Reproductive late effects and testosterone replacement therapy in male childhood cancer survivors: A population-based study (the Fex-Can study)

Nowadays, most children with cancer survive, but many experience long-term effects from their cancer treatment. Treatments like conditioning therapy for hematopoietic stem cell transplantation, high cumulative doses of alkylating agents and radiation can damage the gonads, leading to problems such as infertility and delayed puberty in males. Identifying and addressing these issues in follow-up care is crucial for their overall health and quality of life. However, treatments like testosterone replacement therapy (TRT) may come with their own risks, such as lower muscle mass, poorer physical fitness, and a higher android/gynoid fat ratio increasing the risk of cardiometabolic disease. The aim of this recent population-based study was to assess the prevalence and predictors of the endocrine and reproductive outcomes in male childhood cancer survivors. A secondary aim was to assess possible associations between TRT, and other endocrine, cardiovascular, and psychosocial late effects. The study involved 1212 young adults aged 19–40, identified from Sweden’s National Quality Registry for Childhood Cancer, and combined registry data and self-reports (Table 1).

The study revealed that 3.8% of the survivors self-reported hormone-induced puberty, and 6.0% were undergoing TRT. Notably, both hormone-induced puberty and TRT were significantly associated with hematopoietic stem cell transplantation and cranial radiotherapy, highlighting the impact of cancer treatments on the endocrine function. Hormone induced puberty was also associated with younger age at diagnosis. Furthermore, the study revealed that survivors on TRT were more likely to experience additional health complications, including increased fatigue and depressive symptoms, as well as a higher prevalence of cardiovascular risk factors. They were also less likely to live with a partner, have biological children, or have a current occupation. In the total male cohort, only 28.2% reported having a biological child, with older survivors being more likely to have offspring. Furthermore, the study revealed that childhood cancer survivors treated in the most recent treatment era characterized by less intensive therapies showed reassuring reproductive outcomes and/with a lower frequency of survivors undergoing TRT.

In conclusion, the study provides valuable insights into the prevalence and impact of hormone-induced puberty and TRT in male childhood cancer survivors. While the findings offer reassurance regarding reproductive outcomes after less intensive therapies in recent treatment eras, they also highlight the significant burden of late effects among survivors requiring TRT. These findings underscore the importance of long-term follow-up, timely initiation of effective TRT, and comprehensive support for male childhood cancer survivors. This includes monitoring for associated cardiovascular risks and psychosocial well-being to mitigate adverse effects. Furthermore, survivors should receive comprehensive counseling regarding fertility and late effects to address their complex health needs and optimize their quality of life.

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