Estradiol levels in men with congenital hypogonadotropic hypogonadism and the effects of different modalities of hormonal treatment.

Objective: To evaluate the degree of E2 deficiency in male congenital hypogonadotropic hypogonadism (CHH), and its response to different hormonal treatments.

Design: Retrospective and prospective studies.

Setting: Academic institution.

Patient(s): Untreated or treated CHH, healthy men, untreated men with Klinefelter syndrome (KS).

Intervention(s): Serum sex hormone-binding globulin (SHBG) and total E2 (TE2) as well as bioavailable (BE2) and free (FE2) levels were measured and determined.

Main Outcome Measure(s): Total, bioavailable, and free testosterone, TE2, BE2, FE2 were compared in normal men, untreated and treated CHH and in untreated KS.

Result(s): TE2, BE2, and FE2 levels were very significantly lower in untreated patients with CHH (n=91) than in controls (n=63) and in patients with KS (n=45). The TE2 correlated positively with serum total T in patients with CHH. The TE2 also correlated very positively with serum LH in the combined population of patients with CHH and healthy men, suggesting that low E2 levels in CHH are due to severe LH-driven T deficiency. All fractions of circulating E2 were very significantly higher in patients with CHH receiving T enanthate (n=101) or the FSH-hCG combination (n=88) than in untreated patients with CHH. Contrary to dihydrotestosterone (DHT), both T enanthate and combined FSH-hCG therapy significantly and prospectively increased TE2 levels in patients with CHH.

Conclusion(s): Contrary to KS, the male hypogonadism observed in CHH is associated with profound E2 deficiency, which can be overcome by aromatizable androgen or combined gonadotropin therapy.