Men with nonobstructive azoospermia have Leydig cell hypertrophy but not hyperplasia

PURPOSE: We determined whether testicular histology in men with spermatogenic failure due to nonobstructive azoospermia shows true Leydig cell hyperplasia. MATERIALS AND METHODS: Testicular biopsy specimens from 17 patients evaluated for infertility were retrospectively analyzed. Interstitial, tubular and Leydig cell volume were quantitatively evaluated. The total volume and number of Leydig cells per testicle were then calculated. RESULTS: In 10 patients with obstructive azoospermia testicular histology showed normal spermatogenic function, while 7 had nonobstructive azoospermia. Average testicular volume plus or minus standard deviation was significantly larger in those with obstructive versus nonobstructive azoospermia (18.0 +/- 7.0 versus 9.3 +/- 8.7 cc, p = 0.025). Interstitial versus tubular volume was 32% of the total testis in the obstructive and 63% in the nonobstructive groups (p = 0.003). Although Leydig cell volume was proportionally greater in men with nonobstructive versus obstructive azoospermia (13.3% versus 0.05%, p = 0.045), there was no significant difference in the average number of Leydig cells per testicle (3.96 x 10 and 6.17 x 10, respectively, p = 0.16). The average volume of individual Leydig cells was significantly greater in men with the nonobstructive condition (253.0 +/- 98.7 versus 174.0 +/- 57.7 microm., p = 0.045). CONCLUSIONS: These results suggest that men with nonobstructive azoospermia and those with normal spermatogenesis have an equivalent number of Leydig cells. However, the Leydig cells are hypertrophic and occupy a larger proportion of total testis volume in men with nonobstructive azoospermia. Therefore, patients with spermatogenic failure show Leydig cell hypertrophy but not hyperplasia.