Leydig cell failure with testicular radiation doses <20Gy: The clinical effects of total body irradiation conditioned haematopoietic stem cell transplantation for childhood leukaemia during long‐term follow‐up

Abstract

Objective Testosterone replacement is generally considered likely to be required only at testicular radiation doses in excess of 20Gy. Long‐term data are not available for patients receiving 9‐14.4Gy as part of Total Body Irradiation in childhood. Design Retrospective cohort study. Data collection: notes review, laboratory results, prescription of testosterone. Patients Forty‐two of 96 boys who received Total Body Irradiation (9‐14.4Gy) and Haematopoietic Stem Cell Transplantation for childhood leukaemia at Great Ormond Street Hospital between 1981‐2011 and survived >5 years. Measurements The serum concentrations of testosterone and gonadotrophins and the prescription of testosterone were recorded. Results Of the 42 boys included, 37 (88%) entered puberty spontaneously and 5 required induction. Median length of follow‐up was 19.4 years (range 5‐33.1). At last follow‐up, 23 of the 37 (62%) with spontaneous puberty were receiving testosterone replacement and 4 of the 5 (80%) with induced puberty. Conclusion This study with the benefit of long follow‐up indicates that Leydig cell failure occurs with radiation doses <20Gy. It may occur many years after irradiation and mandates long‐term screening for hypogonadism.

Childhood reproductive hormone levels after pediatric hematopoietic stem cell transplantation in relation to adult testicular function

“…These patients differed regarding diagnosis and treatment regimens, implying a possible genetic component in the risk of Leydig cell failure, which should be addressed in future studies. Another three patients, transplanted after the onset of puberty, developed biochemical testosterone deficiency over time, lending support to Taneja et al that recently reported a substantial risk of deterioration in Leydig cell function in adulthood after pediatric HSCT (22). Taken together, these findings emphasize the need for systematic evaluation of Leydig cell function during puberty and into adulthood to allow timely treatment of testosterone deficiency.…”

Physical Fitness and Frailty in Males after Allogeneic Hematopoietic Stem Cell Transplantation in Childhood: A Long-Term Follow-Up Study

“…Several trials have reinforced the beneficial effects of testosterone therapy on muscle strength and symptoms of frailty [ 31 ]. After pediatric HSCT, gradual deterioration of Leydig cell function has been reported and a clinically significant reduction may first be detected in early adulthood [ 12 , 32 ]. Therefore, male long-term survivors of pediatric HSCT require special attention regarding symptoms of testosterone deficiency.…”

Fertility and sexual dysfunction in young male cancer survivors

“…When the total pelvic radiation dose is 4 Gy or more, molecular changes can occur, 60 and if the dose exceeds 20 Gy, androgen supplementation might be needed in the future. 61 In addition, TKI imatinib is said to damage Leydig cells and cause a decrease in testosterone production. 9 Besides radiation therapy to the brain, immune checkpoint inhibitors, such as nivolumab, may cause pituitary inflammation and may reduce gonadotropin secretion and subsequent testosterone production.…”

“…Although less sensitive than germ cells, Leydig cells are also damaged by radiation. When the total pelvic radiation dose is 4 Gy or more, molecular changes can occur, 60 and if the dose exceeds 20 Gy, androgen supplementation might be needed in the future 61 . In addition, TKI imatinib is said to damage Leydig cells and cause a decrease in testosterone production 9 .…”