Context: The Leucine-75-Proline variant of Apolipoprotein A-I (Apo A-I) leads to a new hereditary systemic amyloidosis involving mostly the liver and kidney.

Objective: To examine the effects of this amyloidosis on testicular structure and function.

Design: This was an observational study in which patients with testicular amyloidosis were characterized.

Setting: The study was carried out at the Endocrinology Department of Brescia University.

Patients or Other Participants: Over a 13-year period, 25 patients were found to be affected by Leu75Pro Apo A-I testicular amylodosis. Thirteen had the testicle as the first or only organ involved (group1), in 12 testicular damage followed that of other organs (group 2).

Interventions: There were no interventions.

Main Outcome Measure: Hormone and lipidic profiles, semen analysis, echographic volume of testicles, testicular histology and genetic analysis were carried out.

Results: Group 1 patients were younger than those of group 2. In group 1, 8 had hypergonadotropic hypogonadism and 5 were normogonadic with high gonadotropins; in group 2 all subjects were hypogonadic. All men had low HDL values. Group 1 patients were macrorchid, whereas the testicular volume was at the highest limit in group 2 (group 1 vs group 2, P<0.05). All men in the first group and 6 in the second group were azoospermic, the remaining had oligoposia. Biopsies showed the germinal epithelium replaced by amyloid. Leydig cells were essentially preserved in normogonadic, but not in hypogonadic patients.

Conclusions: This amyloidosis may determine infertility, macro-orchidism and hypogonadism. Endocrine impairment follows spermatogenic impairment.