New frontiers on the molecular underpinnings of hypospadias according to severity.

Hypospadias, which is characterised by the displacement of the urethral meatus from its typical anatomical location in males, shows various degrees of severity. In this systematic review, we surveyed our current understanding of the genetics of isolated hypospadias in humans according to the severity of the condition. We found that sequencing and genotyping approaches were the preferred methods of study and that single nucleotide polymorphisms were the most common finding associated with hypospadias. Most genes fell into four gene-pathway categories related to androgens, oestrogens, growth factors, or transcription factors. Few hypospadias studies classify their findings by severity. Taken together, we argue that it is advantageous to take into consideration the severity of the condition in search of novel candidates in the aetiology of hypospadias. Abbreviations: AR: androgen receptor; ATF3: activating transcription factor 3; BMP4: bone morphogenetic protein 4; BMP7: bone morphogenetic protein 7; CYP17: steroid 17-alpha-hydroxylase/17,20 lyase; CYP1A1: cytochrome P450 1A1; CYP3A4: cytochrome P450 3A4; CNVs: copy number variants; DGKK: diacylglycerol kinase kappa; ESR1: oestrogen receptor 1; ESR2: oestrogen receptor 2; FGF8: fibroblast growth factor 8; FGF10: fibroblast growth factor 10; FGFR2: fibroblast growth factor receptor 2; HOXA4: homeobox protein Hox-A4; HOXB6: homeobox protein Hox-B6; HSD17B3: hydroxysteroid 17-beta dehydrogenase 3; MAMLD1: mastermind-like domain-containing protein 1; SF-1: splicing factor 1; SHH: sonic hedgehog; SNPs: single nucleotide polymorphisms; SOX9: SRY-box 9; SRD5A2: steroid 5 alpha-reductase 2; SRY: sex-determining region Y protein; STAR: steroidogenic acute regulatory protein; STARD3: StAR-related lipid transfer protein 3; STS: steryl-sulfatase; WT1: Wilms tumour protein; ZEB1: zinc finger oestrogen-box binding homeobox 1.

Transgender identity and cryptorchidism: A case study / Identidad transgénero y criptorquidia: reporte de caso

Abstract Introduction There is a wide range of possible combinations in relation to sex at birth, gender identity, and sexual orientations. Specific medical and psychological treatment needs may also vary depending on these combinations. Objective In order to promote interventions that focus on the perceived needs of those directly involved, the aim of the present case study is to describe the clinical and life experiences of a 43-year old transgender woman with cryptorchidism and examine the interplay between this relative common testicular problem at birth, gender identity, and sexual orientation formation processes from her own perspective. Method An in-depth interview was conducted at a specialized care centre in Mexico City, Mexico. The interview was audio recorded and transcribed for a content analysis. Results The case under analysis was assigned to the male sex and identified herself as a transgender woman and lesbian. Although it is not possible to conclude that her gender identity or sexual orientation is related to her antecedent of cryptorchidism, as she reflected on her related negative experiences, she concluded that her gender identity and sexual orientation trajectories, as well as her life in general, would have been completely different if there were no clinical interventions in her early development. Discussion and conclusion The present case could have been benefited from not receiving early treatment for her cryptorchidism. There is an urgent need for the development of standardized protocols or algorithms for physical and mental health care professionals, which focus on supportive guidance rather than adjustment to parental and medical expectations.

Resumen Este artículo presenta la historia clínica y de vida de una mujer transexual con criptorquidia al nacer. Nuestro objetivo es presentar un estudio de caso en que la identidad transgénero y la criptorquidia, una condición testicular común en niños e identidades trans, podrían cumplir un papel en los procesos de formación de identidad de género. La interacción entre la identidad de género y la orientación sexual también se presenta como entrevistas semiestructuradas destinadas a recopilar datos sobre intervenciones clínicas tempranas según lo informado por la persona. Abogamos por un algoritmo psicológico que abarque la comunicación interprofesional específicamente diseñada para las personas con diferencias de sexo/género, centrándose en la orientación de apoyo en lugar de ajustarse a las expectativas médicas y de los padres.

Evaluation and Management of the Undescended Testis in Puerto Rico: A Single Surgeon's 10 Years of Experience.

OBJECTIVE: Cryptorchidism is an abnormality of the male genitourinary tract in which one or both testes fail to descend into the scrotum. The American Urological Association (AUA) clinical guidelines for the evaluation and treatment of cryptorchidism were recently published. We reviewed our experience with the evaluation and management of our patients and examined our findings with respect to the AUA and European Association of Urology (EAU) guidelines. METHODS: Data were obtained from pediatric patients who underwent a surgical intervention for an undescended testis from 2007 through 2017 at HIMA Hospital and the University Pediatric Hospital (both in Puerto Rico); all the surgeries were performed by the same surgeon. A total of 754 patients were identified; 142 patients were excluded due to lack of follow-up data (N = 612). The data obtained included age, testes locations, radiologic and surgical findings, and postoperative results. RESULTS: At their initial evaluations, a large proportion of the patients (46.4%) came accompanied with radiographic imaging. These findings were consistent with those of the physical examination in 58.5% of the patients and with the surgical findings in 63.1% (sensitivity 77.9%, specificity 45.8%). Our data showed that the median referral age was 24 months, which suggests that there was a significant delay in diagnosis. At the time of surgery, the average age of the patients who required an orchiectomy was 3.93 years, while those who underwent an orchiopexy had an average age of 3.28 years. CONCLUSION: Our data reveal that, despite its lack of usefulness, radiologic imaging continues to be included in the diagnostic workups of children newly identified with cryptorchidism in Puerto Rico. In addition, and contrary to the guidelines, there tends to be a significant delay in treatment with surgical intervention. It is important to continue to educate our referring physicians on the AUA and EUA guidelines in order to create awareness and encourage the proper diagnostic and treatment approach for cryptorchidism.

Age of the mother as a risk factor and timing of hypospadias repair according to severity.

BACKGROUND & OBJECTIVES: Hypospadias is characterized by a displacement of the urethral opening in males that can change from the typical position within the glans penis to a subcoronal position (Type I), to anywhere along the ventral shaft (Type II), to penoscrotal, scrotal, or perineal positions (Type III). We and others have previously reported that age of the mother (≥ 40 years old) is a risk factor for having a child with hypospadias, but there is a scarcity of reports on whether such risk is higher for having a child with the mild (Type I) or the more severe forms (Types II and III). In addition, we aimed to assess the timing of hypospadias repair according to severity. METHODS: Parents of children with hypospadias were interviewed by using a series of questionnaires (n = 128 cases). Severity was confirmed in the clinic and age of the mother was self-reported. Number of surgeries, age of child by the first and the last intervention was also assessed. Ordered logistic regression and the Brant test were employed to calculate risk between mild (Type I) and severe cases (Types II and III), and the assumption of proportional odds, respectively. The Mann-Whitney U Test was used to compare number of surgeries and age by the last repair between mild and severe cases. One-way ANOVA was employed to compare age of the child at the time of first surgery across severities (Types I - III). RESULTS: Women ≥ 40 years of age are 3.89 times [95% CI: 1.20-12.64] at a higher risk for having a child with the more severe forms of the condition than younger women. Repair of Type I was accomplished with 1 intervention whereas more severe cases required 1 - 4 (2 ± 0.5) surgical interventions. The timing for hypospadias repair of Type I cases occurred at an average age of 16.2 ± 4.88 months, of Type II cases occurred at an average age of 20.3 ± 8.15 months whereas the average age of the first hypospadias repair among Type III cases was 12.68 ± 2.52 months. Number of surgeries according to severity (p ≤ 0.0018, z-ratio = 2.91) and age difference for the timing of last repair (p ≤ 0.045, z-ratio = 1.69) were statistically different, but not the age difference for the first repair. CONCLUSIONS: Increased maternal age is associated with the most severe forms of hypospadias. There is room for improvement for the timing of hypospadias repair according to severity.

Concordance of Expert and Parental Opinion about Hypospadias Surgical Outcome Is Severity Dependent.

INTRODUCTION: Hypospadias is a male congenital condition where the opening of the urethral meatus is not located in the typical anatomical position. It has been a challenge for empirical studies to ascertain the level of concordance of opinion among parents and urologists with regard to surgical outcomes according to hypospadias severity. MATERIALS AND METHODS: Parents of children who had undergone hypospadias repair were recruited for this study (n = 104). A set of questionnaires that included some items with Likert scale were created to evaluate postsurgical satisfaction by parents and urologists. SAHLSA-50, a validated instrument for adult Spanish-speaking adults, was used to assess health literacy. Cohen's kappa (κ) coefficient was used to assess interobserver agreement and Chi Square "Goodness of Fit" Test was used to determine probability of satisfaction. FINDINGS: Concordance on the level of satisfaction with surgical outcomes for Type cases I was slight (κ = 0.20; CI 95% 0-0.60), for Type II cases was moderate (κ = 0.54; CI 95% 0.13-0.94), and for Type III cases was substantial (κ = 0.62; CI 95% 0-0.56). However, the probability of satisfaction did not change according to severity (Chi Square "Goodness of Fit" Test; parents, p = 0.84; pediatric urologists, p = 0.92). These results cannot be explained by parental health literacy according to SAHLSA-50 test scores. CONCLUSION: The level of concordance of opinion among parents and urologists with regard to their level of satisfaction with surgical outcomes is related to hypospadias severity, whereby the greatest level of concordance of opinion was achieved among most severe cases. This study underscores the need for longer follow-up to properly assess satisfaction with hypospadias repair, especially for the less severe forms of the condition.

The testosterone metabolite 3α-diol enhances female rat sexual motivation when infused in the nucleus accumbens shell.

AIM: The purpose of this study was to provide a quantitative assessment of female rat sexual behaviors after acute exposure to the A-ring reduced testosterone metabolite, androstanediol (3α-Diol), through the nucleus accumbens (NA) shell. MAIN OUTCOME MEASURES: Quantitative analyses of female rat sexual behaviors and assessment of protein levels for the enzyme glutamic acid decarboxylase isoform 67 (GAD67) and gephyrin, a protein that participates in the clustering of GABA-A receptors in postsynaptic cells, were accomplished. METHODS: Female rats were ovariectomized and primed with estrogen and progesterone to induce sexual behaviors. Females received a 3α-Diol infusion via guided cannula that aimed to the NA shell five minutes prior to a sexual encounter with a stud male. The following parameters were videotaped and measured in a frame by frame analysis: lordosis quotient (LQ), Lordosis rating (LR), frequency and duration of proceptive behaviors (hopping/darting and ear wiggling). Levels of GAD67 and gephyrin were obtained by Western blot analysis two or twenty-four hours after the sexual encounter. RESULTS: Acute exposure to 3α-Diol in the NA shell enhanced LR, ear wiggling, and hopping/darting but not LQ. Some of these behavioral effects were counteracted by co-infusion of 3α-Diol plus the GABAA-receptor antagonist GABAzine. A transient reduction of GAD67 levels in the NA shell was detected. CONCLUSIONS: The testosterone metabolite 3α-Diol enhances sexual proceptivity, but not receptivity, when infused into the NA shell directly. The GABAergic system may participate in the androgen-mediated enhancement of female rat sexual motivation.

The neurosteroid 3alphaDIOL modulates place preference when infused in the basolateral amygdala according to sex.

Three different behavioral tasks were used to study the role of the neurosteroid 5alpha -androstane-3alpha, 17beta-diol (3alphaDIOL) in affective components of behavior when infused into the basolateral amygdala (BLA) of both sexes. Female rats were ovariectomized; half received implants containing estradiol benzoate (OVX-EB), whereas the other half received empty implants (OVX). Male rats were gonadally intact. No differences were noted in male behavior according to the conditioned place preference (CPP) test, the modified Vogel conflict test (VCT), or the elevated plus maze (EPM) upon infusion of 3alphaDIOL. In contrast, 3alphaDIOL modulated CPP and VCT performance among female rats. Therefore, the authors propose that 3alphaDIOL modulates affect through the BLA via a sex-specific mechanism.