Testosterone replacement in congenital hypogonadotropic hypogonadism maintains bone density but has only limited osteoanabolic effects.

Abstract

Congenital hypogonadotropic hypogonadism (CHH) is a rare condition characterized by complete sex steroid deficiency. Therefore, CHH is a unique human model to study the impact of long-term testosterone replacement therapy (TRT) on bone. In this single-center retrospective observational study, we assessed the long-term impact of TRT on femoral and lumbar bone mineral density (BMD) in adult CHH men. A total of 25 patients with CHH were included. Femoral and lumbar BMD was assessed by dual-energy X-ray absorptiometry (DEXA) and reported as T-scores. In six patients (treatment-naive group), BMD was measured before start of TRT. The other 19 (pre-treated group) had received TRT for a median duration of 7years (range 1-41years) before first BMD measurement. Age at which TRT was started ranged from 12 to 57years old. Median time between first and last DEXA scan was 11years (range 2-28). At the first DEXA scan, 83% and 61% of CHH patients had lumbar and femoral osteopenia/osteoporosis, respectively. In the treatment-naive group, the increase in lumbar T-score was 2.19±0.13 (mean ± SEM, p<0.01 between first and last DEXA scan) and 1.47±0.29 at femoral level (p<0.001). For the pre-treated group, the increase in lumbar and femoral T-score was 0.77±0.17 (p<0.001) and 0.19±0.12 (p=0.13), respectively. However, lumbar and femoral osteopenia/osteoporosis persisted in 61% and 48% of CHH patients even after several years of continuous TRT. Additionally, BMD clearly decreased in patients who interrupted TRT. Despite modest improvement after starting TRT, BMD remains in the osteopenic/osteoporotic range in most patients with CHH. However, prolonged TRT prevents further bone loss, both at lumbar and femoral level.