The hypothalamus–pituitary–gonad axis and testicular function in male patients after treatment for haematological malignancies

Abstract

The effect of aggressive chemotherapy on the hypothalamus-pituitary-gonad axis and on testicular function was assessed in nine male patients who had received chemotherapy only (CT, group I) and in 10 males after allogeneic bone marrow transplantation (BMT, group II). The mean time from CT or BMT to the assessment was 3.7 (range, 1.0-11.7) years. The responses of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were assessed by the gonadotropin-releasing hormone (GnRH) test and, in addition, serum basal values for testosterone and sex hormone binding globulin (SHBG) were measured and the free androgen index (FAI) was calculated. In 13/19 patients the human chorionic gonadotropin (hCG) test was performed. In group I, only one patient had an abnormal basal FSH value, but all (100%) had pathologically poor responses to the GnRH test. In contrast, all baseline FSH values were raised in group II (mean, 18; range, 11-30 U L-1), indicating toxic injury to the seminiferous tubules. Also in group II the responses to GnRH weer low throughout the test (90%) and there were no clear peak values. In group II, the basal FSH and its maximum response to GnRH were significantly more affected than in group I (P < 0.001). The difference may be due to the effect of the conditioning regimen. Serum basal LH was raised in three of the patients in group I and they also had abnormal releasing test responses. In group II, baseline LH was abnormal in four patients, but the responses to GnRH were normal. However, the maximum responses to the releasing test was significantly more affected in group II (P = 0.024). Serum testosterone levels were normal in all test subjects in both study groups. However, in two patients in both groups, the serum free androgen index was below the low reference limit, and an impaired response of serum testosterone to hCG stimulation was common (60%). A toxic injury in the testis is common in haematological patients, especially after high-dose chemoradiotherapy. Serum basal testosterone usually remains normal, but even then subnormal serum free androgen index, impaired testosterone response to hCG injection and abnormal response in LH may indicate a deficient androgen status. It may well be that testosterone replacement therapy should be considered in these cases.