LAUSR

Skeletal muscle dysfunction is arguably the most important manifestation of chronic obstructive pulmonary disease (COPD) for patients. It contributes to an inability to go about activities of daily living decreases quality of life, increases office visits and healthcare expenditure. 2 It is only recently this extrapulmonary 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. 4 The sex hormones testosterone, oestrogen and progesterone widely recognised for their role influencing the physical attributes of sexual dimorphism are also recognised for their influence on skeletal muscle homeostasis. Despite this recognition, relatively little attention has been given to the role of sex hormone modulating lifecourse 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 COPDrelated hospitalisation and death. A natural and much needed extension of this research is to investigate the role of sex hormone modulating lifecourse events on skeletal muscle dysfunction later in life in women with COPD. Studies have suggested testosterone treatment may be efficacious in minimising skeletal muscle dysfunction; however, the benefits are overwhelmed by reports of increased adverse cardiovascular events in both men and women. 7 For this reason, selective androgen receptor modulators (SARMs) have been considered as an attractive alternative to testosterone due to tissueselective targeting of the androgen receptors. In the current issue of Thorax, Mohan et al, 2022, report the findings of a phase 2A trial to evaluate the safety and efficacy of the SARM, GSK2881078, in conjunction with a homebased exercise programme in 49 men and 47 postmenopausal women with COPD. In terms of safety, the SARM was well tolerated. In terms of efficacy, lean body mass was increased in both men and women with COPD, which is highly encouraging. However, efficacy in terms of improvements in leg strength was only observed in men. The power and duration of the study may have limited observation of efficacy of the SARM in terms of efficacy in women in the study. In a phase 1b Randomized Control Trial (RCT) of GSK2881078, sexrelated dosing differences for the SARM were observed with women gaining more muscle for the same dose. In the current phase 2b RCT, a 50% lower dose of the SARM was administered to women with COPD. However, other factors such as sex hormone modulating lifecourse events could account for heterogeneity of response to the SARM in terms of skeletal muscle dysfunction in women with COPD. Overall, additional research in larger studies of women with COPD is needed to understand the role of sex hormone modulating lifecourse experiences on skeletal muscle dysfunction later in life. Deepening our understanding of the underlying aetiology these lifecourse experiences influence may lead to discovery of biomarkers enabling precision dosing. This in turn has the potential to expand our understanding androgen sensitivity to mitigate the onset and progression of skeletal muscle dysfunction in COPD.