Gonadal function in adult male patients with congenital adrenal hyperplasia

• Published in: European journal of endocrinology Vol. 178; no. 3; pp. 285 - 294
• Main Authors: Engels, M, Gehrmann, K, Falhammar, H, Webb, E A, Nordenström, A, Sweep, F C, Span, P N, van Herwaarden, A E, Rohayem, J, Richter-Unruh, A, Bouvattier, C, Köhler, B, Kortmann, B B, Arlt, W, Roeleveld, N, Reisch, N, Stikkelbroeck, N M M L, Claahsen-van der Grinten, H L
• Format: Journal Article
• Language: English
• Published: England Bioscientifica Ltd 01.03.2018; Oxford University Press
• Subjects: Adolescent; Adrenal Hyperplasia, Congenital - blood; Adrenal Hyperplasia, Congenital - complications; Adrenal Hyperplasia, Congenital - epidemiology; Adrenal Rest Tumor - blood; Adrenal Rest Tumor - epidemiology; Adult; Aged; Androstenedione - blood; Clinical Study; Cross-Sectional Studies; Europe - epidemiology; Fertility; Genotypes; Gonadotropins - blood; Humans; Hydroxyprogesterones - blood; Hyperplasia; Hypogonadism - blood; Hypogonadism - complications; Male; Medicin och hälsovetenskap; Middle Aged; Odds Ratio; Oligospermia - complications; Prevalence; Semen Analysis; Sperm Count; Sperm Motility; Testicular Neoplasms - blood; Testicular Neoplasms - epidemiology; Testosterone - blood; Young Adult
• ISSN: 0804-4643; 1479-683X; 1479-683X
• DOI: 10.1530/EJE-17-0862

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.