Reproductive Hormones During Minipuberty Suggest Subtle Testicular Impairments in Boys With Hypospadias
Authors' conclusion
Hypospadias severity was significantly associated with birth and placental weight centiles. Testicular Sertoli cell markers (AMH and inhibin B) and the Leydig cell-derived INSL3 were reduced, suggesting subtle testicular dysfunction in boys with hypospadias during minipuberty. Further research to identify implications for future reproductive health is warranted.
Study context
- Population
- Infants with hypospadias at a tertiary hypospadias center during minipuberty (median postnatal age 0.28 years), May 2021–January 2023139 presenting
- Participants
- 113 infants
- Exposure
- Boys with hypospadias vs reference standard for healthy Danish boys (0 SDS); proximal vs distal hypospadias
- Distal hypospadiasn = 89
- Outcome
- Gestational age (GA)-specific reproductive hormone concentrations as SDS vs reference standard for healthy Danish boys (0 SDS); birth weight and placental centiles by hypospadias severity
- Follow-up
- Minipuberty
Methodological detailssingle tertiary hypospadias center
- Single tertiary hypospadias center
Main finding
As reported in the abstract
Reproductive hormone SDS vs 0 SDS
- FSH, median SDS (higher vs 0 SDS, P < .001)
- 0.83 SDS
- Testosterone, median SDS (higher vs 0 SDS, P < .001)
- 0.71 SDS
- Free testosterone, median SDS (higher vs 0 SDS, P < .001)
- 0.83 SDS
- Inhibin B, median SDS (significantly lower)
- −0.38 SDS
- Anti-Müllerian hormone (AMH), median SDS (significantly lower)
- −0.23 SDS
- INSL3, median SDS (significantly lower)
- −0.31 SDS
- Androstenedione, median SDS (significantly lower)
- −0.52 SDS
- DHEAS, median SDS (significantly lower)
- −0.50 SDS
Observational data: associations, not effects.
Further findings
Median
| Outcome | Distal hypospadias | Proximal hypospadias |
|---|---|---|
| EMS by hypospadias severity | 11 | 9 |
- Birth weight and placental centiles by severity · lower with proximal hypospadias · Fisher's exact test
- P = 0.014
- Birth weight and placental centiles by severity · lower with proximal hypospadias · Fisher's exact test
- P = 0.038
- External masculinization score (EMS) by hypospadias severity: 89 boys (79%) had distal hypospadias
Hormone SDS by hypospadias severity
- Hormone SDS did not differ significantly by hypospadias severity
Original publication
Reproductive Hormones During Minipuberty Suggest Subtle Testicular Impairments in Boys With Hypospadias. J Clin Endocrinol Metab. Published 13 November 2025. doi:10.
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