EVIDENCE OF ESTRADIOL-INDUCED CHANGES IN GONADOTROPIN-SECRETION IN MEN WITH FEMINIZING LEYDIG-CELL TUMORS

To study the sex steroid-gonadotrophin relationship, plasma oestradiol (E(2))1 testosterone and gonadotrophin-releasing hormone (GnRH)-induced (100 mu g iv) gonadotrophin response were measured in 42 male partners of infertile couples with normal sperm count (group I) and in 21 men with Leydig cell tumour (LCT, group II) in which a basal evaluation was repeated after tumour removal. Plasma free alpha-subunit (FAS), immunoreactive alpha-inhibin and luteinizing hormone (LH) pulse analysis were assessed in 10 LCT before and in six of them after surgery. Testosterone was significantly (p < 0.01) lower whereas E(2) was significantly (p < 0.001) higher in group II than in group I. Gonadotrophin data were similar in both groups. The mean FAS was higher in group II than in group I and alpha-inhibin was higher than the normal range in 6/10 LCT. In group II, E(2) levels were significantly (p < 0.01) and negatively correlated with testosterone, FSH, GnRH-induced gonadotrophin rise and LH pulse amplitude but not frequency. Significant (p < 0.001) changes were observed after surgery: E(2) and alpha-inhibin fell; testosterone, LH and FSH rose; whereas FAS did not change significantly. The LH pulse amplitude but not frequency increased significantly (p < 0.05). In conclusion E(2) oversecreted by LCT decreased LH and testosterone levels concomitantly. The GnRH-induced gonadotrophin level rose and the LH pulse amplitude decreased when the plasma El level rose, whereas the pulse frequency remained unaffected. A concomitant increase in alpha-inhibin and E(2) is likely to be responsible for the drop in plasma FSH levels. These data support an action of excessive amounts of E(2) at pituitary level, perhaps by decreasing the sensitivity of gonadotrophs to GnRH.