Sleep Disorders are Associated with Testosterone Deficiency and Erectile Dysfunction- A U.S. Claims Database Analysis

Sleep Disorders are Associated with Testosterone Deficiency and Erectile Dysfunction- A U.S. Claims Database Analysis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Help Center Sign In Submit a Preprint Cite Share Download PDF Article Sleep Disorders are Associated with Testosterone Deficiency and Erectile Dysfunction- A U.S. Claims Database Analysis Pranjal Agrawal, Sajya Singh, Corey Able, Taylor Kohn, Amin Herati This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1913602/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 06 Dec, 2022 Read the published version in International Journal of Impotence Research → Version 1 posted 10 You are reading this latest preprint version Abstract The relationship between male genitourinary conditions and sleep disorders has only been reported in small sample sizes. Our objective was to assess the association of erectile dysfunction (ED) and testosterone deficiency with various sleep disorders using a large claims database. The TriNetX Diamond database, a research network of over 220 million patients, was queried in June 2022. In men aged 40–70 years, insomnia (ICD-10 G47.0), sleep apnea (G47.33), and circadian rhythm sleep disorder (G47.2) were each independently assessed to determine the association with ED (N52) and testicular hypofunction (E29.1). A propensity-score-matched control cohort was generated with an absence of sleep disorders (G47 & F51), sleep deprivation (Z72.820), or morbid obesity with alveolar hypoventilation (E66.2). Propensity score matching was performed for age, hypertension (I10-16), hyperlipidemia (E78), diabetes mellitus (E08-13), ischemic heart disease (I20-25), tobacco usage (Z72.0), and obesity (E66). Sensitivity analyses were conducted via a negative polysomnography testing (CPT 1013314) cohort. Men diagnosed with a sleep disorder had significantly higher odds of testosterone deficiency and ED compared to propensity-score matched controls. Our results emphasize the negative impact of poor sleep on diseases of the male genitourinary system by identifying these relationships in the largest cohort in the U.S. reported to date. Sleep Apnea Insomnia Circadian Rhythm Dysfunction Polysomnography Testosterone Deficiency Hypogonadism Erectile Dysfunction Introduction Prolonged disturbances in sleep duration and quality can have detrimental impacts on an individual’s overall health. 1 , 2 Large meta-analyses have identified a dose-dependent relationship between sleep and impactful diseases such as type 2 diabetes mellitus, hypertension, and coronary artery disease. 1 , 3 , 4 Several common health conditions can lead to poor sleep, including circadian rhythm dysfunction, obstructive sleep apnea (OSA), and insomnia. One type of circadian rhythm dysfunction, shift work sleep disorder (SWSD), affects approximately 20% of non-standard shift workers, who represent > 20% of working adults in the United States, and leads to insomnia as well as excessive daytime sleepiness. 5 – 7 Insomnia encompasses many symptoms leading to poor sleep quality and affects up to 30% of individuals in population-based studies. 8 In the general population, sleep apnea is highly prevalent, affecting approximately 33% of men in the United States. OSA has significant associations with the male sex, age ≥ 65 years, and higher BMI. 9 , 10 With a large portion of the adult population affected by these three conditions, it is necessary to investigate the relationship between poor sleep and common diseases of the male genitourinary system, including testosterone deficiency and erectile dysfunction (ED). 11 , 12 Previously, observational studies have shown an increased severity of hypogonadal clinical symptoms among non-standard shift workers; however, they did not well establish the significance of the relationship between sleep quality and low serum testosterone levels . 7 , 12 , 13 Prior studies have linked OSA to ED and decreased libido; although, one recent study showed no association between sleep apnea and ED. 11 , 14 Therefore, the effect of poor sleep quality and duration, particularly related to circadian rhythm dysfunction, sleep apnea, and insomnia, on male-specific genitourinary diseases remains unclear. Based on prior results in the literature, we hypothesize that sleep disturbances are associated with an increased prevalence of testosterone deficiency and ED in men. However, thus far, research on this subject has been confined to small, single-institution cohorts of patients. In this article, we report the results of the first large claims database study to investigate this relationship, utilizing a large study population with a matched cohort. Methods Study Design We conducted a retrospective cohort analysis utilizing electronic health records (EHRs) supplemented with insurance claims from the research network TriNetX Diamond (Cambridge, MA, USA) which provided access to electronic medical records (diagnoses, procedures, medications, laboratory values, genomic information), as well as medical insurance claims and pharmaceutical claims for over 212 million patients from 92 healthcare organizations. Data used in this study was collected and analyzed as of June 2022. Information regarding demographics, diagnoses from International Classification of Disease (ICD-10) codes, and procedures from Current Procedural Terminology (CPT) codes were all recorded and used for analysis. TriNetX adheres to the Health Insurance Portability and Accountability Act (HIPAA) and has received a waiver from Western IRB as all patient data is de-identified as per the standard defined in Section § 164.514(a) of the HIPAA Privacy Rule. Any patient counts less than ten are obfuscated to ensure patient anonymity. Additionally, only aggregate patient counts and statistical summaries are provided to protect all patient health information and retain de-identification. Study Participants The TriNetX database was queried from 2009 through 2021. Selection criteria were based on ICD-10 codes. A patient was considered to have a diagnosis if the corresponding ICD code was linked to the patient’s EHR in the database. Three separate cohorts were created, including men ages 40 to 70 years with a diagnosis of insomnia (ICD-10 G47.0), sleep apnea (G47.33), or circadian rhythm dysfunction (G47.2), respectively. Each of these groups was compared with the control cohort of men ages 40 to 70 years, excluding those with any sleep disorders (G47 & F51), sleep deprivation (Z72.820), or morbid obesity with alveolar hypoventilation (E66.2) who presented for outpatient evaluation (CPT 99211-5). A subgroup analysis was performed with a control cohort of men who underwent polysomnography testing (CPT 95808, 95810, 95811) but did not receive a pre-testing or post-testing diagnosis of sleep disorders (G47 & F51), sleep deprivation (Z72.820), or morbid obesity with alveolar hypoventilation (E66.2). This cohort was compared to the combined cohort of men ages 40 to 70 years with a diagnosis of insomnia, sleep apnea, and/or circadian rhythm dysfunction. Statistical Analyses The primary study outcome was the development of testosterone deficiency (E29.1) and erectile dysfunction (N52) associated with sleep dysfunction at the time of sleep disorder diagnosis or within five years of the index diagnosis. The TriNetX platform was utilized to conduct all analyses. A 1:1 matching was performed contingent on the propensity scores generated using greedy nearest neighbor algorithms with a caliper width of 0.1 pooled standard deviations. In order to alleviate bias ensuing from nearest neighbor algorithms, TriNetX randomizes the order of rows. Propensity score matching was performed with age at index, current age, hypertension (I10-16), hyperlipidemia (E78), diabetes mellitus (E08-13), ischemic heart disease (I20-25), tobacco use (Z72.0), and obesity (E66) as covariates (Supplemental Table 1). An internal control diagnosis of benign prostatic hyperplasia (BPH) (N40) was assessed for detection bias. Absolute values of > 0.1 standardized mean difference on covariate balance were considered positive for covariate imbalance. Statistical significance was defined as a two-sided alpha of less than 0.05. Risk ratios with 95% confidence intervals were calculated for all outcomes. Results Our query of the TriNetX database identified 2,320,606 men diagnosed with sleep apnea, 1,794,007 men diagnosed with insomnia, and 84,130 men diagnosed with circadian rhythm dysfunction with an equivalent number of propensity-score matched control men (Table 1). Men diagnosed with sleep apnea had higher odds of testosterone deficiency (OR 1.66 [95% confidence interval (CI) 1.65–1.67]) and ED (OR 1.02 [95% CI 1.01–1.03]) compared to matched controls. Those diagnosed with insomnia were more likely to have testosterone deficiency (OR 1.74 [95% CI 1.73–1.76]) and ED (OR 1.30 [95% CI 1.30–1.31]) compared to matched controls. Finally, men diagnosed with circadian rhythm dysfunction had significantly higher odds of testosterone deficiency (OR 2.63 [95% CI 2.54–2.73]) and ED (OR 1.54 [95% CI 1.49–1.59]) compared to matched controls. Next, 52,629 men with polysomnography testing but no sleep disorder diagnosis prior to or after testing were identified with an equivalent number of propensity-score matched men with a diagnosis of sleep apnea, insomnia, and/or circadian rhythm dysfunction (Table 2). Men with negative polysomnography testing had significantly lower odds of testosterone deficiency (OR 0.36 [95% CI 0.34–0.38]) and ED (OR 0.41 [95% CI 0.40–0.44]) compared to men with any sleep disorder. When assessing for rates of BPH diagnoses in this same population as an internal control to detect assessment bias, rates of BPH were not higher in men with known sleep disorders than in men without a diagnosis of sleep disorders (Supplemental Table 2). Discussion Poor sleep can be caused by and is comorbid with several highly prevalent conditions in the adult male population. In addition to this bidirectional relationship, poor sleep can impact patients’ perception of the severity of their symptoms. 12 While many studies have described the detrimental impact of poor sleep quality and quantity on overall health in males, less is known about its effect on diseases of the male genitourinary tract. 1 , 3 , 4 , 11 In this study, we found a significant increase in the prevalence of testosterone deficiency and ED associated with the diagnoses of circadian rhythm dysfunction, insomnia, and sleep apnea compared to matched control groups. We also identified a decrease in the prevalence of these conditions among individuals with a negative polysomnography test compared to individuals with an established sleep disorder. By identifying these associations in the largest cohort of male patients reported to date, our results help reinforce prior claims about the negative effect of sleep disturbances on these prevalent urologic conditions. While the relationship between circadian rhythm dysfunction and hormonal deficiency in men is unclear, many studies have observed higher rates of miscarriages, infertility, and menstrual irregularity amongst female non-standard shift workers. 15 A recent literature review by Kohn et al. described the effect of non-standard shift work and SWSD on male genitourinary system diseases, including testosterone deficiency and ED. 12 Poor sleep quality was found to be a risk factor for ED. However, shift work alone did not significantly impact erectile function. 7 While the relationship between non-standard shift work and testosterone deficiency was inconclusive, the authors reported an increase in the severity of hypogonadal clinical symptoms. 7 Our results from a cohort of patients with circadian rhythm dysfunction, which includes SWSD, support these findings by demonstrating an increase in ED and testosterone deficiency; however, our methods did not allow us to investigate individual patients’ symptoms of testosterone deficiency. A recent study evaluating the effect of testosterone deficiency on diurnal testosterone levels described an altered testosterone feedback control on the hypothalamic-pituitary axis in men with testosterone deficiency. 16 Shlykova et al. concluded this was likely due to abnormal central regulating mechanisms that control both diurnal testosterone variation and other circadian rhythms, which we postulate could impact sleep and contribute to circadian rhythm dysfunction. 16 This would increase the association of testosterone deficiency amongst those with this sleep disorder diagnosis, as seen in our study. In addition to the effect of circadian rhythm dysfunction on ED and testosterone deficiency, the inability to fall or stay asleep and the perception of impaired overall sleep can impact sexual function, as demonstrated by our results in men with insomnia. Numerous studies have established a relationship between insomnia and ED, with insomnia severity negatively impacting sexual function, potentially due to alterations in the serum testosterone level. 12 , 17 Testosterone is produced diurnally with a maximum nocturnal rise during the first period of rapid eye movement (REM) sleep. 18 Therefore, insomnia or fragmented sleep could decrease levels of circulating testosterone by altering the sleep-stage structure and/or increasing REM latency. Moreover, sleep deprivation, as is often found in chronic insomnia, inhibits the hypothalamic-pituitary-gonadal axis, further decreasing testosterone levels through decreased luteinizing hormone (LH) production. 19 Conversely, sleep deprivation activates the hypothalamic-pituitary-adrenal axis, leading to apoptosis of Leydig cells through increased corticosteroid release. 19 Further, fatigue secondary to sleep deprivation increases the likelihood of a sedentary lifestyle, which can independently affect testosterone levels through hypothalamic-pituitary-gonadal axis disorders mediated by leptin resistance. In summary, the combined effect of altered sleep structure and impaired Leydig cell function caused by insomnia can result in testosterone deficiency and subsequent ED, corresponding to the findings reported here. Prior reports in the literature have described the positive relationship between OSA and sexual dysfunction, mainly related to libido and ED. 20 , 21 Similarly, we identified an increased prevalence of both testosterone deficiency and ED in our cohort with sleep apnea compared to the control group. Although the underlying association between sleep apnea and ED is still unknown, proposed theories include hypoxemia-induced peripheral neuropathy, a hormonal effect of testosterone, or vascular endothelial dysfunction. 11 A study by Fanfulla et al. demonstrated an altered bulbocavernosus reflex in patients with OSA, suggesting that ED in this population may be due to peripheral nerve dysfunction. 22 Another theory associates ED with increased levels of inflammatory markers in OSA due to the promotion of dysfunctional endothelium. 11 , 25 Numerous studies have found a decreased testosterone level in male patients with OSA. 23 , 24 However, it is also believed that testosterone supplementation worsens OSA, as seen in patients with testosterone deficiency treated with androgen therapy. 11 Interestingly, a review reported that the treatment of OSA using continuous positive airway pressure (CPAP) devices in a small group of patients led to inconsistent results for improving sexual function. However, this intervention is known to improve quality of life and adverse outcomes, including mortality, among adherent users. 11 , 26 , 27 However, a recent randomized trial demonstrated a positive effect on erectile function and sexual desire combined with CPAP and a phosphodiesterase type 5 inhibitor. 28 We identified a significant decrease in the prevalence of ED and testosterone deficiency amongst men undergoing polysomnography testing for sleep disorder evaluation compared to men with an established sleep disorder diagnosis. This controls for the fact that some men in the control group may have undiagnosed sleep disorders, which further strengthens our findings of associations between ED and testosterone deficiency with a sleep disorder diagnosis. We chose to include BPH in our study as a proxy indicator of exposure to urologic care. Most patients with BPH are referred to urologists and are thus more likely to be subsequently screened for testosterone deficiency and ED. By demonstrating similar rates of BPH in both men diagnosed with a sleep disorder and propensity-score matched controls, we accounted for possible differences in exposure to urologists (Supplemental Table 2). Normal sexual function in men requires a complex interplay of psychologic and physiologic factors, which includes a serum testosterone level within the normal range and erectile function. 29 Low serum testosterone is associated with worse sexual function, including libido and erectile function, as well as mental health consequences, such as poor concentration and lethargy. 30 There are many possible causes of testosterone deficiency and ED, which should be systematically addressed during the workup of male sexual dysfunction. Our results emphasize the importance of considering poor sleep quantity and quality in the differential diagnosis of sexual dysfunction. One critical step is to discuss and educate patients about sleep hygiene, which can improve sleep quality with relatively simple and low-cost lifestyle modifications. Urologists should also feel comfortable initiating a workup for sleep disorders as clinically indicated. This can include the use of validated clinical questionnaires, a polysomnography referral, and/or a referral to sleep medicine. Examples of these tools include the Pittsburgh Sleep Quality Index, a validated sleep questionnaire, and the STOP-BANG questionnaire, which screens specifically for OSA. 12 This study has limitations inherent to the TriNetX database and other large health care claims studies, including patient deidentification and potential misclassification of the diagnoses. Further, comorbid conditions predisposing a patient to a sleep disorder that could directly affect a patient’s ED and altered hormone status were unavailable. Additionally, patients lost to follow-up could potentially skew covariate distributions and occurrence of outcomes. However, this study also has multiple strengths, including but not limited to the large, diverse population size the TriNetX database offers. The Diamond Network utilized in this study covers 1.8 million providers and 99% of U.S. healthcare plans. Moreover, the database captures data from patients receiving care at one of the participating healthcare organizations. It links individual identifiers to pharmaceutical data, insurance claims, and other electronic medical records to generate complete health information. Further, by categorizing via CPT codes, we limit our selection bias and increase the generalizability of these findings. With our findings supporting the vital relationship between sleep and common urologic conditions, we suggest that future research should focus on investigating the effect of sleep-based interventions on the prevalence and severity of these diseases. For example, improving sleep hygiene is a low-cost, low-risk way to treat patients with poor sleep that require further study in the setting of ED and testosterone deficiency. These interventions would benefit urologic patients broadly due to the wide-reaching impact of sleep on overall health. Conclusions Sleep disturbances are associated with significantly increased rates of testosterone deficiency and ED, which are both important aspects of normal male sexual function. These results support the importance of screening for poor sleep and common sleep disorders by urologists, as well as the need for future research aimed at assessing the impact of sleep interventions on urologic outcomes. Declarations COMPETING INTERESTS The authors declare no competing interests. Funding :None Disclosures : None References Itani O, Jike M, Watanabe N, Kaneita Y. Short sleep duration and health outcomes: a systematic review, meta-analysis, and meta-regression. Sleep Medicine. 2017;32:246–256. doi: 10.1016/j.sleep.2016.08.006 Knudsen HK, Ducharme LJ, Roman PM. Job stress and poor sleep quality: Data from an American sample of full-time workers. Social Science & Medicine. 2007;64(10):1997–2007. doi: 10.1016/j.socscimed.2007.02.020 Wang Y, Mei H, Jiang YR, et al. Relationship between Duration of Sleep and Hypertension in Adults: A Meta-Analysis. Journal of Clinical Sleep Medicine. 2015;11(09):1047–1056. doi: 10.5664/jcsm.5024 Shan Z, Ma H, Xie M, et al. Sleep Duration and Risk of Type 2 Diabetes: A Meta-analysis of Prospective Studies. Diabetes Care. 2015;38(3):529–537. doi: 10.2337/dc14-2073 Wright KP, Bogan RK, Wyatt JK. Shift work and the assessment and management of shift work disorder (SWD). Sleep Medicine Reviews. 2013;17(1):41–54. doi: 10.1016/j.smrv.2012.02.002 Åkerstedt T, Wright KP. Sleep Loss and Fatigue in Shift Work and Shift Work Disorder. Sleep Medicine Clinics. 2009;4(2):257–271. doi: 10.1016/j.jsmc.2009.03.001 Deng N, Haney NM, Kohn TP, Pastuszak AW, Lipshultz LI. The Effect of Shift Work on Urogenital Disease: a Systematic Review. Curr Urol Rep. 2018;19(8):57. doi: 10.1007/s11934-018-0815-y Roth T. Insomnia: Definition, Prevalence, Etiology, and Consequences. Journal of Clinical Sleep Medicine. 2007;3(5 suppl). doi: 10.5664/jcsm.26929 Hiestand DM, Britz P, Goldman M, Phillips B. Prevalence of Symptoms and Risk of Sleep Apnea in the US Population. Chest. 2006;130(3):780–786. doi: 10.1378/chest.130.3.780 Senaratna CV, Perret JL, Lodge CJ, et al. Prevalence of obstructive sleep apnea in the general population: A systematic review. Sleep Medicine Reviews. 2017;34:70–81. doi: 10.1016/j.smrv.2016.07.002 Cho JW, Duffy JF. Sleep, Sleep Disorders, and Sexual Dysfunction. World J Mens Health. 2019;37(3):261. doi: 10.5534/wjmh.180045 Kohn TP, Kohn JR, Haney NM, Pastuszak AW, Lipshultz LI. The effect of sleep on men’s health. Transl Androl Urol. 2020;9(S2):S178-S185. doi: 10.21037/tau.2019.11.07 Deng N, Kohn TP, Lipshultz LI, Pastuszak AW. The Relationship Between Shift Work and Men’s Health. Sexual Medicine Reviews. 2018;6(3):446–456. doi: 10.1016/j.sxmr.2017.11.009 Kohn TP, Rodriguez KM, Sigalos JT, Hasan A, Pastuszak AW, Lipshultz LI. PD27-08 POOR SLEEP QUALITY IS ASSOCIATED WITH CLINICALLY SIGNIFICANT ERECTILE DYSFUNCTION. Journal of Urology. 2018;199(4S). doi: 10.1016/j.juro.2018.02.1359 Baker FC, Driver HS. Circadian rhythms, sleep, and the menstrual cycle. Sleep Med. 2007;8(6):613–622. doi: 10.1016/j.sleep.2006.09.011 Shlykova N, Davidson E, Krakowsky Y, Bolanos J, Traish A, Morgentaler A. Absent Diurnal Variation in Serum Testosterone in Young Men with Testosterone Deficiency. J Urol. 2020;203(4):817–823. doi: 10.1097/JU.0000000000000630 Seehuus M, Pigeon W. The sleep and sex survey: Relationships between sexual function and sleep. J Psychosom Res. 2018;112:59–65. doi: 10.1016/j.jpsychores.2018.07.005 Luboshitzky R, Zabari Z, Shen-Orr Z, Herer P, Lavie P. Disruption of the Nocturnal Testosterone Rhythm by Sleep Fragmentation in Normal Men. The Journal of Clinical Endocrinology & Metabolism. 2001;86(3):1134–1139. doi: 10.1210/jcem.86.3.7296 Lateef OM, Akintubosun MO. Sleep and Reproductive Health. J Circadian Rhythms. 2020;18:1. doi: 10.5334/jcr.190 Teloken PE, Smith EB, Lodowsky C, Freedom T, Mulhall JP. Defining association between sleep apnea syndrome and erectile dysfunction. Urology. 2006;67(5):1033–1037. doi: 10.1016/j.urology.2005.11.040 Mun JK, Choi SJ, Kang MR, Hong SB, Joo EY. Sleep and libido in men with obstructive sleep apnea syndrome. Sleep Medicine. 2018;52:158–162. doi: 10.1016/j.sleep.2018.07.016 Fanfulla F, Malaguti S, Montagna T, et al. Erectile dysfunction in men with obstructive sleep apnea: an early sign of nerve involvement. Sleep. 2000;23(6):775–781. Li Z, Tang T, Wu W, 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. doi: 10.1016/j.rmed.2016.09.001 Zhang XB, Lin QC, Zeng HQ, Jiang XT, Chen B, Chen X. Erectile Dysfunction and Sexual Hormone Levels in Men With Obstructive Sleep Apnea: Efficacy of Continuous Positive Airway Pressure. Arch Sex Behav. 2016;45(1):235–240. doi: 10.1007/s10508-015-0593-2 Budhiraja R, Parthasarathy S, Quan SF. Endothelial dysfunction in obstructive sleep apnea. J Clin Sleep Med. 2007;3(4):409–415. Bakker JP, Weaver TE, Parthasarathy S, Aloia MS. Adherence to CPAP. Chest. 2019;155(6):1272–1287. doi: 10.1016/j.chest.2019.01.012 Kuhn E, Schwarz EI, Bratton DJ, Rossi VA, Kohler M. Effects of CPAP and Mandibular Advancement Devices on Health-Related Quality of Life in OSA. Chest. 2017;151(4):786–794. doi: 10.1016/j.chest.2017.01.020 Melehan KL, Hoyos CM, Hamilton GS, et al. Randomized Trial of CPAP and Vardenafil on Erectile and Arterial Function in Men With Obstructive Sleep Apnea and Erectile Dysfunction. The Journal of Clinical Endocrinology & Metabolism. 2018;103(4):1601–1611. doi: 10.1210/jc.2017-02389 Chen L, Shi G rui, Huang D dan, et al. Male sexual dysfunction: A review of literature on its pathological mechanisms, potential risk factors, and herbal drug intervention. Biomedicine & Pharmacotherapy. 2019;112:108585. doi: 10.1016/j.biopha.2019.01.046 Pastuszak AW, Moon YM, Scovell J, et al. Poor Sleep Quality Predicts Hypogonadal Symptoms and Sexual Dysfunction in Male Nonstandard Shift Workers. Urology. 2017;102:121–125. doi: 10.1016/j.urology.2016.11.033 Tables Tables 1 and 2 are available in the Supplementary Files section. Additional Declarations There is NO conflict of interest to disclose. Supplementary Files SupplementalTable1.xlsx SupplementalTable2.xlsx Table1.xlsx Table2.xlsx Cite Share Download PDF Status: Published Journal Publication published 06 Dec, 2022 Read the published version in International Journal of Impotence Research → Version 1 posted Editorial decision: revise 20 Sep, 2022 Review # 1 received at journal 30 Aug, 2022 Review # 2 received at journal 23 Aug, 2022 Reviewer # 2 agreed at journal 23 Aug, 2022 Reviewer # 1 agreed at journal 16 Aug, 2022 Reviewers invited by journal 16 Aug, 2022 Submission checks completed at journal 03 Aug, 2022 Unknown event 01 Aug, 2022 Editor assigned by journal 31 Jul, 2022 First submitted to journal 31 Jul, 2022 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-1913602","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":129405695,"identity":"359871be-0159-4041-a0c9-c31bbf419fdf","order_by":0,"name":"Pranjal Agrawal","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA4UlEQVRIiWNgGAWjYNACAxsefvYGEMOCWC0FaTKSPQdAWiSI1fLhsI3BjQQQiwgt5tKHH79gMGDmYbj5/OqGHwUSDPzt3Ql4tVj2pZlZMBiw8TDOzim72QN0mMSZsxvwajE4w2BmwGDAw8MsnZN2gweoxUAil5AW9m9ALRI8bJJn0m7+IU4Lj/EDBgOgNRLsx24TZYtlD08ZQ4JBAo8ETw7bbRmgdQT9Ys7DvvnDhz//7e2PH392880fGzn+9l4CDmNgYJNIADN5DMAkXuVQLcwfIEz2BwRVj4JRMApGwcgEAFrmQRd17IXyAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0002-9952-4888","institution":"Johns Hopkins University","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Pranjal","middleName":"","lastName":"Agrawal","suffix":""},{"id":129405696,"identity":"7c6ca8c2-5d12-43ab-86a0-005102338c1b","order_by":1,"name":"Sajya Singh","email":"","orcid":"https://orcid.org/0000-0002-3662-5032","institution":"Johns Hopkins University School of Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Sajya","middleName":"","lastName":"Singh","suffix":""},{"id":129405697,"identity":"1e4191f5-49a2-4120-92b2-3d66c4ac6238","order_by":2,"name":"Corey Able","email":"","orcid":"","institution":"","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Corey","middleName":"","lastName":"Able","suffix":""},{"id":129405698,"identity":"43979c1b-c590-4e3c-ae4b-84fda512503f","order_by":3,"name":"Taylor Kohn","email":"","orcid":"","institution":"","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Taylor","middleName":"","lastName":"Kohn","suffix":""},{"id":129405699,"identity":"37014713-d336-46e5-a1ca-91863bf82631","order_by":4,"name":"Amin Herati","email":"","orcid":"","institution":"","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Amin","middleName":"","lastName":"Herati","suffix":""}],"badges":[],"createdAt":"2022-07-31 06:10:28","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-1913602/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-1913602/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41443-022-00649-2","type":"published","date":"2022-12-06T05:00:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":29999240,"identity":"230ad1f4-f997-4a4a-ad31-be45f2da6b19","added_by":"auto","created_at":"2022-12-07 08:08:36","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":210815,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1913602/v1/5cd6a83b-aa32-4e29-b7b4-01dc452e143f.pdf"},{"id":25384199,"identity":"5aecdc1b-8083-423f-9f2a-b31898e5a693","added_by":"auto","created_at":"2022-08-18 17:31:02","extension":"xlsx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":13700,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementalTable1.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-1913602/v1/6ed1ca77146a067208f8246b.xlsx"},{"id":25383822,"identity":"a8673a6f-6f1e-48c8-bfee-360b64539a41","added_by":"auto","created_at":"2022-08-18 17:26:02","extension":"xlsx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":11712,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementalTable2.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-1913602/v1/00050bf771afc2676aee02d6.xlsx"},{"id":25384654,"identity":"5f445911-d7c0-4ce2-8275-748e0028ef64","added_by":"auto","created_at":"2022-08-18 17:36:02","extension":"xlsx","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":12059,"visible":true,"origin":"","legend":"","description":"","filename":"Table1.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-1913602/v1/908bbc199daba5f0c15b6221.xlsx"},{"id":25383825,"identity":"e21016a9-7e54-4c74-8f62-46b010d9fdbf","added_by":"auto","created_at":"2022-08-18 17:26:02","extension":"xlsx","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":10636,"visible":true,"origin":"","legend":"","description":"","filename":"Table2.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-1913602/v1/3da11c051257f46e1799f0c7.xlsx"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e conflict of interest to disclose.","formattedTitle":"Sleep Disorders are Associated with Testosterone Deficiency and Erectile Dysfunction- A U.S. Claims Database Analysis","fulltext":[{"header":"Introduction","content":"\u003cp\u003eProlonged disturbances in sleep duration and quality can have detrimental impacts on an individual\u0026rsquo;s overall health.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e Large meta-analyses have identified a dose-dependent relationship between sleep and impactful diseases such as type 2 diabetes mellitus, hypertension, and coronary artery disease.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e,\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e Several common health conditions can lead to poor sleep, including circadian rhythm dysfunction, obstructive sleep apnea (OSA), and insomnia. One type of circadian rhythm dysfunction, shift work sleep disorder (SWSD), affects approximately 20% of non-standard shift workers, who represent\u0026thinsp;\u0026gt;\u0026thinsp;20% of working adults in the United States, and leads to insomnia as well as excessive daytime sleepiness.\u003csup\u003e\u003cspan additionalcitationids=\"CR6\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e Insomnia encompasses many symptoms leading to poor sleep quality and affects up to 30% of individuals in population-based studies.\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e In the general population, sleep apnea is highly prevalent, affecting approximately 33% of men in the United States. OSA has significant associations with the male sex, age\u0026thinsp;\u0026ge;\u0026thinsp;65 years, and higher BMI.\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e,\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eWith a large portion of the adult population affected by these three conditions, it is necessary to investigate the relationship between poor sleep and common diseases of the male genitourinary system, including testosterone deficiency and erectile dysfunction (ED).\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e,\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e Previously, observational studies have shown an increased severity of hypogonadal clinical symptoms among non-standard shift workers; however, they did not well establish the significance of the relationship between sleep quality and low serum testosterone levels .\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e,\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e,\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e Prior studies have linked OSA to ED and decreased libido; although, one recent study showed no association between sleep apnea and ED.\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e,\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eTherefore, the effect of poor sleep quality and duration, particularly related to circadian rhythm dysfunction, sleep apnea, and insomnia, on male-specific genitourinary diseases remains unclear. Based on prior results in the literature, we hypothesize that sleep disturbances are associated with an increased prevalence of testosterone deficiency and ED in men. However, thus far, research on this subject has been confined to small, single-institution cohorts of patients. In this article, we report the results of the first large claims database study to investigate this relationship, utilizing a large study population with a matched cohort.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Design\u003c/h2\u003e \u003cp\u003e We conducted a retrospective cohort analysis utilizing electronic health records (EHRs) supplemented with insurance claims from the research network TriNetX Diamond (Cambridge, MA, USA) which provided access to electronic medical records (diagnoses, procedures, medications, laboratory values, genomic information), as well as medical insurance claims and pharmaceutical claims for over 212\u0026nbsp;million patients from 92 healthcare organizations. Data used in this study was collected and analyzed as of June 2022. Information regarding demographics, diagnoses from International Classification of Disease (ICD-10) codes, and procedures from Current Procedural Terminology (CPT) codes were all recorded and used for analysis.\u003c/p\u003e \u003cp\u003eTriNetX adheres to the Health Insurance Portability and Accountability Act (HIPAA) and has received a waiver from Western IRB as all patient data is de-identified as per the standard defined in Section \u0026sect;\u0026nbsp;164.514(a) of the HIPAA Privacy Rule. Any patient counts less than ten are obfuscated to ensure patient anonymity. Additionally, only aggregate patient counts and statistical summaries are provided to protect all patient health information and retain de-identification.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eStudy Participants\u003c/h2\u003e \u003cp\u003eThe TriNetX database was queried from 2009 through 2021. Selection criteria were based on ICD-10 codes. A patient was considered to have a diagnosis if the corresponding ICD code was linked to the patient\u0026rsquo;s EHR in the database. Three separate cohorts were created, including men ages 40 to 70 years with a diagnosis of insomnia (ICD-10 G47.0), sleep apnea (G47.33), or circadian rhythm dysfunction (G47.2), respectively. Each of these groups was compared with the control cohort of men ages 40 to 70 years, excluding those with any sleep disorders (G47 \u0026amp; F51), sleep deprivation (Z72.820), or morbid obesity with alveolar hypoventilation (E66.2) who presented for outpatient evaluation (CPT 99211-5). A subgroup analysis was performed with a control cohort of men who underwent polysomnography testing (CPT 95808, 95810, 95811) but did not receive a pre-testing or post-testing diagnosis of sleep disorders (G47 \u0026amp; F51), sleep deprivation (Z72.820), or morbid obesity with alveolar hypoventilation (E66.2). This cohort was compared to the combined cohort of men ages 40 to 70 years with a diagnosis of insomnia, sleep apnea, and/or circadian rhythm dysfunction.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analyses\u003c/h2\u003e \u003cp\u003eThe primary study outcome was the development of testosterone deficiency (E29.1) and erectile dysfunction (N52) associated with sleep dysfunction at the time of sleep disorder diagnosis or within five years of the index diagnosis. The TriNetX platform was utilized to conduct all analyses. A 1:1 matching was performed contingent on the propensity scores generated using greedy nearest neighbor algorithms with a caliper width of 0.1 pooled standard deviations. In order to alleviate bias ensuing from nearest neighbor algorithms, TriNetX randomizes the order of rows. Propensity score matching was performed with age at index, current age, hypertension (I10-16), hyperlipidemia (E78), diabetes mellitus (E08-13), ischemic heart disease (I20-25), tobacco use (Z72.0), and obesity (E66) as covariates (Supplemental Table\u0026nbsp;1). An internal control diagnosis of benign prostatic hyperplasia (BPH) (N40) was assessed for detection bias. Absolute values of \u0026gt;\u0026thinsp;0.1 standardized mean difference on covariate balance were considered positive for covariate imbalance. Statistical significance was defined as a two-sided alpha of less than 0.05. Risk ratios with 95% confidence intervals were calculated for all outcomes.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eOur query of the TriNetX database identified 2,320,606 men diagnosed with sleep apnea, 1,794,007 men diagnosed with insomnia, and 84,130 men diagnosed with circadian rhythm dysfunction with an equivalent number of propensity-score matched control men (Table\u0026nbsp;1). Men diagnosed with sleep apnea had higher odds of testosterone deficiency (OR 1.66 [95% confidence interval (CI) 1.65\u0026ndash;1.67]) and ED (OR 1.02 [95% CI 1.01\u0026ndash;1.03]) compared to matched controls. Those diagnosed with insomnia were more likely to have testosterone deficiency (OR 1.74 [95% CI 1.73\u0026ndash;1.76]) and ED (OR 1.30 [95% CI 1.30\u0026ndash;1.31]) compared to matched controls. Finally, men diagnosed with circadian rhythm dysfunction had significantly higher odds of testosterone deficiency (OR 2.63 [95% CI 2.54\u0026ndash;2.73]) and ED (OR 1.54 [95% CI 1.49\u0026ndash;1.59]) compared to matched controls.\u003c/p\u003e \u003cp\u003eNext, 52,629 men with polysomnography testing but no sleep disorder diagnosis prior to or after testing were identified with an equivalent number of propensity-score matched men with a diagnosis of sleep apnea, insomnia, and/or circadian rhythm dysfunction (Table\u0026nbsp;2). Men with negative polysomnography testing had significantly lower odds of testosterone deficiency (OR 0.36 [95% CI 0.34\u0026ndash;0.38]) and ED (OR 0.41 [95% CI 0.40\u0026ndash;0.44]) compared to men with any sleep disorder.\u003c/p\u003e \u003cp\u003eWhen assessing for rates of BPH diagnoses in this same population as an internal control to detect assessment bias, rates of BPH were not higher in men with known sleep disorders than in men without a diagnosis of sleep disorders (Supplemental Table\u0026nbsp;2).\u003c/p\u003e "},{"header":"Discussion","content":"\u003cp\u003ePoor sleep can be caused by and is comorbid with several highly prevalent conditions in the adult male population. In addition to this bidirectional relationship, poor sleep can impact patients\u0026rsquo; perception of the severity of their symptoms.\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e While many studies have described the detrimental impact of poor sleep quality and quantity on overall health in males, less is known about its effect on diseases of the male genitourinary tract.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e,\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e,\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e In this study, we found a significant increase in the prevalence of testosterone deficiency and ED associated with the diagnoses of circadian rhythm dysfunction, insomnia, and sleep apnea compared to matched control groups. We also identified a decrease in the prevalence of these conditions among individuals with a negative polysomnography test compared to individuals with an established sleep disorder. By identifying these associations in the largest cohort of male patients reported to date, our results help reinforce prior claims about the negative effect of sleep disturbances on these prevalent urologic conditions.\u003c/p\u003e \u003cp\u003eWhile the relationship between circadian rhythm dysfunction and hormonal deficiency in men is unclear, many studies have observed higher rates of miscarriages, infertility, and menstrual irregularity amongst female non-standard shift workers.\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e A recent literature review by Kohn et al. described the effect of non-standard shift work and SWSD on male genitourinary system diseases, including testosterone deficiency and ED.\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e Poor sleep quality was found to be a risk factor for ED. However, shift work alone did not significantly impact erectile function.\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e While the relationship between non-standard shift work and testosterone deficiency was inconclusive, the authors reported an increase in the severity of hypogonadal clinical symptoms.\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e Our results from a cohort of patients with circadian rhythm dysfunction, which includes SWSD, support these findings by demonstrating an increase in ED and testosterone deficiency; however, our methods did not allow us to investigate individual patients\u0026rsquo; symptoms of testosterone deficiency.\u003c/p\u003e \u003cp\u003eA recent study evaluating the effect of testosterone deficiency on diurnal testosterone levels described an altered testosterone feedback control on the hypothalamic-pituitary axis in men with testosterone deficiency.\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e Shlykova et al. concluded this was likely due to abnormal central regulating mechanisms that control both diurnal testosterone variation and other circadian rhythms, which we postulate could impact sleep and contribute to circadian rhythm dysfunction.\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e This would increase the association of testosterone deficiency amongst those with this sleep disorder diagnosis, as seen in our study.\u003c/p\u003e \u003cp\u003eIn addition to the effect of circadian rhythm dysfunction on ED and testosterone deficiency, the inability to fall or stay asleep and the perception of impaired overall sleep can impact sexual function, as demonstrated by our results in men with insomnia. Numerous studies have established a relationship between insomnia and ED, with insomnia severity negatively impacting sexual function, potentially due to alterations in the serum testosterone level.\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e,\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eTestosterone is produced diurnally with a maximum nocturnal rise during the first period of rapid eye movement (REM) sleep.\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e Therefore, insomnia or fragmented sleep could decrease levels of circulating testosterone by altering the sleep-stage structure and/or increasing REM latency. Moreover, sleep deprivation, as is often found in chronic insomnia, inhibits the hypothalamic-pituitary-gonadal axis, further decreasing testosterone levels through decreased luteinizing hormone (LH) production.\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e Conversely, sleep deprivation activates the hypothalamic-pituitary-adrenal axis, leading to apoptosis of Leydig cells through increased corticosteroid release.\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e Further, fatigue secondary to sleep deprivation increases the likelihood of a sedentary lifestyle, which can independently affect testosterone levels through hypothalamic-pituitary-gonadal axis disorders mediated by leptin resistance. In summary, the combined effect of altered sleep structure and impaired Leydig cell function caused by insomnia can result in testosterone deficiency and subsequent ED, corresponding to the findings reported here.\u003c/p\u003e \u003cp\u003ePrior reports in the literature have described the positive relationship between OSA and sexual dysfunction, mainly related to libido and ED.\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e,\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e Similarly, we identified an increased prevalence of both testosterone deficiency and ED in our cohort with sleep apnea compared to the control group. Although the underlying association between sleep apnea and ED is still unknown, proposed theories include hypoxemia-induced peripheral neuropathy, a hormonal effect of testosterone, or vascular endothelial dysfunction.\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e A study by Fanfulla et al. demonstrated an altered bulbocavernosus reflex in patients with OSA, suggesting that ED in this population may be due to peripheral nerve dysfunction.\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e Another theory associates ED with increased levels of inflammatory markers in OSA due to the promotion of dysfunctional endothelium.\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e,\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e Numerous studies have found a decreased testosterone level in male patients with OSA.\u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e,\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e However, it is also believed that testosterone supplementation worsens OSA, as seen in patients with testosterone deficiency treated with androgen therapy.\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eInterestingly, a review reported that the treatment of OSA using continuous positive airway pressure (CPAP) devices in a small group of patients led to inconsistent results for improving sexual function. However, this intervention is known to improve quality of life and adverse outcomes, including mortality, among adherent users.\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e,\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e,\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e However, a recent randomized trial demonstrated a positive effect on erectile function and sexual desire combined with CPAP and a phosphodiesterase type 5 inhibitor.\u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eWe identified a significant decrease in the prevalence of ED and testosterone deficiency amongst men undergoing polysomnography testing for sleep disorder evaluation compared to men with an established sleep disorder diagnosis. This controls for the fact that some men in the control group may have undiagnosed sleep disorders, which further strengthens our findings of associations between ED and testosterone deficiency with a sleep disorder diagnosis. We chose to include BPH in our study as a proxy indicator of exposure to urologic care. Most patients with BPH are referred to urologists and are thus more likely to be subsequently screened for testosterone deficiency and ED. By demonstrating similar rates of BPH in both men diagnosed with a sleep disorder and propensity-score matched controls, we accounted for possible differences in exposure to urologists (Supplemental Table\u0026nbsp;2).\u003c/p\u003e \u003cp\u003eNormal sexual function in men requires a complex interplay of psychologic and physiologic factors, which includes a serum testosterone level within the normal range and erectile function.\u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e Low serum testosterone is associated with worse sexual function, including libido and erectile function, as well as mental health consequences, such as poor concentration and lethargy.\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e There are many possible causes of testosterone deficiency and ED, which should be systematically addressed during the workup of male sexual dysfunction. Our results emphasize the importance of considering poor sleep quantity and quality in the differential diagnosis of sexual dysfunction. One critical step is to discuss and educate patients about sleep hygiene, which can improve sleep quality with relatively simple and low-cost lifestyle modifications. Urologists should also feel comfortable initiating a workup for sleep disorders as clinically indicated. This can include the use of validated clinical questionnaires, a polysomnography referral, and/or a referral to sleep medicine. Examples of these tools include the Pittsburgh Sleep Quality Index, a validated sleep questionnaire, and the STOP-BANG questionnaire, which screens specifically for OSA.\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eThis study has limitations inherent to the TriNetX database and other large health care claims studies, including patient deidentification and potential misclassification of the diagnoses. Further, comorbid conditions predisposing a patient to a sleep disorder that could directly affect a patient\u0026rsquo;s ED and altered hormone status were unavailable. Additionally, patients lost to follow-up could potentially skew covariate distributions and occurrence of outcomes. However, this study also has multiple strengths, including but not limited to the large, diverse population size the TriNetX database offers. The Diamond Network utilized in this study covers 1.8\u0026nbsp;million providers and 99% of U.S. healthcare plans. Moreover, the database captures data from patients receiving care at one of the participating healthcare organizations. It links individual identifiers to pharmaceutical data, insurance claims, and other electronic medical records to generate complete health information. Further, by categorizing via CPT codes, we limit our selection bias and increase the generalizability of these findings.\u003c/p\u003e \u003cp\u003eWith our findings supporting the vital relationship between sleep and common urologic conditions, we suggest that future research should focus on investigating the effect of sleep-based interventions on the prevalence and severity of these diseases. For example, improving sleep hygiene is a low-cost, low-risk way to treat patients with poor sleep that require further study in the setting of ED and testosterone deficiency. These interventions would benefit urologic patients broadly due to the wide-reaching impact of sleep on overall health.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusions","content":"\u003cp\u003eSleep disturbances are associated with significantly increased rates of testosterone deficiency and ED, which are both important aspects of normal male sexual function. These results support the importance of screening for poor sleep and common sleep disorders by urologists, as well as the need for future research aimed at assessing the impact of sleep interventions on urologic outcomes.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eCOMPETING INTERESTS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e:None\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDisclosures\u003c/strong\u003e: None\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eItani O, Jike M, Watanabe N, Kaneita Y. Short sleep duration and health outcomes: a systematic review, meta-analysis, and meta-regression. Sleep Medicine. 2017;32:246\u0026ndash;256. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.sleep.2016.08.006\u003c/span\u003e\u003cspan address=\"10.1016/j.sleep.2016.08.006\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKnudsen HK, Ducharme LJ, Roman PM. Job stress and poor sleep quality: Data from an American sample of full-time workers. Social Science \u0026amp; Medicine. 2007;64(10):1997\u0026ndash;2007. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.socscimed.2007.02.020\u003c/span\u003e\u003cspan address=\"10.1016/j.socscimed.2007.02.020\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang Y, Mei H, Jiang YR, et al. Relationship between Duration of Sleep and Hypertension in Adults: A Meta-Analysis. Journal of Clinical Sleep Medicine. 2015;11(09):1047\u0026ndash;1056. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.5664/jcsm.5024\u003c/span\u003e\u003cspan address=\"10.5664/jcsm.5024\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShan Z, Ma H, Xie M, et al. Sleep Duration and Risk of Type 2 Diabetes: A Meta-analysis of Prospective Studies. Diabetes Care. 2015;38(3):529\u0026ndash;537. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.2337/dc14-2073\u003c/span\u003e\u003cspan address=\"10.2337/dc14-2073\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWright KP, Bogan RK, Wyatt JK. Shift work and the assessment and management of shift work disorder (SWD). Sleep Medicine Reviews. 2013;17(1):41\u0026ndash;54. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.smrv.2012.02.002\u003c/span\u003e\u003cspan address=\"10.1016/j.smrv.2012.02.002\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e\u0026Aring;kerstedt T, Wright KP. Sleep Loss and Fatigue in Shift Work and Shift Work Disorder. Sleep Medicine Clinics. 2009;4(2):257\u0026ndash;271. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jsmc.2009.03.001\u003c/span\u003e\u003cspan address=\"10.1016/j.jsmc.2009.03.001\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDeng N, Haney NM, Kohn TP, Pastuszak AW, Lipshultz LI. The Effect of Shift Work on Urogenital Disease: a Systematic Review. Curr Urol Rep. 2018;19(8):57. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s11934-018-0815-y\u003c/span\u003e\u003cspan address=\"10.1007/s11934-018-0815-y\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRoth T. Insomnia: Definition, Prevalence, Etiology, and Consequences. Journal of Clinical Sleep Medicine. 2007;3(5 suppl). doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.5664/jcsm.26929\u003c/span\u003e\u003cspan address=\"10.5664/jcsm.26929\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHiestand DM, Britz P, Goldman M, Phillips B. Prevalence of Symptoms and Risk of Sleep Apnea in the US Population. Chest. 2006;130(3):780\u0026ndash;786. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1378/chest.130.3.780\u003c/span\u003e\u003cspan address=\"10.1378/chest.130.3.780\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSenaratna CV, Perret JL, Lodge CJ, et al. Prevalence of obstructive sleep apnea in the general population: A systematic review. Sleep Medicine Reviews. 2017;34:70\u0026ndash;81. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.smrv.2016.07.002\u003c/span\u003e\u003cspan address=\"10.1016/j.smrv.2016.07.002\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCho JW, Duffy JF. Sleep, Sleep Disorders, and Sexual Dysfunction. World J Mens Health. 2019;37(3):261. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.5534/wjmh.180045\u003c/span\u003e\u003cspan address=\"10.5534/wjmh.180045\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKohn TP, Kohn JR, Haney NM, Pastuszak AW, Lipshultz LI. The effect of sleep on men\u0026rsquo;s health. Transl Androl Urol. 2020;9(S2):S178-S185. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.21037/tau.2019.11.07\u003c/span\u003e\u003cspan address=\"10.21037/tau.2019.11.07\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDeng N, Kohn TP, Lipshultz LI, Pastuszak AW. The Relationship Between Shift Work and Men\u0026rsquo;s Health. Sexual Medicine Reviews. 2018;6(3):446\u0026ndash;456. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.sxmr.2017.11.009\u003c/span\u003e\u003cspan address=\"10.1016/j.sxmr.2017.11.009\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKohn TP, Rodriguez KM, Sigalos JT, Hasan A, Pastuszak AW, Lipshultz LI. PD27-08 POOR SLEEP QUALITY IS ASSOCIATED WITH CLINICALLY SIGNIFICANT ERECTILE DYSFUNCTION. Journal of Urology. 2018;199(4S). doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.juro.2018.02.1359\u003c/span\u003e\u003cspan address=\"10.1016/j.juro.2018.02.1359\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBaker FC, Driver HS. Circadian rhythms, sleep, and the menstrual cycle. Sleep Med. 2007;8(6):613\u0026ndash;622. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.sleep.2006.09.011\u003c/span\u003e\u003cspan address=\"10.1016/j.sleep.2006.09.011\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShlykova N, Davidson E, Krakowsky Y, Bolanos J, Traish A, Morgentaler A. Absent Diurnal Variation in Serum Testosterone in Young Men with Testosterone Deficiency. J Urol. 2020;203(4):817\u0026ndash;823. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/JU.0000000000000630\u003c/span\u003e\u003cspan address=\"10.1097/JU.0000000000000630\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSeehuus M, Pigeon W. The sleep and sex survey: Relationships between sexual function and sleep. J Psychosom Res. 2018;112:59\u0026ndash;65. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jpsychores.2018.07.005\u003c/span\u003e\u003cspan address=\"10.1016/j.jpsychores.2018.07.005\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLuboshitzky R, Zabari Z, Shen-Orr Z, Herer P, Lavie P. Disruption of the Nocturnal Testosterone Rhythm by Sleep Fragmentation in Normal Men. The Journal of Clinical Endocrinology \u0026amp; Metabolism. 2001;86(3):1134\u0026ndash;1139. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1210/jcem.86.3.7296\u003c/span\u003e\u003cspan address=\"10.1210/jcem.86.3.7296\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLateef OM, Akintubosun MO. Sleep and Reproductive Health. J Circadian Rhythms. 2020;18:1. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.5334/jcr.190\u003c/span\u003e\u003cspan address=\"10.5334/jcr.190\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTeloken PE, Smith EB, Lodowsky C, Freedom T, Mulhall JP. Defining association between sleep apnea syndrome and erectile dysfunction. Urology. 2006;67(5):1033\u0026ndash;1037. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.urology.2005.11.040\u003c/span\u003e\u003cspan address=\"10.1016/j.urology.2005.11.040\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMun JK, Choi SJ, Kang MR, Hong SB, Joo EY. Sleep and libido in men with obstructive sleep apnea syndrome. Sleep Medicine. 2018;52:158\u0026ndash;162. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.sleep.2018.07.016\u003c/span\u003e\u003cspan address=\"10.1016/j.sleep.2018.07.016\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFanfulla F, Malaguti S, Montagna T, et al. Erectile dysfunction in men with obstructive sleep apnea: an early sign of nerve involvement. Sleep. 2000;23(6):775\u0026ndash;781.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi Z, Tang T, Wu W, 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\u0026ndash;134. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.rmed.2016.09.001\u003c/span\u003e\u003cspan address=\"10.1016/j.rmed.2016.09.001\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhang XB, Lin QC, Zeng HQ, Jiang XT, Chen B, Chen X. Erectile Dysfunction and Sexual Hormone Levels in Men With Obstructive Sleep Apnea: Efficacy of Continuous Positive Airway Pressure. Arch Sex Behav. 2016;45(1):235\u0026ndash;240. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s10508-015-0593-2\u003c/span\u003e\u003cspan address=\"10.1007/s10508-015-0593-2\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBudhiraja R, Parthasarathy S, Quan SF. Endothelial dysfunction in obstructive sleep apnea. J Clin Sleep Med. 2007;3(4):409\u0026ndash;415.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBakker JP, Weaver TE, Parthasarathy S, Aloia MS. Adherence to CPAP. Chest. 2019;155(6):1272\u0026ndash;1287. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.chest.2019.01.012\u003c/span\u003e\u003cspan address=\"10.1016/j.chest.2019.01.012\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKuhn E, Schwarz EI, Bratton DJ, Rossi VA, Kohler M. Effects of CPAP and Mandibular Advancement Devices on Health-Related Quality of Life in OSA. Chest. 2017;151(4):786\u0026ndash;794. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.chest.2017.01.020\u003c/span\u003e\u003cspan address=\"10.1016/j.chest.2017.01.020\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMelehan KL, Hoyos CM, Hamilton GS, et al. Randomized Trial of CPAP and Vardenafil on Erectile and Arterial Function in Men With Obstructive Sleep Apnea and Erectile Dysfunction. The Journal of Clinical Endocrinology \u0026amp; Metabolism. 2018;103(4):1601\u0026ndash;1611. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1210/jc.2017-02389\u003c/span\u003e\u003cspan address=\"10.1210/jc.2017-02389\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen L, Shi G rui, Huang D dan, et al. Male sexual dysfunction: A review of literature on its pathological mechanisms, potential risk factors, and herbal drug intervention. Biomedicine \u0026amp; Pharmacotherapy. 2019;112:108585. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.biopha.2019.01.046\u003c/span\u003e\u003cspan address=\"10.1016/j.biopha.2019.01.046\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePastuszak AW, Moon YM, Scovell J, et al. Poor Sleep Quality Predicts Hypogonadal Symptoms and Sexual Dysfunction in Male Nonstandard Shift Workers. Urology. 2017;102:121\u0026ndash;125. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.urology.2016.11.033\u003c/span\u003e\u003cspan address=\"10.1016/j.urology.2016.11.033\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"Tables 1 and 2 are available in the Supplementary Files section."}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"international-journal-of-impotence-research","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"ijir","sideBox":"Learn more about [International Journal of Impotence Research](http://www.nature.com/ijir/)","snPcode":"41443","submissionUrl":"https://mts-ijir.nature.com/cgi-bin/main.plex","title":"International Journal of Impotence Research","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Sleep Apnea, Insomnia, Circadian Rhythm Dysfunction, Polysomnography, Testosterone Deficiency, Hypogonadism, Erectile Dysfunction","lastPublishedDoi":"10.21203/rs.3.rs-1913602/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-1913602/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThe relationship between male genitourinary conditions and sleep disorders has only been reported in small sample sizes. Our objective was to assess the association of erectile dysfunction (ED) and testosterone deficiency with various sleep disorders using a large claims database. The TriNetX Diamond database, a research network of over 220\u0026nbsp;million patients, was queried in June 2022. In men aged 40\u0026ndash;70 years, insomnia (ICD-10 G47.0), sleep apnea (G47.33), and circadian rhythm sleep disorder (G47.2) were each independently assessed to determine the association with ED (N52) and testicular hypofunction (E29.1). A propensity-score-matched control cohort was generated with an absence of sleep disorders (G47 \u0026amp; F51), sleep deprivation (Z72.820), or morbid obesity with alveolar hypoventilation (E66.2). Propensity score matching was performed for age, hypertension (I10-16), hyperlipidemia (E78), diabetes mellitus (E08-13), ischemic heart disease (I20-25), tobacco usage (Z72.0), and obesity (E66). Sensitivity analyses were conducted via a negative polysomnography testing (CPT 1013314) cohort. Men diagnosed with a sleep disorder had significantly higher odds of testosterone deficiency and ED compared to propensity-score matched controls. Our results emphasize the negative impact of poor sleep on diseases of the male genitourinary system by identifying these relationships in the largest cohort in the U.S. reported to date.\u003c/p\u003e","manuscriptTitle":"Sleep Disorders are Associated with Testosterone Deficiency and Erectile Dysfunction- A U.S. Claims Database Analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-08-18 17:26:00","doi":"10.21203/rs.3.rs-1913602/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"revise","date":"2022-09-20T10:35:13+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"This content is not available.","date":"2022-08-30T22:52:55+00:00","index":1,"fulltext":"This content is not available."},{"type":"editorInvitedReview","content":"This content is not available.","date":"2022-08-23T16:08:58+00:00","index":2,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2022-08-23T15:25:53+00:00","index":2,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2022-08-16T23:56:30+00:00","index":1,"fulltext":"This content is not available."},{"type":"reviewersInvited","content":"","date":"2022-08-16T20:46:59+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2022-08-03T09:13:13+00:00","index":"","fulltext":""},{"type":"checksFailed","content":"","date":"2022-08-01T10:20:02+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2022-07-31T06:05:45+00:00","index":"","fulltext":""},{"type":"submitted","content":"International Journal of Impotence Research","date":"2022-07-31T06:05:45+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"international-journal-of-impotence-research","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"ijir","sideBox":"Learn more about [International Journal of Impotence Research](http://www.nature.com/ijir/)","snPcode":"41443","submissionUrl":"https://mts-ijir.nature.com/cgi-bin/main.plex","title":"International Journal of Impotence Research","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"c3231c0f-9219-49eb-8191-bf5533e63d2f","owner":[],"postedDate":"August 18th, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2022-12-07T08:08:32+00:00","versionOfRecord":{"articleIdentity":"rs-1913602","link":"https://doi.org/10.1038/s41443-022-00649-2","journal":{"identity":"international-journal-of-impotence-research","isVorOnly":false,"title":"International Journal of Impotence Research"},"publishedOn":"2022-12-06 05:00:00","publishedOnDateReadable":"December 6th, 2022"},"versionCreatedAt":"2022-08-18 17:26:00","video":"","vorDoi":"10.1038/s41443-022-00649-2","vorDoiUrl":"https://doi.org/10.1038/s41443-022-00649-2","workflowStages":[]},"version":"v1","identity":"rs-1913602","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-1913602","identity":"rs-1913602","version":["v1"]},"buildId":"wLkW0s4AflPzk-lpfg-fK","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}