Circulating testosterone levels and health outcomes in chronic obstructive pulmonary disease: results from ECLIPSE and ERICA

Pavey, Holly; Polkey, Michael I; Bolton, Charlotte E; Cheriyan, Joseph; McEniery, Carmel M; Wilkinson, Ian; Mohan, Divya; Casaburi, Richard; Miller, Bruce E; Tal-Singer, Ruth; Fisk, Marie

Abstract

The relationship of circulating testosterone levels with health outcomes in people with chronic obstructive pulmonary disease (COPD) is unknown.

Aim
To determine whether serum testosterone levels predict hospitalised acute exacerbations of COPD (H-AECOPD), cardiovascular disease outcome, and mortality in people with COPD.

Methods
Separate analyses were carried out on two observational, multicentre COPD cohorts, Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE) and Evaluation of the Role of Inflammation in Chronic Airways Disease (ERICA), both of which had serum testosterone measured using a validated liquid chromatography assay at the same laboratory. Data from 1296 male participants in ECLIPSE and 386 male, 239 female participants in ERICA were analysed. All analyses were sex-specific. Multivariate logistic regression was used to determine associations with H-AECOPD during follow-up (3 years ECLIPSE, 4.5 years ERICA), a composite endpoint of cardiovascular hospitalisation and cardiovascular death, and all-cause mortality.

Results
Mean (SD) testosterone levels were consistent across cohorts; 459 (197) and 455 (200) ng/dL for males in ECLIPSE and ERICA, respectively, and in ERICA females: 28 (56) ng/dL. Testosterone was not associated with H-AECOPD (ECLIPSE: OR: 0.76, p=0.329, ERICA males: OR (95% CI): 1.06 (0.73 to 1.56), p=0.779, ERICA females: OR: 0.77 (0.52 to 1.12), p=0.178) or cardiovascular hospitalisation and death. Testosterone was associated with all-cause mortality in Global Initiative for Obstructive Lung Disease (GOLD) stage 2 male patients only, in ECLIPSE (OR: 0.25, p=0.007) and ERICA (OR: (95% CI): 0.56 (0.32 to 0.95), p=0.030).

Conclusions
Testosterone levels do not relate to H-AECOPD or cardiovascular outcome in COPD, but are associated with all-cause mortality in GOLD stage 2 COPD male patients, although the clinical significance of this finding is uncertain.

Citation

Pavey, H., Polkey, M. I., Bolton, C. E., Cheriyan, J., McEniery, C. M., Wilkinson, I., Mohan, D., Casaburi, R., Miller, B. E., Tal-Singer, R., & Fisk, M. (2023). Circulating testosterone levels and health outcomes in chronic obstructive pulmonary disease: results from ECLIPSE and ERICA. BMJ Open Respiratory Research, 10(1), Article e001601. https://doi.org/10.1136/bmjresp-2022-001601

• Journal Article Type: Article
• Acceptance Date: May 30, 2023
• Online Publication Date: Jun 14, 2023
• Publication Date: 2023-06
• Deposit Date: Jun 18, 2023
• Publicly Available Date: Jun 29, 2023
• Journal: BMJ Open Respiratory Research
• Electronic ISSN: 2052-4439
• Publisher: BMJ Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 10
• Issue: 1
• Article Number: e001601
• DOI: https://doi.org/10.1136/bmjresp-2022-001601
• Keywords: Clinical Relevance, Hospitalization, COPD Exacerbations, Male, Pulmonary Disease, Chronic Obstructive, COPD epidemiology, Female, Humans, Clinical Epidemiology, Cardiovascular Diseases, Inflammation
• Public URL: https://nottingham-repository.worktribe.com/output/21917419
• Additional Information: This is the peer reviewed version of the following article: Pavey H, Polkey MI, Bolton CE, et al. Circulating testosterone levels and health outcomes in chronic obstructive pulmonary disease: results from ECLIPSE and ERICA. BMJ Open Respir Res 2023;10:e001601, which has been published in final form at http://dx.doi.org/10.1136/bmjresp-2022-001601