SAT-449 Novel 11-oxyandrogens and Other Biomarkers in Relation to Male Infertility in Classic Congenital Adrenal Hyperplasia

Abstract Disclosure: S. Vaid: None. D. Bick: None. J. Marko: None. Z. Kuang: None. X. Li: None. A. Moon: None. A. Poch: None. P. Shin: None. Background: Men with classic CAH due to 21- hydroxylase deficiency (21OHD) commonly have subfertility secondary to poor disease control and/or testicular adrenal rest tumors (TART). Objective: Evaluate novel biomarkers including 11-oxyandrogens and standard biomarkers of disease control in relation to semen analysis and TART findings in males with classic CAH. Methods: A cross-sectional study was conducted at the National Institutes of Health Clinical Center as part of a Natural History Study (NCT00250159). Adult males underwent hormonal testing, semen analysis, and testicular ultrasound. Categorical and continuous data were compared between groups using Fisher’s exact test and Wilcoxon rank-sum test, respectively. Spearman rank correlation coefficients were calculated to assess the relationship between two continuous variables. Results: Thirty-eight men with classic CAH [28 (SW) (73.7%) and 10 (SV) (26.3%)] participated. 22(57.9%) had TART, 8(21.1%) had hypogonadotropic hypogonadism (HH), 7(18.4%) had azoospermia, and 5(13.2%) had oligospermia. Patients were receiving glucocorticoids at hydrocortisone equivalent dose mean ± SD: 30.4±16.1 mg/day. Patients with low vs normal total motile sperm count (TMSC) had higher median(IQR) 11-Ketotestosterone (11KT) [347(94.5-516) vs 67.4(11.0-107) ng/dL; P=0.006], 11-OHtestosterone (11OHT) [134(36.8-203) vs 22(3.6-35) ng/dL; P=0.004], 11-hydroxyandrostenedione (11OHA4) [908(125-2150) vs 207(21.5-365) ng/dL; P=0.03], 11KT:Testosterone (T) [1(0.1-1.3) vs 0.1(0-0.3); P=0.015], 11OHT:T [0.3(0.1-0.7) vs 0.04(0-0.1); P=0.01], higher estrone (E1) [123(68.5-189) vs 44.0(24.5-96.5) pg/mL; P=0.04], higher estradiol (E2) [25(21.6-36.5) vs 18.5(12.0-23.3) pg/mL; P=0.006] and higher E2:T [0.07 (0.06-0.13) vs 0.03(0.02-0.06); P=0.005]. Patients with TART vs without had lower median(IQR) sperm concentration [18(0-42) vs 47(34-72) 106/mL; P=0.010], lower percent motility % [54(0-66) vs 65(55-71); P=0.05], lower TMSC x 106/mL [24(0-70) vs 109(31-173); P=0.01], higher 11KT [180(27-376) vs 76.2(2.6-107) ng/dL; P=0.02], higher 11OHT [32.0(11-153) vs 23(0.5-38.6) ng/dL; P=0.03], higher 11KT:T [0.17(0.04-1) vs 0.14(0-0.3); P=0.03], and higher 11OHT:T [0.08(0.02-0.5) vs 0.04(0-0.08); P=0.03]. No differences were observed in 17 hydroxyprogesterone, androstenedione, FSH, T, A4:T and prevalence of HH. 11KT:T and 11OHT:T correlated inversely with sperm concentration: (rs=-0.48, P=0.003; rs=-0.49, P=0.002). Conclusion: 11-Oxyandrogens, 11KT:T and 11OHT:T, unlike the standard hormonal measurements of disease control, might serve as useful biomarkers in the evaluation of male infertility in CAH. Excess estrogens and the presence of TART also play a role. Presentation: Saturday, July 12, 2025