Human chorionic gonadotropin therapy in adolescent boys with constitutional delayed puberty vs those with β-thalassemia major

We studied 12 adolescent boys with β-thalassemia major and delayed puberty (age, 15.8 ± 1 years) with Tanner I sexual development treated with a long-term low-transfusion regimen. Ten nonthalassemic adolescents (> 14 years) with constitutional delay of growth and puberty (CDGP) served as controls. Auxologic parameters and testicular size were measured, and bone age was determined. Measurement of basal gonadotropin (luteinizing hormone [LH] and follicle-stimulating hormone [FSH]) and testosterone (T) levels taken at 8 am revealed prepubertal levels in both groups of patients. Human chorionic gonadotropin (hCG, 2500 U/m 2) was injected intramuscularly twice weekly for 6 months, and anthropometric data, testicular diameter, and serum T concentrations were remeasured after 1 and 6 months. The testicular diameter after 6 month of hCG therapy was significantly correlated with the testicular diameter and T level after 1 month of therapy (r = 0.93 and 0.39, respectively, P <. 01). After 6 months of hCG therapy, the mean growth velocity (GV) increased from 4.1 to 8.6 cm/y in thalassemic patients and from 4.6 to 10.3 cm/y in those with CDGP during hCG therapy. In thalassemic boys, the mean T concentration increased from 0.93 to 2.7 nmol/L (mean increase = 1.8 nmol/L) vs an increase from 0.47 to 4.81 nmol/L (mean increase = 4.32 nmol/L) in those with CDGP. All adolescents with CDGP, but only 7 the 12 thalassemic adolescents, had T secretion above 2 nmol/L after 6 months of hCG therapy and maintained their growth and pubertal development for a year after stopping hCG. The 5 thalassemic patients with defective T secretion after hCG therapy had significantly higher ferritin level (1985 ± 658 ng/mL) vs the other 7 patients (1100 ± 425 ng/mL). These findings denoted significant testicular dysfunction in those patients with higher iron overload (testicular siderosis). Statural GV was significantly correlated with insulin-like growth factor 1 (IGF-1) concentrations and testicular diameter after hCG therapy (r = 0.5 and 0.43 respectively, P <. 001). In summary, hCG therapy was effective in treating 7 of 12 (58%) of thalassemic adolescents with delayed puberty. In the rest of patients (5/12, 46%) with significantly higher iron overload, hCG therapy failed to stimulate testicular growth and adequate T. Proper iron chelation appears to protect against testicular dysfunction. In the first group of patients, hCG therapy can be used for the treatment of their hypogonadism, whereas T replacement remains the therapy of choice for the second group. © 2004 Elsevier Inc. All rights reserved.