{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:28:40Z","timestamp":1787027320081,"version":"build-2736575974"},"reference-count":56,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,10,10]],"date-time":"2023-10-10T00:00:00Z","timestamp":1696896000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Reprod. Health"],"abstract":"<jats:p>\n                    Obstructive sleep apnoea syndrome (OSAS) is an under-recognized medical disease. The main risk factors for OSAS are male sex, older age, obesity, and metabolic syndrome, that are also associated with male hypogonadism (MH). Therefore, obesity has been classically identified as the most evident link between OSAS and MH. However, OSAS is\n                    <jats:italic>per se<\/jats:italic>\n                    linked to the development of MH by a combined effect of hypoxia, increased night-time awakenings, reduced sleep efficiency and fragmented sleep. Similarly, MH might represent a risk factor for OSAS, mainly related to sleep disturbances that are frequently associated with low testosterone. Data on testosterone replacement therapy (TRT) in patients with OSAS are limited. Nevertheless, TRT is generally contraindicated by guidelines in the presence of untreated or severe OSAS. TRT might in fact worse OSAS symptoms in different ways. Furthermore, OSAS has been proposed to be a risk factor for secondary polycythaemia and TRT might exacerbate polycythaemia. Therefore, TRT in hypogonadal men affected by untreated OSAS or severe OSAS should be considered with caution and in a personalised way. Nevertheless, the type and dosage of TRT should be considered, as short-term high-dose TRT might worsen OSAS, whereas long-term lower doses could eventually determine a clinical improvement of symptoms of OSAS. Here we reviewed the data on the association between OSAS, MH and TRT, including the opportunity of assessment of patients who develop signs and symptoms of OSAS during TRT by polysomnography.\n                  <\/jats:p>","DOI":"10.3389\/frph.2023.1219239","type":"journal-article","created":{"date-parts":[[2023,10,10]],"date-time":"2023-10-10T02:23:10Z","timestamp":1696904590000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["The complex relation between obstructive sleep apnoea syndrome, hypogonadism and testosterone replacement therapy"],"prefix":"10.3389","volume":"5","author":[{"given":"Andrea","family":"Graziani","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Grande","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Ferlin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,10,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1007\/s00408-021-00426-w","article-title":"Evaluation and management of adults with obstructive sleep apnea syndrome","volume":"199","author":"Lee","year":"2021","journal-title":"Lung"},{"key":"B2","first-page":"10","article-title":"Obstructive sleep apnea syndrome\u2014a review for primary care physicians and pulmonologists","volume":"104","author":"Singh","year":"2021","journal-title":"R I Med J"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000988","article-title":"Obstructive sleep apnea and cardiovascular disease: a scientific statement from the American heart association","volume":"144","author":"Yeghiazarians","year":"2021","journal-title":"Circulation"},{"key":"B4","doi-asserted-by":"publisher","first-page":"323","DOI":"10.3390\/medicina57040323","article-title":"Orofacial myofunctional therapy in obstructive sleep apnea syndrome: a pathophysiological perspective","volume":"57","author":"Koka","year":"2021","journal-title":"Medicina"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1006","DOI":"10.1093\/aje\/kws342","article-title":"Increased prevalence of sleep-disordered breathing in adults","volume":"177","author":"Peppard","year":"2013","journal-title":"Am J Epidemiol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1186\/s12974-020-01905-2","article-title":"The relationship between inflammation and neurocognitive dysfunction in obstructive sleep apnea syndrome","volume":"17","author":"Liu","year":"2020","journal-title":"J Neuroinflammation"},{"key":"B7","doi-asserted-by":"publisher","first-page":"4572","DOI":"10.3390\/jcm11154572","article-title":"Correlation between apnea severity and sagittal cephalometric features in a population of patients with polysomnographically diagnosed obstructive sleep apnea","volume":"11","author":"Pollis","year":"2022","journal-title":"J Clin Med"},{"key":"B8","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1007\/s11325-021-02412-1","article-title":"Obstructive sleep apnea syndrome in non-obese patients","volume":"26","author":"Antonaglia","year":"2022","journal-title":"Sleep Breath"},{"key":"B9","doi-asserted-by":"publisher","first-page":"10277","DOI":"10.3390\/ijerph181910277","article-title":"Prevalence of obstructive sleep apnea syndrome: a single-center retrospective study","volume":"18","author":"Santilli","year":"2021","journal-title":"Int J Environ Res Public Health"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1135","DOI":"10.1164\/rccm.201907-1284OC","article-title":"Pitolisant for daytime sleepiness in patients with obstructive sleep apnea who refuse continuous positive airway pressure treatment. A randomized trial","volume":"201","author":"Dauvilliers","year":"2020","journal-title":"Am J Respir Crit Care Med"},{"key":"B11","doi-asserted-by":"publisher","first-page":"732","DOI":"10.3390\/jcm8050732","article-title":"Substance abuse and male hypogonadism","volume":"8","author":"Duca","year":"2019","journal-title":"J Clin Med"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2020.00211","article-title":"Male hypogonadism and disorders of sex development","volume":"11","author":"Grinspon","year":"2020","journal-title":"Front Endocrinol"},{"key":"B13","doi-asserted-by":"publisher","first-page":"2385","DOI":"10.1007\/s40618-022-01859-7","article-title":"Adult- and late-onset male hypogonadism: the clinical practice guidelines of the Italian Society of Andrology and Sexual Medicine (SIAMS) and the Italian Society of Endocrinology (SIE)","volume":"45","author":"Isidori","year":"2022","journal-title":"J Endocrinol Invest"},{"key":"B14","article-title":"Hypogonadism","volume-title":"StatPearls","author":"Sizar","year":"2022"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1988","DOI":"10.3390\/ijms22041988","article-title":"Metabolic syndrome and reproduction","volume":"22","author":"Lotti","year":"2021","journal-title":"Int J Mol Sci"},{"key":"B16","doi-asserted-by":"publisher","first-page":"714","DOI":"10.1038\/s41443-021-00496-7","article-title":"Functional hypogonadism among patients with obesity, diabetes, and metabolic syndrome","volume":"34","author":"Louters","year":"2022","journal-title":"Int J Impot Res"},{"key":"B17","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1016\/j.ucl.2016.01.005","article-title":"Obesity and hypogonadism","volume":"43","author":"Lamm","year":"2016","journal-title":"Urol Clin N Am"},{"key":"B18","doi-asserted-by":"publisher","first-page":"789","DOI":"10.1007\/s11325-022-02655-6","article-title":"Obstructive sleep apnea and serum total testosterone: a system review and meta-analysis","volume":"27","author":"Wang","year":"2023","journal-title":"Sleep Breath"},{"key":"B19","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1111\/andr.13111","article-title":"Association between obstructive sleep apnea and male serum testosterone: a systematic review and meta-analysis","volume":"10","author":"Su","year":"2022","journal-title":"Andrology"},{"key":"B20","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1016\/j.jacc.2013.05.045","article-title":"Obstructive sleep apnea","volume":"62","author":"Drager","year":"2013","journal-title":"J Am Coll Cardiol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1111\/crj.13175","article-title":"The relationship between obstructive sleep apnea syndrome and obesity: a new perspective on the pathogenesis in terms of organ crosstalk","volume":"14","author":"Kuvat","year":"2020","journal-title":"Clin Respir J"},{"key":"B22","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1111\/cen.13723","article-title":"Hypogonadism and male obesity: focus on unresolved questions","volume":"89","author":"Grossmann","year":"2018","journal-title":"Clin Endocrinol"},{"key":"B23","doi-asserted-by":"publisher","first-page":"8194","DOI":"10.3390\/ijms23158194","article-title":"Adipose tissue dysfunction and obesity-related male hypogonadism","volume":"23","author":"Genchi","year":"2022","journal-title":"Int J Mol Sci"},{"key":"B24","doi-asserted-by":"publisher","first-page":"531","DOI":"10.4103\/aja.aja_44_18","article-title":"Secondary male hypogonadism: a prevalent but overlooked comorbidity of obesity","volume":"20","author":"Molina-Vega","year":"2018","journal-title":"Asian J Androl"},{"key":"B25","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1111\/jsr.12027","article-title":"The effects of testosterone on ventilatory responses in men with obstructive sleep apnea: a randomised, placebo-controlled trial","volume":"22","author":"Killick","year":"2013","journal-title":"J Sleep Res"},{"key":"B26","doi-asserted-by":"publisher","first-page":"12","DOI":"10.5534\/wjmh.180017","article-title":"Obstructive sleep apnea and testosterone deficiency","volume":"37","author":"Kim","year":"2019","journal-title":"World J Mens Health"},{"key":"B27","doi-asserted-by":"publisher","first-page":"3394","DOI":"10.1210\/jcem.87.7.8663","article-title":"Decreased pituitary-gonadal secretion in men with obstructive sleep apnea","volume":"87","author":"Luboshitzky","year":"2002","journal-title":"J Clin Endocrinol Metab"},{"key":"B28","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1590\/S1808-86942011000100015","article-title":"Avalia\u00e7\u00e3o dos n\u00edveis s\u00e9ricos de testosterona em pacientes com s\u00edndrome da apneia obstrutiva do sono","volume":"77","author":"Molina","year":"2011","journal-title":"Braz J Otorhinolaryngol"},{"key":"B29","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1097\/MED.0000000000000069","article-title":"The relationship between sleep disorders and testosterone","volume":"21","author":"Wittert","year":"2014","journal-title":"Curr Opin Endocrinol Diabetes Obes"},{"key":"B30","doi-asserted-by":"publisher","first-page":"83","DOI":"10.17925\/EE.2019.15.2.83","article-title":"Male obesity-related secondary hypogonadism\u2014pathophysiology, clinical implications and management","volume":"15","author":"Fernandez","year":"2019","journal-title":"Eur Endocrinol"},{"key":"B31","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1007\/BF03345209","article-title":"Testosterone levels in obese male patients with obstructive sleep apnea syndrome: relation to oxygen desaturation, body weight, fat distribution and the metabolic parameters","volume":"26","author":"Gambineri","year":"2003","journal-title":"J Endocrinol Invest"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2021.622496","article-title":"Obstructive sleep apnea is associated with low testosterone levels in severely obese men","volume":"12","author":"Tan\u010di\u0107-Gaji\u0107","year":"2021","journal-title":"Front Endocrinol"},{"key":"B33","doi-asserted-by":"publisher","first-page":"2602","DOI":"10.1210\/jc.2007-2622","article-title":"The association of testosterone levels with overall sleep quality, sleep architecture, and sleep-disordered breathing","volume":"93","author":"Barrett-Connor","year":"2008","journal-title":"J Clin Endocrinol Metab"},{"key":"B34","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1159\/000183509","article-title":"Sleep apnea in hemodialysis patients: the lack of testosterone effect on its pathogenesis","volume":"40","author":"Millman","year":"1985","journal-title":"Nephron"},{"key":"B35","doi-asserted-by":"publisher","first-page":"3605","DOI":"10.1210\/jc.2003-030236","article-title":"The short-term effects of high-dose testosterone on sleep, breathing, and function in older men","volume":"88","author":"Liu","year":"2003","journal-title":"J Clin Endocrinol Metab"},{"key":"B36","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1111\/j.1365-2265.2012.04413.x","article-title":"Effects of testosterone therapy on sleep and breathing in obese men with severe obstructive sleep apnoea: a randomized placebo-controlled trial","volume":"77","author":"Hoyos","year":"2012","journal-title":"Clin Endocrinol"},{"key":"B37","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1111\/andr.12132","article-title":"Increased sexual desire with exogenous testosterone administration in men with obstructive sleep apnea: a randomized placebo-controlled study","volume":"4","author":"Melehan","year":"2016","journal-title":"Andrology"},{"key":"B38","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1111\/bju.14149","article-title":"Impact of testosterone replacement therapy on thromboembolism, heart disease and obstructive sleep apnoea in men","volume":"121","author":"Cole","year":"2018","journal-title":"BJU Int"},{"key":"B39","doi-asserted-by":"publisher","first-page":"1297","DOI":"10.1016\/j.jsxm.2020.03.006","article-title":"Obstructive sleep apnea is associated with polycythemia in hypogonadal men on testosterone replacement therapy","volume":"17","author":"Lundy","year":"2020","journal-title":"J Sex Med"},{"key":"B40","doi-asserted-by":"publisher","first-page":"1715","DOI":"10.1210\/jc.2018-00229","article-title":"Testosterone therapy in men with hypogonadism: an endocrine society clinical practice guideline","volume":"103","author":"Bhasin","year":"2018","journal-title":"J Clin Endocrinol Metab"},{"key":"B41","doi-asserted-by":"publisher","first-page":"1241","DOI":"10.1111\/j.1743-6109.2007.00553.x","article-title":"Testosterone therapy and obstructive sleep apnea: is there a real connection?","volume":"4","author":"Hanafy","year":"2007","journal-title":"J Sex Med"},{"key":"B42","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1016\/j.sxmr.2020.04.004","article-title":"Obstructive sleep apnea and testosterone therapy","volume":"9","author":"Payne","year":"2021","journal-title":"Sex Med Rev"},{"key":"B43","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1111\/cen.14633","article-title":"Society for endocrinology guidelines for testosterone replacement therapy in male hypogonadism","volume":"96","author":"Jayasena","year":"2022","journal-title":"Clin Endocrinol"},{"key":"B44","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1016\/j.sxmr.2020.09.004","article-title":"Controversies in testosterone therapy","volume":"9","author":"Twitchell","year":"2021","journal-title":"Sex Med Rev"},{"key":"B45","doi-asserted-by":"publisher","first-page":"970","DOI":"10.1111\/andr.12770","article-title":"European Academy of Andrology (EAA) guidelines on investigation, treatment and monitoring of functional hypogonadism in males","volume":"8","author":"Corona","year":"2020","journal-title":"Andrology"},{"key":"B46","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1016\/j.jsmc.2016.08.003","article-title":"Testosterone deficiency and sleep apnea","volume":"11","author":"Burschtin","year":"2016","journal-title":"Sleep Med Clin"},{"key":"B47","doi-asserted-by":"publisher","first-page":"68","DOI":"10.12688\/f1000research.10102.1","article-title":"Treatment of hypogonadism: current and future therapies","volume":"6","author":"Thirumalai","year":"2017","journal-title":"F1000Res"},{"key":"B48","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1080\/13685538.2017.1378320","article-title":"Sleep disturbance as a clinical sign for severe hypogonadism: efficacy of testosterone replacement therapy on sleep disturbance among hypogonadal men without obstructive sleep apnea","volume":"21","author":"Shigehara","year":"2018","journal-title":"Aging Male"},{"key":"B49","doi-asserted-by":"publisher","first-page":"301","DOI":"10.5152\/TurkThoracJ.2021.20051","article-title":"Effect of obstructive sleep apnea on bone mineral density","volume":"22","author":"Sadaf","year":"2021","journal-title":"Turk Thorac J"},{"key":"B50","doi-asserted-by":"publisher","first-page":"911","DOI":"10.1007\/s40618-021-01702-5","article-title":"Testosterone supplementation and bone parameters: a systematic review and meta-analysis study","volume":"45","author":"Corona","year":"2022","journal-title":"J Endocrinol Invest"},{"key":"B51","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1111\/j.1365-2265.1988.tb03680.x","article-title":"Reversible reproductive dysfunction in men with obstructive sleep apnoea","volume":"28","author":"Santamaria","year":"1988","journal-title":"Clin Endocrinol"},{"key":"B52","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1210\/jcem-68-2-352","article-title":"Neuroendocrine dysfunction in sleep apnea: reversal by continuous positive airways pressure therapy","volume":"68","author":"Grunstein","year":"1989","journal-title":"J Clin Endocrinol Metab"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2019.00551","article-title":"Effects of CPAP on testosterone levels in patients with obstructive sleep apnea: a meta-analysis study","volume":"10","author":"Cignarelli","year":"2019","journal-title":"Front Endocrinol"},{"key":"B54","doi-asserted-by":"publisher","first-page":"1323","DOI":"10.1007\/s11154-022-09755-4","article-title":"Sleep, testosterone and cortisol balance, and ageing men","volume":"23","author":"Liu","year":"2022","journal-title":"Rev Endocr Metab Disord"},{"key":"B55","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1111\/j.1439-0272.2008.00914.x","article-title":"Sexual functions of men with obstructive sleep apnoea syndrome and hypogonadism may improve upon testosterone administration: a pilot study","volume":"41","author":"Zhuravlev","year":"2009","journal-title":"Andrologia"},{"key":"B56","doi-asserted-by":"publisher","first-page":"1529","DOI":"10.5664\/jcsm.7992","article-title":"The effects of transgender hormone therapy on sleep and breathing: a case series","volume":"15","author":"Robertson","year":"2019","journal-title":"J Clin Sleep Med"}],"container-title":["Frontiers in Reproductive Health"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/frph.2023.1219239\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,10]],"date-time":"2023-10-10T02:23:21Z","timestamp":1696904601000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/frph.2023.1219239\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,10]]},"references-count":56,"alternative-id":["10.3389\/frph.2023.1219239"],"URL":"https:\/\/doi.org\/10.3389\/frph.2023.1219239","relation":{},"ISSN":["2673-3153"],"issn-type":[{"value":"2673-3153","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,10]]},"article-number":"1219239"}}