Role of Estrogen in Allergic Reactions
Before puberty, boys tend to suffer from allergies and asthma more frequently than do girls. However, after puberty, these conditions are more common in women than in men. Women who suffer from acute asthma, which is related to allergies, are 60% more likely than men to require emergency intervention or hospitalization. Further, women suffer more frequent and more severe anaphylaxis, which is a potentially fatal severe allergic reaction that can inhibit a patient’s ability to breathe and lead to stroke. Researchers have wondered for years why the sex difference in tendency to experience anaphylaxis exists, and recent research points to a potential role of estrogen.
Estrogen Exacerbates Allergic Reactions
Estrogen refers to the main female sex hormones, which are critical in female reproduction and menstrual cycles. Estrogen promotes female characteristics, such as the growth of breasts, and also serves a number of critical physiological functions. Estrogen is used medically for a number of purposes, including birth control (it is contained in oral contraceptives), hormone replacement therapy, and the treatment of certain cancers, such as breast and prostate cancer.
Researchers at the National Institute of Allergy and Infectious Diseases (NIAID), which is one of the National Institutes of Health (NIH) published their relevant findings in The Journal of Allergy and Clinical Immunology. The researchers showed that when exposed to allergens, female mice endured longer and more severe anaphylaxis than did male mice. However, when estrogen levels were reduced in female mice, the sex differences disappeared.
To do this experiment, researchers ovariectomized the female mice, meaning they removed their ovaries. Because ovaries produce estrogen, this procedure minimizes the amount of estrogen circulating in female mice’s bodies. They then compared allergic reactions and anaphylaxis in male mice, regular female mice, and female mice lacking ovaries.
To induce anaphylaxis, the researchers used histamine, which is a natural component of the immune system that causes inflammation, combined with immunoglobulins, or antibodies that initiate allergic reactions when stimulated. Not only did the female mice that lacked ovaries display anaphylactic reactions that were more similar to their male counterparts than did non-ovariectomized female mice, but when researchers injected an estrogen hormone called estradiol into these ovariectomized mice, the mice also suffered more severe anaphylaxis. These results point to a clear role of estrogen in promoting more severe allergic reactions.
Why Does Estrogen Affect Allergies?
After recognizing that estrogen is a key player in allergic reactions and in their severity, researchers asked what it is about estrogen that allows it to exacerbate anaphylaxis. A set of experiments then led to the discovery that estrogen enhances the swelling and blood vessel dilation associated with anaphylaxis because it increases the activity of endothelial nitric oxide synthase (eNOS), which is an enzyme that causes these symptoms. When researchers blocked eNOS activity in female mice, they again observed the disappearance of sex differences in allergic reactions and anaphylaxis.
It is important to note that these studies were conducted in mice, and so it is not yet clear whether the findings apply to humans as well. Because neither physicians nor scientists can ethically induce anaphylaxis in human patients, nor can they remove ovaries in human patients for the sake of experimentation, studies parallel to those conducted in mice cannot be recapitulated in humans. However, additional experimentation is likely to help confirm whether these findings in mice do in fact extend to humans.
What it Means for Allergy Treatment
Though removing the ovaries of mice to understand the impact of estrogen on different physiological reactions is arguably reasonable for scientific research, it is highly unlikely that female patients with severe allergies would want to remove their ovaries or deplete their systems of estrogen. Thus, the finding that estrogen exacerbates allergic reactions helps us understand the difference in reactions in men and women but does not provide a practical treatment option.
It does, however, provide a useful lesson to females with severe allergies. Namely, it is especially important to avoid allergens and to carry an EpiPen when estrogen levels are high. Estrogen levels are high throughout puberty, just before menstruation, or when estrogen is being used for medical purposes. For example, women undergoing hormone replacement therapy following menopause may be at higher risk for anaphylactic reactions than those who do not undergo hormone replacement therapy. On the other hand, parents of young girls can rest assured that when their daughters are pre-pubescent, their estrogen levels are low, making them less susceptible to anaphylaxis than they may be later in life.
However, the finding that estrogen imparts its effect on allergies by specifically increasing the activity of a certain enzyme – i.e. eNOS – provides a more promising route to treatment. For instance, medications may be developed that specifically inhibit the activity of eNOS in those who suffer severe allergic reactions or anaphylaxis.
It is clear that adult women are more susceptible to severe allergic reactions and complications arising from asthma than are adult men. New research helps clarify the existence of sex differences by demonstrating the key role of estrogen in promoting more severe reactions. By increasing the activity of eNOS, estrogen indirectly enhances swelling and inflammation, which are dangerous characteristics of anaphylaxis. Understanding the critical role of both estrogen and eNOS can enable patients to employ more effective strategies to prevent severe allergic reactions and anaphylaxis and also open up doors to the development of more effective allergy treatment options. Specifically, medications that are able to block eNOS activity may be a particularly powerful way to help women with severe allergies experience fewer or less severe anaphylactic reactions.