Inventing the wheel: understanding heterogeneity of response to skeletal muscle dysfunction interventions in women with COPD

Skeletal muscle dysfunction is arguably the most important manifestation of chronic obstructive pulmonary disease (COPD) to patients.It contributes to an inability to go about activities of daily living decreases quality of life, increases office visits and healthcare expenditure 1,2 .It is only recently this extra-pulmonary complication of COPD has been given attention in terms of research and pharmacological interventions.However, the historical bias of a large body of medical research performed in men still overwhelms and limits our understanding of heterogeneity and sensitivity of responses to skeletal muscle dysfunction interventions in women.Women with COPD have a higher prevalence of musculoskeletal comorbidities, muscle wasting and weakness than men 3,4 .The sex hormones testosterone, estrogen and progesterone widely recognized for their role influencing the physical attributes of sexual dimorphism are also recognized for their influence on skeletal muscle homeostasis 5 .Despite this recognition, relatively little attention has been given to the role of sex hormone modulating life-course events on skeletal muscle dysfunction in women with COPD.Nonetheless, strides have been made recently in assessing the relationship between aspects of female reproductive health with risk of COPD and associated outcomes.In close to 300,000 women in the UK Biobank, parity > 3, late menarche and early menopause were associated with increased risk of COPD-related hospitalization and death 6 .A natural and much needed extension of this research is to investigate the role of sex hormone modulating life-course events on skeletal muscle dysfunction later in life in women with COPD.Studies have suggested testosterone treatment may be efficacious in minimizing skeletal muscle dysfunction however, the benefits are overwhelmed by reports of increased adverse cardiovascular events in both males and females 5,7 .For this reason, selective androgen receptor modulators (SARMs) have been considered as an attractive alternative