Endocrine Abstracts

JOINT3286

Introduction: Hypospadias is a common congenital urological condition associated with testicular dysfunction, such as reduced semen quality and subclinical hypogonadism. The severity of dysfunction varies, and is influenced by the degree of undervirilization and prenatal factors (e.g. being born small for gestational age). Despite these associations, testicular morphology—specifically parenchymal inhomogeneity and microcalcifications—remains understudied in men born with hypospadias. This study investigates testicular morphology in boys and men with hypospadias compared to controls using ultrasound. Specifically, we examine changes across puberty and their associations with clinical, prenatal, and lifestyle factors.

Methods: Cross-sectional case-control study: evaluation of testicular ultrasound studies of 244 boys/men born with hypospadias (Tanner 1: n = 17; Tanner 2-4: n = 27; Tanner 5: n = 200) and 51 controls (all Tanner 5) by three physicians (junior doctor, senior urologist and pediatric endocrinologist). Homogeneity and microcalcifications were scored on a 4-point and 3-point Likert scale, respectively. Associations were sought with clinical data (e.g. hormone assays, semen characteristics and physical exam) and maternal, dietary and substance factors (through a questionnaire).

Results: Substantial interobserver agreement was seen for microcalcifications (κ=0.735, P < 0.001) and inhomogeneity (κ=0.647, P < 0.001). Testicular inhomogeneity was more common in men born with hypospadias compared to controls (P = 0.004), also when divided in subgroups mild (P = 0.006), severe (P < 0.001), and complex hypospadias (P < 0.001). Descriptive analysis showed increasing abnormalities with puberty progression. Furthermore, associations were found between inhomogeneous testicular parenchyma and reduced semen quality, number of penile surgeries, shorter adult stretched penile length, being born small for gestational age and unhealthy lifestyle (i.e. smoking, drug use, high alcohol consumption and/or fast food intake). No difference in the prevalence of testicular microcalcifications was found between men born with hypospadias and controls (P = 0.599).

Discussion: More frequent testicular parenchymal inhomogeneity was found in men born with hypospadias and multiple associations were seen between testicular inhomogeneity and testicular and prenatal factors. We therefore hypothesize testicular inhomogeneity could serve as a relevant, non-invasive marker hinting towards possible impaired testicular function in men born with hypospadias. Screening may be recommended starting from late puberty as the first morphological changes are typically observed at this stage and could help determine which men need to be referred for endocrine or fertility work-up. Future research should explore long-term implications, particularly the link to sub- and infertility and potential risk to develop testicular germ cell malignancies.