ID-LC-MS/MS Analysis of Hormones in Sleep Apnea

As the relationship between obstructive sleep apnea (OSA) and comprehensive sex hormone profiles, including free testosterone, in men remains unclear, researchers affiliated with Shanxi Medical University (Taiyuan, China) aimed to explore the independent association between OSA risk and a panel of sex hormone indices after adjusting for obesity. Sex hormones (including testosterone) and sex hormone-binding globulin (SHBG) were measured via isotope dilution liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS) and immunoassays. A paper based on this research was published in the journal Sexual Medicine.¹

Why is Sleep Apnea a Serious Health Concern, Particularly for Men?

OSA is a common sleep disorder in which the upper airway repeatedly collapses during sleep, causing breathing to stop and start throughout the night and resulting in poor, fragmented sleep.² Recent data suggests that the condition is becoming increasingly common, now affecting roughly one in four adult men in the United States, placing a significant strain on both public health and the economy.³ Beyond its most recognizable symptoms of daytime drowsiness and breathing interruptions during sleep, OSA can cause widespread harm to multiple organ systems throughout the body.⁴ In addition, it is closely associated with serious comorbidities, such as hypertension, cardiovascular disease, sudden cardiac death, diabetes, and chronic kidney disease.⁵

While the effects of OSA on heart health and metabolism are well established, a significant number of male patients also show notably low testosterone levels. The condition is increasingly recognized as a key contributor to low testosterone in men. This hormonal deficiency not only affects sexual health and quality of life but also worsens existing metabolic problems, creating a cycle in which hormonal and breathing issues feed into and reinforce each other. ^6,7

What Did the Study Find About the Relationship Between Sleep Apnea Risk and Testosterone Levels in Men?

The study analyzed data from 2218 adult men drawn from a large health survey conducted in 2015–2016. Sleep apnea risk was estimated using a validated scoring tool and divided into low-, medium-, and high-risk groups. The main outcomes examined were total testosterone, a protein that binds to hormones in the blood, and a measure of freely available testosterone. Secondary outcomes included estrogen levels, the ratio of testosterone to estrogen, and how common low testosterone was across the groups.¹

The results showed that men with a higher risk of sleep apnea had significantly lower levels of total testosterone and the hormone-binding protein. No significant differences were found for freely available testosterone or estrogen levels. Low testosterone was notably more common in the high-risk group, affecting more than four in ten men compared to fewer than one in eight in the low-risk group. The hormone-binding protein appeared to play a meaningful role in explaining the link between sleep apnea and lower testosterone levels.¹

“OSA risk is associated with a hormonal profile of low total testosterone and sex hormone-binding globulin,” report the authors of the paper,¹ “ but preserved free testosterone, a relationship strongly moderated by body mass index.”

“Routine screening for sex hormone-binding globulin in obese OSA patients,” the authors continue,¹ “may help prevent misdiagnosis of hypogonadism and guide targeted intervention.”

The researchers believe that future research should prioritize mechanistic studies of SHBG regulation and intervention trials assessing OSA treatment’s hormonal benefits.¹

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References

1. Ji, Y.; Hua, P.; Gao, H. et al. Association Between Obstructive Sleep Apnea and Sex Hormones in U.S. Adult Males: A Population-Based study. Sex Med. 2026, 14 (4), qfag042. DOI: 10.1093/sexmed/qfag042
2. Locke, B. W.; Lee, J. J.; Sundar, K. M. OSA and Chronic Respiratory Disease: Mechanisms and Epidemiology. Int J Environ Res Public Health 2022, 19 (9), 5473. DOI: 10.3390/ijerph19095473
3. Mangione, C. M.; Barry, M. J.; Nicholson, W. K. et al. Screening for Obstructive Sleep Apnea in Adults: US Preventive Services Task Force Recommendation Statement. JAMA 2022, 328 (19), 1945-1950. DOI: 10.1001/jama.2022.20304
4. Lee, J. J.; Sundar, K. M. Evaluation and Management of Adults with Obstructive Sleep Apnea Syndrome. Lung 2021, 199 (2), 87-101. DOI: 10.1007/s00408-021-00426-w
5. Lv, R.; Liu, X.; Zhang, Y. et al. Pathophysiological Mechanisms and Therapeutic Approaches in Obstructive Sleep Apnea Syndrome. Signal Transduct Target Ther. 2023, 8 (1), 218. DOI: 10.1038/s41392-023-01496-3
6. Liu, P. Y.; Reddy, R. T. Sleep, Testosterone and Cortisol Balance, and Ageing Men. Rev Endocr Metab Disord. 2022, 23 (6),1323-1339. DOI: 10.1007/s11154-022-09755-4
7. Kim, S. D.; Cho, K. S. Obstructive Sleep Apnea and Testosterone Deficiency. World J Mens Health. 2019, 37 (1), 12-18. DOI: 10.5534/wjmh.180017