Congenital hypogonadotropic hypogonadism in men as a cause of estradiol deficiency
Severine Trabado1, Luigi Maione2, Sylvie Salenave1, Stéphanie Baron1, Françoise Galland1, Antonio-Agostino Sinisi2, Sylvie Brailly-Tabard1 & Jacques Young1
Context: Congenital hypogonadotropic hypogonadism (CHH), is a rare disorder associated with severe testosterone deficiency and with impaired bone mineral mass (BMM) acquisition and osteoporosis. Estradiol (E2) play a major role in bone development and maintain in BMM in humans.
Objective: To evaluate in detail the degree of E2 deficiency in adult men with CHH.
Design and patients: Using a sensitive E2 assay, we measured serum total E2 (TE2) and bioavailable E2 (BE2) in 83 untreated CHH men (31.1±11.6 years (mean±S.D.)) comparatively to 63 similarly aged (34.0±11.4 years) normal men and to 33 subjects with Klinefelter syndrome (34.5±11.8). In these three groups we also measured SHBG and free E2 (FE2).
Results: In CHH men, total E2 (7.4±4.2 vs 17.6±6.6 pg/ml in controls; mean±S.D.; P<0.0001) and bioavailable serum E2 (5.1±3.5 vs 13.7±5.7 pg/ml; P<0.0001) as well as FE2 (0.21±0.13 vs 0.59±0.23 pg/ml; P<0.0001) were very significantly lower than in normal men and than in subjects with Klinefelter syndrome (TE2: 16.0±7.2 pg/ml, BE2: 12.4±5.7 pg/ml and FE2: 0.53±0.22 pg/ml in the later respectively; P<0.01). Mean (±S.D.) serum SHBG concentrations were 28.2±10.3, 40.0±24.8 and 27.4±15.1 (nmol/l) in controls, CHH and Klinefelter respectively. In CHH patients serum total E2 was positively correlated with serum total testosterone (r=0.35, P<0.03). Finally, in CHH and normal men taken on the whole, serum TE2 levels were very positively correlated (R=0.57; P<0.0001) with serum LH levels indicating a relationship between the low E2 levels and the severity of LH-drived testosterone deficiency in CHH.
Conclusion: Our data demonstrate that hypogonadism in CHH men is a condition clearly associated with a deep E2 deficiency. The therapeutic relevance of these results will be discussed.