Feminizing testicular Leydig cell tumor: hormonal profile before and after unilateral orchidectomy

The effect of chronic hyperestrogenism on gonadal function was studied in three men who had estrogen-secreting Leydig cell tumors before unilateral orchidectomy and for 11-43 months after surgery. All three men had low plasma gonadotropin and testosterone levels and increased estradiol levels. Impairment of testicular steroidogenesis was also suggested by increased progesterone to 17-hydroxyprogesterone and 17-hydroxyprogesterone to androstenedione ratios in both spermatic venous plasma and the medium of Leydig tumor cells from one patient incubated in vitro. Before surgery, spermatogenesis was abnormal in two men. Testicular endocrine function and spermatogenesis did not return to normal after surgery. During the follow-up period, plasma gonadotropin levels were high in all three men, and testosterone was low normal. Estradiol levels decreased to normal immediately after surgery and then returned to the upper normal limit. The response to hCG stimulation in one man was subnormal. We conclude that chronic hyperestrogenism produced hypothalamo-pituitary inhibition as well as direct steroidogenic blockade at the testicular level. Long term impairment of both endocrine and exocrine testicular functions may be secondary to slowly reversible (or irreversible) estrogen-induced damage to tubular and Leydig cells.