Effects of Chemotherapy-Induced Testicular Damage on Inhibin, Gonadotropin, and Testosterone Secretion: A Prospective Longitudinal Study

To investigate the role of inhibin in the control of follicle-stimulating hormone (FSH) secretion, we have measured levels of immunoreactive inhibin (ir-inhibin), inhibin B, Pro-alpha C containing inhibins, FSH, luteinizing hormone (LH), and testosterone in twelve men with hematological malignancies before, during, and after chemotherapy. Inhibin B levels fell significantly by 1 month from a mean +/- SE baseline level of 273.2 +/- 32.8 pg/mL, reaching a nadir of 52.6 +/- 15.3 pg/mL at 4 months (P < 0.0001). FSH levels increased within the first month from a baseline level of 3.9 +/- 0.6 IU/L, reaching a peak level of 22.4 +/- 3.3 IU/L at 4 months (P < 0.0001). FSH and inhibin B were significantly and inversely correlated (r = 0.69, P < 0.0001). Pro-alpha C containing inhibin levels increased significantly (P < 0.05) at 3 months and were significantly and positively correlated with FSH (r = 0.38, P = 0.002). LH levels increased significantly but to a much lesser extent than FSH, the increase becoming evident only 4 months after treatment commenced (P < 0.03). Levels of ir-inhibin and testosterone remained unchanged throughout the study. These data provide strong support to the hypothesis that inhibin B is the physiologically important form of inhibin in men, negatively regulating FSH secretion at the pituitary. Furthermore, they suggest that FSH stimulates inhibin alpha-subunit secretion by the testis.