(085) OPTIMAL RESTORATION OF SPERMATOGENESIS FOLLOWING TESTOSTERONE THERAPY USING HCG AND FSH

Abstract Introduction Testosterone monotherapy impedes spermatogenesis and often renders the male user azo- or severely oligospermic. Prior studies have demonstrated that rescue Human Chorionic Gonadotropin (HCG) and Clomiphene Citrate therapy can restore semen parameters, but report that just under half of men will respond favorably. Objective In the present study, we hypothesized that direct gonadotropic stimulation with HCG and purified Follicle Stimulating Hormone (FSH) (in lieu of indirect clomiphene-mediated FSH release) would result in improved recovery of spermatogenesis in oligospermic men with a history of testosterone use. Secondarily, we questioned whether concomitant use of Testosterone therapy during HCG/FSH “rebooting” of the testicles would dampen spermatogenic recovery as compared to those ceasing Testosterone therapy. Methods We performed a retrospective cohort study and identified 288 patients prescribed injections of 3000 IU HCG three times a week (TIW) and 75 IU FSH TIW from January 2020-March 2024 (we termed this therapy “reboot”). We then excluded those patients without prior use of testosterone replacement therapy (TRT), those with only one documented semen analysis, and those starting with normospermia (>15 million [M] sperm per mL). Our final cohort included 77 patients meeting these strict criteria, 50 of whom were not on concurrent testosterone replacement therapy during reboot (No TRT), and 27 of whom were (Concurrent TRT). Patient demographics, testicular size, hormone levels, and semen analyses during treatment were then compared between groups. Student’s t-test and One or Two-way ANOVA with multiple comparisons were used. P < 0.05 deemed significance. Results Within our cohort, 74% of all treated patients demonstrated an improvement in their semen parameters (mean duration of treatment 7 months); mean sperm concentrations increased from 2.2 M/mL to 15.2 M/mL after reboot (p < 0.0001 by paired t-test). Of those patients starting with azoospermia, 64.9% demonstrated return of sperm and 13.5% reached normospermia. Of those starting with severe oligospermia (<5 M/mL), 58.3% reached normospermia, and of those starting with oligospermia (>5 but <15 M/mL) 87.5% reached normospermia. Concurrent TRT during HCG/FSH reboot did not dampen spermatogenic recovery: 2.2 M/mL to 16.8 M/mL in the No TRT group and 2.2 M/mL to 12.3 M/mL in the Concurrent TRT group (p < 0.0001 by paired t-test). Conclusions We report the largest retrospective cohort study to date investigating the utility of gonadotropic HCG/FSH “reboot” therapy in restoring spermatogenesis in men with a history of testosterone use. Setting the groundwork for future prospective studies, we report improved recovery of spermatogenesis with this therapeutic regimen vs. conventional HCG/clomiphene citrate therapy. Moreover, we demonstrate that concurrent TRT does not impede HCG/FSH mediated spermatogenic recovery. Disclosure No.