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Ann Am Thorac Soc
Ann Am Thorac Soc
AnnalsATS
Annals of the American Thoracic Society
2329-6933
2325-6621
American Thoracic Society

202406-605LE
10.1513/AnnalsATS.202406-605LE
Letters
Reply: Exploring the Role of Testosterone in the Differential Outcomes of Continuous Positive Airway Pressure and Glucagon-like peptide 1 Treatments in Obstructive Sleep Apnea
https://orcid.org/0000-0003-0963-255X
Ryan Silke 1 2 *
O’Donnell Cliona 1 2
1 St. Vincent’s University Hospital
Dublin, Ireland
2 University College Dublin
Dublin, Ireland
* Corresponding author (e-mail: silke.ryan@ucd.ie).
1 9 2024
1 9 2024
1 9 2024
21 9 13461347
Copyright © 2024 by the American Thoracic Society
2024
https://creativecommons.org/licenses/by-nc-nd/4.0/ This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0. For commercial usage and reprints, please e-mail Diane Gern.
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pmcFrom the Authors:

We thank Dr. Lin and coworkers for their interest in our paper, and we could not agree more with their comment that the differential effects of continuous positive airway pressure (CPAP) therapy and GLP-1 (glucagon-like peptide-1)–mediated weight loss on cardiovascular diseases (CVDs) in obstructive sleep apnea (OSA) requires further detailed investigation. Our proof-of-concept randomized controlled trial supported a benefit of CPAP on early vascular inflammation and unstable coronary artery plaque volume that was not seen with GLP-1 analog treatment despite significant reduction in body weight (1). However, our study was not designed to provide insight into the underlying mechanisms. The detailed pathophysiology of CVDs in OSA remains incompletely understood but for certain encompasses a multifactorial process with various triggering factors, particularly intermittent hypoxia and sleep fragmentation, mediating cardiovascular adverse processes through numerous intermediate pathways, including sympathetic activation, inflammation, oxidative stress, and metabolic dysregulation (2, 3). Lin and colleagues propose a restoration of testosterone concentrations by CPAP as a potential reason for our findings. We did not measure hormone concentrations in our study and as consequence cannot provide evidence for or against this hypothesis. Nonetheless, we would like to advise caution with respect to this proposition. Although several lines of evidence suggest that OSA is associated with low testosterone concentrations in men and that those might play a permissive role in CVD processes (4), there is limited support that CPAP can restore testosterone concentrations, and in fact, several meta-analyses have corroborated the lack of improvement (5, 6). Furthermore and with respect to our study, despite limited numbers, we did not observe a sex-specific response to CPAP or an impact of menopause status. Therefore, we cannot support the theory that change in testosterone concentrations played a causative role in the amelioration of CVD by CPAP in our cohort. Nonetheless, as stated above, we fully concur with Lin and coworkers that the role of sex hormones in the complex relationship between OSA and cardiovascular comorbidities warrants thorough exploration, and there is a clear demand for targeted translational studies.

Author disclosures are available with the text of this letter at www.atsjournals.org.
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References

1 O’Donnell C Crilly S O’Mahony A O’Riordan B Traynor M Gitau R et al. Continuous positive airway pressure but not GLP1-mediated weight loss improves early cardiovascular disease in obstructive sleep apnea: a randomized proof-of-concept study Ann Am Thorac Soc 2024 21 464 473 38096106
2 Ryan S Mechanisms of cardiovascular disease in obstructive sleep apnoea J Thorac Dis 2018 10 S4201 S4211 30687536
3 Ryan S Cummins EP Farre R Gileles-Hillel A Jun JC Oster H et al. Understanding the pathophysiological mechanisms of cardiometabolic complications in obstructive sleep apnoea: towards personalised treatment approaches Eur Respir J 2020 56 1902295 32265303
4 Wang H Lu J Xu L Yang Y Meng Y Li Y et al. Obstructive sleep apnea and serum total testosterone: a system review and meta-analysis Sleep Breath 2023 27 789 797 35904664
5 Cignarelli A Castellana M Castellana G Perrini S Brescia F Natalicchio A et al. Effects of CPAP on testosterone levels in patients with obstructive sleep apnea: a meta-analysis study Front Endocrinol (Lausanne) 2019 10 551 31496991
6 Zhang XB Jiang XT Du YP Yuan YT Chen B Efficacy of continuous positive airway pressure on testosterone in men with obstructive sleep apnea: a meta-analysis PLoS One 2014 9 e115033 25503098
