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Peer-reviewedCC BY 4.0Clinical Endocrinology

Pubertal Dynamics of Sertoli and Leydig Cell Dysfunction in Klinefelter Syndrome

  • Tredez Axelle1
  • Christine Lefevre1
  • Simon Boussion2
  • Cindy Colson2
  • Iva Gueorguieva1
  • Francois Marcelli3
  • Anne Laure Barbotin4,5
  • Pascal Pigny6,7
  • Hamza Benderradji3,5,8
  • Clara Leroy1,3
8 affiliations
  1. 1Department of Pediatric Endocrinology, DevGen, Reference Centre for Genital Development Abnormalities, CHU Lille University of Lille Lille France
  2. 2Department of Genetic, DevGen, Reference Centre for Genital Development Abnormalities, CHU Lille University of Lille Lille France
  3. 3Department of Andrology, Urology and Renal Transplantation University of Lille, CHU Lille Lille France
  4. 4Department of Reproductive Biology‐Spermiology‐CECOS University of Lille, CHU Lille Lille France
  5. 5University of Lille, CHU‐Lille, Inserm U1172, Lille Neuroscience & Cognition Lille France
  6. 6Department of Biochemistry and Molecular Biology, Hormonology, Metabolism–Nutrition and Oncology Unit, CHU‐Lille University of Lille Lille France
  7. 7U1277‐CANTHER‐Cancer‐Heterogeneity Plasticity and Resistance to Therapies, Inserm, CHU Lille University of Lille Lille France
  8. 8Department of Endocrinology, Diabetology, and Metabolism University of Lille, CHU Lille Lille France
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Abstract

Context: Klinefelter syndrome (KS), defined by a 47, XXY karyotype, is commonly associated with progressive testicular failure. The precise timing of Sertoli and Leydig cell dysfunction during puberty remains unclear.

Objective: To determine the onset and progression of testicular insufficiency during puberty in KS, and to assess whether diagnostic timing (prenatal vs postnatal) impacts pubertal phenotype.

Methods: We conducted a retrospective, single‐centre study of 57 patients with KS aged 9–25 years, followed from the prepubertal period at Lille University Hospital. Longitudinal clinical and hormonal data were analysed according to pubertal stage rather than chronological age.

Results: All patients entered puberty spontaneously at a physiological age (mean 12.6 years), but experienced a slow pubertal tempo (mean duration: 4.08 years). Sertoli cell dysfunction appeared within 12 months of pubertal onset, with rising FSH and declining AMH and inhibin B levels. Inhibin B concentrations never reached the reference range for Tanner stage 5 and declined below the adult threshold (92 pg/mL) 2 years after pubertal onset. Leydig cell dysfunction, defined by elevated LH and low‐normal testosterone, emerged after 36 months. At puberty completion, 94% had Sertoli cell insufficiency (i.e. FSH level > 7.19 IU/L) and 80% had Leydig cell insufficiency (LH > 5.88 IU/L). Postnatally diagnosed patients exhibited significantly higher LH (p = 0.03) and lower inhibin B (p = 0.01) levels.

Conclusion: Testicular insufficiency in KS begins approximately 18 months after pubertal onset, with Sertoli cell failure preceding Leydig cell decline. Early diagnosis and longitudinal monitoring are essential to guide endocrine management and to support individualized counselling regarding fertility preservation strategies, which should be considered according to pubertal stage rather than chronological age.

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Cite

BibTeXRIS
BibTeX
@article{axelle2026pubertal,
  title = {{Pubertal Dynamics of Sertoli and Leydig Cell Dysfunction in Klinefelter Syndrome}},
  author = {Tredez Axelle and Christine Lefevre and Simon Boussion and Cindy Colson and Iva Gueorguieva and Francois Marcelli and Anne Laure Barbotin and Pascal Pigny and Hamza Benderradji and Clara Leroy},
  journal = {Clinical Endocrinology},
  year = {2026},
  month = jun,
  doi = {10.1111/cen.70159},
  url = {https://doi.org/10.1111/cen.70159},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Pubertal Dynamics of Sertoli and Leydig Cell Dysfunction in Klinefelter Syndrome
AU  - Tredez Axelle
AU  - Christine Lefevre
AU  - Simon Boussion
AU  - Cindy Colson
AU  - Iva Gueorguieva
AU  - Francois Marcelli
AU  - Anne Laure Barbotin
AU  - Pascal Pigny
AU  - Hamza Benderradji
AU  - Clara Leroy
PY  - 2026
DA  - 2026/06/11
JO  - Clinical Endocrinology
DO  - 10.1111/cen.70159
UR  - https://doi.org/10.1111/cen.70159
AB  - Context: Klinefelter syndrome (KS), defined by a 47, XXY karyotype, is commonly associated with progressive testicular failure. The precise timing of Sertoli and Leydig cell dysfunction during puberty remains unclear.  Objective: To determine the onset and progression of testicular insufficiency during puberty in KS, and to assess whether diagnostic timing (prenatal vs postnatal) impacts pubertal phenotype.  Methods: We conducted a retrospective, single‐centre study of 57 patients with KS aged 9–25 years, followed from the prepubertal period at Lille University Hospital. Longitudinal clinical and hormonal data were analysed according to pubertal stage rather than chronological age.  Results: All patients entered puberty spontaneously at a physiological age (mean 12.6 years), but experienced a slow pubertal tempo (mean duration: 4.08 years). Sertoli cell dysfunction appeared within 12 months of pubertal onset, with rising FSH and declining AMH and inhibin B levels. Inhibin B concentrations never reached the reference range for Tanner stage 5 and declined below the adult threshold (92 pg/mL) 2 years after pubertal onset. Leydig cell dysfunction, defined by elevated LH and low‐normal testosterone, emerged after 36 months. At puberty completion, 94% had Sertoli cell insufficiency (i.e. FSH level > 7.19 IU/L) and 80% had Leydig cell insufficiency (LH > 5.88 IU/L). Postnatally diagnosed patients exhibited significantly higher LH (p = 0.03) and lower inhibin B (p = 0.01) levels.  Conclusion: Testicular insufficiency in KS begins approximately 18 months after pubertal onset, with Sertoli cell failure preceding Leydig cell decline. Early diagnosis and longitudinal monitoring are essential to guide endocrine management and to support individualized counselling regarding fertility preservation strategies, which should be considered according to pubertal stage rather than chronological age.
SN  - 0300-0664
SN  - 1365-2265
ER  -