Estrogen metabolism and impaired spermatogenesis in germ cell tumors of the testis

We evaluated spermatogenesis in 36 patients with germ cell tumors [11 with seminoma (S) and 25 with nonseminoma (NS)] in terms of sperm concentration and histological score (Johnsen's mean score) of spermatogenesis in the ipsilateral and contralateral testes. We also measured the steroid concentration in the spermatic vein of the tumor-bearing side and performed biochemical and immunohistochemical studies of aromatase activity of the tumor to investigate the mechanism of exocrine and endocrine testicular dysfunction, with particular emphasis on the role of estrogen metabolism. The sperm concentration was significantly lower in patients with S (42.9 +/- 40.7 x 10(6)/mL) and NS (17.6 +/- 20.8 x 10(6)/mL) compared to normal adult men (114.4 +/- 41.2 x 10(6) mL; P < 0.01). The histological score was lower in patients with NS than in patients with S. The histological score was highest in the contralateral testis, followed by the ipsilateral testis far from the tumor and the ipsilateral testis near the tumor in both the S and NS groups. Serum levels of estradiol and hCG were significantly elevated in both the systemic and spermatic veins of patients with NS compared to normal values, but they were within normal limits in patients with S. The histological score count in the contralateral testis was significantly and inversely correlated with the tumor weight and serum levels of hCG and estradiol. Aromatase activity examined in 9 tumors (5 S and 4 NS) and 6 ipsilateral nonneoplastic testis (3 S and 3 NS) was significantly higher in both neoplastic and nonneoplastic testes in NS patients (tumor, 5.343 +/- 4.027; nontumor, 14.647 +/- 7.688 pmol/h . pg protein) compared to S patients (tumor, 0.622 +/- 0.408; nontumor, 1.979 +/- 1.164 pmol/h . pg protein). Aromatase immunoreactivity was observed in Leydig cells of the nonneoplastic testis in both S and NS patients and in interstitial or stromal cells in 16 of 25 of NS patients and none of S patients. Our results suggest that impaired spermatogenesis in patients with testicular germ cell tumor is caused by increased tumor size in both NS and S patients and/or by increased aromatization and in situ estrogen production In Leydig cells of the nonneoplastic testis and in interstitial or stromal cells of the tumor in patients with NS.