity of factor XII and prekallikrein. These proteins help start a chain reaction. This reaction leads to the production of a chemical called bradykinin.3
Too much bradykinin makes blood vessels leak fluid into nearby tissues. This fluid causes the swelling seen in HAE attacks.3
Because of this, many people see more attacks during puberty. This is a time when natural estrogen levels rise. Medicines that contain estrogen can also cause this reaction. It is a direct link between hormones and your symptoms.1,4
HAE with normal C1-INH
There are different types of HAE. Some people have HAE with normal C1-esterase inhibitor (C1-INH) levels. On standard blood tests, their protein levels look normal. However, this type is very sensitive to estrogen. It often affects people with high estrogen levels.5
In this type, genetic changes make the body overreact to hormones. Changes in genes like factor XII or plasminogen are common. These genes become hypersensitive when estrogen is present. This is why some people only have symptoms when their hormone levels shift. Understanding this connection helps you and your doctor find the right care.5
Pregnancy and family planning
Pregnancy is a time of major hormonal shifts. For people with HAE, pregnancy is unpredictable. Some people feel better and have fewer attacks. Others find that attacks happen more often.1,2
While attacks can happen anytime, clinical data show that the frequency often increases during the first trimester due to the initial surge in hormones, and then may stabilize or increase again in the third. The postpartum period is a very high-risk time for attacks due to the rapid drop in hormones and the physical impact of delivery.1,2
If you plan to have a baby, talk to an HAE specialist. You need a clear birth plan. This plan should include access to C1-INH concentrates for labor and delivery. These treatments help keep you safe during and after the birth of your child.1,2
It is also worth noting that HAE is an inherited condition. This means that if one parent has HAE, there is a 50 percent chance their child will also have the condition. Talk with your doctor about any concerns you may have.1
Safe birth control options for people of child-bearing age
Many common birth control pills contain a type of estrogen called ethinyl estradiol. This chemical is a very strong trigger for HAE swelling. People with HAE should avoid combined oral contraceptives that contain this ingredient.1,2
There are safer choices for you to consider. Progestin-only options are often a better choice. These include the "mini-pill," progestin injections, or progestin implants.2
Another safe choice is a non-hormonal option, such as a copper intrauterine device (IUD). These methods do not use estrogen.
Always talk to your HAE specialist and your gynecologist together. They can help you choose a method that protects you without increasing your risk of attacks.
Safe options for people experiencing menopause
Menopause is another time when hormones shift. During this stage, natural estrogen levels begin to drop. This change can cause symptoms like hot flashes and night sweats. Many people use hormone replacement therapy (HRT) to manage these symptoms. However, most HRT drugs contain estrogen, which can trigger HAE attacks.1,2
If you are entering menopause, you have options that do not involve estrogen. Some non-hormonal medicines can help with hot flashes. These include certain antidepressants or nerve pain medicines.2
If your menopause symptoms are severe, some doctors may suggest low-dose progestin. Some people may be able to use topical estrogen creams if they are only needed for local symptoms, such as vaginal dryness, but this must be done with caution. Always discuss these risks with your healthcare team.2
Understand your triggers and have a plan
HAE is a complex condition, but understanding your triggers can help you live a better life. Estrogen is a major biological trigger for people with HAE. It increases bradykinin and leads to painful swelling. This is true during puberty, pregnancy, and menopause.1-3
You can take control by choosing the right medicines. Work with an HAE specialist to create a plan for every stage of your life. By managing your hormones, you can reduce the number of attacks you experience.1-3
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