The impact of estrogen replacement during perimenopause on lung function and airway inflammation in the VCD mouse model.

Background: Menopause associated asthma impacts a subset of women and is less responsive to current treatments. Mechanisms driving this late onset asthma are unknown. We recently developed a mouse model of menopause associated asthma using a combination of 4- Vinylcyclohexene Diepoxide (VCD) and House Dust Mite (HDM) exposures. The goal of this study was to determine how hormone replacement therapy during perimenopause impacts lung function and inflammation. Methods: The experimental groups included menopausal mice (VCD) with and without exposure to HDM (to model allergic airways disease) and menopausal mice with and without hormone replacement therapy (HRT; via estrogen pellet implantation). Lung function during methacholine challenge was assessed by Flexivent. Serum, BALF and histological samples were collected for assessment. Results: Mice that received HRT during perimenopause had enhanced airway hyperresponsiveness (AHR) detected by total airway resistance (Rrs), tissue damping (G) and downward shifts in PV-Curves compared to controls, independent of HDM challenge. While HRT in perimenopause resulted in decreased eosinophils in the HDM model, neutrophil levels and mucus production were unchanged. Mice receiving HRT in perimenopause also had significantly increased collagen production and inflammation associated with large and small airways, independent of HDM challenge. Conclusions: HRT given during perimenopause may be detrimental to lung responses, including increased AHR and decreased lung function, as well as increased tissue inflammation and airway remodeling.