Relationship between Anogenital Distance and Testicular Position in Male Infants with Cryptorchidism with and without Hypospadias

Relationship between Anogenital Distance and Testicular Position in Male Infants with Cryptorchidism with and without Hypospadias | 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 Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Relationship between Anogenital Distance and Testicular Position in Male Infants with Cryptorchidism with and without Hypospadias Salah Nagla, Shaymaa Elrifaey, hend abdelnabi, ayman hagras, ahmed arafa, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5822825/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 18 Mar, 2025 Read the published version in International Urology and Nephrology → Version 1 posted You are reading this latest preprint version Abstract Purpose Anogenital distance (AGD) may indicate hypoverilization and subsequently serve as a predictor future reproduction. In both undescended testis with and without hypospadias, our goal was to study the relationship between testicular position and AGD. Methods From March 2021 to January 2023, the study was conducted on male infants with and without hypospadias and age-matched controls. Based on the infants' ages, we divided them into four. Group I: under six months, Group II: 7–12 months, Group III: between a year and eighteen months, and Group IV: 19 months up to two years of age. From the verge of the anus to the penile base, the AGD was measured. Clinical examination resulted in the classification of testicular location as high scrotal, inguinal, and non-palpable. Results Patients with cryptorchidism had AGD means that were substantially lower than those of controls in Groups I, II, III, and IV, respectively (31 ± 2, 33 ± 3), (35.9 ± 4, 37.9 ± 5), (39.9 ± 1.2, 41 ± 1.5), and (40 ± 1.9, 44 ± 1.7). The group of patients with cryptorchidism and hypospadias differed significantly from the controls and those without hypospadias. AGD in patients with upper scrotal locations was substantially shorter. Penile length and AGD of the examined groups exhibited a positive and significant connection. Conclusions Shorter AGD is linked to a higher prevalence of hypospadias and cryptorchidism in male babies in comparison to normal children. The position of the undescended testis is higher in relation to a shorter AGD. Cryptorchidism Anogenital Distance Hypospadias Figures Figure 1 Introduction Numerous studies have found an increase in the occurrence of undescended testicles, hypospadias and reduced sperm quality ( 1 , 2 ). The correlation between hypospadias and cryptorchidism is documented, and it is possible that these conditions are signs of testicular dysgenesis syndrome (TDS), a condition marked by aberrant fetal testicular development with distinct causes ( 2 ). It was postulated that exposure to environmental pollutants causes endocrine disruptors, which are thought to cause hypoverilization ( 3 ). Testes and penis shrink because of fetal androgen deprivation, raising the possibility of hypospadias ( 4 ). One could think of anogenital distance (AGD) as a quantifiable biomarker for hypoverilization and exposure to endocrine disruptors in the human fetus ( 5 ). It was discovered that there was a significant correlation between AGD and aberrant genital length in animal models, as well as impaired testicular function as shown by testosterone and sperm production ( 6 , 7 ). Furthermore, AGD serves as an indicator of prenatal exposure to modified androgen levels in animal models in addition to intrauterine exposure to varying environmental pollutants ( 7 ). Testicular descent arrest from the belly to the scrotum can happen at the scrotal neck, in the inguinal region, or anywhere in between ( 8 ). Hormonal treatment of cryptorchidism is only beneficial in minority of cases which could be explained in the future by the hormonal response according to the state of hypoverilization which could be assessed by AGD. The purpose of this study was to compare AGD and testicular location in Egyptian children with cryptorchidism with and without hypospadias to normative data. Those data may help in early prediction of fertility affection leading to proper early management. Methods The infants were recruited from our departments out-patient clinics between March 2021 and January 2023. Control groups were of matched age without urogenital anomalies. Inclusion criteria Unilateral cryptorchidism with or without distal penile hypospadias in male infants (1–24 months). Exclusion criteria Infants with chronic disease or malignancy Atrophic or vanished testis For all studied groups thorough clinical assessment and medical history. measurement of the penile length, AGD, position of the urethral aperture, and size of the testes during genital examination. Measurement of stretched penile length using the traditional technique for measuring penile length (CPLM). The penis was held at a straight angle to the pubic ramus on the unmarked wooden spatula while its terminal portion was engaged and secured against the pubic ramus. A pencil was used to indicate the distance on the spatula between the pubic ramus and the tip of the glans while the penis was being stretched to the point of maximum resistance. Next, the distance between the spatula's tip and the designated spot was measured and recorded using a measuring tape ( 9 ). Measurement of Anogenital Distance measured from the centre of the anal verge to the base of penile shaft using Vernier callipers ( 10 ). Statistical analysis : The data were analysed using version 16 of the SPSS software (SPSS Inc., Texas, USA), with the results expressed as mean ± standard deviation (SD). ANOVA was used to evaluate numerical variables between the study groups, and Tukey's test was used as a post hoc test to compare results between groups. where the variables were normally distributed, the student t-test was used for independent samples; where the variables weren't, the Mann-Whitney U test was used for independent samples. The Chi square test was used to compare categorical data. The threshold of 0.05 for P values to be deemed statistically significant*. Parametric data is correlated using linear regression and Pearson correlation. AGD was measured twice by the same physician to prevent intra-observer variability. Measurements of stretched penile length and anogenital distance were made using intra-observer variability, in which the same individual made two measurements. Cohen kappa (κ) statistics were used to determine the intra-observer agreement in measurement interpretation: stretched penile length was 0.84 κ, AGD 0.81κ. If κ ≤ 0.20, there was weak agreement, fair agreement, moderate agreement, significant agreement, 0.61–0.80 agreement, and strong agreement if κ > 0.40. Results Group I (60 infants): less than 6 months, Group II (42 infants): 7–12 months, Group III ( 17 ): 13–18 months, and Group IV (31infants): 19–24 months were the age categories of the studied 150 infants. Tables 1 and 2 present the comparison between these groups and the controls (n = 150). In all groups I , II , III , and IV , the mean AGD was significantly lesser in patients with undescended testicles than controls (31 ± 2.2, 33.3 ± 3.3 respectively) (p 0.024*), 35.8 ± 4.2, 37.9 ± 5.4 respectively) (p0.001*), 39.9 ± 1.2, 41.3 ± 1.5 respectively) (p 0.003*), and 40 ± 1.9, 44 ± 1.7 respectively) (p 0.001*). Between patients with undescended testicles who had hypospadias or not and controls, AGD revealed a significant difference (P 0.001*) (table 3 ) . In comparison to other testicular sites, the AGD of patients with upper scrotal placements was substantially shorter in the right and left testis in table 4. In the groups under investigation, penile length and AGD exhibited a substantial positive connection (r 0.469, r² 0.22, P 0.001*) (Fig. 1 ). Discussion A vital component of the new-born’s physical check-up is the evaluation of the genitalia ( 11 ). Common congenital urogenital anomalies include hypospadias and undescended testis, with incidences of 0.2–1% and 2–9%, respectively ( 2 ). They share numerous risk factors, even though their aetiology is still poorly understood. Additionally, several studies have linked parental exposure to environmental pollutants to a high frequency of hypospadias and undescended testes, implying that these exposures have a role in both the pathogenic processes and hypoverilization ( 2 , 12 , 13 , 14 ). In all four age categories, the current study showed that AGD was substantially shorter than controls in patients with undescended testis with hypospadias. Numerous investigations concurred with our findings. Thankamony et al ( 15 ) discovered that, in comparison to healthy controls, with undescended testis or hypospadias had considerably lower mean AGD and penile length metrics (24.6 ± 6.3, 29.8 ± 7 respectively, p < 0.0001). Patients with hypospadias had significantly shorter penis (24.6 ± 6, 29.8 ± 6.8 respectively, p < 0.0001) and smaller AGDs. This was in line with previous articles ( 10 , 13 , 14 , 16 , 17 ). Furthermore, AGD with cryptorchidism was shown to be substantially shorter than that of the control normal neonates (2 ± 0.22 vs 2.4 ± 0.2 cm, P < 0.01) as shown by Jiang et al ( 17 ), and even after preterm and low birth weight infants were removed, statistically significant disparities persisted (2.3 ± 0.1 vs 2 ± 0.2 cm; (2.4 ± 0.2) cm vs (2 ± 0.12) cm. Although there was no statistical difference, the neonates with higher-position cryptorchidism had a shorter AGD (F = 0.434, P > 0.05). Furthermore, they concluded that there were no discernible variations in the AGD between unilateral and bilateral cryptorchidism (2 ± 0.13 vs 2 ± 0.2 cm, P > 0.05). Although, there was no statistical difference, infants with higher testicular positions appeared to have shorter AGDs in a study by Jain and Singal ( 18 ). There was no discernible difference in AGD between cases exhibiting bilateral and unilateral undescended testes. AGD is reported to be longer in females with virilizing congenital adrenal hyperplasia and to be lower in males with lower amounts of testosterone, lower-quality semen, and lower reproductive rates ( 19 , 20 ). Furthermore, research on animals indicates that AGD is a good indicator for testicular function. Furthermore, the anti-androgen dose-dependent decrease in AGD in rats is linked to symptoms such micro-penis, hypospadias, and cryptorchidism ( 13 ). Furthermore, in rat fetal development, endocrine disruptors appeared to influence genitalia genesis ( 14 ). Suzuki et al ( 21 ) shown how environmental pollutants such dioxins, bisphenol A, and phthalates can cause hormonal disruptions. The number of urinary pesticides in the mothers' late gestation and the anogenital distance in male infants have a positive correlation, suggesting that the former may serve as a helpful indicator of the impact of environmental chemicals on human hypoverilization and testis descent ( 22 , 23 , 24 ). One could argue that AGD reflects hypoverilization. We believe that to plan future prenatal and postnatal therapy for numerous hypoverilization illnesses, including cryptorchidism, a nomogram for AGD data should be developed. Furthermore, the anticipated response based on the degree of hypoverilization, which the AGD should be able to determine, may serve as a guide for the future of hormone therapy in certain cases of cryptorchidism. Limitations of the study To get precise information about AGD and its relationship to hypospadias and cryptorchidism, multicentre studies are advised. Additionally, the number of new-borns involved in each group is limited, necessitating an increase to draw reliable conclusions; still, our study is a step toward achieving future reference values for AGD in neonates. Conclusion Shorter AGD is linked to a higher prevalence of hypospadias and cryptorchidism in male babies. Furthermore, a shorter AGD is linked to a higher location of the undescended testis. This finding gives us an alarm to start hormonal and semen assessement in early adolescence for preservation of future fertility. Declarations Ethical approval was obtained before data collection at our university under number 32868/01/19 and the parents provided written informed consent. The article adhered to the ethical guidelines of Declaration of Helsinki and its modifications. Data availability : When asked from the authors Funding : No funds, grants, or other support was received. Conflict of interest: The authors have no relevant financial or non-financial interests to disclose. Authors’ contribution statements: Authors are responsible for correctness of the statements provided in the manuscript. All authors whose names appear on the submission made substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data; or the creation of new software used in the work; drafted the work or revised it critically for important intellectual content; approved the version to be published; and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. References Alaee E, Gharib MJ, Fouladinejad M (2014) Penile Length and Anogenital Distance in Male Newborns from Different Iranian Ethnicities in Golestan Province. Iran Red Crescent Med J. 16 (12): e16729. doi: 10.5812/ircmj.16729 Toppari J, Virtanen HE, Main KM, et al ( 2010) Cryptorchidism, and hypospadias as a sign of testicular dysgenesis syndrome (TDS): environmental connection. Birth Defects Res A Clin Mol Teratol. 88:910-919. doi: 10.1002/bdra.20707 Thacharodi A, Hassan S, Acharya G, et al (2023) Endocrine disrupting chemicals and their effects on the reproductive health in men. Environ Res. 1; 236 (Pt 2):116825. doi: 10.1016/j.envres.2023.116825 Park JY, Lim G, Oh KW, et al (2015) Penile length, digit length, and anogenital distance according to birth weight in newborn male infants. Korean J Urol. 56: 248-253. doi: 10.4111/kju.2015.56.3.248 Arbuckle TE, Hauser R, Swan SH, et al (2008) Meeting report: Measuring endocrine-sensitive endpoints within the first years of life. Environ Health Perspect. 116:948-951. doi: 10.1289/ehp.11226 Martino-Andrade A.J, Morais RN, Botelho GG, et al (2009) Coadministration ofactive phthalates results in disruption of foetal testicular function inrats. Int J Androl. 32, 704-712. doi: 10.1111/j.1365-2605.2008.00939.x Pan J, Liu P, Yu X, Zhang Z, Liu J ( 2024) The adverse role of endocrine disrupting chemicals in the reproductive system. Front Endocrinol (Lausanne). 17; 14-1324993. DOI: 10.3389/fendo.2023.1324993 Shankar VV, Kulkarni R ( 2014) Undescended Testes: Embryological and Clinical Importance. Int J Anat Res. 2(3): 456-58. https://api.semanticscholar.org/CorpusID:74447373 Matuszczak E, Hermanowicz A, Komarowska M, et al (2013)Serum AMH in physiology and pathology of male gonads. Int J Endocrinol. 1-6. DOI: 10.1155/2013/128907 Hsieh MH, Breyer BN, Eisenberg ML, et al (2008) Associations among hypospadias, cryptorchidism, anogenital distance, and endocrine disruption. Curr Urol Rep. 9: 137-142. DOI: 10.1007/s11934-008-0025-0 Mecarini F, Fanos V, Crisponi G (2021) Genital anomalies in newborns. J Perinatol. 41(9): 2124-2133. doi: 10.1038/s41372-021-00991-1 Gaspari L, Paris F, Jandel C, et al ( 2011) Prenatal environmental risk factors for genital malformations in a population of 1442 French male new-borns:a nested case–control study. Hum Reprod. 26:3155-3162. doi: 10.1093/humrep/der283 Dean A, Sharpe RM (2013) Clinical review:Anogenital distance or digit length ratio as measures of fetal androgen exposure: relationship to male reproductive developme. J Clin Endocrinol Metab. Jun;98(6):2230-8. DOI: 10.1210/jc.2012-4057 Welsh M, Saunders PT, Fisken M, et al (2008) Identification in rats of a programming window for reproductive tract masculinization, disruption of which leads to hypospadias and cryptorchidism. J Clin Invest. 118:1479-1490. DOI: 10.1172/JCI34241 Thankamony A, Lek N, Carroll D, et al (2014) Anogenital distance and penile length in infants with hypospadias or cryptor­chidism: comparison with normative data. Environ Health Perspect. 122:207-211. DOI: 10.1289/ehp.1307178 Papadopoulou E, Vafeiadi M, Agramunt S, et al (2013) Anogenital distances in newborns and children from Spain and Greece: predictors, tracking and reliability. Paediatr Perinat Epidemiol. 27:89-99. DOI: 10.1111/ppe.12022 Jiang DP , Geng HQ , Lin HW , et al (2015) Relationship between anogenital distance and cryptorchidism in human newborns. Nat J. Androl. 21(5): 432-435. PMID: 26117942 Jain VG , Singal AK (2013) Shorter anogenital distance correlates with undescended testis: a detailed genital anthropometric analysis in human newborns. Hum Repord. 28(9): 2343-9. doi: 10.1093/humrep/det286 Eisenberg ML, Shy M, Walters RC, et al (2012) The relationship between anogenital distance and azoospermia in adult men. Int J Androl. 35: 726-730. doi: 10.1111/j.1365-2605.2012.01275.x Mendiola J, Stahlhut RW, Jorgensen N, et al (2011) Shorter anogenital distance predicts poorer semen quality in young men in Rochester, New York. Environ Health Perspect. 119: 958- 963. doi: 10.1289/ehp.1103421 Suzuki Y, Yoshinaga J, Mizumoto Y, et al (2012) Foetal exposure to phthalate esters and anogenital distance in male newborns. Int J Androl. 35:236-244. doi: 10.1111/j.1365-2605.2011.01190.x Qian Y, Shao H, Ying X, et al (2020) The Endocrine Disruption of Prenatal Phthalate Exposure in Mother and Offspring. Front Public Health. 28: 8-366. doi: 10.3389/fpubh.2020.00366 Yesildemir O, Celik MN (2024) The Effect of Various Environmental Pollutants on the Reproductive Health in Children: A Brief Review of the Literature. 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Toxics. 8: 10(1)- 26. doi: 10.3390/toxics10010026 Tables Table (1): Demographic data of the studied groups Groups Controls (n=150) Patients (n=150) Age (months) Weight (kg) Length (cm) Penile length (cm) AGD (mm) I: 1-6 m Controls (n=43) 3.26 ± 1.92 5.22 ± 1.1 58.96 ± 4.31 3.68 ± 0.5 33.27 ± 3.3 Patients (n=60) 3.42 ± 1.3 5.89 ± 1 59.93 ± 4.6 3.67 ± 0.4 31 ± 2.2 P value 0.215 0.990 0.418 0.971 0.024 * II: 6-12 m Controls (n=57) 9.54 ± 1.7 8.92 ± 1 71.92 ± 4 3.82 ± 0.4 37.95 ± 5.4 Patients (n=42) 9.26 ± 1.9 8.6 ± 0.8 71.7 ± 3 3.79 ± 0.3 35.8 ± 4.2 P value 0.123 0.990 0.770 0.092 0.001 * III: 12-18 m Controls (n=18) 14.2 ± 1.7 10.8 ± 1.4 81± 3.7 3.9 ± 0.24 41.3 ± 1.5 Patients (n=17) 14.9 ± 2 10.4 ± 0.3 80.3 ± 2.5 3.9 ± 0.3 39.8 ± 1.2 P value 0.250 0.305 0.884 0.788 0.003 * IV: 18-24 m Controls (n=32) 22.25 ± 1.7 12.7 ± 0.6 86.4 ± 3.3 4.5 ± 0.7 44 ± 1.7 Patients (n=31) 21.8 ± 1.8 12.6 ± 0.9 86.2 ± 1.6 4.6 ± 0.7 40 ± 1.86 P value 0.354 0.162 0.941 0.846 0.001 * Table (2) : Site of the undescended testes in the patients Site of the testis Cryptorchidism without hypospadias n=54 Cryptorchidism with hypospadias n=96 Chi-Square P value 1.Upper scrotal: Rt testis Lt testis Rt testis Lt testis 48.890 0.001 * 5 11 31 34 2. Inguinal: 16 12 10 9 3. Un-palpable: 5 4 8 3 Table (3): Comparison between the groups’ AGD (controls and patients with or without hypospadias Parameter Controls n=150 (Mean ± SD) Cryptorchidism without hypospadias n=54 (Mean ± SD) Cryptorchidism with hypospadias n=96 (Mean ± SD) F value ANOVA P value AGD (mm): 37.9 ± 5.8 35.8 ± 4.2 34.5 ± 4.3 18.4 0.001 * Post Hoc analysis (Tukey’s test) on results of one-way ANOVA on comparison between the above groups: Shows the significant difference was between the patient’s group of cryptorchidism with hypospadias and the other 2 groups (P = 0.001*). With no significant difference between controls and patients’ group of cryptorchidism without hypospadias (P = 0.951). Table (4): Comparison between the patients’ AGD and site of their testis Lt testis Upper scrotal n=45 (Mean ± SD) Inguinal n=23 (Mean ± SD) Unpalpable n=7 (Mean ± SD) F value ANOVA P value AGD (mm): 39.4 ± 2 37.8 ± 3 35.4 ± 3 4.7 0.01 * Post Hoc analysis (Tukey’s test) on results of one-way ANOVA on comparison between the above groups: Shows the significant difference was between the upper scrotal and inguinal positions of the left testis (P = 0.028*). With no significant difference between the unpalpable testis and both inguinal and upper scrotal positions of the left testis (P = 0.743 and 0.173 respectively). Rt testis Upper scrotal n=36 (Mean ± SD) Inguinal n=26 (Mean ± SD) Unpalpable n=13 (Mean ± SD) F value ANOVA P value AGD (mm): 37.8 ± 3.5 35 ± 4 34.8 ± 2 7.178 0.001 * Post Hoc analysis (Tukey’s test) on results of one-way ANOVA on comparison between the above groups: Shows the significant difference was between the upper scrotal and inguinal positions of the right testis (P = 0.001*). With no significant difference between the unpalpable testis and both inguinal and upper scrotal positions of the right testis (P = 0.170 and 0.990 respectively). Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 18 Mar, 2025 Read the published version in International Urology and Nephrology → Version 1 posted 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. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board 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-5822825","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":404165608,"identity":"35104c74-597a-47cb-a017-8fa8aae14d07","order_by":0,"name":"Salah Nagla","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA8ElEQVRIiWNgGAWjYFAC5gZmEMXHwMP4gIHhADFaGCFa2Bh4mA1I1sImQZQW+faDjZ8Ld9jZtbGfPVbNU3NHjp+B+eGjG3i0GJxJbJaeeSY5uY0nL+02z7FnxpINbMbGOfi0MCQ2SPO2MSezMeSY3eZhO5y44QAPmzQ+LfL9D5t/87bVJ7PxvzEr5vlHhBaGG4ltQFsO27FJ5JgxAxmEtRjceNhmzdt2PIFN4o2x5Ny+w8aSzQT8It+ffPg2b1u1PT9/juGHN98Oy/GzNz98jNdhUJDYACSYeEBMZiKUg4A9iGD8QaTqUTAKRsEoGFkAAPUSSjNBH4aRAAAAAElFTkSuQmCC","orcid":"","institution":"Tanta University","correspondingAuthor":true,"prefix":"","firstName":"Salah","middleName":"","lastName":"Nagla","suffix":""},{"id":404165609,"identity":"c9eddb81-c3a6-4fbf-aa56-696b5c313d81","order_by":1,"name":"Shaymaa Elrifaey","email":"","orcid":"","institution":"Tanta University","correspondingAuthor":false,"prefix":"","firstName":"Shaymaa","middleName":"","lastName":"Elrifaey","suffix":""},{"id":404165610,"identity":"3c751ff3-17e4-4280-a818-dcd20f5afcd6","order_by":2,"name":"hend abdelnabi","email":"","orcid":"","institution":"Tanta University","correspondingAuthor":false,"prefix":"","firstName":"hend","middleName":"","lastName":"abdelnabi","suffix":""},{"id":404165611,"identity":"cfc68416-c7ee-4173-a1e7-153ca43fa2ac","order_by":3,"name":"ayman hagras","email":"","orcid":"","institution":"Tanta University","correspondingAuthor":false,"prefix":"","firstName":"ayman","middleName":"","lastName":"hagras","suffix":""},{"id":404165612,"identity":"d6412b49-d056-45cc-bf2a-d00197d34004","order_by":4,"name":"ahmed arafa","email":"","orcid":"","institution":"Tanta University","correspondingAuthor":false,"prefix":"","firstName":"ahmed","middleName":"","lastName":"arafa","suffix":""},{"id":404165613,"identity":"1d68a135-134b-4679-b31e-0a97991156b7","order_by":5,"name":"mohamed hamza","email":"","orcid":"","institution":"Tanta University","correspondingAuthor":false,"prefix":"","firstName":"mohamed","middleName":"","lastName":"hamza","suffix":""},{"id":404165614,"identity":"9a590197-2db6-4180-bfff-08cfb5c1c3f7","order_by":6,"name":"waleed dawood","email":"","orcid":"","institution":"Alexandria University","correspondingAuthor":false,"prefix":"","firstName":"waleed","middleName":"","lastName":"dawood","suffix":""}],"badges":[],"createdAt":"2025-01-13 22:38:06","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5822825/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5822825/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s11255-025-04429-x","type":"published","date":"2025-03-18T15:58:21+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":74244699,"identity":"7fc1b9e0-443c-4e54-8f52-d8797e021172","added_by":"auto","created_at":"2025-01-20 09:52:11","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":31943,"visible":true,"origin":"","legend":"\u003cp\u003eCorrelation between penile length and AGD of studied groups (r 0.469, r² 0.22, P 0.001*)\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-5822825/v1/233e120be2a74fb5ac17fab2.png"},{"id":79121263,"identity":"a289fb53-1fd9-4cc0-9413-59509302017e","added_by":"auto","created_at":"2025-03-24 16:11:48","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1327807,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5822825/v1/6a90475b-5f6e-4e0b-b18a-d2fe29606b17.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Relationship between Anogenital Distance and Testicular Position in Male Infants with Cryptorchidism with and without Hypospadias","fulltext":[{"header":"Introduction","content":"\u003cp\u003eNumerous studies have found an increase in the occurrence of undescended testicles, hypospadias and reduced sperm quality (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). The correlation between hypospadias and cryptorchidism is documented, and it is possible that these conditions are signs of testicular dysgenesis syndrome (TDS), a condition marked by aberrant fetal testicular development with distinct causes (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). It was postulated that exposure to environmental pollutants causes endocrine disruptors, which are thought to cause hypoverilization (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Testes and penis shrink because of fetal androgen deprivation, raising the possibility of hypospadias (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). One could think of anogenital distance (AGD) as a quantifiable biomarker for hypoverilization and exposure to endocrine disruptors in the human fetus (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). It was discovered that there was a significant correlation between AGD and aberrant genital length in animal models, as well as impaired testicular function as shown by testosterone and sperm production (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Furthermore, AGD serves as an indicator of prenatal exposure to modified androgen levels in animal models in addition to intrauterine exposure to varying environmental pollutants (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Testicular descent arrest from the belly to the scrotum can happen at the scrotal neck, in the inguinal region, or anywhere in between (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). Hormonal treatment of cryptorchidism is only beneficial in minority of cases which could be explained in the future by the hormonal response according to the state of hypoverilization which could be assessed by AGD. The purpose of this study was to compare AGD and testicular location in Egyptian children with cryptorchidism with and without hypospadias to normative data. Those data may help in early prediction of fertility affection leading to proper early management.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThe infants were recruited from our departments out-patient clinics between March 2021 and January 2023. Control groups were of matched age without urogenital anomalies.\u003c/p\u003e\u003cp\u003e \u003cb\u003eInclusion criteria\u003c/b\u003e \u003c/p\u003e\u003cul\u003e \u003cli\u003e \u003cp\u003eUnilateral cryptorchidism with or without \u003cb\u003edistal penile\u003c/b\u003e hypospadias in male infants (1–24 months).\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e\u003cp\u003e \u003cb\u003eExclusion criteria\u003c/b\u003e \u003c/p\u003e\u003cul\u003e \u003cli\u003e \u003cp\u003eInfants with chronic disease or malignancy\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eAtrophic or vanished testis\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e\u003cp\u003e \u003cstrong\u003eFor all studied groups\u003c/strong\u003e \u003c/p\u003e\u003cp\u003ethorough clinical assessment and medical history. measurement of the penile length, AGD, position of the urethral aperture, and size of the testes during genital examination.\u003c/p\u003e\u003cp\u003e \u003cstrong\u003eMeasurement of stretched penile length\u003c/strong\u003e \u003c/p\u003e\u003cp\u003eusing the traditional technique for measuring penile length (CPLM). The penis was held at a straight angle to the pubic ramus on the unmarked wooden spatula while its terminal portion was engaged and secured against the pubic ramus. A pencil was used to indicate the distance on the spatula between the pubic ramus and the tip of the glans while the penis was being stretched to the point of maximum resistance. Next, the distance between the spatula's tip and the designated spot was measured and recorded using a measuring tape (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e \u003cstrong\u003e\u003cb\u003eMeasurement of Anogenital Distance\u003c/b\u003e\u003c/strong\u003e \u003c/p\u003e\u003cp\u003emeasured from the centre of the anal verge to the base of penile shaft using Vernier callipers (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e \u003cb\u003eStatistical analysis\u003c/b\u003e: The data were analysed using version 16 of the SPSS software (SPSS Inc., Texas, USA), with the results expressed as mean ± standard deviation (SD). ANOVA was used to evaluate numerical variables between the study groups, and Tukey's test was used as a post hoc test to compare results between groups. where the variables were normally distributed, the student t-test was used for independent samples; where the variables weren't, the Mann-Whitney U test was used for independent samples. The Chi square test was used to compare categorical data. The threshold of 0.05 for P values to be deemed statistically significant*. Parametric data is correlated using linear regression and Pearson correlation. AGD was measured twice by the same physician to prevent intra-observer variability. Measurements of stretched penile length and anogenital distance were made using intra-observer variability, in which the same individual made two measurements. Cohen kappa (κ) statistics were used to determine the intra-observer agreement in measurement interpretation: stretched penile length was 0.84 κ, AGD 0.81κ. If κ ≤ 0.20, there was weak agreement, fair agreement, moderate agreement, significant agreement, 0.61–0.80 agreement, and strong agreement if κ \u0026gt; 0.40.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eGroup \u003cb\u003eI\u003c/b\u003e (60 infants): less than 6 months, Group \u003cb\u003eII\u003c/b\u003e (42 infants): 7\u0026ndash;12 months, Group \u003cb\u003eIII\u003c/b\u003e (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e): 13\u0026ndash;18 months, and Group \u003cb\u003eIV\u003c/b\u003e (31infants): 19\u0026ndash;24 months were the age categories of the studied 150 infants. Tables\u0026nbsp;1 and 2 present the comparison between these groups and the controls (n\u0026thinsp;=\u0026thinsp;150). In all groups \u003cb\u003eI\u003c/b\u003e, \u003cb\u003eII\u003c/b\u003e, \u003cb\u003eIII\u003c/b\u003e, and \u003cb\u003eIV\u003c/b\u003e, the mean AGD was significantly lesser in patients with undescended testicles than controls (31\u0026thinsp;\u0026plusmn;\u0026thinsp;2.2, 33.3\u0026thinsp;\u0026plusmn;\u0026thinsp;3.3 respectively) (p 0.024*), 35.8\u0026thinsp;\u0026plusmn;\u0026thinsp;4.2, 37.9\u0026thinsp;\u0026plusmn;\u0026thinsp;5.4 respectively) (p0.001*), 39.9\u0026thinsp;\u0026plusmn;\u0026thinsp;1.2, 41.3\u0026thinsp;\u0026plusmn;\u0026thinsp;1.5 respectively) (p 0.003*), and 40\u0026thinsp;\u0026plusmn;\u0026thinsp;1.9, 44\u0026thinsp;\u0026plusmn;\u0026thinsp;1.7 respectively) (p 0.001*). Between patients with undescended testicles who had hypospadias or not and controls, AGD revealed a significant difference (P 0.001*) (table 3\u003cb\u003e)\u003c/b\u003e. In comparison to other testicular sites, the AGD of patients with upper scrotal placements was substantially shorter in the right and left testis in table 4. In the groups under investigation, penile length and AGD exhibited a substantial positive connection (r 0.469, r\u0026sup2; 0.22, P 0.001*) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eA vital component of the new-born\u0026rsquo;s physical check-up is the evaluation of the genitalia (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). Common congenital urogenital anomalies include hypospadias and undescended testis, with incidences of 0.2\u0026ndash;1% and 2\u0026ndash;9%, respectively (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). They share numerous risk factors, even though their aetiology is still poorly understood. Additionally, several studies have linked parental exposure to environmental pollutants to a high frequency of hypospadias and undescended testes, implying that these exposures have a role in both the pathogenic processes and hypoverilization (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). In all four age categories, the current study showed that AGD was substantially shorter than controls in patients with undescended testis with hypospadias. Numerous investigations concurred with our findings. \u003cb\u003eThankamony et al\u003c/b\u003e (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e) discovered that, in comparison to healthy controls, with undescended testis or hypospadias had considerably lower mean AGD and penile length metrics (24.6\u0026thinsp;\u0026plusmn;\u0026thinsp;6.3, 29.8\u0026thinsp;\u0026plusmn;\u0026thinsp;7 respectively, p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001). Patients with hypospadias had significantly shorter penis (24.6\u0026thinsp;\u0026plusmn;\u0026thinsp;6, 29.8\u0026thinsp;\u0026plusmn;\u0026thinsp;6.8 respectively, p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001) and smaller AGDs. This was in line with previous articles (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). Furthermore, AGD with cryptorchidism was shown to be substantially shorter than that of the control normal neonates (2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.22 vs 2.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.2 cm, P\u0026thinsp;\u0026lt;\u0026thinsp;0.01) as shown by \u003cb\u003eJiang et al\u003c/b\u003e (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e), and even after preterm and low birth weight infants were removed, statistically significant disparities persisted (2.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1 vs 2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.2 cm; (2.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.2) cm vs (2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12) cm. Although there was no statistical difference, the neonates with higher-position cryptorchidism had a shorter AGD (F\u0026thinsp;=\u0026thinsp;0.434, P\u0026thinsp;\u0026gt;\u0026thinsp;0.05). Furthermore, they concluded that there were no discernible variations in the AGD between unilateral and bilateral cryptorchidism (2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.13 vs 2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.2 cm, P\u0026thinsp;\u0026gt;\u0026thinsp;0.05). Although, there was no statistical difference, infants with higher testicular positions appeared to have shorter AGDs in a study by \u003cb\u003eJain and Singal\u003c/b\u003e (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). There was no discernible difference in AGD between cases exhibiting bilateral and unilateral undescended testes. AGD is reported to be longer in females with virilizing congenital adrenal hyperplasia and to be lower in males with lower amounts of testosterone, lower-quality semen, and lower reproductive rates (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). Furthermore, research on animals indicates that AGD is a good indicator for testicular function. Furthermore, the anti-androgen dose-dependent decrease in AGD in rats is linked to symptoms such micro-penis, hypospadias, and cryptorchidism (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). Furthermore, in rat fetal development, endocrine disruptors appeared to influence genitalia genesis (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). \u003cb\u003eSuzuki et al\u003c/b\u003e (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e) shown how environmental pollutants such dioxins, bisphenol A, and phthalates can cause hormonal disruptions. The number of urinary pesticides in the mothers' late gestation and the anogenital distance in male infants have a positive correlation, suggesting that the former may serve as a helpful indicator of the impact of environmental chemicals on human hypoverilization and testis descent (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). One could argue that AGD reflects hypoverilization. We believe that to plan future prenatal and postnatal therapy for numerous hypoverilization illnesses, including cryptorchidism, a nomogram for AGD data should be developed. Furthermore, the anticipated response based on the degree of hypoverilization, which the AGD should be able to determine, may serve as a guide for the future of hormone therapy in certain cases of cryptorchidism.\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eLimitations of the study\u003c/strong\u003e \u003cp\u003eTo get precise information about AGD and its relationship to hypospadias and cryptorchidism, multicentre studies are advised. Additionally, the number of new-borns involved in each group is limited, necessitating an increase to draw reliable conclusions; still, our study is a step toward achieving future reference values for AGD in neonates.\u003c/p\u003e \u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eShorter AGD is linked to a higher prevalence of hypospadias and cryptorchidism in male babies. Furthermore, a shorter AGD is linked to a higher location of the undescended testis. This finding gives us an alarm to start hormonal and semen assessement in early adolescence for preservation of future fertility.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003eEthical approval was obtained before data collection at our university under number 32868/01/19\u003c/em\u003e\u003c/strong\u003e and the parents provided written informed consent. The article adhered to the ethical guidelines of Declaration of Helsinki and its modifications.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eData availability\u003c/em\u003e\u003c/strong\u003e: When asked from the authors\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e: No funds, grants, or other support was received.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest:\u0026nbsp;\u003c/strong\u003eThe authors have no relevant financial or non-financial interests to disclose.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAuthors\u0026rsquo; contribution\u003c/em\u003e\u003c/strong\u003e \u003cstrong\u003e\u003cem\u003estatements:\u0026nbsp;\u003c/em\u003e\u003c/strong\u003eAuthors are responsible for correctness of the statements provided in the manuscript. All authors whose names appear on the submission made substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data; or the creation of new software used in the work; drafted the work or revised it critically for important intellectual content; approved the version to be published; and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003e\u003cstrong\u003eAlaee E, Gharib MJ, Fouladinejad M\u003c/strong\u003e (2014) Penile Length and Anogenital Distance in Male Newborns from Different Iranian Ethnicities in Golestan Province. 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Korean J Urol. 56: 248-253. doi: 10.4111/kju.2015.56.3.248\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003eArbuckle TE, Hauser R, Swan SH, et al \u003c/strong\u003e(2008) Meeting report: Measuring endocrine-sensitive endpoints within the first years of life. Environ Health Perspect. 116:948-951. doi: 10.1289/ehp.11226\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003eMartino-Andrade A.J, Morais RN, Botelho GG, et al\u003c/strong\u003e (2009) Coadministration ofactive phthalates results in disruption of foetal testicular function inrats. Int J Androl. 32, 704-712. doi: 10.1111/j.1365-2605.2008.00939.x\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003ePan J, Liu P, Yu X, Zhang Z, Liu J (\u003c/strong\u003e2024) The adverse role of endocrine disrupting chemicals in the reproductive system. Front Endocrinol (Lausanne). 17; 14-1324993. DOI: 10.3389/fendo.2023.1324993\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003eShankar VV, Kulkarni R (\u003c/strong\u003e2014) Undescended Testes: Embryological and Clinical Importance. Int J Anat Res. 2(3): 456-58. https://api.semanticscholar.org/CorpusID:74447373 \u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003eMatuszczak E, Hermanowicz A, Komarowska M, et al \u003c/strong\u003e(2013)Serum AMH in physiology and pathology of male gonads. Int J Endocrinol. 1-6. DOI: 10.1155/2013/128907\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003eHsieh MH, Breyer BN, Eisenberg ML, et al\u003c/strong\u003e (2008) Associations among hypospadias, cryptorchidism, anogenital distance, and endocrine disruption. Curr Urol Rep. 9: 137-142. DOI: 10.1007/s11934-008-0025-0\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003eMecarini F, Fanos V, Crisponi G\u003c/strong\u003e (2021) Genital anomalies in newborns. J Perinatol. 41(9): 2124-2133. doi: 10.1038/s41372-021-00991-1\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003eGaspari L, Paris F, Jandel C, et al (\u003c/strong\u003e2011) Prenatal environmental risk factors for genital malformations in a population of 1442 French male new-borns:a nested case\u0026ndash;control study. Hum Reprod. 26:3155-3162. doi: 10.1093/humrep/der283\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003eDean A, Sharpe RM\u003c/strong\u003e (2013) Clinical review:Anogenital distance or digit length ratio as measures of fetal androgen exposure: relationship to male reproductive developme. J Clin Endocrinol Metab. Jun;98(6):2230-8. DOI: 10.1210/jc.2012-4057\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003eWelsh M, Saunders PT, Fisken M, et al\u003c/strong\u003e (2008) Identification in rats of a programming window for reproductive tract masculinization, disruption of which leads to hypospadias and cryptorchidism. J Clin Invest. 118:1479-1490. DOI: 10.1172/JCI34241\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003eThankamony A, Lek N, Carroll D, et al\u003c/strong\u003e (2014) Anogenital distance and penile length in infants with hypospadias or cryptor\u0026shy;chidism: comparison with normative data. Environ Health Perspect. 122:207-211. DOI: 10.1289/ehp.1307178\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003ePapadopoulou E, Vafeiadi M, Agramunt S, et al\u003c/strong\u003e (2013) Anogenital distances in newborns and children from Spain and Greece: predictors, tracking and reliability. Paediatr Perinat Epidemiol. 27:89-99. DOI: 10.1111/ppe.12022\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003eJiang DP\u003c/strong\u003e\u003cstrong\u003e, \u003c/strong\u003e\u003cstrong\u003eGeng HQ\u003c/strong\u003e\u003cstrong\u003e, \u003c/strong\u003e\u003cstrong\u003eLin HW\u003c/strong\u003e\u003cstrong\u003e, \u003c/strong\u003e\u003cstrong\u003eet al\u003c/strong\u003e (2015) Relationship between anogenital distance and cryptorchidism in human newborns. Nat J. Androl. 21(5): 432-435. \u003cu\u003ePMID: 26117942\u003c/u\u003e\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003eJain VG\u003c/strong\u003e\u003cstrong\u003e, \u003c/strong\u003e\u003cstrong\u003eSingal AK\u003c/strong\u003e (2013) Shorter anogenital distance correlates with undescended testis: a detailed genital anthropometric analysis in human newborns. Hum Repord. 28(9): 2343-9. doi: 10.1093/humrep/det286\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003eEisenberg ML, Shy M, Walters RC, et al\u003c/strong\u003e (2012) The relationship between anogenital distance and azoospermia in adult men. Int J Androl. 35: 726-730. doi: 10.1111/j.1365-2605.2012.01275.x\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003eMendiola J, Stahlhut RW, Jorgensen N, et al\u003c/strong\u003e (2011) Shorter anogenital distance predicts poorer semen quality in young men in Rochester, New York. Environ Health Perspect. 119: 958- 963. doi: 10.1289/ehp.1103421\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003eSuzuki Y, Yoshinaga J, Mizumoto Y, et al\u003c/strong\u003e (2012) Foetal exposure to phthalate esters and anogenital distance in male newborns. Int J Androl. 35:236-244. doi: 10.1111/j.1365-2605.2011.01190.x\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003eQian Y, Shao H, Ying X, et al\u003c/strong\u003e (2020) The Endocrine Disruption of Prenatal Phthalate Exposure in Mother and Offspring. Front Public Health. 28: 8-366. doi: 10.3389/fpubh.2020.00366\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003eYesildemir O, Celik MN\u003c/strong\u003e (2024) The Effect of Various Environmental Pollutants on the Reproductive Health in Children: A Brief Review of the Literature. Curr Nutr Rep. 13(3): 382-392. doi: 10.1007/s13668-024-00557-5\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003eLong M, Wiels\u0026oslash;e M, Bonefeld-Jorgensen EC\u003c/strong\u003e (2022) Dioxin-like Activity in Pregnant Women and Indices of Fetal Growth: The ACCEPT Birth Cohort. Toxics. 8: 10(1)- 26. doi: 10.3390/toxics10010026\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable (1):\u0026nbsp;\u003c/strong\u003eDemographic data of the studied groups\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroups\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eControls (n=150)\u003c/p\u003e\n \u003cp\u003ePatients (n=150)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge\u0026nbsp;\u003c/strong\u003e(months)\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 95px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eWeight\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e(kg)\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLength\u0026nbsp;\u003c/strong\u003e(cm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePenile length\u003c/strong\u003e(cm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAGD\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e(mm)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eI:\u0026nbsp;\u003c/strong\u003e1-6 m\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eControls\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e(n=43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e3.26 \u0026plusmn; 1.92\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 95px;\"\u003e\n \u003cp\u003e5.22 \u0026plusmn; 1.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e58.96 \u0026plusmn; 4.31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e3.68 \u0026plusmn; 0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e33.27 \u0026plusmn; 3.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePatients\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e(n=60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e3.42 \u0026plusmn; 1.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 95px;\"\u003e\n \u003cp\u003e5.89 \u0026plusmn; 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e59.93 \u0026plusmn; 4.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e3.67 \u0026plusmn; 0.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e31 \u0026plusmn; 2.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP value\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e0.215\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 95px;\"\u003e\n \u003cp\u003e0.990\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e0.418\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e0.971\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e0.024\u003cstrong\u003e*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eII:\u0026nbsp;\u003c/strong\u003e6-12 m\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eControls\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e(n=57)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e9.54 \u0026plusmn; 1.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 95px;\"\u003e\n \u003cp\u003e8.92 \u0026plusmn; 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e71.92 \u0026plusmn; 4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e3.82 \u0026plusmn; 0.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e37.95 \u0026plusmn; 5.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePatients\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e(n=42)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e9.26 \u0026plusmn; 1.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 95px;\"\u003e\n \u003cp\u003e8.6 \u0026plusmn; 0.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e71.7 \u0026plusmn; 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e3.79 \u0026plusmn; 0.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e35.8 \u0026plusmn; 4.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP value\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e0.123\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 95px;\"\u003e\n \u003cp\u003e0.990\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e0.770\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e0.092\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e0.001\u003cstrong\u003e*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eIII:\u0026nbsp;\u003c/strong\u003e12-18 m\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eControls\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e(n=18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e14.2 \u0026plusmn; 1.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 95px;\"\u003e\n \u003cp\u003e10.8 \u0026plusmn; 1.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e81\u0026plusmn; 3.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e3.9 \u0026plusmn; 0.24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e41.3 \u0026plusmn; 1.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePatients\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e(n=17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e14.9 \u0026plusmn; 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 95px;\"\u003e\n \u003cp\u003e10.4 \u0026plusmn; 0.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e80.3 \u0026plusmn; 2.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e3.9 \u0026plusmn; 0.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e39.8 \u0026plusmn; 1.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP value\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e0.250\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 95px;\"\u003e\n \u003cp\u003e0.305\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e0.884\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e0.788\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e0.003\u003cstrong\u003e*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eIV:\u0026nbsp;\u003c/strong\u003e18-24 m\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eControls\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e(n=32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e22.25 \u0026plusmn; 1.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 95px;\"\u003e\n \u003cp\u003e12.7 \u0026plusmn; 0.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e86.4 \u0026plusmn; 3.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e4.5 \u0026plusmn; 0.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e44 \u0026plusmn; 1.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePatients\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e(n=31)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e21.8 \u0026plusmn; 1.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 95px;\"\u003e\n \u003cp\u003e12.6 \u0026plusmn; 0.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e86.2 \u0026plusmn; 1.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e4.6 \u0026plusmn; 0.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e40 \u0026plusmn; 1.86\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP value\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e0.354\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 95px;\"\u003e\n \u003cp\u003e0.162\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e0.941\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e0.846\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e0.001\u003cstrong\u003e*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eTable (2)\u003c/strong\u003e: Site of the undescended testes in the patients\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"615\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 127px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSite of the testis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 162px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCryptorchidism without hypospadias\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en=54\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 150px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCryptorchidism with hypospadias n=96\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eChi-Square\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 127px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e1.Upper scrotal:\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRt testis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLt testis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRt testis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLt testis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"4\" valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e48.890\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"4\" style=\"width: 74px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.001\u003cstrong\u003e*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e5\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e11\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e31\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e34\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 127px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e2. Inguinal:\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 127px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e3. Un-palpable:\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e5\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eTable (3):\u0026nbsp;\u003c/strong\u003eComparison between the groups\u0026rsquo; AGD (controls and patients with or without hypospadias\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"656\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eParameter\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eControls\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en=150\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(Mean \u0026plusmn; SD)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 156px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCryptorchidism without hypospadias\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en=54\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(Mean \u0026plusmn; SD)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCryptorchidism with hypospadias\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en=96\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(Mean \u0026plusmn; SD)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eF value\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eANOVA\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAGD (mm):\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e37.9 \u0026plusmn; 5.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 156px;\"\u003e\n \u003cp\u003e35.8 \u0026plusmn; 4.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e34.5 \u0026plusmn; 4.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e18.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75px;\"\u003e\n \u003cp\u003e0.001\u003cstrong\u003e*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\" style=\"width: 656px;\"\u003e\n \u003cul\u003e\n \u003cli\u003e\u003cstrong\u003ePost Hoc analysis (Tukey\u0026rsquo;s test)\u003c/strong\u003e on results of one-way ANOVA on comparison between the above groups:\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eShows the significant difference was between the patient\u0026rsquo;s group of cryptorchidism with hypospadias and the other 2 groups (P = 0.001*).\u003c/li\u003e\n \u003cli\u003eWith no significant difference between controls and patients\u0026rsquo; group of cryptorchidism without hypospadias (P = 0.951). \u0026nbsp;\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eTable (4):\u0026nbsp;\u003c/strong\u003eComparison between the patients\u0026rsquo; AGD and site of their testis\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"642\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLt testis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUpper scrotal\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en=45\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(Mean \u0026plusmn; SD)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eInguinal\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en=23\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(Mean \u0026plusmn; SD)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eUnpalpable\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en=7\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(Mean \u0026plusmn; SD)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eF value\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eANOVA\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAGD (mm):\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e39.4 \u0026plusmn; 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e37.8 \u0026plusmn; 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e35.4 \u0026plusmn; 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e4.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96px;\"\u003e\n \u003cp\u003e0.01\u003cstrong\u003e*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\" style=\"width: 642px;\"\u003e\n \u003cul\u003e\n \u003cli\u003e\u003cstrong\u003ePost Hoc analysis (Tukey\u0026rsquo;s test)\u003c/strong\u003e on results of one-way ANOVA on comparison between the above groups:\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eShows the significant difference was between the upper scrotal and inguinal positions of the left testis (P = 0.028*).\u003c/li\u003e\n \u003cli\u003eWith no significant difference between the unpalpable testis and both inguinal and upper scrotal positions of the left testis (P = 0.743 and 0.173 respectively). \u0026nbsp;\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRt testis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUpper scrotal\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en=36\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(Mean \u0026plusmn; SD)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eInguinal\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en=26\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(Mean \u0026plusmn; SD)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eUnpalpable\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en=13\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(Mean \u0026plusmn; SD)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eF value\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eANOVA\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAGD (mm):\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e37.8 \u0026plusmn; 3.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e35 \u0026plusmn; 4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e34.8 \u0026plusmn; 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e7.178\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96px;\"\u003e\n \u003cp\u003e0.001\u003cstrong\u003e*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\" style=\"width: 642px;\"\u003e\n \u003cul\u003e\n \u003cli\u003e\u003cstrong\u003ePost Hoc analysis (Tukey\u0026rsquo;s test)\u003c/strong\u003e on results of one-way ANOVA on comparison between the above groups:\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eShows the significant difference was between the upper scrotal and inguinal positions of the right testis (P = 0.001*).\u003c/li\u003e\n \u003cli\u003eWith no significant difference between the unpalpable testis and both inguinal and upper scrotal positions of the right testis (P = 0.170 and 0.990 respectively). \u0026nbsp;\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"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":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Cryptorchidism, Anogenital Distance, Hypospadias","lastPublishedDoi":"10.21203/rs.3.rs-5822825/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5822825/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eAnogenital distance (AGD) may indicate hypoverilization and subsequently serve as a predictor future reproduction. In both undescended testis with and without hypospadias, our goal was to study the relationship between testicular position and AGD.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eFrom March 2021 to January 2023, the study was conducted on male infants with and without hypospadias and age-matched controls. Based on the infants' ages, we divided them into four. Group I: under six months, Group II: 7\u0026ndash;12 months, Group III: between a year and eighteen months, and Group IV: 19 months up to two years of age. From the verge of the anus to the penile base, the AGD was measured. Clinical examination resulted in the classification of testicular location as high scrotal, inguinal, and non-palpable.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003ePatients with cryptorchidism had AGD means that were substantially lower than those of controls in Groups I, II, III, and IV, respectively (31\u0026thinsp;\u0026plusmn;\u0026thinsp;2, 33\u0026thinsp;\u0026plusmn;\u0026thinsp;3), (35.9\u0026thinsp;\u0026plusmn;\u0026thinsp;4, 37.9\u0026thinsp;\u0026plusmn;\u0026thinsp;5), (39.9\u0026thinsp;\u0026plusmn;\u0026thinsp;1.2, 41\u0026thinsp;\u0026plusmn;\u0026thinsp;1.5), and (40\u0026thinsp;\u0026plusmn;\u0026thinsp;1.9, 44\u0026thinsp;\u0026plusmn;\u0026thinsp;1.7). The group of patients with cryptorchidism and hypospadias differed significantly from the controls and those without hypospadias. AGD in patients with upper scrotal locations was substantially shorter. Penile length and AGD of the examined groups exhibited a positive and significant connection.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eShorter AGD is linked to a higher prevalence of hypospadias and cryptorchidism in male babies in comparison to normal children. The position of the undescended testis is higher in relation to a shorter AGD.\u003c/p\u003e","manuscriptTitle":"Relationship between Anogenital Distance and Testicular Position in Male Infants with Cryptorchidism with and without Hypospadias","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-01-20 09:52:07","doi":"10.21203/rs.3.rs-5822825/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"17dcc0e4-3cb9-4156-8e4a-cbb5de6d3667","owner":[],"postedDate":"January 20th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-03-24T16:09:48+00:00","versionOfRecord":{"articleIdentity":"rs-5822825","link":"https://doi.org/10.1007/s11255-025-04429-x","journal":{"identity":"international-urology-and-nephrology","isVorOnly":false,"title":"International Urology and Nephrology"},"publishedOn":"2025-03-18 15:58:21","publishedOnDateReadable":"March 18th, 2025"},"versionCreatedAt":"2025-01-20 09:52:07","video":"","vorDoi":"10.1007/s11255-025-04429-x","vorDoiUrl":"https://doi.org/10.1007/s11255-025-04429-x","workflowStages":[]},"version":"v1","identity":"rs-5822825","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5822825","identity":"rs-5822825","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}