Hormone replacement therapy (HRT) use associated with menopause can lead to the development of asthma in women, a large Danish study has found.
The observational study, published in Chest, comprised 379,649 women 40-65 years from the Danish National Patient Register – 34,533 with a new diagnosis of asthma between 1995 and 2018 and 345,116 controls without asthma.
An asthma diagnosis was defined as initiation of inhaled corticosteroids including two redeemed prescriptions within two years. Cases of COPD, defined as use of LAMA, LABA or LAMA plus LABA, were excluded.
The study found the prevalence of HRT use of any kind in the asthma group was 34.4% compared with 24.2% in the control group (P < .001).
“Women who were receiving active HRT had an adjusted HR of 1.63 (95% CI, 1.55-1.71; P < .001) of new asthma developing compared with those who were not receiving therapy,” the study said.
The median time from initiation of HRT to asthma diagnosis was 862 days.
“When we stratified the analysis into the subtypes of active HRT, we found that oestrogen as monotherapy and in combination with progesterone increased the HR of new asthma, whereas monotherapy with progesterone decreased the HR of new asthma (P < .001).”
The study also found that termination of active HRT was associated with subsequent discontinuation of asthma treatment (adjusted HR 2.12; 95% CI, 1.96-2.37; P < .001).
The researchers said their findings were concerning.
“We believe these results are sufficiently clear to warrant physicians reviewing their HRT prescribing practices. Side effects of HRT, such as cardiac disease and oestrogen-dependant malignancies, are well known, but typically are related to long-term treatment. Development of asthma happens during active HRT, indicating an acute effect.”
“This raises the question of what happens in women who already have asthma at the time they initiate HRT. This needs addressing because these women may be at an increased risk of exacerbations and admissions.”
They said the mechanisms of hormone-associated asthma were as yet undetermined.
“The relationships among menopause, asthma, and HRT are complex, and it is not possible to determine a causal relationship through this study.”
“It is possible that it is not the level of oestrogen itself, but rather the unstable levels of oestrogen in relationship to menopause, that trigger asthma. This should be investigated in a mechanistic setting, probably including both animal and human models.”