Inhaled anti-asthma therapies following hormone therapy in women: a nationwide cohort study

Abstract

Research question: Does menopausal hormone therapy (HT) with exogenous oestrogens and progestogens change the use of inhaled anti-asthma medications in women with asthma?

Methods: In a population-based matched cohort study using the Danish registries, we included women with asthma aged 45-65 years from 1 June 1995 to 30 June 2018. We investigated whether HT with oestrogen and/or progestogens was associated with changes in use of inhaled anti-asthma therapies in the 12 months following initiation. We used exposure density matching to match exposed subjects with unexposed subjects on age, household income and level of education. An exposed subject was defined as receiving HT. We calculated mean dose of medications and odds ratios of increases in the 12 months following HT initiation.

Results: We included 139 483 women with asthma, of whom 116 014 (83.2%) were unexposed subjects and 23 469 (16.8%) exposed subjects. Mean±sd age was 53.0±5.2 years. Initiation of HT was not consistently associated with increased mean doses of inhaled corticosteroids (ICS), or long- and short-acting β₂-agonists. Women receiving systemic oestrogens had increased odds ratios of large increases (>100 µg) in ICS at 6 months (OR 1.09; 95% CI 1.04-1.13; p<0.001) and 9 months (OR 1.07; 95% CI 1.03-1.12; p<0.001). Progestogens were protective against increases in ICS at 6 and 9 months (OR 0.87; 95% CI 0.82-0.93; p<0.001; and OR 0.86; 95% CI 0.81-0.91; p<0.001).

Conclusion: Initiation of HT did not change the use of inhaled medications in asthma. However, detrimental effects of oestrogen, as well as beneficial effects of progestogens, cannot be excluded.

FIGURE 1

Flow chart of the study population. From the original 582 546 women with asthma, 23 469 women were identified as receiving hormone therapy (exposed) and, subsequently, each exposed woman was matched with five unexposed women.

FIGURE 2

Change in use of inhaled corticosteroids (ICS) among exposed versus unexposed women in the first 12 months following the index date. a) Hormone therapy as a compound exposure; b) hormone therapy divided into specific substances.

FIGURE 3

Change in use of long-acting β₂-agonists (LABA) among exposed versus unexposed women in the first 12 months following the index date. LABA are divided into the four different subtypes of LABA: a) formoterol; b) indacaterol; c) salmeterol; d) vilanterol.

FIGURE 4

Change in use of short-acting β₂-agonists (SABA) among exposed versus unexposed women in the first 12 months following the index date. SABA are divided into the two different subtypes of SABA: a) salbutamol and b) terbutaline.