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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

202404-431LE
10.1513/AnnalsATS.202404-431LE
Letters
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/0000-0001-9923-5747
Lin Yu-Hsiang 1 2 *
Wang Tsai-Yu 1 2
Wu Chun-Te 1 2
1 Chang Gung Memorial Hospital-Linkou
Taoyuan City, Taiwan
2 Chang Gung University
Taoyuan, Taiwan
* Corresponding author (e-mail: laserep@cgu.edu.tw).
1 9 2024
1 9 2024
1 9 2024
21 9 13451346
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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pmcTo the Editor:

Having read the study by O’Donnell and colleagues (1), we were intrigued by the differential outcomes observed between continuous positive airway pressure (CPAP) and glucagon-like peptide 1 (GLP-1)-mediated weight loss in treating patients with obstructive sleep apnea (OSA). This well-conducted randomized proof-of-concept study not only highlighted the effectiveness of CPAP in reducing early cardiovascular disease markers but also prompted further consideration of underlying hormonal mechanisms, particularly the role of testosterone, which might explain the observed variances in treatment outcomes (as depicted in Figure 1).

Figure 1. Conceptual model of treatment dynamics and hypothetical pathways in obstructive sleep apnea (OSA) management. The figure illustrates the dynamic and temporally disparate responses to treatments for OSA. Glucagon-like peptide 1’s (GLP-1’s) effect on body weight (BW) loss, indicated by the dotted arrow, portrays a delayed influence on OSA improvement, as opposed to the immediate impact of continuous positive airway pressure (CPAP), shown by the solid red arrow. Benign prostatic hyperplasia (BPH) is encased in a dashed border to indicate its speculative addition to the traditional OSA management framework, affecting nocturia and sleep quality, which then influences testosterone concentrations and metabolic syndrome (Met S), delineated in a green dashed border, highlighting these as emerging considerations. The overarching pathway culminates in vascular inflammation, the endpoint of interest, with all antecedent factors potentially contributing to its modulation.

The study efficiently illustrated how CPAP significantly ameliorates vascular inflammation, as evidenced by reductions in aortic wall target-to-background ratios and unstable plaque volumes, outcomes not mirrored by the GLP-1 group despite notable weight loss. This leads us to hypothesize that testosterone concentrations, often disrupted in patients with OSA, may play a critical mediating role in these disparate responses.

As we previously discussed in the World Journal of Urology (2), both OSA and benign prostatic hyperplasia (BPH) are linked through shared clinical manifestations such as nocturia and their association with lower testosterone concentrations and metabolic syndrome. Our hypothesis posits that nocturia-related sleep disruptions lead to a decrease in antidiuretic hormone secretion, which in turn exacerbates nocturnal polyuria. This hormone imbalance can disrupt the circadian rhythm and subsequently suppress the hypothalamic-pituitary-gonadal axis, thereby reducing testosterone production (3). This insufficiency in testosterone aggravates metabolic syndrome, further complicating the clinical picture of BPH and intensifying nocturia (refer to Figure 1).

In addition, low testosterone concentrations resultant from metabolic syndrome can contribute to obesity, a significant factor in OSA. This relationship suggests that OSA might activate vicious cycles involving antidiuretic hormone and testosterone as observed in BPH, thus perpetuating a complex interplay of hormone dysregulation. It is notable that O’Donnell and colleagues (1) reported slower and less significant reductions in the apnea–hypopnea index for the GLP-1 group compared with the CPAP group. We surmise that this difference arises because CPAP directly alleviates airway obstruction, thereby rapidly reducing sleep disturbances and potentially allowing quicker normalization of testosterone concentrations (4).

Given the immediate impact of CPAP on reducing airway obstruction and the subsequent rapid improvement in sleep quality, it is plausible to propose that such amelioration could directly elevate testosterone concentrations. However, the benefits of increased testosterone, such as improvements in muscle mass, bone mineral density, and lipid profiles, take time to manifest (5). This delayed systemic response might explain why vascular inflammation improvements were not as pronounced in the GLP-1 group within the 24-week study period. If the study duration extended to 1 year or more, we might observe significant enhancements in cardiovascular outcomes after the normalization of sleep patterns and testosterone concentrations in the GLP-1 group.

This study primarily included a younger male demographic (20–60 yr old), with a relatively low presence of BPH or its mild forms, similar to the population described by Li and colleagues (4). As age increases, the influence of BPH on these vicious cycles could potentially disrupt the beneficial effects of CPAP on testosterone concentrations, suggesting that future studies on CPAP’s efficacy in treating OSA should consider including parameters such as improvement in nocturia and, for males, the specific impact on BPH symptoms.

In conclusion, although the study by O’Donnell and colleagues (1) provides critical insights into the management of OSA and its cardiovascular implications, it also opens up an avenue for further exploration into the hormonal underpinnings that may influence treatment outcomes. A more comprehensive approach, incorporating the assessment of testosterone concentrations and nocturia improvement, could provide deeper insights into the interconnections between sleep, hormonal health, and cardiovascular risk in patients with OSA (as illustrated in Figure 1).

Author Contributions: Y.-H.L.: conceptualization, writing original draft, writing, review, and editing. T.-Y.W.: conceptualization. C.-T.W.: conceptualization.

Data-sharing statement: This letter to the editor is based on previously published literature and does not involve any new data collected by the authors. All analyses and discussions are derived from publicly available sources, which are cited within the letter. Therefore, there are no data sets generated or analyzed during the present study.

Institutional review board review of human research: The authors hereby acknowledge that the present letter is an analysis of existing literature and does not contain any original human research. This work did not involve any human participants, tissues, biological samples, or medical records and, as such, did not require the review or approval of an institutional review board. Therefore, the requirements of the Declaration of Helsinki concerning human research are not applicable to this letter. No informed consent process is implicated for the same reason.

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 Lin YH Wu CT Juang HH Exploring the complex interplay: BPH, nocturia, and aging male health World J Urol 2024 42 105 38407677
3 Leproult R Van Cauter E Effect of 1 week of sleep restriction on testosterone levels in young healthy men JAMA 2011 305 2173 2174 21632481
4 Li Z Tang T Wu W Gu L Du J Zhao T et al. Efficacy of nasal continuous positive airway pressure on patients with OSA with erectile dysfunction and low sex hormone levels Respir Med 2016 119 130 134 27692134
5 Saad F Aversa A Isidori AM Zafalon L Zitzmann M Gooren L Onset of effects of testosterone treatment and time span until maximum effects are achieved Eur J Endocrinol 2011 165 675 685 21753068
