Asthma, the Sex Difference

Jessica A. Kynyk; John G. Mastronarde; Jennifer W. McCallister


Curr Opin Pulm Med. 2011;17(1):6-11. 

In This Article

Menstrual-linked Asthma

As previously discussed, there are trends in asthma prevalence and severity, which seem to coincide with key transition points in a woman's reproductive life. Accordingly, it has been hypothesized that the female sex hormones influence the development of asthma and its severity. A subset of women with asthma experience exacerbations that seem to be linked to their menstrual cycle,[55–60] but data are inconclusive in determining the point in the menstrual cycle at which time they are at greatest risk.[60–63] Of women of reproductive age with asthma, 20–40% report worsening of asthma symptoms or a decrease in pulmonary function during the premenstrual or menstrual period.[55–59] In some series, clinically significant changes in pulmonary function and asthma control related to these self-reported changes in symptoms are infrequent,[57,58] but in others, menstrual-related changes in asthma symptoms are associated with increased healthcare utilization[55,56,61,62] and near-fatal asthma episodes.[7,56,61] Studies evaluating the effectiveness of oral contraceptives in blunting premenstrual worsening of asthma have been inconclusive.[57,64]

Attempts to correlate menstrual-related asthma symptoms with physiologic and inflammatory changes have proven problematic.[65••,66–68] A few small studies have shown that markers of inflammation such as exhaled nitric oxide, sputum eosinophils, and serum leukotriene C4 concentrations are elevated in women with menstrual-related asthma symptoms,[69–71] raising the possibility that some women with asthma may have an exaggerated inflammatory response to asthma triggers coinciding with naturally occurring fluctuations in sex hormones. It is interesting to consider that if this enhanced inflammatory response related to hormonal changes is a true phenomenon, then it may also be related to the exaggerated BHR seen in some women with asthma.

With this information, it is clear that some, but not all, women with asthma may become symptomatic during the premenstrual or menstrual phase with an unclear influence of exogenous hormone therapy on these symptoms. For clinicians, it is important to directly query about this phenomenon, as many women will not associate their worsened asthma control with their menstrual cycle and this sex-specific pattern of disease worsening may be missed with potential implications for treatment. Several small series using leukotriene receptor antagonists,[70] intramuscular progesterone,[72] or premenstrual long-acting β2-agonists[73] have shown some beneficial effects of treatment but there is a lack of solid clinical data on treatment options for menstrual-related symptoms. For now, treatment according to currently published guidelines with attention to identifying potential sex-related triggers and emphasis on patient education regarding identification of potential asthma triggers seems the most prudent approach.


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