Endocrine outcome and seminal parameters in young adult men born with hypospadias: A cross-sectional cohort study

Lloyd J W Tack; Anne-Françoise Spinoit; Piet Hoebeke; Stefan Riedl; Alexander Springer; Ursula Tonnhofer; Manuela Hiess; Julia Weninger; Ahmed Mahmoud; Kelly Tilleman; Erik Van Laecke; Anders Juul; Jakob Albrethsen; Elfride De Baere; Julie Van De Velde; Hannah Verdin; Martine Cools

doi:10.1016/j.ebiom.2022.104119

Endocrine outcome and seminal parameters in young adult men born with hypospadias: A cross-sectional cohort study

Lloyd J W Tack, Anne-Françoise Spinoit, Piet Hoebeke, Stefan Riedl, Alexander Springer, Ursula Tonnhofer, Manuela Hiess, Julia Weninger, Ahmed Mahmoud, Kelly Tilleman, Erik Van Laecke, Anders Juul, Jakob Albrethsen, Elfride De Baere, Julie Van De Velde, Hannah Verdin, Martine Cools^*

^*Corresponding author af dette arbejde

Afdeling for Vækst og Reproduktion

Abstract

BACKGROUND: Hypospadias affects around 1/200 newborn males. Intrauterine testicular dysfunction may underlie a subset of cases. The long-term endocrine and reproductive outcomes in these men remain largely unknown.

METHODS: Cross-sectional study in Ghent and Vienna University Hospitals to assess the endocrine and seminal parameters of young adult men (16-21 years) born with non-syndromic hypospadias (NSH) (n = 193) compared to healthy typical males (n = 50). Assessments included physical exam, semen analysis, hormone assays and exome-based gene panel analysis (474 genes).

FINDINGS: All participants had experienced a spontaneous puberty, in spite of higher LH and INSL3 levels than typical males. Oligo- or azoospermia was observed in 32/172 (18·6%; 99%-CI: 12·2-27·4%) of NSH men; but in 5/16 (31·3%; 99%-CI: 11·1;62·4%) of complex NSH men and in 13/22 (59·1%; 99%-CI: 33·2-80·7%) of those born small for gestational age (SGA). No (likely) pathogenic coding variants were found in the investigated genes. Suboptimal statural growth affected 8/23 (34·8%; 99%-CI: 15·4-61·0%) of men born SGA with NSH.

INTERPRETATION: Spermatogenesis is significantly compromised in NSH men, especially in those born SGA or those with complex NSH. Long-term andrological follow-up is recommended, including end-pubertal semen analysis. No clear monogenic causes could be demonstrated in our cohort even in proximal or complex NSH. Being born SGA with NSH is frequently associated with poor catch-up growth, requiring growth hormone therapy in some.

FUNDING: Research grants from the European Society of Paediatric Endocrinology, the Belgian Society of Pediatrics, the Belgian Society of Pediatric Endocrinology and Diabetology and the Research Foundation Flanders (FWO).

Originalsprog	Engelsk
Artikelnummer	104119
Tidsskrift	EBioMedicine
Vol/bind	81
Antal sider	15
DOI	https://doi.org/10.1016/j.ebiom.2022.104119
Status	Udgivet - jul. 2022

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10.1016/j.ebiom.2022.104119

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Tack, L. J. W., Spinoit, A.-F., Hoebeke, P., Riedl, S., Springer, A., Tonnhofer, U., Hiess, M., Weninger, J., Mahmoud, A., Tilleman, K., Van Laecke, E., Juul, A., Albrethsen, J., De Baere, E., Van De Velde, J., Verdin, H., & Cools, M. (2022). Endocrine outcome and seminal parameters in young adult men born with hypospadias: A cross-sectional cohort study. EBioMedicine, 81, Artikel 104119. https://doi.org/10.1016/j.ebiom.2022.104119

Tack, LJW, Spinoit, A-F, Hoebeke, P, Riedl, S, Springer, A, Tonnhofer, U, Hiess, M, Weninger, J, Mahmoud, A, Tilleman, K, Van Laecke, E, Juul, A , Albrethsen, J, De Baere, E, Van De Velde, J, Verdin, H & Cools, M 2022, 'Endocrine outcome and seminal parameters in young adult men born with hypospadias: A cross-sectional cohort study', EBioMedicine, bind 81, 104119. https://doi.org/10.1016/j.ebiom.2022.104119

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title = "Endocrine outcome and seminal parameters in young adult men born with hypospadias: A cross-sectional cohort study",

abstract = "BACKGROUND: Hypospadias affects around 1/200 newborn males. Intrauterine testicular dysfunction may underlie a subset of cases. The long-term endocrine and reproductive outcomes in these men remain largely unknown.METHODS: Cross-sectional study in Ghent and Vienna University Hospitals to assess the endocrine and seminal parameters of young adult men (16-21 years) born with non-syndromic hypospadias (NSH) (n = 193) compared to healthy typical males (n = 50). Assessments included physical exam, semen analysis, hormone assays and exome-based gene panel analysis (474 genes).FINDINGS: All participants had experienced a spontaneous puberty, in spite of higher LH and INSL3 levels than typical males. Oligo- or azoospermia was observed in 32/172 (18·6%; 99%-CI: 12·2-27·4%) of NSH men; but in 5/16 (31·3%; 99%-CI: 11·1;62·4%) of complex NSH men and in 13/22 (59·1%; 99%-CI: 33·2-80·7%) of those born small for gestational age (SGA). No (likely) pathogenic coding variants were found in the investigated genes. Suboptimal statural growth affected 8/23 (34·8%; 99%-CI: 15·4-61·0%) of men born SGA with NSH.INTERPRETATION: Spermatogenesis is significantly compromised in NSH men, especially in those born SGA or those with complex NSH. Long-term andrological follow-up is recommended, including end-pubertal semen analysis. No clear monogenic causes could be demonstrated in our cohort even in proximal or complex NSH. Being born SGA with NSH is frequently associated with poor catch-up growth, requiring growth hormone therapy in some.FUNDING: Research grants from the European Society of Paediatric Endocrinology, the Belgian Society of Pediatrics, the Belgian Society of Pediatric Endocrinology and Diabetology and the Research Foundation Flanders (FWO).",

author = "Tack, {Lloyd J W} and Anne-Fran{\c c}oise Spinoit and Piet Hoebeke and Stefan Riedl and Alexander Springer and Ursula Tonnhofer and Manuela Hiess and Julia Weninger and Ahmed Mahmoud and Kelly Tilleman and {Van Laecke}, Erik and Anders Juul and Jakob Albrethsen and {De Baere}, Elfride and {Van De Velde}, Julie and Hannah Verdin and Martine Cools",

year = "2022",

month = jul,

doi = "10.1016/j.ebiom.2022.104119",

language = "English",

volume = "81",

journal = "EBioMedicine",

issn = "2352-3964",

publisher = "Elsevier BV",

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TY - JOUR

T1 - Endocrine outcome and seminal parameters in young adult men born with hypospadias

T2 - A cross-sectional cohort study

AU - Tack, Lloyd J W

AU - Spinoit, Anne-Françoise

AU - Hoebeke, Piet

AU - Riedl, Stefan

AU - Springer, Alexander

AU - Tonnhofer, Ursula

AU - Hiess, Manuela

AU - Weninger, Julia

AU - Mahmoud, Ahmed

AU - Tilleman, Kelly

AU - Van Laecke, Erik

AU - Juul, Anders

AU - Albrethsen, Jakob

AU - De Baere, Elfride

AU - Van De Velde, Julie

AU - Verdin, Hannah

AU - Cools, Martine

PY - 2022/7

Y1 - 2022/7

N2 - BACKGROUND: Hypospadias affects around 1/200 newborn males. Intrauterine testicular dysfunction may underlie a subset of cases. The long-term endocrine and reproductive outcomes in these men remain largely unknown.METHODS: Cross-sectional study in Ghent and Vienna University Hospitals to assess the endocrine and seminal parameters of young adult men (16-21 years) born with non-syndromic hypospadias (NSH) (n = 193) compared to healthy typical males (n = 50). Assessments included physical exam, semen analysis, hormone assays and exome-based gene panel analysis (474 genes).FINDINGS: All participants had experienced a spontaneous puberty, in spite of higher LH and INSL3 levels than typical males. Oligo- or azoospermia was observed in 32/172 (18·6%; 99%-CI: 12·2-27·4%) of NSH men; but in 5/16 (31·3%; 99%-CI: 11·1;62·4%) of complex NSH men and in 13/22 (59·1%; 99%-CI: 33·2-80·7%) of those born small for gestational age (SGA). No (likely) pathogenic coding variants were found in the investigated genes. Suboptimal statural growth affected 8/23 (34·8%; 99%-CI: 15·4-61·0%) of men born SGA with NSH.INTERPRETATION: Spermatogenesis is significantly compromised in NSH men, especially in those born SGA or those with complex NSH. Long-term andrological follow-up is recommended, including end-pubertal semen analysis. No clear monogenic causes could be demonstrated in our cohort even in proximal or complex NSH. Being born SGA with NSH is frequently associated with poor catch-up growth, requiring growth hormone therapy in some.FUNDING: Research grants from the European Society of Paediatric Endocrinology, the Belgian Society of Pediatrics, the Belgian Society of Pediatric Endocrinology and Diabetology and the Research Foundation Flanders (FWO).

AB - BACKGROUND: Hypospadias affects around 1/200 newborn males. Intrauterine testicular dysfunction may underlie a subset of cases. The long-term endocrine and reproductive outcomes in these men remain largely unknown.METHODS: Cross-sectional study in Ghent and Vienna University Hospitals to assess the endocrine and seminal parameters of young adult men (16-21 years) born with non-syndromic hypospadias (NSH) (n = 193) compared to healthy typical males (n = 50). Assessments included physical exam, semen analysis, hormone assays and exome-based gene panel analysis (474 genes).FINDINGS: All participants had experienced a spontaneous puberty, in spite of higher LH and INSL3 levels than typical males. Oligo- or azoospermia was observed in 32/172 (18·6%; 99%-CI: 12·2-27·4%) of NSH men; but in 5/16 (31·3%; 99%-CI: 11·1;62·4%) of complex NSH men and in 13/22 (59·1%; 99%-CI: 33·2-80·7%) of those born small for gestational age (SGA). No (likely) pathogenic coding variants were found in the investigated genes. Suboptimal statural growth affected 8/23 (34·8%; 99%-CI: 15·4-61·0%) of men born SGA with NSH.INTERPRETATION: Spermatogenesis is significantly compromised in NSH men, especially in those born SGA or those with complex NSH. Long-term andrological follow-up is recommended, including end-pubertal semen analysis. No clear monogenic causes could be demonstrated in our cohort even in proximal or complex NSH. Being born SGA with NSH is frequently associated with poor catch-up growth, requiring growth hormone therapy in some.FUNDING: Research grants from the European Society of Paediatric Endocrinology, the Belgian Society of Pediatrics, the Belgian Society of Pediatric Endocrinology and Diabetology and the Research Foundation Flanders (FWO).

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U2 - 10.1016/j.ebiom.2022.104119

DO - 10.1016/j.ebiom.2022.104119

M3 - Journal article

C2 - 35759917

SN - 2352-3964

VL - 81

JO - EBioMedicine

JF - EBioMedicine

M1 - 104119

ER -

Endocrine outcome and seminal parameters in young adult men born with hypospadias: A cross-sectional cohort study

Abstract

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