madman
Super Moderator
Testosterone Therapy in Men on Active Surveillance (2022)
Tristan Chun, Jacob Tannenbaum, Haley Watts, Igor Voznesensky, Wael Almajed, and Wayne J.G. Hellstrom*
Abstract
In recent decades, although prostate cancer (PCa) mortality has dramatically decreased, addressing the quality of life for PCa survivors has become an area of great interest. This is especially important among men who are enrolled in active surveillance (AS) to manage their PCa. Since men with PCa are likely to experience erectile dysfunction, decreased libido, and loss of lean muscle mass secondary to testosterone deficiency (TD) as a consequence of antitumor therapies or advanced age, testosterone therapy (TTh) is typically the indicated treatment to alleviate the symptoms of TD. However, due to the theoretical causal relationship of increased testosterone levels leading to PCa development, the usage of TTh in men who have been diagnosed with PCa has long been the subject of debate. As there is an increased number of men with PCa who are enrolling in AS for the management of PCa, there needs to be an evaluation of the safety and efficacy of TTh in this cohort. Recently, the previous relationship between TTh and PCa has been challenged, and emerging evidence suggests that TTh may not be directly associated with PCa development or progression. Instead, TTh usage may safely improve the quality of life for those men on AS. This review summarizes and analyzes the latest findings on the use of TTh in men on AS for PCa.
Introduction
Testosterone deficiency (TD) is defined by the American Urological Association (AUA) as a serum total testosterone level below 300 ng/dL.1 The AUA provides additional guidelines that expound on the indication for testosterone therapy (TTh) in TD, including the need for two independent measurements of morning serum testosterone levels taken on separate occasions, the presence of hypogonadal symptoms, and the measurement of confounding hormone levels, namely prolactin and luteinizing hormone.
Serum testosterone levels meeting the criteria for TD have been observed in up to 38.7% of men older than the age of 45.2 Considering this observation, it is estimated that up to 5.6% of men between the ages of 30 and 79 experience symptomatic TD, with a significant increase in prevalence with age.3 TTh has been utilized to treat individuals with classical TD/hypogonadism and has been demonstrated to promote many health benefits and foster an improved quality of life with enhanced erectile function, increased libido, elevated bone mineral density, and augmented lean body mass.4
Further, TTh has demonstrated significant benefits in reducing insulin resistance in obese men and facilitating decreased fat mass and increased skeletal muscle, thereby reducing the risk of sequential type 2 diabetes and metabolic syndrome.5 Adverse side effects reported with TTh include polycythemia, gynecomastia, and lowered HDL cholesterol.6
As TTh usage becomes more widespread, it is important to understand its role in the management of hypogonadal men living with prostate cancer (PCa). PCa is a prevalent malignancy, with an estimated 268,490 new cases expected among American men in 2022.7 One of the most significant risk factors for PCa is age, with an average age of diagnosis at 66 and an increased risk in aging populations.8 When PCa is low grade, slowly progressing, and limited locally to the prostate gland, active surveillance (AS) is an accepted treatment option that does not burden patients with the adverse effects of radiation, chemotherapy, or anti-androgen therapies.
Although patients suitable for AS are not considered to be at immediate risk for fulminant PCa, they remain at risk for other ailments of aging men. An additional common affliction of aging males is hypogonadism, with more than 12%, 20%, 30%, and 50% of males experiencing hypogonadism in their fifth, sixth, seventh, and eighth decade of life, respectively.9 The standard of care for men suffering from hypogonadism is TTh, which subjectively improves their quality of life.
In recent years, there have been vast improvements in PCa treatment outcomes and a notable decrease of around 50% in the rate of PCa mortality, with an associated increase in the number of men on AS.10 Many of these individuals will live longer but, in turn, may suffer the consequences of hypogonadism or TD, such as erectile dysfunction, loss of lean body mass, decreased libido, and a decrease in quality of life.11 Subjects in this cohort would likely benefit from TTh. However, its utility cannot be wholeheartedly endorsed without a complete understanding of the risk–benefit profile. In this communication, the available evidence on TTh’s safety, efficacy, and potential usage in men on AS is reviewed.
*Testosterone and PCa
*TTh in Men on AS
Conclusion
In recent years, several investigations have begun to question the entrenched belief of T and DHT uniformly as drivers of PCa. After evaluating the current literature addressing the possible benefits of TTh utility in improving the quality of life of men on AS for PCa, it is evident there may be less risk and more benefit than previously understood. Although there are limited studies regarding TTh for men with hypogonadism and on AS, the results of these early studies are promising, as they have documented little to no association between TTh and PCa progression for this population. Given that an increasing number of men are electing AS as a treatment strategy for PCa, clinicians should consider the importance of PCa management plans and how to optimize quality-of-life measures.
It is hoped that future studies continue to explore and expand investigations on TTh use for men on AS to eliminate the uncertainty regarding a therapy that could potentially improve the quality of life and overall well-being of PCa patients. These studies should also focus on providing information for a risk–benefit analysis that patients may reference when making healthcare decisions.
Tristan Chun, Jacob Tannenbaum, Haley Watts, Igor Voznesensky, Wael Almajed, and Wayne J.G. Hellstrom*
Abstract
In recent decades, although prostate cancer (PCa) mortality has dramatically decreased, addressing the quality of life for PCa survivors has become an area of great interest. This is especially important among men who are enrolled in active surveillance (AS) to manage their PCa. Since men with PCa are likely to experience erectile dysfunction, decreased libido, and loss of lean muscle mass secondary to testosterone deficiency (TD) as a consequence of antitumor therapies or advanced age, testosterone therapy (TTh) is typically the indicated treatment to alleviate the symptoms of TD. However, due to the theoretical causal relationship of increased testosterone levels leading to PCa development, the usage of TTh in men who have been diagnosed with PCa has long been the subject of debate. As there is an increased number of men with PCa who are enrolling in AS for the management of PCa, there needs to be an evaluation of the safety and efficacy of TTh in this cohort. Recently, the previous relationship between TTh and PCa has been challenged, and emerging evidence suggests that TTh may not be directly associated with PCa development or progression. Instead, TTh usage may safely improve the quality of life for those men on AS. This review summarizes and analyzes the latest findings on the use of TTh in men on AS for PCa.
Introduction
Testosterone deficiency (TD) is defined by the American Urological Association (AUA) as a serum total testosterone level below 300 ng/dL.1 The AUA provides additional guidelines that expound on the indication for testosterone therapy (TTh) in TD, including the need for two independent measurements of morning serum testosterone levels taken on separate occasions, the presence of hypogonadal symptoms, and the measurement of confounding hormone levels, namely prolactin and luteinizing hormone.
Serum testosterone levels meeting the criteria for TD have been observed in up to 38.7% of men older than the age of 45.2 Considering this observation, it is estimated that up to 5.6% of men between the ages of 30 and 79 experience symptomatic TD, with a significant increase in prevalence with age.3 TTh has been utilized to treat individuals with classical TD/hypogonadism and has been demonstrated to promote many health benefits and foster an improved quality of life with enhanced erectile function, increased libido, elevated bone mineral density, and augmented lean body mass.4
Further, TTh has demonstrated significant benefits in reducing insulin resistance in obese men and facilitating decreased fat mass and increased skeletal muscle, thereby reducing the risk of sequential type 2 diabetes and metabolic syndrome.5 Adverse side effects reported with TTh include polycythemia, gynecomastia, and lowered HDL cholesterol.6
As TTh usage becomes more widespread, it is important to understand its role in the management of hypogonadal men living with prostate cancer (PCa). PCa is a prevalent malignancy, with an estimated 268,490 new cases expected among American men in 2022.7 One of the most significant risk factors for PCa is age, with an average age of diagnosis at 66 and an increased risk in aging populations.8 When PCa is low grade, slowly progressing, and limited locally to the prostate gland, active surveillance (AS) is an accepted treatment option that does not burden patients with the adverse effects of radiation, chemotherapy, or anti-androgen therapies.
Although patients suitable for AS are not considered to be at immediate risk for fulminant PCa, they remain at risk for other ailments of aging men. An additional common affliction of aging males is hypogonadism, with more than 12%, 20%, 30%, and 50% of males experiencing hypogonadism in their fifth, sixth, seventh, and eighth decade of life, respectively.9 The standard of care for men suffering from hypogonadism is TTh, which subjectively improves their quality of life.
In recent years, there have been vast improvements in PCa treatment outcomes and a notable decrease of around 50% in the rate of PCa mortality, with an associated increase in the number of men on AS.10 Many of these individuals will live longer but, in turn, may suffer the consequences of hypogonadism or TD, such as erectile dysfunction, loss of lean body mass, decreased libido, and a decrease in quality of life.11 Subjects in this cohort would likely benefit from TTh. However, its utility cannot be wholeheartedly endorsed without a complete understanding of the risk–benefit profile. In this communication, the available evidence on TTh’s safety, efficacy, and potential usage in men on AS is reviewed.
*Testosterone and PCa
*TTh in Men on AS
Conclusion
In recent years, several investigations have begun to question the entrenched belief of T and DHT uniformly as drivers of PCa. After evaluating the current literature addressing the possible benefits of TTh utility in improving the quality of life of men on AS for PCa, it is evident there may be less risk and more benefit than previously understood. Although there are limited studies regarding TTh for men with hypogonadism and on AS, the results of these early studies are promising, as they have documented little to no association between TTh and PCa progression for this population. Given that an increasing number of men are electing AS as a treatment strategy for PCa, clinicians should consider the importance of PCa management plans and how to optimize quality-of-life measures.
It is hoped that future studies continue to explore and expand investigations on TTh use for men on AS to eliminate the uncertainty regarding a therapy that could potentially improve the quality of life and overall well-being of PCa patients. These studies should also focus on providing information for a risk–benefit analysis that patients may reference when making healthcare decisions.
