Changes in gonadotropin regulation in both behavioral and phenotypic disturbances of sexual differentiation in men

Determinations of gonadotropins and testosterone were performed in 22 men with hypospadias (H), seven male-to-female transsexuals (T) and in 16 normal men (N), all of similar age. The response of serum FSH and LH to GnRH was determined in six subjects in each group. Oligospermia was found in five of 13 patients with H. All patients with transsexualism revealed normospermia. Both the patients with H and with T had significantly higher mean serum concentrations of LH than the normals (H: 16.96 +/- 13.83 mIU/ml; T: 15.30 +/- 6.50 mIU/ml; vs 5.73 +/- 3.66 mIU/ml in N). Also, an exaggerated response of LH to GnRH was found in both H and T. No negative correlations were demonstrated between serum LH and testosterone in either the H or the T. Rather, higher mean serum LH occurred together with higher mean serum testosterone in severe H. A significant elevation of basal serum FSH was found in H (H: 7.24 +/- 2.14 mIU/ml vs N: 4.84 +/- 1.65 mIU/ml), which might be related to underlying gonadal injury. No increase of serum basal FSH concentration was found in T patients, but the FSH response to GnRH was higher than in N. It is concluded that hypospadias, a phenotypic disturbance of sexual differentiation, represents a less-specific change in the gonadotropin regulation, while male transsexualism reveals hypergonadotropism with a specifically increased evocability of gonadotropins not coexisting with signs of gonadal injury.