Abstract
In both cardiovascular disease and cancer, there are established sex-based differences in prevalence and outcomes. Males and females may also differ in terms of risk of cardiotoxicity following cancer therapy, including heart failure, cardiomyopathy, atherosclerosis, thromboembolism, arrhythmias, and myocarditis. Here, we describe sex-based differences in the epidemiology and pathophysiology of cardiotoxicity associated with anthracyclines, hematopoietic stem cell transplant (HCT), hormone therapy and immune therapy. Relative to males, the risk of anthracycline-induced cardiotoxicity is higher in prepubertal females, lower in premenopausal females, and similar in postmenopausal females. For autologous hematopoietic cell transplant, several studies suggest an increased risk of late heart failure in female lymphoma patients, but sex-based differences have not been shown for allogeneic hematopoietic cell transplant. Hormone therapies including GnRH (gonadotropin-releasing hormone) modulators, androgen receptor antagonists, selective estrogen receptor modulators, and aromatase inhibitors are associated with cardiotoxicity, including arrhythmia and venous thromboembolism. However, sex-based differences have not yet been elucidated. Evaluation of sex differences in cardiotoxicity related to immune therapy is limited, in part, due to low participation of females in relevant clinical trials. However, some studies suggest that females are at increased risk of immune checkpoint inhibitor myocarditis, although this has not been consistently demonstrated. For each of the aforementioned cancer therapies, we consider sex-based differences according to cardiotoxicity management. We identify knowledge gaps to guide future mechanistic and prospective clinical studies. Furthering our understanding of sex-based differences in cancer therapy cardiotoxicity can advance the development of targeted preventive and therapeutic cardioprotective strategies.
Overview
- The study focuses on sex-based differences in the epidemiology and pathophysiology of cardiotoxicity associated with anthracyclines, hematopoietic stem cell transplant (HCT), hormone therapy, and immune therapy. The hypothesis being tested is that there are sex-based differences in the risk and management of cardiotoxicity related to these cancer therapies. The methodology used for the experiment includes a review of existing literature on the topic. The primary objective of the study is to identify knowledge gaps and guide future mechanistic and prospective clinical studies to advance the development of targeted preventive and therapeutic cardioprotective strategies.
Comparative Analysis & Findings
- The study compares the outcomes observed under different experimental conditions or interventions detailed in the study. The results show that the risk of anthracycline-induced cardiotoxicity is higher in prepubertal females, lower in premenopausal females, and similar in postmenopausal females. For autologous hematopoietic cell transplant, several studies suggest an increased risk of late heart failure in female lymphoma patients, but sex-based differences have not been shown for allogeneic hematopoietic cell transplant. Hormone therapies including GnRH modulators, androgen receptor antagonists, selective estrogen receptor modulators, and aromatase inhibitors are associated with cardiotoxicity, including arrhythmia and venous thromboembolism. However, sex-based differences have not yet been elucidated. Evaluation of sex differences in cardiotoxicity related to immune therapy is limited, in part, due to low participation of females in relevant clinical trials. However, some studies suggest that females are at increased risk of immune checkpoint inhibitor myocarditis, although this has not been consistently demonstrated. For each of the aforementioned cancer therapies, the study considers sex-based differences according to cardiotoxicity management.
Implications and Future Directions
- The study's findings highlight the importance of understanding sex-based differences in cancer therapy cardiotoxicity to advance the development of targeted preventive and therapeutic cardioprotective strategies. The study identifies knowledge gaps that need to be addressed in future research, such as elucidating sex-based differences in immune checkpoint inhibitor myocarditis and further exploring the role of hormone therapies in cardiotoxicity. The study suggests possible future research directions, including mechanistic studies to understand the underlying mechanisms of sex-based differences in cardiotoxicity and prospective clinical studies to evaluate the effectiveness of targeted cardioprotective strategies in different populations.