Impact of Estrogen Replacement Therapy on Hypogonadal Survivors of Childhood Cancer

Abstract

Background: Hypogonadism is a significant late complication in childhood cancer survivors (CCS). The aim of this study was to elucidate the benefits and limitations of estrogen replacement therapy (ERT) for CCS with hypogonadism. Methods: Seventeen CCS were divided into two groups: gonadal hypogonadism (GH) group (n=8) and central hypogonadism (CH) group (n=9). Pearson correlation coefficients were used to investigate the impact of cancer management on final height, bone density, and uterine development. Results: Seven of GH group had hematologic malignancies, and all of them underwent total body irradiation before bone marrow transplantation. The GH group showed significant positive correlations between the onset age of disease treatment and final height (p < 0.05, R = 0.712) and uterine size following ERT (p < 0.05, R = 0.775). All CCS in the CH group had brain tumors, and seven of them received chemotherapy. There were trends towards positive and negative correlations between the onset age of disease treatment and final height (p = 0.09, R = 0.527) or uterine size (p = 0.07, R = -0.669), respectively. A negative correlation trend was observed between the age at ERT initiation and final height (p = 0.07, R = -0.769) or bone density (p = 0.18, R = -0.626) in six CH patients who received growth hormone therapy. Five CCS in both groups experienced osteoporosis, despite receiving ERT. Conclusion: Individualized management strategies beyond ERT are essential to reduce long-term complications in CCSs with hypogonadism, considering the type and timing of cancer treatment.