madman
Super Moderator
Hypogonadism and its treatment among prostate cancer survivors
Edward J. Choi ● Perry Xu ● Farouk M. el-Khatib ● Linda M. Huynh ● Faysal A. Yaf
Abstract
Adult-onset hypogonadism (AOH) is associated with sexual dysfunction, poor bone mineralization, decreased muscle mass, metabolic syndrome disorder, and cognitive suppression. Historically, testosterone has been contraindicated in men with a history of prostate cancer. However, there has been a modern resurgence in re-evaluating this belief. Not only can testosterone be safely utilized to alleviate AOH symptoms in prostate cancer survivors, but it has been also touted as a treatment option for aggressive prostatic cancer. While much work remains in understanding the relationship between testosterone and prostate cancer, those who survive this disease should not be automatically turned away from an opportunity to be treated and restored.
Introduction
Adult-onset hypogonadism (AOH) is characterized by the low levels of testosterone in conjunction with symptoms of androgen deficiency, which includes sexual dysfunction, reduced libido, hot flashes, gynecomastia, diminished muscle mass, bone density loss, depressed mood, and sleep disturbances [1–4]. Furthermore, metabolic disorders, such as type 2 diabetes mellitus, hypertension, and obesity, are significantly associated with decreased testosterone levels [5, 6]. AOH and its complications are chronic processes with large population studies reporting that the average adult male experiences an annual decline of 0.8–1.6% in their total testosterone (TT) and, more dramatically, a 2–3% drop in free testosterone (FT) [7, 8]. The Massachusetts Male Aging Study (MMAS) found the prevalence of AOH to be 6.0% among men 40–69 years old, rising to 12.3% after 8.8 years of follow-up [8]. Inferring from the MMAS, the incidence of AOH approaches 481,000 annually in the United States [9]. In a similar vein, the risk of prostate cancer also coincides with aging as 0.005% of men younger then 39 years are at risk, while 13.7% of men between 60 and 79 years of age will develop prostate cancer [10]. Thus, with aging, a greater proportion of men will be diagnosed with AOH in conjunction with prostate cancer [11].
Since the early 1990s, prostate cancer-specific mortality rates have steadily fallen coinciding with the introduction of widespread prostate-specific antigen (PSA) screening and improved surgical technique [12–14]. In the United States, it is estimated that in 2020 there will be 191,930 new cases of prostate cancer, 33,330 related deaths, and ~3.1 million men currently alive with the diagnosis [15]. In light of this, modern management has begun to incorporate quality and longevity of life after definitive therapy to assist patients in managing decreased libido and sexual dysfunction secondary to treatment [11, 16]. Historically, testosterone replacement therapy (TRT) has been contraindicated in men with prostate cancer due to fears of exacerbating their disease [17, 18]. However, modern studies on the application of TRT in survivors of prostate cancer has vastly transformed our understanding [19, 20]. In this review, we aim to discuss the historical significance of testosterone in prostate cancer, the studies that led to the introduction of the “saturation model”, and the current application of testosterone in prostate cancer survivors.
Testosterone physiology and the prostate
Androgens are a group of sex hormones, which include testosterone and its more potent metabolite, dihydrotestosterone (DHT) [21]. Approximately 90% of circulating testosterone is produced in the testes by Leydig cells, while the remaining 10% are from the adrenal glands [21, 22]. DHT is synthesized locally by the conversion of circulating testosterone within the prostate, testes, hair follicles, and adrenal glands [21, 23]. During puberty, a surge in androgens causes the prostate to swell in volume 10-fold, while, in adulthood, DHT continues to promote linear prostatic growth—implicated as the pathophysiology of benign prostate hypertrophy [24–26]. While inhibition of local DHT production has been proven to reduce cancer progression, exogenous androgen administration has not been clearly linked to increased risk of prostate malignancy [27–29].
*Early understanding of testosterone and prostate cancer
*Modern understanding of testosterone and prostate cancer
*Testosterone levels and prostate cancer
*Testosterone levels and prostate-specific antigen (PSA)
*Hypogonadism in prostate cancer survivors
*Treating hypogonadism in prostate cancer survivors
*Prostate cancer recurrence with testosterone replacement therapy
*Protective benefits of testosterone replacement therapy
*Treating prostate cancer with testosterone
Conclusions
AOH causes a devastating burden on the quality of life for survivors of prostate cancer. Furthermore, AOH and its comorbidities further contribute to the risk for oncologic recurrence and progression. While testosterone levels have been historically associated as the driver of prostate cancer, there has been a modern resurgence in re-evaluating this belief. Not only has TRT been safely utilized to alleviate AOH symptoms in select groups of prostate cancer survivors, but exposure to supraphysiologic levels of testosterone has been on the forefront as a treatment option for aggressive prostatic disease. While much work remains in understanding the relationship between testosterone and prostate cancer, those who survive this disease should not be automatically turned away from an opportunity to be treated and restored.
Edward J. Choi ● Perry Xu ● Farouk M. el-Khatib ● Linda M. Huynh ● Faysal A. Yaf
Abstract
Adult-onset hypogonadism (AOH) is associated with sexual dysfunction, poor bone mineralization, decreased muscle mass, metabolic syndrome disorder, and cognitive suppression. Historically, testosterone has been contraindicated in men with a history of prostate cancer. However, there has been a modern resurgence in re-evaluating this belief. Not only can testosterone be safely utilized to alleviate AOH symptoms in prostate cancer survivors, but it has been also touted as a treatment option for aggressive prostatic cancer. While much work remains in understanding the relationship between testosterone and prostate cancer, those who survive this disease should not be automatically turned away from an opportunity to be treated and restored.
Introduction
Adult-onset hypogonadism (AOH) is characterized by the low levels of testosterone in conjunction with symptoms of androgen deficiency, which includes sexual dysfunction, reduced libido, hot flashes, gynecomastia, diminished muscle mass, bone density loss, depressed mood, and sleep disturbances [1–4]. Furthermore, metabolic disorders, such as type 2 diabetes mellitus, hypertension, and obesity, are significantly associated with decreased testosterone levels [5, 6]. AOH and its complications are chronic processes with large population studies reporting that the average adult male experiences an annual decline of 0.8–1.6% in their total testosterone (TT) and, more dramatically, a 2–3% drop in free testosterone (FT) [7, 8]. The Massachusetts Male Aging Study (MMAS) found the prevalence of AOH to be 6.0% among men 40–69 years old, rising to 12.3% after 8.8 years of follow-up [8]. Inferring from the MMAS, the incidence of AOH approaches 481,000 annually in the United States [9]. In a similar vein, the risk of prostate cancer also coincides with aging as 0.005% of men younger then 39 years are at risk, while 13.7% of men between 60 and 79 years of age will develop prostate cancer [10]. Thus, with aging, a greater proportion of men will be diagnosed with AOH in conjunction with prostate cancer [11].
Since the early 1990s, prostate cancer-specific mortality rates have steadily fallen coinciding with the introduction of widespread prostate-specific antigen (PSA) screening and improved surgical technique [12–14]. In the United States, it is estimated that in 2020 there will be 191,930 new cases of prostate cancer, 33,330 related deaths, and ~3.1 million men currently alive with the diagnosis [15]. In light of this, modern management has begun to incorporate quality and longevity of life after definitive therapy to assist patients in managing decreased libido and sexual dysfunction secondary to treatment [11, 16]. Historically, testosterone replacement therapy (TRT) has been contraindicated in men with prostate cancer due to fears of exacerbating their disease [17, 18]. However, modern studies on the application of TRT in survivors of prostate cancer has vastly transformed our understanding [19, 20]. In this review, we aim to discuss the historical significance of testosterone in prostate cancer, the studies that led to the introduction of the “saturation model”, and the current application of testosterone in prostate cancer survivors.
Testosterone physiology and the prostate
Androgens are a group of sex hormones, which include testosterone and its more potent metabolite, dihydrotestosterone (DHT) [21]. Approximately 90% of circulating testosterone is produced in the testes by Leydig cells, while the remaining 10% are from the adrenal glands [21, 22]. DHT is synthesized locally by the conversion of circulating testosterone within the prostate, testes, hair follicles, and adrenal glands [21, 23]. During puberty, a surge in androgens causes the prostate to swell in volume 10-fold, while, in adulthood, DHT continues to promote linear prostatic growth—implicated as the pathophysiology of benign prostate hypertrophy [24–26]. While inhibition of local DHT production has been proven to reduce cancer progression, exogenous androgen administration has not been clearly linked to increased risk of prostate malignancy [27–29].
*Early understanding of testosterone and prostate cancer
*Modern understanding of testosterone and prostate cancer
*Testosterone levels and prostate cancer
*Testosterone levels and prostate-specific antigen (PSA)
*Hypogonadism in prostate cancer survivors
*Treating hypogonadism in prostate cancer survivors
*Prostate cancer recurrence with testosterone replacement therapy
*Protective benefits of testosterone replacement therapy
*Treating prostate cancer with testosterone
Conclusions
AOH causes a devastating burden on the quality of life for survivors of prostate cancer. Furthermore, AOH and its comorbidities further contribute to the risk for oncologic recurrence and progression. While testosterone levels have been historically associated as the driver of prostate cancer, there has been a modern resurgence in re-evaluating this belief. Not only has TRT been safely utilized to alleviate AOH symptoms in select groups of prostate cancer survivors, but exposure to supraphysiologic levels of testosterone has been on the forefront as a treatment option for aggressive prostatic disease. While much work remains in understanding the relationship between testosterone and prostate cancer, those who survive this disease should not be automatically turned away from an opportunity to be treated and restored.
