M Engels1,2, K Gehrmann3, H Falhammar4,5, E A Webb6,7, A Nordenström8, F C Sweep2, P N Span9, A E van Herwaarden2, J Rohayem10, A Richter-Unruh10, C Bouvattier11, B Köhler3, B B Kortmann12, W Arlt6,7, N Roeleveld13, N Reisch14, N M M L Stikkelbroeck15, H L Claahsen-van der Grinten1. 1. Department of Pediatrics, Amalia Children's Hospital, Radboud University Medical Center, Nijmegen, the Netherlands. 2. Department of Laboratory Medicine, Radboud Institute for Molecular Life Sciences (RIMLS), Radboud University Medical Center, Nijmegen, the Netherlands. 3. Klinik für Pädiatrie m.S. Endokrinologie und Diabetologie, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany. 4. Department of Endocrinology, Metabolism and Diabetes, Karolinska University Hospital, Stockholm, Sweden. 5. Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden. 6. Institute of Metabolism and Systems Research (IMSR), University of Birmingham, Birmingham, UK. 7. Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK. 8. Department of Women's and Children's Health, Division of Pediatric Endocrinology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden. 9. Department of Radiation Oncology, Radiotherapy & OncoImmunology laboratory, RIMLS, Radboud University Medical Center, Nijmegen, the Netherlands. 10. Centre of Reproductive Medicine and Andrology, Clinical Andrology, University Hospital Münster, Münster, Germany. 11. Endocrinologie Pédiatrique, Centre de Référence des Maladies Rares du Développement Sexuel, Hôpital Bicêtre, Université Paris-Sud, Le Kremlin-Bicêtre, France. 12. Department of Pediatric Urology, Radboud University Medical Center, Nijmegen, the Netherlands. 13. Department for Health Evidence, Radboud University Medical Center, Nijmegen, the Netherlands. 14. Medizinische Klinik IV, Klinikum der Universität München, München, Germany. 15. Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.
Abstract
CONTEXT: Current knowledge on gonadal function in congenital adrenal hyperplasia (CAH) is mostly limited to single-center/country studies enrolling small patient numbers. Overall data indicate that gonadal function can be compromised in men with CAH. OBJECTIVE: To determine gonadal function in men with CAH within the European 'dsd-LIFE' cohort. DESIGN: Cross-sectional clinical outcome study, including retrospective data from medical records. METHODS: Fourteen academic hospitals included 121 men with CAH aged 16-68 years. Main outcome measures were serum hormone concentrations, semen parameters and imaging data of the testes. RESULTS: At the time of assessment, 14/69 patients had a serum testosterone concentration below the reference range; 7 of those were hypogonadotropic, 6 normogonadotropic and 1 hypergonadotropic. In contrast, among the patients with normal serum testosterone (55/69), 4 were hypogonadotropic, 44 normogonadotropic and 7 hypergonadotropic. The association of decreased testosterone with reduced gonadotropin concentrations (odds ratio (OR) = 12.8 (2.9-57.3)) was weaker than the association between serum androstenedione/testosterone ratio ≥1 and reduced gonadotropin concentrations (OR = 39.3 (2.1-732.4)). Evaluation of sperm quality revealed decreased sperm concentrations (15/39), motility (13/37) and abnormal morphology (4/28). Testicular adrenal rest tumor (TART)s were present in 39/80 patients, with a higher prevalence in patients with the most severe genotype (14/18) and in patients with increased current 17-hydroxyprogesterone 20/35) or androstenedione (12/18) serum concentrations. Forty-three children were fathered by 26/113 patients. CONCLUSIONS: Men with CAH have a high risk of developing hypothalamic-pituitary-gonadal disturbances and spermatogenic abnormalities. Regular assessment of endocrine gonadal function and imaging for TART development are recommended, in addition to measures for fertility protection.
CONTEXT: Current knowledge on gonadal function in congenital adrenal hyperplasia (CAH) is mostly limited to single-center/country studies enrolling small patient numbers. Overall data indicate that gonadal function can be compromised in men with CAH. OBJECTIVE: To determine gonadal function in men with CAH within the European 'dsd-LIFE' cohort. DESIGN: Cross-sectional clinical outcome study, including retrospective data from medical records. METHODS: Fourteen academic hospitals included 121 men with CAH aged 16-68 years. Main outcome measures were serum hormone concentrations, semen parameters and imaging data of the testes. RESULTS: At the time of assessment, 14/69 patients had a serum testosterone concentration below the reference range; 7 of those were hypogonadotropic, 6 normogonadotropic and 1 hypergonadotropic. In contrast, among the patients with normal serum testosterone (55/69), 4 were hypogonadotropic, 44 normogonadotropic and 7 hypergonadotropic. The association of decreased testosterone with reduced gonadotropin concentrations (odds ratio (OR) = 12.8 (2.9-57.3)) was weaker than the association between serum androstenedione/testosterone ratio ≥1 and reduced gonadotropin concentrations (OR = 39.3 (2.1-732.4)). Evaluation of sperm quality revealed decreased sperm concentrations (15/39), motility (13/37) and abnormal morphology (4/28). Testicular adrenal rest tumor (TART)s were present in 39/80 patients, with a higher prevalence in patients with the most severe genotype (14/18) and in patients with increased current 17-hydroxyprogesterone 20/35) or androstenedione (12/18) serum concentrations. Forty-three children were fathered by 26/113 patients. CONCLUSIONS: Men with CAH have a high risk of developing hypothalamic-pituitary-gonadal disturbances and spermatogenic abnormalities. Regular assessment of endocrine gonadal function and imaging for TART development are recommended, in addition to measures for fertility protection.
Authors: Hedi L Claahsen-van der Grinten; Phyllis W Speiser; S Faisal Ahmed; Wiebke Arlt; Richard J Auchus; Henrik Falhammar; Christa E Flück; Leonardo Guasti; Angela Huebner; Barbara B M Kortmann; Nils Krone; Deborah P Merke; Walter L Miller; Anna Nordenström; Nicole Reisch; David E Sandberg; Nike M M L Stikkelbroeck; Philippe Touraine; Agustini Utari; Stefan A Wudy; Perrin C White Journal: Endocr Rev Date: 2022-01-12 Impact factor: 19.871
Authors: Katharina Gehrmann; Manon Engels; Elena Bennecke; Claire Bouvattier; Henrik Falhammar; Baudewijntje P C Kreukels; Anna Nordenstrom; Nicole Reisch; Nicole Gehrmann; Nike M M L Stikkelbroeck; Marcus Quinkler; Hedi L Claahsen-van der Grinten Journal: J Endocr Soc Date: 2019-04-24