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Androgens, aging, and prostate health (2022)
Karin Welén · Jan‑Erik Damber
Abstract
Due to late-onset hypogonadism (LOH), there is increased usage of testosterone replacement therapy (TRT) in the aging male population. Since the prostate is a target organ for androgens and anti-androgenic strategies are used to treat and palliate benign prostate hyperplasia (BPH) and prostate cancer (PC), the prevalence of both increases with age, and the possible influence of TRT on prostate health becomes highly relevant. The present review summarizes existing data on the associations between endogenous hormone concentrations and prostate growth and concludes that circulating concentrations of androgens do not appear to be associated with the risks of development of BPH or initiation or progression of PC. The explanation for these findings relates to an apparent insensitivity of prostatic tissue to changes in testosterone concentrations within the physiological range.
1 Introduction
In recent years there has been a significant increase in the use of testosterone treatment in men with “late-onset hypogonadism” (LOH). From 2010 to 2013 in the US, approximately 80% of the testosterone prescriptions were for men between 40 and 74 years of age [1]. One reason for this is the awareness that LOH is associated with several significant health problems such as metabolic disorders, sexual dysfunction, osteopenia, and psychological stress [2]. Testosterone replacement therapy (TRT) has been used with the purpose to improve or even reverse these symptoms [3, 4]. TRT for LOH has however been questioned by the US food and drug administration (FDA) concerning the large increase in testosterone prescriptions, and how to define the group of patients with LOH in order to make more strict treatment recommendations. FDA also had concerns because of some support for an increased risk of cardiac problems, but not due to possible risks for prostate diseases [5], although conclusive evidence for its safety is still largely lacking.
The prostate gland is an androgen target organ. In clinical medicine, strategies to minimize the stimulatory influences of androgens are successfully used to treat common prostate disorders such as prostate cancer (PC) and benign prostate hyperplasia (BPH). Consequently, it has long been believed that higher levels of testosterone increase the risk of PC and BPH. Since TRT is increasingly used in the aged male population the influence of such therapy on prostate diseases is of major importance. The aim of the present review was therefore to elucidate and discuss the role of testosterone, aging, and TRT on prostate health.
2 Benign prostate hyperplasia (BPH)
2.1 Androgens in BPH development
2.2 Aging as a risk factor for BPH
2.3 The metabolic syndrome in BPH
2.4 Senescence in the etiology of BPH
3 Prostate Cancer
3.1 Androgens in prostate cancer development
3.1.1 Higher levels of endogenous testosterone do not drive PC
3.1.2 Saturation of the AR limits the effect of testosterone
3.1.3 Lower levels of endogenous testosterone as a risk factor for aggressive disease
3.2 Aging as a risk factor for prostate cancer
3.2.1 Age‑related inflammation in PC development
3.2.2 Aging of the prostate microenvironment
3.2.3 The metabolic syndrome as a risk factor for PC
4 Screening of prostate cancer
4.1 PC screening in men with hypogonadism
5 Prostate health in men with TRT
5.1 TRT and risk of developing BPH
5.2 TRT and risk of developing prostate cancer
5.3 TRT in men diagnosed with PC
5.3.1 TRT in men with low‑risk PC
5.3.2 TRT in men treated for PC
6 Potential role of selective androgen receptor modulators (SARMs) in prostate health
6.1 Therapeutic potential of SARMs in PC
7 Summary
There is increased usage of TRT in the aging male population mostly due to LOH, a condition associated with important health deteriorations. Since the prostate is a target organ for androgens and the anti-androgenic strategies that are used to treat and palliate BPH and PC, the possible influence of TRT on prostate health becomes apparent
The present review summarizes existing data on the associations between endogenous hormone concentrations and prostate growth and concludes that circulating concentrations of androgens do not appear to be associated with the risk of development of BPH. On the contrary, TRT appears to be associated with improvement of BPH-associated symptoms. It becomes obvious that other factors than androgens are crucial for the development of clinical BPH, such as the metabolic syndrome and its components, inflammation, and cellular senescence.
Analysis of existing data on the associations between endogenous hormone concentrations and PC indicates that circulating androgens do not appear to be associated with the risk of PC initiation or progression. The explanation for this apparent controversy regarding the efficacy of anti-androgen strategies for PC could relate to the prostate AR saturation model, which can explain why physiological levels of testosterone do not affect PC cells. PSA levels are in general lower in men with LOH and may mask cancer. Therefore, monitoring of PSA before and during TRT is recommended. Patients on TRT should be treated as eugonadal men regarding prostate check-ups, meaning that MRI and biopsies should be performed with the same indications (at the same PSA values). TRT of hypogonadal men does not in general increase the risk for PC. Men with low-risk PC or patients cured of PC, and with hypogonadism, could probably safely be treated with TRT, while in patients with advanced prostate cancer a more restricted attitude to TRT is reasonable.
Karin Welén · Jan‑Erik Damber
Abstract
Due to late-onset hypogonadism (LOH), there is increased usage of testosterone replacement therapy (TRT) in the aging male population. Since the prostate is a target organ for androgens and anti-androgenic strategies are used to treat and palliate benign prostate hyperplasia (BPH) and prostate cancer (PC), the prevalence of both increases with age, and the possible influence of TRT on prostate health becomes highly relevant. The present review summarizes existing data on the associations between endogenous hormone concentrations and prostate growth and concludes that circulating concentrations of androgens do not appear to be associated with the risks of development of BPH or initiation or progression of PC. The explanation for these findings relates to an apparent insensitivity of prostatic tissue to changes in testosterone concentrations within the physiological range.
1 Introduction
In recent years there has been a significant increase in the use of testosterone treatment in men with “late-onset hypogonadism” (LOH). From 2010 to 2013 in the US, approximately 80% of the testosterone prescriptions were for men between 40 and 74 years of age [1]. One reason for this is the awareness that LOH is associated with several significant health problems such as metabolic disorders, sexual dysfunction, osteopenia, and psychological stress [2]. Testosterone replacement therapy (TRT) has been used with the purpose to improve or even reverse these symptoms [3, 4]. TRT for LOH has however been questioned by the US food and drug administration (FDA) concerning the large increase in testosterone prescriptions, and how to define the group of patients with LOH in order to make more strict treatment recommendations. FDA also had concerns because of some support for an increased risk of cardiac problems, but not due to possible risks for prostate diseases [5], although conclusive evidence for its safety is still largely lacking.
The prostate gland is an androgen target organ. In clinical medicine, strategies to minimize the stimulatory influences of androgens are successfully used to treat common prostate disorders such as prostate cancer (PC) and benign prostate hyperplasia (BPH). Consequently, it has long been believed that higher levels of testosterone increase the risk of PC and BPH. Since TRT is increasingly used in the aged male population the influence of such therapy on prostate diseases is of major importance. The aim of the present review was therefore to elucidate and discuss the role of testosterone, aging, and TRT on prostate health.
2 Benign prostate hyperplasia (BPH)
2.1 Androgens in BPH development
2.2 Aging as a risk factor for BPH
2.3 The metabolic syndrome in BPH
2.4 Senescence in the etiology of BPH
3 Prostate Cancer
3.1 Androgens in prostate cancer development
3.1.1 Higher levels of endogenous testosterone do not drive PC
3.1.2 Saturation of the AR limits the effect of testosterone
3.1.3 Lower levels of endogenous testosterone as a risk factor for aggressive disease
3.2 Aging as a risk factor for prostate cancer
3.2.1 Age‑related inflammation in PC development
3.2.2 Aging of the prostate microenvironment
3.2.3 The metabolic syndrome as a risk factor for PC
4 Screening of prostate cancer
4.1 PC screening in men with hypogonadism
5 Prostate health in men with TRT
5.1 TRT and risk of developing BPH
5.2 TRT and risk of developing prostate cancer
5.3 TRT in men diagnosed with PC
5.3.1 TRT in men with low‑risk PC
5.3.2 TRT in men treated for PC
6 Potential role of selective androgen receptor modulators (SARMs) in prostate health
6.1 Therapeutic potential of SARMs in PC
7 Summary
There is increased usage of TRT in the aging male population mostly due to LOH, a condition associated with important health deteriorations. Since the prostate is a target organ for androgens and the anti-androgenic strategies that are used to treat and palliate BPH and PC, the possible influence of TRT on prostate health becomes apparent
The present review summarizes existing data on the associations between endogenous hormone concentrations and prostate growth and concludes that circulating concentrations of androgens do not appear to be associated with the risk of development of BPH. On the contrary, TRT appears to be associated with improvement of BPH-associated symptoms. It becomes obvious that other factors than androgens are crucial for the development of clinical BPH, such as the metabolic syndrome and its components, inflammation, and cellular senescence.
Analysis of existing data on the associations between endogenous hormone concentrations and PC indicates that circulating androgens do not appear to be associated with the risk of PC initiation or progression. The explanation for this apparent controversy regarding the efficacy of anti-androgen strategies for PC could relate to the prostate AR saturation model, which can explain why physiological levels of testosterone do not affect PC cells. PSA levels are in general lower in men with LOH and may mask cancer. Therefore, monitoring of PSA before and during TRT is recommended. Patients on TRT should be treated as eugonadal men regarding prostate check-ups, meaning that MRI and biopsies should be performed with the same indications (at the same PSA values). TRT of hypogonadal men does not in general increase the risk for PC. Men with low-risk PC or patients cured of PC, and with hypogonadism, could probably safely be treated with TRT, while in patients with advanced prostate cancer a more restricted attitude to TRT is reasonable.
