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The role of testosterone in men’s health: is it time for a new approach? (2022)
Ananias C. Diokno
Abstract
Purpose Because of many unanswered questions regarding men’s health, a literature review was performed to better understand the role of testosterone and testosterone replacement therapy (TRT) in the management of hypogonadism and aging-related prostate gland diseases (ARPGD) including prostate cancer (PCa) and benign prostatic hyperplasia (BPH) with lower urinary tract symptoms (LUTS).
Methods The PubMed database was screened for pertinent peer-reviewed articles published during the last four decades that culminated in the positions and recommendations in this paper.
Results Hypogonadism seriously impacts men’s health, and the diagnosis remains controversial. The incidence of ARPGD is projected to increase worldwide and treatment still has significant limitations. There is compelling evidence that lower, not higher, testosterone levels trigger the development of PCa and BPH through androgen receptor over-expression. TRT was found to be safe and effective in treating hypogonadism including in PCa survivors and those harboring PCa. There is also evidence that TRT might reduce the incidence and prevalence of ARPGD.
Conclusions and recommendations This review synthesize a wide-ranging compendium of basic science and clinical research that strongly encourages altering the present approach to diagnosing and treating men with hypogonadism and ARPGD. These fndings underscore the importance of avoiding significant testosterone decline and support the use of TRT. Ten recommendations are offered as a framework for the way forward. It is now time for clinicians, payers, researchers, funding agencies, professional associations, and patient advocacy groups to embrace this new paradigm to increase longevity and improve the quality of life.
Introduction
Huggins and Hodges first identified the benefit of androgen ablation therapy for the treatment of metastatic prostate cancer in 1941 [1]. Charles Huggins was subsequently awarded a Nobel Prize in Medicine and his observations have remained urologic dogma. Since then, there have been significant improvements in the diagnosis of prostate diseases (PSA, needle biopsy, Gleason Score, MRI, etc.). Treatment of significant intracapsular and localized extracapsular prostate cancer now includes surgical and/or radiation therapy which is often curative. However, despite the development of new drugs that focus on androgen deprivation therapy (ADT) for patients with advanced prostate cancer, a cure remains elusive. Furthermore, the prolongation of life requires enduring the many untoward signs and symptoms of hypogonadism and the many discomforts caused by metastatic disease. As androgens stimulate prostate growth and as testosterone supplementation has been associated with other systemic side effects, there has been reluctance to employ testosterone replacement therapy (TRT) in hypogonadism and aging-related prostate gland diseases (ARPGD) that include prostate cancer (PCa) and benign prostatic hyperplasia (BPH) with associated lower urinary tract symptoms (LUTS).
The public health burden of these conditions is formidable. Based on prevalence data in the US. men 40–69 years of age, Araujo estimated that approximately 2.4 million men are androgen-defcient [2]. Globally, PCa is the most commonly diagnosed cancer in men with an estimated annual incidence of 1.6 million and an annual estimated death rate of 366,000 [3]. In 2017, the burden of disease measured in Years Lived with Disease reported for BPH/LUTS and PCa was approximately 2.4 million and 843,227, respectively [4]. Thus, there remains a great opportunity to improve men’s health and reduce the accompanying public health burden, not only by treating but also by preventing these diseases [5].
Over the past decades, data has accumulated from the bench and the bedside suggesting that the conventional wisdom regarding the role of testosterone in the diagnosis and management of these illnesses has been overly restrictive. An extensive PubMed review provides compelling evidence that the judicious use of testosterone can alleviate the many untoward consequences of these maladies [6, 7]. In the light of the unrelenting challenges associated with hypogonadism and ARPGD, it is time to alter our longstanding approach to the diagnosis and treatment of these conditions.
*Serum testosterone and hypogonadism
*Definitions of hypogonadism
-Clinical hypogonadism
-Biochemical/laboratory hypogonadism
*Testosterone replacement therapy criteria: the debate continues
*Experience with testosterone replacement therapy: safe and effective
-Hypogonadism
-Hypogonadism with prostate cancer and lower urinary tract symptoms
*The prostate cell and tumorigenesis
*Androgen deprivation therapy (ADT) and tumorigenesis in advanced PCa
*A clinical risk factor: the rate and degree of testosterone decline
Conclusion
Despite decades of significant diagnostic and therapeutic advances, hypogonadism and ARPGD (PCa and BPH with LUTS) remain a serious challenge to men’s health and wellbeing. This review cites a limited number of the many basic sciences and clinical publications from respected thought leaders that correlated declining levels of testosterone, not only to hypogonadism but also to ARPGD. These publications also explain and justify the use of testosterone replacement therapy for the treatment of hypogonadism, even in patients with cancer of the prostate and BPH with LUTS. It is also possible that the diligent monitoring of declining testosterone levels will better enable disease prevention. Though a number of these studies were underpowered or retrospective, in toto, the consistency of these findings over decades merits serious consideration. The chance to significantly improve men’s quality of life and longevity at a lower financial cost is an opportunity that must not be ignored. Ten recommendations are offered as a framework for the way forward. It is now time for clinicians, payers, researchers, funding agencies, professional associations, and patient advocacy groups to consider this new paradigm and proceed in a timely manner.
Ananias C. Diokno
Abstract
Purpose Because of many unanswered questions regarding men’s health, a literature review was performed to better understand the role of testosterone and testosterone replacement therapy (TRT) in the management of hypogonadism and aging-related prostate gland diseases (ARPGD) including prostate cancer (PCa) and benign prostatic hyperplasia (BPH) with lower urinary tract symptoms (LUTS).
Methods The PubMed database was screened for pertinent peer-reviewed articles published during the last four decades that culminated in the positions and recommendations in this paper.
Results Hypogonadism seriously impacts men’s health, and the diagnosis remains controversial. The incidence of ARPGD is projected to increase worldwide and treatment still has significant limitations. There is compelling evidence that lower, not higher, testosterone levels trigger the development of PCa and BPH through androgen receptor over-expression. TRT was found to be safe and effective in treating hypogonadism including in PCa survivors and those harboring PCa. There is also evidence that TRT might reduce the incidence and prevalence of ARPGD.
Conclusions and recommendations This review synthesize a wide-ranging compendium of basic science and clinical research that strongly encourages altering the present approach to diagnosing and treating men with hypogonadism and ARPGD. These fndings underscore the importance of avoiding significant testosterone decline and support the use of TRT. Ten recommendations are offered as a framework for the way forward. It is now time for clinicians, payers, researchers, funding agencies, professional associations, and patient advocacy groups to embrace this new paradigm to increase longevity and improve the quality of life.
Introduction
Huggins and Hodges first identified the benefit of androgen ablation therapy for the treatment of metastatic prostate cancer in 1941 [1]. Charles Huggins was subsequently awarded a Nobel Prize in Medicine and his observations have remained urologic dogma. Since then, there have been significant improvements in the diagnosis of prostate diseases (PSA, needle biopsy, Gleason Score, MRI, etc.). Treatment of significant intracapsular and localized extracapsular prostate cancer now includes surgical and/or radiation therapy which is often curative. However, despite the development of new drugs that focus on androgen deprivation therapy (ADT) for patients with advanced prostate cancer, a cure remains elusive. Furthermore, the prolongation of life requires enduring the many untoward signs and symptoms of hypogonadism and the many discomforts caused by metastatic disease. As androgens stimulate prostate growth and as testosterone supplementation has been associated with other systemic side effects, there has been reluctance to employ testosterone replacement therapy (TRT) in hypogonadism and aging-related prostate gland diseases (ARPGD) that include prostate cancer (PCa) and benign prostatic hyperplasia (BPH) with associated lower urinary tract symptoms (LUTS).
The public health burden of these conditions is formidable. Based on prevalence data in the US. men 40–69 years of age, Araujo estimated that approximately 2.4 million men are androgen-defcient [2]. Globally, PCa is the most commonly diagnosed cancer in men with an estimated annual incidence of 1.6 million and an annual estimated death rate of 366,000 [3]. In 2017, the burden of disease measured in Years Lived with Disease reported for BPH/LUTS and PCa was approximately 2.4 million and 843,227, respectively [4]. Thus, there remains a great opportunity to improve men’s health and reduce the accompanying public health burden, not only by treating but also by preventing these diseases [5].
Over the past decades, data has accumulated from the bench and the bedside suggesting that the conventional wisdom regarding the role of testosterone in the diagnosis and management of these illnesses has been overly restrictive. An extensive PubMed review provides compelling evidence that the judicious use of testosterone can alleviate the many untoward consequences of these maladies [6, 7]. In the light of the unrelenting challenges associated with hypogonadism and ARPGD, it is time to alter our longstanding approach to the diagnosis and treatment of these conditions.
*Serum testosterone and hypogonadism
*Definitions of hypogonadism
-Clinical hypogonadism
-Biochemical/laboratory hypogonadism
*Testosterone replacement therapy criteria: the debate continues
*Experience with testosterone replacement therapy: safe and effective
-Hypogonadism
-Hypogonadism with prostate cancer and lower urinary tract symptoms
*The prostate cell and tumorigenesis
*Androgen deprivation therapy (ADT) and tumorigenesis in advanced PCa
*A clinical risk factor: the rate and degree of testosterone decline
Conclusion
Despite decades of significant diagnostic and therapeutic advances, hypogonadism and ARPGD (PCa and BPH with LUTS) remain a serious challenge to men’s health and wellbeing. This review cites a limited number of the many basic sciences and clinical publications from respected thought leaders that correlated declining levels of testosterone, not only to hypogonadism but also to ARPGD. These publications also explain and justify the use of testosterone replacement therapy for the treatment of hypogonadism, even in patients with cancer of the prostate and BPH with LUTS. It is also possible that the diligent monitoring of declining testosterone levels will better enable disease prevention. Though a number of these studies were underpowered or retrospective, in toto, the consistency of these findings over decades merits serious consideration. The chance to significantly improve men’s quality of life and longevity at a lower financial cost is an opportunity that must not be ignored. Ten recommendations are offered as a framework for the way forward. It is now time for clinicians, payers, researchers, funding agencies, professional associations, and patient advocacy groups to consider this new paradigm and proceed in a timely manner.
