P12 - ECE_3277 - Effects of modified release hydrocortisone on reproductive function in males with congenital adrenal hyperplasia. insights from CALLIOPE: a multicenter, prospective study

Abstract

Patients with congenital adrenal hyperplasia (CAH) frequently experience impaired reproductive function, including altered spermatogenesis and the development of testicular adrenal rest tumors (TARTs). Modified-release hydrocortisone (MR-HC), by mimicking the circadian rhythm of cortisol, has shown benefits in hormonal control and quality of life. However, the specific impact of this new treatment on male reproductive function in CAH patients remains poorly explored. To evaluate the effectiveness of MR-HC on male reproductive function in adult patients with CAH. Between July 2024 and May 2025, adult male patients with confirmed CAH were enrolled in the prospective, longitudinal, multicenter CALLIOPE study. Participants were assessed before and approximately 6 months after switching from conventional therapy to an equivalent dose of MR-HC. Assessments included semen analysis, hormonal profiling, and multiparametric testicular ultrasound to evaluate TARTs. Metabolic parameters were also analyzed. 32 patients (mean age 29.5 ± 7 years) were enrolled. TARTs were detectable in 20 (62.5%). After 5.7 months of MR-HC treatment (IQR 25-75: 4.11-6.21), a significant increase was observed in sperm concentration [+72.3% (95% CI: +22.79;+121.81, P = .006)] and total sperm count in the ejaculate [+71.84% (95% CI: +6.97;+136.72, P = .032)], whereas no significant changes were found in qualitative parameters (progressive motility and morphology). Ultrasound analysis showed a trend toward a reduction in total TART volume [−0.24 mL (95% CI: −0.60;+0.12 mL; P = .055)]. Hormonal analysis revealed unchanged Testosterone, Androstenedione and 17OH-Progesterone levels, with a significant increase in LH levels (P = .047), suggesting reduced suppression of the hypothalamic-pituitary-gonadal axis. Our findings suggest a beneficial effect of MR-HC therapy on semen parameters and TARTs volume in adult male patients with CAH. These results highlight the need for further studies in larger cohorts with long-term follow-up to fully characterize the efficacy profile of MR-HC on reproductive function.