Abstract
Context. Hypogonadotropic hypogonadism (HH) is a clinical condition defined by subnormal serum testosterone levels with low serum gonadotropins, which leads to infertility and reduced testicular function in men. HH may be prenatal or congenital (CHH) or acquired (AHH), the latter most commonly related to injury at the hypothalamic/pituitary level. Since diverse medical specialists usually deal with these two disorders, a direct comparison of clinical characteristics and reproductive hormone levels in patients with CHH and AHH has never been performed in a large series. Patients and methods. 201 men with CHH (Kallmann syndrome 52%; normosmic CHH 48%) and 479 men with AHH were included. Causes for AHH included pituitary tumors (74.6%), other intracranial tumors (12.7%; craniopharyngioma 9.1%), infiltrative diseases (3.5%), and other causes (9.2%). We excluded patients with idiopathic late-onset or metabolically-related AHH from this analysis. Testicular volume (TV), serum gonadotropins, total and bioavailable testosterone (TT and BT), estradiol (E2) and testicular peptides inhibin B (IB), AMH and INSL3 were measured at a single center in the absence of any hormone replacement. Results. TV was greater in patients with AHH (16.2±6.3 mL) than in those with CHH (3.4±2.7 mL; p<0.0001). Testicular hypotrophy (mean TV<12 mL) was found in 30% of patients with AHH and in 97% of those with CHH (p<0.0001). When adjusted for age and BMI, men with AHH still had a larger mean TV than those with CHH (p<0.0001). Cryptorchidism was more frequent in patients with CHH than in those with AHH (20.4 vs 0.2%, p<0.0001). Micropenis was found exclusively in patients with CHH. TT levels were higher in patients with AHH (1.4±0.9 ng/mL) than in those with CHH (0.4±0.3 mL, p<0.0001). LH, FSH, BT and E2 were higher in patients with AHH than in those with CHH (p<0.0001 for all parameters), as were IB and INSL3 levels (126±87 vs 59±55 pg/mL, and 566±372 vs 60±40 pg/mL, respectively, p<0.001). In contrast, serum AMH and SHBG levels were lower in patients with AHH than in those with CHH (246±234 vs 46±38 pmol/L, and 35±22 vs 26±21 nmol/L, respectively, p<0.0001). Comparing hormone characteristics across different AHH subgroups, patients with craniopharyngioma (n=44) had lower TV (7.7±5.3 mL) and lower TT, BT, E2, IB and INSL3 levels than those with AHH caused by any other etiology (p<0.05 for all parameters). Conclusions. Our data demonstrate distinct profiles of clinical presentation and reproductive hormones between CHH and AHH. Clinical and hormonal impairment is more severe in patients with CHH than in those with AHH. Preservation of the gonadotrope/testicular axis activity during the fetal, neonatal and pubertal periods in patients with AHH likely accounts for these differences. Among AHH etiologies, patients with craniopharyngioma have the most severe impairment, likely as a result of the intrinsic severity of these tumors, the age at onset, and/or the aggressiveness of the available therapeutic procedures.
Age-related changes in serum reproductive hormone levels and prevalence of androgen deficiency in Chinese community-dwelling middle-aged and aging men
