madman
Super Moderator
An Approach to Testosterone Therapy in Men After Treatment for Localized Prostate (2022) Cancer
Aubrey Reeves, David W. Barham, * and Faysal A. Yafi
Abstract
Testosterone therapy (TTh) is a well-established and safe treatment for men with testosterone deficiency. Historically, great caution has been used in the use of testosterone in men with prostate cancer (PCa) given the pioneering work by Huggins and Hodges showing castration decreased serum acid phosphatase in men with metastatic PCa. For the past several decades new theories including the saturation, model have gained traction and as a result, the treatment of testosterone deficiency in men with PCa has been transformed. In men treated for localized PCa with prostatectomy, a growing body of evidence exists supporting its safety and efficacy in these men. In addition, it has been suggested that TTh may decrease biochemical recurrence. The data are more limited in men treated with radiation and there are no studies currently with a control group. Overall, the body of literature continues to grow suggesting the safety of TTh in well-selected men treated for localized PCa.
Introduction
Testosterone therapy (TTh) in hypogonadal males is a well-established and proven standard of care to ameliorate the signs and symptoms of low testosterone, including low libido, low energy, fatigue, decreased muscle mass, and decreased bone density.1,2
However, the history of testosterone deficiency and management has long been paralleled by a perennial discussion concerning its complex relationship with prostate cancer (PCa).
Attempts to elucidate the intricacies of the relationship between testosterone and PCa have given rise to a variety of models, the most historically pervasive being the androgen (AR) hypothesis model, first documented in the 1940s by Huggins and Hodges. This hypothesis represents a belief that there is a direct relationship between the level of ARs and the development or acceleration of PCa—a relationship reported by Huggins and Hodges following their findings of PCa regression in men who underwent castration or high-dose estrogen therapy and PCa growth in men given exogenous testosterone.3 This pioneering research led to a Nobel prize for Huggins in 1966 and also resulted in the twentieth-century dominance of the AR hypothesis as a primary informer of clinical decision-making concerning PCa. This work led to the popularization of androgen deprivation therapy (ADT), a treatment still employed today in severe or metastatic PCa.
Further studies reporting findings inconsistent with the AR hypothesis prompted the development of the saturation model, which postulated the existence of an AR saturation point, above which testosterone has no influence on the growth of PCa.4 In 2014, Morgentaler et al. published findings from a double-blind placebo-controlled study, consistent with the saturation model, which demonstrated a lack of significant variation in prostate-specific antigen (PSA) levels in men undergoing testosterone gel therapy, provided their baseline testosterone level was >250 ng/dL.5 These findings were also supported by a 2013 Rastrelli et al. study that noted the minimal impact of increasing testosterone on PSA levels once a concentration of 230–260ng/dL was achieved.6
Although there is still much to learn about the relationship between testosterone and PCa, there is currently insufficient data to suggest an increase in PCa risk or recurrence in those undergoing testosterone replacement therapy.7 However, there remains a United States Food and Drug Administration warning on TTh listing known or suspected PCa as a contraindication. Furthermore, the American Urological Association (AUA) guidelines on testosterone deficiency state there is inadequate evidence to quantify the risk-benefit of ratio of TTh in men with PCa.2 This review aims to provide a better understanding of the literature related to TTh in men treated with radical prostatectomy (RP) or radiation therapy (RT) to allow the clinician the ability to engage in shared decision-making when counseling men with testosterone deficiency and definitively treated PCa.
Results and Discussion
*Men treated with surgery
*Men treated with radiation
Conclusion
Overall, the use of TTh in men treated for localized PCa appears safe (Tables 1 and 2). The practice patterns of many urologists are changing in favor of using TTh. However, higher levels of evidence are needed to ultimately prove its safety. Hopefully, we will get to a point with stronger guideline statements in favor of TTh.
Aubrey Reeves, David W. Barham, * and Faysal A. Yafi
Abstract
Testosterone therapy (TTh) is a well-established and safe treatment for men with testosterone deficiency. Historically, great caution has been used in the use of testosterone in men with prostate cancer (PCa) given the pioneering work by Huggins and Hodges showing castration decreased serum acid phosphatase in men with metastatic PCa. For the past several decades new theories including the saturation, model have gained traction and as a result, the treatment of testosterone deficiency in men with PCa has been transformed. In men treated for localized PCa with prostatectomy, a growing body of evidence exists supporting its safety and efficacy in these men. In addition, it has been suggested that TTh may decrease biochemical recurrence. The data are more limited in men treated with radiation and there are no studies currently with a control group. Overall, the body of literature continues to grow suggesting the safety of TTh in well-selected men treated for localized PCa.
Introduction
Testosterone therapy (TTh) in hypogonadal males is a well-established and proven standard of care to ameliorate the signs and symptoms of low testosterone, including low libido, low energy, fatigue, decreased muscle mass, and decreased bone density.1,2
However, the history of testosterone deficiency and management has long been paralleled by a perennial discussion concerning its complex relationship with prostate cancer (PCa).
Attempts to elucidate the intricacies of the relationship between testosterone and PCa have given rise to a variety of models, the most historically pervasive being the androgen (AR) hypothesis model, first documented in the 1940s by Huggins and Hodges. This hypothesis represents a belief that there is a direct relationship between the level of ARs and the development or acceleration of PCa—a relationship reported by Huggins and Hodges following their findings of PCa regression in men who underwent castration or high-dose estrogen therapy and PCa growth in men given exogenous testosterone.3 This pioneering research led to a Nobel prize for Huggins in 1966 and also resulted in the twentieth-century dominance of the AR hypothesis as a primary informer of clinical decision-making concerning PCa. This work led to the popularization of androgen deprivation therapy (ADT), a treatment still employed today in severe or metastatic PCa.
Further studies reporting findings inconsistent with the AR hypothesis prompted the development of the saturation model, which postulated the existence of an AR saturation point, above which testosterone has no influence on the growth of PCa.4 In 2014, Morgentaler et al. published findings from a double-blind placebo-controlled study, consistent with the saturation model, which demonstrated a lack of significant variation in prostate-specific antigen (PSA) levels in men undergoing testosterone gel therapy, provided their baseline testosterone level was >250 ng/dL.5 These findings were also supported by a 2013 Rastrelli et al. study that noted the minimal impact of increasing testosterone on PSA levels once a concentration of 230–260ng/dL was achieved.6
Although there is still much to learn about the relationship between testosterone and PCa, there is currently insufficient data to suggest an increase in PCa risk or recurrence in those undergoing testosterone replacement therapy.7 However, there remains a United States Food and Drug Administration warning on TTh listing known or suspected PCa as a contraindication. Furthermore, the American Urological Association (AUA) guidelines on testosterone deficiency state there is inadequate evidence to quantify the risk-benefit of ratio of TTh in men with PCa.2 This review aims to provide a better understanding of the literature related to TTh in men treated with radical prostatectomy (RP) or radiation therapy (RT) to allow the clinician the ability to engage in shared decision-making when counseling men with testosterone deficiency and definitively treated PCa.
Results and Discussion
*Men treated with surgery
*Men treated with radiation
Conclusion
Overall, the use of TTh in men treated for localized PCa appears safe (Tables 1 and 2). The practice patterns of many urologists are changing in favor of using TTh. However, higher levels of evidence are needed to ultimately prove its safety. Hopefully, we will get to a point with stronger guideline statements in favor of TTh.
