Randomized study of the effects of testosterone administration on severity of asthma in horses.

Overview

• This study investigated whether administering testosterone affects the severity of severe asthma in horses, comparing its effects to those of dexamethasone, a known asthma treatment.
• The results showed that testosterone mildly improved lung function but was not as effective as dexamethasone in reducing symptoms or airway inflammation in horses with severe asthma.

Background and Objective

• Previous human studies indicated low testosterone is linked to poorer lung function in asthmatics.
• Androgen (testosterone) treatments helped improve airway obstruction in women with asthma.
• This study aimed to evaluate if testosterone improves clinical signs, lung function, airway neutrophilia (a type of airway inflammation), and remodeling in horses diagnosed with severe asthma.

Study Design and Methods

• Subjects: 10 horses all affected by severe asthma, taken from a research herd.
• Study Type: Randomized, blinded, crossover study where each horse served as its own control.
• Treatments:
  • Dexamethasone (a corticosteroid) administered orally at 0.06 mg/kg once daily for 10 days.
  • Testosterone cypionate given as a single intramuscular injection at 0.35 mg/kg.
• Washout period of 2 weeks between treatments to avoid carryover effects.
• Assessments:
  • Clinical respiratory scores measured on days 0, 2, 5, and 10 to track symptoms.
  • Lung function tests conducted on days 0, 5, and 10 focusing on parameters like pulmonary elastance, pleural pressure, and pulmonary resistance.
  • Bronchoalveolar lavage fluid (BALF) cytology and airway remodeling evaluated on days 0 and 10.
• Data analysis used mixed linear models appropriate for crossover studies.

Key Findings

• Clinical Scores:
  • Dexamethasone significantly improved respiratory clinical scores (median score decreased from 12 to 5; P < .001).
  • Testosterone administration did not significantly change clinical scores (10 to 9; P = .6).
• Lung Function – Pulmonary Elastance:
  • Elastance measures lung stiffness; lower values indicate improvement.
  • Both treatments improved pulmonary elastance, but dexamethasone showed a much stronger effect (from 5.1 to 0.5) compared to testosterone (4.5 to 3.0).
• Pleural Pressure and Pulmonary Resistance:
  • Only dexamethasone decreased pleural pressure and pulmonary resistance, measures related to airflow and ease of breathing.
• Airway Neutrophilia and Remodeling:
  • Neither treatment changed the number of neutrophils (airway inflammation) or the degree of airway structural remodeling after treatment.

Conclusions and Implications

• Testosterone administration led to mild improvement in lung mechanics but did not significantly reduce clinical signs of asthma in horses.
• Dexamethasone was more effective in improving symptoms, lung function, and airway mechanics.
• Neither treatment was effective in reducing airway inflammation (neutrophilia) or structural remodeling in the short term.
• The findings indicate while testosterone has some positive effects on lung function, it cannot replace corticosteroids for treating severe equine asthma.
• These results contribute to understanding hormonal influence on asthma but suggest testosterone alone is insufficient as a treatment.