Calcinosis escrotal: ¿una entidad idiopática? / Scrotal Calcinosis: an Idiopathic Entity?

La calcinosis escrotal es una enfermedad benigna e infrecuente que se presenta en adultos de mediana edad, con múltiples nódulos asintomáticos a nivel de la piel del escroto. Algunos autores vinculan la aparición de estas lesiones a la calcificación secundaria de quistes epidérmicos o ecrinos. Cuando no se encuentra relacionada con dichas entidades ni con alteraciones del metabolismo fosfocálcico, el cuadro se considera idiopático. El tratamiento de elección es quirúrgico, en caso de impacto en la calidad de vida o relevancia estética para el paciente. (AU)

Scrotal calcinosis is a rare, benign disease that presents in middle-aged adults with multiple asymptomatic nodules on the skin of the scrotum. Some authors link the appearance of these lesions to the secondary calcification of epidermal or eccrine cysts. When it is not related to these entities or to alterations in phosphocalcic metabolism, the condition is considered idiopathic. The treatment of choice is surgical, in case of impact on the quality of life or aesthetic relevance for the patient. (AU)

The importance of updated criteria in breeding soundness examination of commercial Nellore bulls for the herd reproductive improvement / [Importância de critérios atualizados na avaliação andrológica de touros Nelore a campo para a evolução reprodutiva do rebanho]

The aim of this work was to compare results of breeding soundness examination (BSE) of Nellore bulls (n=1257) according to evaluation criteria from two different classification tables (traditional-Table1 used since 1997 and an updated-Table2-proposed in 2020). Data were separated into 3 categories: questionable animals in Table1 and Table2 (Q1Q2), animals approved in Table1 and questionable in Table2 (A1Q2) and animals approved in Table1 and Table2 (A1A2). BSE parameters were submitted to ANOVA (P<005), according to age groups. Higher (P<0.0001) scrotal perimeter (PE) were observed in A1A2 category (18-24m=33.4±2.4cm; 24-36m=34.5±2.2cm; 36-48m=36.6±1.7cm; >48m=38.6±1.7cm) compared to A1Q2 (18-24m=29.05±0.98cm; 24-36m=30.3±0.6cm; 36-48m=32.9±1.0cm; >48m=34.8±1.0cm) and to Q1Q2 (24-36m=26.8±2.0cm; 36-48m=30.0±0.1cm; >48m=31.3±1.1cm), for all age groups. At the age of 36-48months (Q1Q2=2.7±0.3; A1Q2=3.2±0.3; A1A2=3.3±0.6) and >48months (Q1Q2=3.0±0.4; A1Q2=3.3±0.5; A1A2=3.4±0.5), animals with better andrological classifications presented higher (P<0.05) body condition score (BCS). Additionally, at age >48m, higher sperm Motility (P=0.0250) and Vigor (P=0.0335) were observed in animals A1Q2 (Mot=55.5±14.7%; V=3.21±0.82) and A1A2 (Mot=55.8±12.2%; V=3.23±0.81) compared to Q1Q2 (Mot=50.2±17.4%; V=2.77±0.82). It was concluded that bulls approved using strict selection criteria demonstrated higher PE and BCS, regardless of the age. The utilization of updated classification tables is highly recommended for further reproductive potential development of Nellore bulls in the field.(AU)

O objetivo deste estudo foi comparar os resultados obtidos no exame andrológico a campo de touros Nelore (n=1257) de acordo com os critérios de avaliação de duas tabelas de classificação (uma tabela tradicional - tabela 1 - proposta em 1997 e uma nova tabela atualizada - tabela 2 - proposta em 2020). Os dados foram separados em três categorias: animais questionáveis nas tabelas 1 e 2 (Q1Q2), animais aprovados na tabela 1 e questionáveis na tabela 2 (A1Q2) e animais aprovados nas tabelas 1 e 2 (A1A2). Os parâmetros foram submetidos à análise de variância (P<0,05), por faixa etária. Observou-se maior (P<0,0001) PE no grupo A1A2 (18-24m=33,4±2,4cm; 24-36m=34,5±2,2cm; 36-48m=36,6±1,7cm; >48m=38,6±1,7cm) em comparação ao grupo A1Q2 (18-24m=29,05±0,98cm; 24-36m=30,3±0,6cm; 36-48m=32,9±1,0cm; >48m=34,8±1,0cm) e este maior (P<0,0001) que Q1Q2 (24-36m=26,8±2,0cm; 36-48m=30,0±0,1cm; >48m=31,3±1,1cm) em todas as idades. Nas faixas etárias 36-48m (Q1Q2=2,7±0,3; A1Q2=3,2±0,3; A1A2=3,3±0,6) e >48m (Q1Q2=3,0±0,4;A1Q2=3,3±0,5; A1A2=3,4±0,5), animais com melhor classificação andrológica apresentaram melhor (P<0,05) escore de condição corporal (ECC). Adicionalmente, na idade >48m, maiores motilidade (P=0,0250) e vigor (P=0,0335) foram observados nos animais A1Q2 (Mot=55,5±14,7%; V=3,21±0,82) e A1A2 (Mot=55,8±12,2%; V=3,23±0,81) comparados aos animais Q1Q2 (Mot=50,2±17,4%; V=2,77±0,82). Concluiu-se que touros aprovados na tabela com critérios mais rigorosos de classificação (tabela 2) apresentaram maior PE e ECC, independentemente da idade. Assim, a utilização de tabelas classificatórias atualizadas é fundamental para maior desenvolvimento do potencial reprodutivo de touros Nelore a campo.(AU)

The association between anogenital distance and benign prostatic hyperplasia related lower urinary tract symptoms in Chinese aging men.

PURPOSE: We conducted the study to investigate the relationship between anogenital distance (AGD) and benign prostatic hyperplasia (BPH) related lower urinary tract symptoms (LUTS). METHODS: From May 2018 to January 2020, 220 subjects: 110 men with BPH-related LUTS (BPH-LUTS group) and 110 men without any urination complaints (control group) were selected. Clinical questionnaires, detailed physical examinations, including AGDas (distance between the anus and posterior base of the scrotum) and AGDap (distance between the anus and upper penis) measurements, and blood tests were all assessed. RESULTS: The two groups were similar in terms of basic features (P > 0.05). The AGDap and AGDas in the control group were significantly shorter than the BPH-LUTS group (P < 0.001). Adjusted multivariate analyses showed that AGDas was significantly related to International Prostate Symptom Score (IPSS), post-voiding residual volume (PVR), total prostate volume (TPV) and maximum urine flow rate (Qmax) (P = 0.002, P = 0.009, P = 0.001, P = 0.028, respectively). However, the associations between AGDap and IPSS score, PVR, TPV, Qmax and total testosterone (TT) were all negligible (P > 0.05 for all). The associations between TT and BPH-LUTS related evaluations were also negligible (P > 0.05 for all). Furthermore, the study revealed that the AGDas cut-off values for mild, moderate, and severe symptom (based on IPSS score) in BPH-LUTS cases were 27.4 mm and 46.8 mm [area under curve (AUC): 0.802 and AUC: 0.779, respectively], respectively. CONCLUSION: Longer AGDas was related to more severe BPH related symptoms. It may be useful to consider AGD as a marker for BPH-LUTS. Further well-designed studies are remained to be done to explore the intriguing problem.

Potencial reprodutivo (PR) de touros Nelore avaliados por parâmetros andrológicos e comportamento sexual. Classificação por pontos: nova proposição / [Reproductive potential of Nelore bulls evaluated by andrological parameters and sexual behavior. Classification by points - a new proposition]

Este estudo teve por objetivo comparar variações de parâmetros andrológicos e comportamentais de touros Nelore de diferentes faixas etárias, calcular seu potencial reprodutivo (PR) e propor uma nova tabela de classificação por pontos, de acordo com as médias atualmente alcançadas por eles nas características estudadas. Foram utilizados dados de 6162 exames andrológicos de touros da raça Nelore, entre 12 e 80 meses de idade, em regime de monta natural. O número de touros classificados como aptos consistiu em 88,9% dos animais avaliados (n=5480), sendo 51,6% desses considerados excelentes (n=2827), 41,2% muito bons (n=2257) e 7,2% considerados bons (n=394). Entre os animais questionáveis (n=682; 11,1%), 79,6% foram classificados como inaptos temporários (n=542) e 20,4% (n=139) como animais descarte, de acordo com o exame andrológico, independentemente do teste da libido. O número de touros classificados como excelentes se reduziu para 752 (12,2%) quando dados de comportamento sexual foram incluídos para definição do seu PR. Concluiu-se que o uso de tabelas de classificação andrológica por pontos com atualizações técnicas beneficia a seleção mais apurada de touros Nelore. O teste da libido é ferramenta importante para a determinação do PR, o qual permite melhor aproveitamento dos reprodutores.(AU)

This study aimed to compare variations of andrological and behavioral parameters from Nelore bulls of different ages, to calculate their reproductive potential (RP) and propose a new classification table by points, considering current averages in each reproductive trait studied. Data were collected from 6162 breeding soundness examinations of Nelore bulls aged between 12 and 80 months, under natural mating. According to andrological parameters, regardless of the libido test, the number of bulls classified as approved was 88.9% (n= 5480), being 51.6% considered as excellent (n= 2827), 41.2% very good (n= 2257) and 7.2% considered as good (n= 394). Among the animals considered as questionable (n= 682; 11.1%), 79.6% were classified as temporarily reproved (n= 542) and 20.4% (n= 139) as discarded animals. The number of bulls classified as excellent decreased to 752 (12.2%) when sexual behavior data were included to define their RP. It was concluded that the use of tables for andrological classification by points with technical updates improves the reproductive selection of Nelore bulls. The libido test is an important tool for RP determination which provides better utilization of the sires.(AU)

Short anogenital distance is associated with testicular germ cell tumour development.

BACKGROUND: Testicular germ cell tumour is a multifactorial disease in which various genetic and environmental factors play a role. Testicular germ cell tumour is part of the testicular dysgenesis syndrome which includes also cryptorchidism, hypospadias, oligo/azoospermia and short anogenital distance. OBJECTIVES: The primary objective was to examine anogenital distance in testicular germ cell tumour cases and healthy fertile controls. The secondary objective was to assess the (CAG)n polymorphism of the Androgen Receptor gene in relationship with anogenital distances and testicular germ cell tumour development. MATERIAL AND METHODS: 156 testicular germ cell tumour patients and 110 tumour-free normozoospermic controls of Spanish origin. All subjects underwent full andrological workup (including semen and hormone analysis) and genetic analysis (Androgen Receptor (CAG)n). The main outcome measures were the anopenile distance (AGDap), the anoscrotal distance (AGDas) and AR(CAG)n. RESULT: We observed significantly shorter anogenital distances in the group of testicular germ cell tumour patients in respect to controls (P < .001) independently from sperm count and testis histology. Threshold values, applicable only to our cohort, were calculated for anogenital distances with the best sensitivity and specificity. Subjects with AGDap and AGDas below threshold showed a significantly increased risk for testicular germ cell tumour (OR = 4.97, 95% CI = 2.01-12.33, P = .001 and OR = 4.11, 95% CI = 1.89-8.92, P ≤ .001, respectively). No significant correlation was observed between AR(CAG)n polymorphism and anogenital distances. The median values of the AR(CAG)n were similar between cases and controls, excluding a major role for this polymorphism in the etiopathogenesis of these testicular dysgenesis syndrome components. CONCLUSIONS: Ours is the first study focusing on anogenital distances in testicular germ cell tumour patients. We identified short anogenital distances (which is a surrogate biomarker of androgen action during foetal life) as a significant risk factor for this disease. After further validation of our preliminary data, anogenital distance measurement could become part of testicular germ cell tumour screening in order to better define those individuals who would benefit from long-term active follow-up.

The relationship between premature ejaculation and anogenital distance.

Premature ejaculation is a common male sexual disease in andrology practice. The goal of essay is to investigate the relation of anogenital distance that predicts prenatal testosterone exposure with premature ejaculation. Between January and May 2019, 150 men were participated in the study. The patients were evaluated with anamnesis and physical examination; age, smoking, alcohol consumption, intravaginal ejaculation latency time, body mass index, premature ejaculation diagnostic tool, distance from anal point to scrotum and distance from anal point to penis were recorded. According to premature ejaculation diagnostic tool score, the patients were classified as premature ejaculation group (score ≥11) and control group (score <11). The mean of the male age was 30.73 ± 4.40 years. The mean intravaginal ejaculation latency time score was 3.42 ± 2.71 min. Two groups were compared using the distance from anal point to scrotum distance from anal point to penis. In the premature ejaculation group, the distances were found lower (77.46 ± 2.31 and 54.78 ± 2.56 mm) than the control group (81.32 ± 3.11 and 58.16 ± 3.48 mm). There were statistical differences between two groups (p < .001). It was concluded that it is likely to have a negative relationship between anogenital distance and premature ejaculation diagnostic tool score.

Effects of an anti-gonadotrophin releasing hormone vaccine on the morphology, structure and function of bull testes.

Castration reduces aggressive and sexual behaviour and provides better carcass quality in bull calves. Vaccination against gonadotrophin-releasing hormone (GnRH) is used as an alternative to surgical castration for the purposes of reducing pain and distress in the animals. Currently, no anti-GnRH vaccine has been authorized for use in cattle in the European Union. The aim of the present study was to assess the effect of an anti-GnRH swine-specific vaccine (Improvac®, Zoetis, USA) on the morphology, structure and function of bull testes. Animals were vaccinated at days 1, 21 and 104 of the experimental period and were classified based on their live weight into the following two groups: LIGHT (172.9 ±â€¯30.00 kg) and HEAVY (323.8 ±â€¯37.79 kg). The scrotal circumference was measured on day 1 and prior to slaughter (day 164). At slaughter, the sperm motility and concentration in the caudae epididymis were assessed. Testes were weighed, measured and examined using ultrasound, and then tissue samples were collected and fixed in formalin. Histological and immunohistochemical studies were performed on the testes to measure the diameter of the seminiferous tubules and assess the testicular cell populations. The results revealed that suppression of testicular development was associated with the use of the Improvac® vaccine, which resulted in a smaller size of the testes and impaired spermatid production. However, the effect of Improvac® was more pronounced and consistent in calves vaccinated at a low live weight than at a heavy live weight, which suggested that vaccination is more effective when calves are vaccinated before or early during puberty. However, testes from calves vaccinated at a low live weight were more prone to the development of intraluminal concretions in the seminiferous tubules.

Anogenital distance in children born of mothers with polycystic ovary syndrome: the Odense Child Cohort.

STUDY QUESTION: Are higher testosterone levels during pregnancy in women with polycystic ovary syndrome (PCOS) associated with longer offspring anogenital distance (AGD)? SUMMARY ANSWER: AGD was similar in 3-month-old children born of mothers with PCOS compared to controls. WHAT IS KNOWN ALREADY: AGD is considered a marker of prenatal androgenization. STUDY DESIGN, SIZE, DURATION: Maternal testosterone levels were measured by mass spectrometry at Gestational Week 28 in 1127 women. Maternal diagnosis of PCOS before pregnancy was defined according to Rotterdam criteria. Offspring measures included AGD from anus to posterior fourchette (AGDaf) and clitoris (AGDac) in girls and to scrotum (AGDas) and penis (AGDap) and penile width in boys and body composition (weight and BMI SD scores) at age 3 months. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study was part of the prospective study, Odense Child Cohort (OCC), and included mothers with PCOS (n = 139) and controls (n = 1422). The control population included women with regular menstrual cycles (<35 days) before conception and no signs of androgen excess (hirsutism and/or acne). MAIN RESULTS AND THE ROLE OF CHANCE: AGD measures were comparable in offspring of women with PCOS compared to controls (all P > 0.2) despite significantly higher maternal levels of total testosterone (mean: 2.4 versus 2.0 nmol/l) and free testosterone (mean: 0.005 versus 0.004 nmol/l) in women with PCOS versus controls (both P < 0.001). In women with PCOS, maternal testosterone was an independent positive predictor of offspring AGDas and AGDap in boys. Maternal testosterone levels did not predict AGD in girls born of mothers with PCOS or in boys or girls born of women in the control group. LIMITATIONS, REASONS FOR CAUTION: The diagnosis of PCOS was based on retrospective information and questionnaires during pregnancy. Women participating in OCC were more ethnically homogenous, leaner, more educated and less likely to smoke compared to the background population. Our study findings, therefore, need to be reproduced in prospective study cohorts with PCOS, in more obese study populations and in women of other ethnicities. WIDER IMPLICATIONS OF THE FINDINGS: Our finding of the same AGD in girls born of mothers with PCOS compared to controls expands previous results of studies reporting longer AGD in adult women with PCOS. Our results suggest that longer AGD in adult women with PCOS could be the result of increased testosterone levels in puberty, perhaps in combination with weight gain. STUDY FUNDING/COMPETING INTEREST(S): Financial grants for the study were provided by the Danish Foundation for Scientific Innovation and Technology (09-067180), Ronald McDonald Children Foundation, Odense University Hospital, the Region of Southern Denmark, the Municipality of Odense, the Mental Health Service of the Region of Southern Denmark, The Danish Council for Strategic Research, Program Commission on Health, Food and Welfare (2101-08-0058), Odense Patient data Explorative Network, Novo Nordisk Foundation (grant no. NNF15OC00017734), the Danish Council for Independent Research and the Foundation for research collaboration between Rigshospitalet and Odense University Hospital and the Health Foundation (Helsefonden). There is no conflict of interest of any author that could be perceived as prejudicing the impartiality of the research reported.

[Study of anogenital distance as a diagnostic tool for prostate cancer]. / Análisis de la distancia anogenital como herramienta diagnóstica del cáncer de próstata.

INTRODUCTION AND OBJECTIVE: The distance from the genitals to the anus (anogenital distance [AGD]) reflects androgen concentration during prenatal development in mammals. At the present time, there is only one study suggesting the relationship between AGD and risk of prostate cancer (CaP). The goal of this study was to assess the performance and clinical utility of AGD, as a biomarker of prenatal androgenic milieu, and risk of CaP in a larger population, in CaP diagnosis. MATERIAL AND METHODS: A case-control study was conducted on 260 men seen in a hospital outpatient clinic where underwent a physical and andrological examination and completed a brief questionnaire. CaP patients were confirmed by biopsy of the tumor. Controls were men without CaP seen in the urology outpatient clinic for routine examinations. Two variants of AGD (from the anus to the posterior base of the scrotum [AGDAS] and to the cephalad insertion of the penis [AGDAP]) were measured. Parametric and non-parametric tests and receiver operating characteristic (COR) analyses were used to determine relationships between AGD and presence of CaP. RESULTS: The highest area under the curve (0.69; 95% CI 0.60 to 0.78 and 0.69; 95% CI 0.61 to 0.77) was obtained for the Gleason=7 subgroup with the AGDAS and AGDAP measurement, with a sensitivity and specificity of 83% and 55%, and 91% and 41%, the predictive positive value of 39% and 35% and negative value of 90% and 93% respectively. CONCLUSION: AGD may be a useful clinical tool for the CaP diagnosis.

[Prostate cancer is associated with the anogenital distance, a biomarker of prenatal androgen milieu.] / El cáncer de próstata está asociado con la distancia anogenital, un biomarcador del ambiente androgénico prenatal.

OBJECTIVE: To evaluate the associationbetween anogenital distance (AGD), as a biomarker ofprenatal androgen milieu, and risk of prostate cancer(PCa). METHODS: A case-control study was conducted on260 men attending a university hospital where theyunderwent physical and andrological examination andcompleted a brief questionnaire. PCa patients were confirmedby biopsy of the tumor. Controls were men withoutPCa attending the urology outpatient clinic for routineexaminations. Two variants of AGD [from the anus to theposterior base of the scrotum (AGDAS) and to the cephaladinsertion of the penis (AGDAP)] were measured.Unconditional multiple logistic regression was used toestimate the association between AGD measurementsand presence of PCa, and Odds Ratios and 95% confidenceintervals (CI) were calculated. RESULTS: Cases showed significantly shorter AGDAPand AGDAS than controls. Subjects with AGDAP andAGDAS in the lowest compared to the upper tertile were2.6 times (95% CI 1.2-5.6) and 3.2 times (95% CI 1.5-6.9) more likely to have PCa, respectively. CONCLUSIONS: We found that shorter measurementsof both distances (AGDAS and AGDAP) were associatedwith higher risk of PCa. A previous study reportedsimilar results, showing that longer AGDAP was associatedwith lower risk of PCa, but this relationship was notfound for AGDAS, as it was in our study with a largersample size.

OBJETIVO: Evaluar la asociación entre la distancia anogenital (AGD) como biomarcador de la ventana androgénica prenatal y el riesgo de padecer cáncer de próstata (PCa).MATERIAL Y MÉTODO: Estudio de casos y controles realizado en 260 pacientes. Todos los pacientes fueron sometidos a examen físico y andrológico y completaron un breve cuestionario. Los pacientes con PCa tenían diagnóstico histológico por biopsia prostática. Los controles fueron varones sin sospecha de PCa que acudieron a la consulta externa de Urología para exámenes rutinarios. Se midieron dos variantes de AGD [del ano a la base posterior del escroto (AGDAS) y del ano a la inserción dorsal del pene (AGDAP)]. Se utilizóanálisis de regresión logística múltiple para estimar la asociación entre las medidas de AGD y la presencia de PCa. Se calcularon Odds Ratios (ORs) e intervalos de confianza (IC) 95%. RESULTADOS: Los casos mostraron unas AGDAP y AGDAS  significativamente más cortas que los controles.Los pacientes con AGDAP y AGDAS en el tercil inferior comparado con los pacientes del tercil superior mostraron 2,6 (IC 95% 1,2-5,6) y 3,2 veces (IC 95% 1,5-6,9) más riesgo, respectivamente, de padecer PCa. CONCLUSIONES: Encontramos que las medidas acortadas de ambas AGDs se asociaron con un mayor riesgo de padecer PCa. Un estudio previo obtuvo resultados similares, mostrando que una AGDAP alargada se asoció con un menor riesgo de padecer PCa, pero noobservó ninguna relación con respecto a la AGDAS, como sí objetivamos en este estudio con un mayor tamaño muestral.

Anogenital distance is associated with semen quality but not reproductive hormones in 1106 young men from the general population.

STUDY QUESTION: Is anogenital distance (AGD) associated with semen quality and reproductive hormones in men from the general population? SUMMARY ANSWER: Short AGD measured from the anus to the base of scrotum (AGDAS) was associated with reduced sperm counts and morphology but not with sperm motility or reproductive hormones. WHAT IS KNOWN ALREADY: AGD is longer in males than in females. In rodents, AGD is a well-established and sensitive marker of disruption during the masculinization programming window in utero and it has been suggested to be so in humans as well. Therefore, the average AGD would be expected to be shorter in men with poor semen quality, which some studies have confirmed while others have not. STUDY DESIGN, SIZE, DURATION: This cross-sectional population-based study was of 1106 men included between 2012 and 2016. PARTICIPANTS/MATERIALS, SETTING, METHODS: Men from the general Danish population (median age 19 years), unselected with regard to fertility status and semen quality, delivered a semen sample, had a blood sample drawn, which was analyzed for concentrations of reproductive hormones, and answered a comprehensive questionnaire. They also had a physical examination performed including determination of AGD measured as the distance between anus and scrotum (AGDAS) and penis (AGDAP). Odds ratios (OR) and 95% CI were estimated for a man having abnormal semen parameters according to the World Health Organization's reference values or a low/high concentration of reproductive hormones (defined as the lowest or highest 10%) depending on AGD. AGD was categorized in four strata: ≤10th percentile, 10th-30th percentile, 30th-50th percentile and >50th percentile. MAIN RESULTS AND THE ROLE OF CHANCE: Men with the 10% shortest AGDAS had a more than doubled risk (OR: 2.19, 95% CI: 1.40-3.42) of being in the subfertile range for either sperm concentration (<15 million/mL) or sperm morphology (<4%) compared to men with AGDAS above the median (reference). Men in the 10th-30th percentile also had an increased OR of 1.48 (95% CI: 1.06-2.08) but not men in the 30th-50th percentile (OR: 1.14, 95% CI: 0.81-1.62). AGDAP was only weakly related to semen quality. AGD was not associated with testicular volume or any of the reproductive hormones. LIMITATIONS, REASONS FOR CAUTION: Limitations include the potential non-differential misclassification of reproductive outcomes based on a single semen and blood sample and some between-examiner differences in AGD measurements which introduces noise and may result in an underestimation of observed associations. WIDER IMPLICATIONS OF THE FINDINGS: Our study of men from the general population confirmed associations between AGD and semen quality, supporting the hypothesis that AGD in humans could be a marker of fetal testicular development. This suggests that the low semen quality in Danish men may partly be explained by prenatal factors. STUDY FUNDING/COMPETING INTEREST(S): The study has received financial support from the ReproUnion (L.P.); the Research fund of Rigshospitalet, Copenhagen University Hospital (N.J.); Grants R01ES016863-04 and R01ES016863-02S4; National Institute of Environmental Health Sciences (NIEHS) and National Institute of Environmental Health Sciences grant (P30ES023515) (S.S.); the European Union (Contract numbers BMH4-CT96-0314, QLK4-CT-1999-01422, QLK4-CT-2002-00603, FP7/2007-2013, DEER Grant agreement no. 212844); the Danish Ministry of Health; the Danish Environmental Protection Agency; A.P. Møller and wife Chastine McKinney Møllers foundation; and Svend Andersens Foundation. None of the funders had any role in the study design, collection, analysis or interpretation of data, writing of the paper or publication decisions. The authors have nothing to declare. TRIAL REGISTRATION NUMBER: N/A.

Anogenital distance is determined during early gestation in humans.

STUDY QUESTION: Does cord blood androgen level obtained at birth affect the AGD in human newborns? SUMMARY ANSWER: In human newborns, though males have a significantly longer AGD compared to females (as early as 22 weeks of gestation) the AGD is not affected by androgen levels at birth in both the sexes. WHAT IS KNOWN ALREADY: Animal studies have reported a critical time period in early fetal life, termed the masculinization programming window (MPW) during which AGD is fixed by in utero androgen action and is unaffected by testosterone levels later during gestation. Thus, AGD may serve as a lifelong biomarker of androgen exposure during this window. This MPW is hypothesized to occur in humans at 8-14 weeks of gestation during which AGD is fixed. The effect of androgens (testosterone) on AGD after the MPW in humans is not known. Furthermore, altered AGD has been associated with various human reproductive health disorders in both males and females. STUDY DESIGN, SIZE, DURATION: A prospective descriptive cohort study was performed using data from randomly selected neonates (n = 205) born at a single center over a period of 1 year (August 2015 to August 2016). PARTICIPANTS/MATERIALS, SETTING, METHODS: AGDs in male (n = 117) and female infants (n = 88) together with penile width, glans girth and stretched penile length were measured by trained caregivers. Gestation ranged from 22 to 41 weeks and infants were examined within 24 h of birth (within 48-72 h in very sick preterm infants after clinical stabilization). AGD-1 was measured from the center of the anus to the posterior base of scrotum in males or to the posterior fourchette in females. AGD-2 was measured from the center of the anus to the anterior base of the penis in males or to the clitoris in females. Sex steroid hormones (testosterone, 17-OH progesterone (17-OHP) and androstenedione) were measured in serum prepared from umbilical cord blood samples taken at birth, using liquid chromatography-tandem mass spectrometry. MAIN RESULTS AND THE ROLE OF CHANCE: Males had a significantly lower gestational age (mean ± SD; 34.6 ± 4.9 versus 36.1 ± 4.1 weeks, P = 0.04), and a significantly longer AGD-1 (mean ± SD; 21.6 ± 6.0 versus 12.7 ± 3.8 mm, P < 0.001) and AGD-2 (41.9 ± 8.7 versus 33.9 ± 7.1 mm, P = 0.004) compared to female infants, respectively. The cord serum testosterone levels were significantly higher for male than female infants [median, interquartile range; 13.0 (7.3, 20.5) versus 4.1 (2.5, 5.9), ng/dl, P < 0.001]. There was no difference in levels of 17-OHP (P = 0.697) or androstenedione (P = 0.601) between the two sexes. On multiple regression analysis after adjusting for potential confounders, none of the AGD's in both males and females correlated with any sex steroid hormonal levels. We also provide normative charts for penile length, penile width and glans girth in preterm and term infants. LIMITATIONS, REASONS FOR CAUTION: No data were collected on family history of genital malformation, infertility or hormonal disorders, parental endocrine-disrupting chemical exposure or diet pattern, any of which might have influenced the AGD and/or sex steroid hormone levels in the offspring. WIDER IMPLICATIONS OF THE FINDINGS: Our results suggest that AGD in humans, like animals, is fixed in early gestation (likely during the hypothesized MPW) and is unaffected by androgen levels thereafter. Thus, AGD can serve as a biomarker of in utero androgen action during early gestation (likely 8-14 weeks) in humans. As such, causes of human newborn and adult reproductive health disorders, such as endocrine disruptors, should be explored during early gestation. However, further larger studies are needed to help corroborate these findings. STUDY FUNDING/COMPETING INTERESTS: No specific funding was obtained for this study, and all authors have no conflict of interest to declare.

Anogenital distance and reproductive outcomes in 9- to 11-year-old boys: the INMA-Granada cohort study.

BACKGROUND: Studies examining the association of anogenital distance (AGD), a biomarker of prenatal androgen exposure, with sexual development in children are lacking. OBJECTIVE: To assess the association between AGD measures and reproductive outcomes, including puberty onset, testicular volume, reproductive hormone levels, and urogenital malformations in boys aged 9-11 years. MATERIALS AND METHODS: A cross-sectional study was conducted among children belonging to the Spanish Environment and Childhood (INMA) Project, a population-based birth cohort study. The present sample included 279 boys for whom data were available on AGD, pubertal stage, testicular volume, and relevant covariates. Out of the boys with AGD data, 187 provided a blood sample for hormone analysis. AGD was measured from the center of the anus to the base of the scrotum. Pubertal development was assessed according to Tanner stage of genital development (G1-G5), and testicular volume was measured with an orchidometer. RESULTS: After adjusting for potential confounders, logistic regression analysis showed that AGD was positively associated with testicular volume but not with Tanner stage (>G1 vs. G1), serum hormone levels, or undescended testis. Regardless of their age, body mass index, and Tanner stage (G1 or >G1), boys with longer AGD showed increased odds of a testicular volume >3 mL (OR = 1.06, 95%CI = 1.00-1.19 per 10% increment in AGD; and OR = 3.14, 95%CI = 0.99-9.94 for AGD >42 mm vs. <33 mm). DISCUSSION: Longer AGD was associated with testicular growth, an indicator of gonadarche, but not with other reproductive outcomes. CONCLUSIONS: Although AGD was positively associated with testicular volume, it remains unclear whether AGD predicts testis size at puberty or is related to puberty onset.

Relationships of plasma insulin-like peptide 3, testosterone, inhibin, and insulin-like growth factor-I concentrations with scrotal circumference and testicular weight in Japanese Black beef bull calves.

This study was conducted to clarify the relationships of plasma concentrations of insulin-like peptide 3 (INSL3), testosterone, inhibin, and insulin-like growth factor-I (IGF-I) with scrotal circumference and testicular weight in Japanese Black beef bull calves (n = 20), from birth to pre-puberty. Monthly blood sampling (0 to 7 months) and scrotal circumference measurements (0 to 7 months) were performed. Testicular weight was recorded immediately after castration at 7 months. Plasma INSL3, testosterone, inhibin, and IGF-I concentrations were measured either by enzyme immunoassay or time-resolved fluorescence immunoassay. The correlation coefficients of these hormonal concentrations with scrotal circumference were significant (P < 0.0001) and it was higher for INSL3 (r = 0.647) than for testosterone (r = 0.597), IGF-I (r = 0.400), and inhibin (r = -0.453). Calves with heavier testes (> 60 g) at castration (7 months) had higher (P < 0.05) plasma INSL3 (from 3 to 7 months) and inhibin (from 1 to 4 months) concentrations than those with lighter testes (< 60 g). The calves with heavier testes at castration had larger (P < 0.05) scrotal circumference than those with lighter testes from 3 to 7 months. In conclusion, blood INSL3 concentrations may be the best functional indicator among the hormones analyzed for determining total testicular volume during pre-puberty in bull calves. In addition, inhibin and INSL3 concentrations in early calfhood may be functional predictors for testicular weight at pre-puberty.

Anatomy of genital reaffirmation surgery (male-to-female): Vaginoplasty using penile skin graft with scrotal flaps.

Gender reaffirmation surgery is the final step in an individual's transition to their preferred gender. A clear understanding of the anatomy pertinent to this procedure is essential by the surgeon and patient. In male-to-female transgenders, female genitalia is constructed using the individual's penile skin to form the neovaginal canal and their scrotal skin folds post orchiectomy to create the labia majora. The surgical precursors of the remaining anatomical structures of the female genitalia are as follows: the clitoris is crafted from the glans penis and hence retains its innervation, the labia minora is formed using excess penile skin tissue, and the long male urethra is shortened to that of its feminine counterpart. The main goal of these reconstructive methods is to create a functionally and aesthetically acceptable vagina and vulva, as well as normal voiding function and satisfactory sexual function. Surgical text descriptions were enhanced by the creation of new anatomic illustrations. Review of the relevant literature regarding the anatomy, procedure development, and outcomes is presented. Vaginoplasty utilizing penile skin grafts with scrotal flaps provides an aesthetically acceptable and psychologically satisfying results with normal voiding and sexual function. An advantage includes preserved erogenous sensation. Complications can arise, including chronic inflammation and fistula formation. The anatomy of vaginoplasty using penile skin grafts with scrotal flaps supports patients seeking male-to-female gender reaffirmation surgery. Clin. Anat. 31:140-144, 2018. © 2017 Wiley Periodicals, Inc.

Pediatric scrotal ultrasound: review and update.

In this pictorial essay the authors review the normal sonographic gray-scale and Doppler appearance of the pediatric scrotum with an emphasis on technique. The authors present an update on ultrasound diagnosis and outcomes in testicular torsion and differentiation from other acute scrotal processes, as well as sonographic imaging of testicular microlithiasis and uncommon or atypical scrotal masses including splenogonadal fusion, polyorchidism, meconium peritonitis and epidermoid cyst. Further, the authors discuss testicular neoplasms in the context of testicular microlithiasis.

Effect of breed, plane of nutrition and age on growth, scrotal development, metabolite concentrations and on systemic gonadotropin and testosterone concentrations following a GnRH challenge in young dairy bulls.

The onset of puberty in the bull is regulated by the timing of early GnRH pulsatility release from the hypothalamus, which has been demonstrated to be affected by plane of nutrition during calf-hood. The aim of this study was to determine the effect of plane of nutrition on growth rate, scrotal development, metabolite concentrations and exogenous gonadotrophin (GnRH) induced release of luteinizing hormone (LH), follicle stimulating hormone (FSH) and testosterone (TT) in pre-pubertal bulls of two contrasting dairy breeds. Holstein-Friesian and Jersey bull calves were assigned to either a high or low plane of nutrition from 3 to 49 weeks of age. Intensive blood sampling was conducted at 16, 24 and 32 weeks of age, every 15 min from 30 min prior to intravenous administration of exogenous GnRH to 135 min after. Monthly blood samples were also collected and analyzed for insulin like growth factor 1 (IGF-1), insulin, leptin, adiponectin and metabolite concentration. Insulin and IGF-1 were higher in bulls on a high plane of nutrition (P < 0.001) but were not affected by breed (P > 0.05). Leptin was not affected by plane of nutrition or breed (P > 0.05). Adiponectin tended to be higher in bulls on a high plane of nutrition (P = 0.05), but was not affected by breed (P > 0.05). Bulls on a high plane of nutrition had a greater concentration of LH in response to GnRH (P < 0.05) but there was no effect of breed (P > 0.05). FSH concentration was not influenced by breed or plane of nutrition but FSH concentrations did decrease with age (P < 0.01), while, LH was not affected by age (P > 0.05). Jersey bulls, particularly those on a high plane of nutrition, had higher TT production in the pre-pubertal period (P < 0.001). Using 28 cm as a proxy for age at puberty, bulls on a high plane of nutrition were predicted to reach puberty earlier than bulls on a low plane. In conclusion, the data clearly demonstrate that a high plane of nutrition positively affects several key nutritional and reproductive hormones which are critical to the endocrinological functionality of the hypothalamic-pituitary-testicular axis in dairy-bred bull calves.

Effect of racial crossing on the scrotum-testicular biometry in sheep submitted to scrotal insulation / Efeito do cruzamento racial sobre a biometria escroto-testicular em ovinos submetidos à insulação escrotal

The objective of this study was to evaluate the effect of the racial crossing on scrotum-testicular biometric characteristics of four sheep Santa Ines and four crossbred (Santa Ines x Dorper) submitted to scrotal insulation, following the return of these characteristics to values previously reported. For this, two measurements were made regarding the scrotal circumference (SC), length (L) and testicular width (W) before treatments. The testicular volume (V) was calculated by the formula V=2 [(r2) x π x H]. The pouches were made with double-layer plastic, internally lined with cotton, and fixed around the spermatic funiculus and scrotum with adhesive tape and bandage remaining in this position for seven days. Measurements were made every seven days, totaling 15 measurements throughout the experiment. The data were submitted to analysis of variance (ANOVA) to a randomized block design with two blocks, 15 treatments and four replications. The variables analyzed were subjected to Dunnett test at 5% probability, to compare the values obtained before and after insulation. For comparison between the breeds, the variables were submitted to Tukey test at 5% probability. All animals studied suffered significant influence (P<0.05) after scrotal insulation, but Santa Ines returned to the values previously observed in a shorter period than the crossbred. In summary, sheep Santa Ines have a higher resistance than crossbred animals when subjected to thermal stress induced by scrotal insulation.(AU)

Objetivou-se neste trabalho avaliar o efeito do cruzamento sobre as características biométricas escroto-testiculares de carneiros da raça Santa Inês e mestiços (Santa Inês x Dorper), submetidos à insulação escrotal, acompanhando o retorno dessas características aos valores previamente observados. Para isso, foram realizadas duas mensurações referentes à circunferência escrotal (CE), comprimento (C) e largura testicular (L), antes da insulação. O volume testicular (V) foi calculado pela fórmula V=2 [(r2) x π x h]. As bolsas de insulação foram fixadas ao redor do funículo espermático e escroto com fita adesiva e esparadrapo, permanecendo por sete dias. Após o período de insulação, as mensurações foram realizadas a cada sete dias, totalizando 15 mensurações durante todo o experimento. Os dados obtidos foram submetidos à análise de variância (ANOVA) para um delineamento em blocos casualizados, com dois blocos, 15 tratamentos e quatro repetições. As variáveis analisadas foram submetidas ao teste de Dunnett a 5% de probabilidade, para comparar os valores obtidos antes e após a insulação. Para a comparação entre as raças, as variáveis foram submetidas ao teste de Tukey a 5% de probabilidade. Todos os animais estudados sofreram influência significativa (P<0,05) após a insulação escrotal, porém os carneiros da raça Santa Inês retornaram aos valores anteriormente observados em um espaço de tempo mais curto do que os mestiços. Conclui-se que carneiros da raça Santa Inês apresentam maior resistência do que animais mestiços quando submetidos ao estresse térmico induzido pela insulação escrotal.(AU)

Effects of long-acting GnRH antagonist, degarelix acetate, on plasma insulin-like peptide 3, testosterone and luteinizing hormone concentrations, and scrotal circumference in male goats.

We recently reported that plasma insulin-like peptide 3 (INSL3) concentrations increased soon after endogenous and exogenous stimulations of LH in male goats and bulls. However, the effects of LH suppression on INSL3 secretion are unknown in domestic animals. Here, we examined the effects of a long-acting GnRH antagonist (degarelix acetate; 4 mg/kg) on the secretions of plasma INSL3 and testosterone in two phases, an immediate and a long-term phase in male goats (n = 6; aged, 13-16 months). During the immediate phase, blood was taken at 15-minute intervals for 8 hours on Days -5, 0, and 3. The GnRH antagonist was administered after 2-hour sampling of Day 0. Moreover, a daily blood sample was taken from Day 0 to Day 7, followed by twice a week until 9 weeks and finally at week 10. The scrotal circumference was recorded before treatment and continued biweekly until week 10. Concentrations of LH, INSL3, and testosterone in plasma were determined by EIA and the pulsatile nature of secretion analyzed using pulse XP software. The mean concentrations, pulse frequency (per hour), and pulse amplitude (peak-nadir) of plasma LH and testosterone reduced from pretreatment to posttreatment Day 0 and Day 3 (P < 0.05). A decline in mean concentrations, pulse frequency, and pulse amplitude of INSL3 was exhibited on posttreatment Day 3 compared with pretreatment (P < 0.01). During long-term sampling, a decline (P < 0.01) in plasma testosterone and INSL3 concentrations was observed 1 day after treatment and remained lower until 8.5 weeks after treatment, and thereafter returned to pretreatment levels. A reduction in scrotal circumference was recorded 4 weeks after treatment and remained lower until 10 weeks after treatment (P < 0.05). In conclusion, the acute regulation of INSL3 by LH was confirmed by reduction of plasma INSL3 levels within 3 days after GnRH antagonist treatment in male goats. Although the onset of suppression of testosterone was more rapid than that of INSL3, the low levels persisted for 8.5 weeks for both hormones, and subsequently the concentrations returned to pretreatment levels. A significant reduction in testicular size was also observed. The quick, long-lasting, and transient suppression of testosterone and INSL3 after a single injection implies a potential application of this antagonist in reversible long-term chemical castration in male goats.