HAE and hormones: How menopause affects attack frequency
Fact-checked by Menopause can influence hereditary angioedema (HAE), but its effects vary from person to person. While some women notice fewer or milder swelling attacks after menopause, others experience no change or even worsening symptoms. Because hormonal changes can impact disease severity in some people with HAE, menopause may require adjustments to the treatment plan.
HAE is caused by inherited genetic mutations that lead to excessive production of bradykinin, a signaling molecule that increases the permeability of blood vessels. As a consequence, fluid accumulates in tissues, leading to swelling attacks that can affect any part of the body.
Hormonal factors are known to influence HAE severity. In women, the hormonal changes that come with menopause could influence the frequency or severity of swelling attacks, and certain medications used to manage menopausal symptoms may not be safe. Understanding the relationship between menopause and HAE can help patients work with their care team to manage symptoms safely during this stage of life.
The role of estrogen in bradykinin production
Estrogen is one of the main female sex hormones and plays an important role in the development and function of the reproductive system. It also supports bone, heart, and brain health, and is involved in regulating blood vessel permeability.
Researchers have shown that estrogen can raise bradykinin levels by boosting the levels and/or activity of proteins involved in its production. It also reduces the activity of angiotensin-converting enzyme, one of the enzymes responsible for breaking down bradykinin, helping the protein last longer in the body.
Beyond its role in bradykinin production, estrogen may increase the production of bradykinin receptors, making tissues more responsive to the signaling molecule. Together, these effects can make swelling attacks more likely and help explain the relationship between estrogen and angioedema.
How menopause may affect HAE attacks
Because estrogen can increase bradykinin activity, HAE symptoms often worsen when estrogen levels are high, such as during puberty, pregnancy, or when taking estrogen-containing contraceptives.
Menopause is the life stage during which female reproductive hormones decline and fertility is lost. In the transition to menopause (perimenopause), levels of reproductive hormones, including estrogen and progesterone, begin to fluctuate and eventually drop, ultimately causing menstruation to stop.
This decline in estrogen can help ease swelling attacks for some people with HAE, but the response differs widely among individuals. Some women experience fewer attacks after menopause, likely because of lower estrogen levels, while others report worsening symptoms or no meaningful change.
Researchers do not yet fully understand why women respond differently, but individual sensitivity to hormonal fluctuations and other factors likely play a role.
Because symptoms can change over time, women should continue monitoring their attacks during and after menopause and discuss any changes with their healthcare provider.
Safety of hormone replacement therapy with HAE
Hormone replacement therapy (HRT) is an essential part of managing menopause symptoms for many women. It supplements the body with estrogen and other hormones, helping to ease uncomfortable symptoms such as hot flashes, night sweats, and vaginal dryness that arise as these hormones drop.
However, the boost in estrogen from these medications could trigger severe swelling attacks, so caution must be used when considering HRT in HAE patients. Oral or injected estrogen-containing medications are known to worsen angioedema symptoms for up to 80% of people with HAE, so it is generally recommended that estrogen treatments are avoided during menopause.
If treatment for menopausal symptoms is needed, doctors may instead recommend HRT options that don’t contain estrogen at all or nonhormonal therapies that work to ease symptoms through other mechanisms.
Discussing hormonal changes with your specialist
It can be overwhelming to manage both women’s health and HAE challenges at the same time. It’s important to work closely with one’s care team during the menopause transition to ensure that both HAE and menopausal symptoms are managed as effectively as possible.
Patients should alert their HAE specialist when they begin experiencing symptoms of perimenopause or menopause, particularly if they also notice changes in attack frequency or severity. Based on individual factors, the doctor may recommend adjustments to preventive or rescue HAE treatments during this time.
Specialists will also help patients weigh the need for HRT against the risk of swelling attacks. It’s a good idea for the HAE specialist to coordinate with the person’s gynecologist when making these decisions to ensure all aspects of health are accounted for.
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