Prior testosterone replacement therapy may impact spermatogenic response to combined gonadotropin therapy in severe congenital hypogonadotropic hypogonadism

Objective To study the effect of prior testosterone replacement therapy (TRT) on the spermatogenic response to combined gonadotropin therapy (CGT) in severe and partial phenotype congenital hypogonadotropic hypogonadism (CHH) patients. Design Retrospective cohort study. Setting Tertiary care center. Patients Patients of CHH without (n = 17) and with prior TRT (n = 18) were subdivided into severe and partial groups, based on mean testicular volume ≤ 3 cc and > 3 cc respectively. Intervention Participants were treated with hMG at a dose of 75–150 U 3/week and gradually escalating doses of hCG until maximum dose (2000 U 3/week or 5000 U 2/week) or serum total testosterone of ≥ 3.5 ng/ml was reached. Main outcome measures Final mean TV, trough serum testosterone (T), sperm concentration Results Thirty-five patients (20 severe, baseline mean TV of 3.6 ± 2.7 ml) were started on CGT at 24.8 ± 6.1 years. The median duration of prior TRT was 38 (IQR 10–63.75) months in the exposed group. After 33 ± 12 months, final mean TV was 8.9 ± 5.5 ml, 86% achieved serum testosterone > 3.5 ng/ml and 70% achieved spermatogenesis [median 5 (0–12.6) million/ml]. Patients without prior TRT had significantly higher peak sperm count than those with prior- TRT (median 9 vs 0.05 million/ml, p = 0.004). This effect of prior TRT was more pronounced in severe phenotype patients (median 7 vs 0 million/ml, p = 0.01). Conclusion Prior-TRT may interfere with spermatogenic response to CGT in CHH patients, especially in those with a severe phenotype.