Semen quality and testicular adrenal rest tumour development in 46,XY congenital adrenal hyperplasia: the importance of optimal hormonal replacement

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  • 1 Department of Clinical and Surgical Andrology, Center of Reproductive Medicine and Andrology, University of Münster, Münster, Nordrhein-Westfalen, Germany
  • 2 Department of Pediatric Endocrinology and Diabetes, Helios-Klinikum Krefeld, Krefeld, Nordrhein-Westfalen, Germany
  • 3 Department of Pediatric Endocrinology and Diabetes, University of Magdeburg, Children's Hospital Magdeburg, Magdeburg, Sachsen-Anhalt, Germany
  • 4 Department of Pediatric Endocrinology and Diabetes, Children's Hospital Bonn, University of Bonn, Bonn, Nordrhein-Westfalen, Germany
  • 5 Department of Pediatric Endocrinology and Diabetes, Children's Hospital Dresden, University of Dresden, Dresden, Sachsen, Germany
  • 6 Department of Pediatric Endocrinology and Diabetes, Children's Hospital Herford, Herford, Nordrhein-Westfalen, Germany
  • 7 Department of Pediatrics and Pediatric Hematology and Oncology, Children's Hospital Oldenburg, University of Oldenburg, Oldenburg, Niedersachsen, Germany
  • 8 Department of Pediatric Endocrinology and Diabetes, Children's Hospital Augsburg, University of Augsburg, Augsburg, Bayern, Germany
  • 9 Pediatric Endocrinology practice, Augsburg, Bayern, Germany
  • 10 Department of Pediatrics, Evangelisches Klinikum Bethel, Bielefeld, Nordrhein-Westfalen, Germany
  • 11 Department of Pediatric Endocrinology and Diabetes, Children's Hospital, Esslingen, Baden-Württemberg, Germany
  • 12 Department of Pediatric Endocrinology and Diabetes, Children's Hospital, Charity, University of Berlin, Berlin, Germany
  • 13 Pediatric Endocrinology practice, Bremen, Germany
  • 14 Department of Pediatric Endocrinology and Diabetes, Children's Hospital, University of Bochum, Bochum, Nordrhein-Westfalen, Germany
  • 15 Department of Pediatric Endocrinology and Diabetes, Children's Hospital, University of Essen, Essen, Nordrhein-Westfalen, Germany
  • 16 Institute for Doping Analytics and Sports Biochemistry, Dresden, Sachsen, Germany
  • 17 Department of Pediatric Endocrinology and Diabetes, Children's Hospital, University of Münster, Münster, Nordrhein-Westfalen, Germany

Correspondence should be addressed to J Rohayem; Email: Julia.Rohayem@ukmuenster.de

Objective

To study the impact of the quality of therapeutic control on fertility and on the prevalence of testicular adrenal rest tumours (TART) in young males with congenital adrenal hyperplasia (CAH).

Design

Combined cross-sectional and retrospective clinical study.

Methods

Twenty-nine patients and age-matched controls underwent clinical investigation, including semen analysis, testicular and adrenal ultrasound imaging, and serum and hair steroid analysis. The quality of therapeutic control was categorized as ‘poor’, ‘moderate’ or ‘medium’. Evaluation of current control was based on concentrations of 17-hydroxy-progesterone and androstenedione in serum and 3 cm hair; previous control was categorized based on serum 17-hydroxy-progesterone concentrations during childhood and puberty, anthropometric and puberty data, bone age data and adrenal sizes.

Results

Semen quality was similar in males with CAH and controls (P  = 0.066), however patients with ‘poor’ past control and large TART, or with ‘poor’ current CAH control had low sperm counts. Follicle-stimulating hormone was decreased, if current CAH control was ‘poor’ (1.8 ± 0.9 U/L; ‘good’: 3.9 ± 2.2 U/L); P  = 0.015); luteinizing hormone was decreased if it was ‘poor’ (1.8 ± 0.9 U/L; P  = 0.041) or ‘moderate’ (1.9 ± 0.6 U/L; ‘good’: 3.0 ± 1.3 U/L; P  = 0.025). None of the males with ‘good’ past CAH control, 50% of those with ‘moderate’ past control and 80% with ‘poor past control had bilateral TART. The prevalence of TART in males with severe (class null or A) CYP21A2 mutations was 53% and 25% and 0% in those with milder class B and C mutations, respectively.

Conclusions

TART development is favoured by inadequate long-term hormonal control in CAH. Reduced semen quality may be associated with large TART. Gonadotropin suppression by adrenal androgen excess during the latest spermatogenic cycle may contribute to impairment of spermatogenesis.

Supplementary Materials

    • supplementary table 1
    • supplementary table 2: Hormone concentrations in hair and serum of CAH males and age-matched controls Colors illustrate categorization of results of CAH males, green indicating “good” current therapeutic control, yellow “moderate” and red “poor” current CAH control, based on cut-offs as defined in Table 1
    • Supplementary Figure 1 Parameters used for definition of the quality of current congenital adrenal hyperplasia control: 17-hydroxy-progesterone (17-OHP) and androstenedione (A4) concentrations in serum and in 3 cm of root-near hair.

 

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