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Women on HRT More Prone to Severe Asthma

11 October 2011

Hormone replacement therapy (HRT) may cause asthma onset or severe worsening requiring hospitalization, according to a study of postmenopausal Danish women.

Klaus Bønnelykke, MD, from the Copenhagen Studies on Asthma in Childhood (COPSAC) group, and a pediatrician at the Danish Pediatric Asthma Center in Copenhagen, presented the results of the study at the European Respiratory Society 2011 Annual Congress.

The researchers looked at the risk for a severe asthma attack requiring hospitalization in women taking HRT.
"Postmenopausal HRT seems to increase the risk of severe asthma causing hospitalization. This has an important clinical implication, especially in secondary prophylaxis. If a clinician sees a woman on HRT who shows severe [asthmatic] exacerbations, it might be clinically relevant to stop the HRT," said Dr. Bønnelykke.

Previous studies have suggested that HRT causes the onset of asthma in women previously unaffected, but because this study did not have access to the asthma history of the women studied, it is not known whether HRT caused the asthma and associated hospitalization or whether HRT worsened existing disease.

"Our data appear to be associated with women who had not experienced hospitalization previously, so hospitalization seems to occur more in women not having asthma, or at least having mild asthma, before the start of HRT," said Dr. Bønnelykke.

Results showed a 40% increased risk for hospitalization due to asthma, and a higher risk with longer duration of HRT use. A 29% increased risk was found with less than 3 years of HRT use, a 34% increased risk was found with 3 to 10 years of HRT use, and a 51% increased risk was found with more than 10 years of HRT use.

Dr. Bønnelykke explained that asthma appears to be linked to hormone fluctuations. Asthma is roughly twice as common in boys as girls before puberty, but afterward, it becomes more common in girls, suggesting a link to female sex hormones.

"As a pediatrician, I am particularly interested in the role of hormones in asthma around puberty, but also later. Many studies have shown a role for sex hormones around pregnancy, menopause, and the effect on asthma."
Dr. Bønnelykke and colleagues drew data from the Danish Diet, Cancer, and Health cohort (1993 to 1997) on 23,138 postmenopausal women. Information was sourced on hormone use and potential confounders of any asthma-related findings, including smoking status, environmental tobacco smoke exposure, occupational exposure, educational level, body mass index, physical activity, parity, number of children, and hysterectomy.

"These women were followed prospectively, according to the Danish Hospital Discharge Register, which was linked to each woman's personal identification number. This provided valid measures of asthma incidence. The women were followed for around 10 years," the Danish investigator said.

Some observational studies have suggested that HRT can affect asthma, but those studies have not led to any general awareness of this association. We require randomized controlled trials to be sure, but observational evidence is growing. However, this potential link needs to be balanced with the positive effects of HRT," he observed.

However, Dr. Bønnelykke stressed that in this study, they saw an effect on severe asthma resulting in hospitalization, which makes the association more important in terms of risk/benefit for women receiving treatment. "For some women it might be worth avoiding HRT, because we know that hospitalization for acute asthma is associated with severe disease and a worse prognosis in the long term."

Regarding the question of which patients on HRT are more susceptible to asthma, Dr. Bønnelykke said that because of the heterogeneity of the disease, it is difficult to determine which patients are likely to experience a severe attack of asthma and which should avoid HRT.

"The most important clinical implication is in secondary prevention; clinicians should be cautious with women taking HRT who start experiencing asthmatic symptoms and, in these cases, it might be wise to stop HRT," he advised.

As with previously reported concerns around risks of HRT, it is important for both women and healthcare professionals to balance the risks against the benefits for each individual, and to continue to review the risk-benefit balance if new symptoms appear.

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