madman
Super Moderator
Testosterone and Benign Prostatic Hyperplasia
Giulia Rastrelli, MD, PhD, Linda Vignozzi, MD, PhD, Giovanni Corona, MD, PhD, and Mario Maggi, MD
ABSTRACT
Introduction: Benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS) are frequent in aging. Nonetheless, their pathogenesis is largely unknown. The androgen dependence of the first phases of prostate development have inspired the historical view that higher testosterone (T) may be involved in BPH occurrence; however, recent evidence suggests a different scenario.
Aim: To review the available knowledge on the pathogenesis of BPH particularly concerning the role of T and the possible connections with metabolic impairments.
Methods: Relevant records were retrieved by an extensive search in Medline, including the following keywords ("testosterone"[MeSH Terms] OR "testosterone"[All Fields]) AND ("prostatic hyperplasia"[MeSH Terms] OR ("prostatic"[All Fields] AND "hyperplasia"[All Fields]) OR "prostatic hyperplasia"[All Fields] OR ("benign"[All Fields] AND "prostatic"[All Fields] AND "hyperplasia"[All Fields]) OR "benign prostatic hyperplasia"[All Fields]). There were no limitations in terms of publication date or study design.
Main outcome measures: Preclinical and clinical studies have been reported, with special emphasis on our contribution and interpretation.
Results: Inflammation is a key aspect of BPH development. Along with infectious agents, prostate inflammation can be triggered by metabolic stimuli, such as dyslipidemia, an important component of metabolic syndrome (MetS). Low T and hyperestrogenism frequently occur in MetS. Mounting evidence shows that low, rather than high, T and hyperestrogenism may favor prostate inflammation. Considering these data as a whole, we postulate that BPH is the result of the action of multiple factors, which reinforce their mutual detrimental effects.
Conclusion: T is not detrimental for the prostate, and treating hypogonadism could even produce relief from LUTS and limit prostatic inflammation, which generates and maintains the process leading to BPH.
CONCLUSION: A JOINT HYPOTHESIS FOR PATHOGENESIS OF BPH
The pathogenesis of BPH remains incompletely understood. Inflammation is a key aspect of this process; however, how this mechanism is initiated is a subject for further research. Along with infectious agents, metabolic stimuli, such as dyslipidemia, are emerging as pivotal elements in the development of prostatic enlargement. MetS is often accompanied by low T and a relative hyperestrogenism. Mounting evidence shows that low, rather than high, T levels favor prostate inflammation and that hyperestrogenism also may play a role. Considering all these data, we postulate that BPH results from the actions of multiple factors occurring together or at different time points, which can reinforce and favor their mutual detrimental effects. The initial steps in this process are likely to occur early in life with an overt or subclinical prostatitis, probably influenced by infectious agents. The resulting prostatic inflammation could be amplified and maintained by metabolic derangements occurring in such conditions as MetS. Low T and the relative hyperestrogenism secondary to MetS could further exacerbate the immune process, leading to a chronic inflammation. When prostatitis becomes chronic, a number of cytokines are produced that act in the tissue to maintain the pathological condition. On the other hand, several growth factors are secreted, and their elevated concentrations lead to prostate remodeling and enlargement. The resulting mechanical obstruction and inflammatory damage are the basis of BPH and its associated urinary symptoms.
This hypothesis, based on existing experimental evidence, remains to be proven with ad hoc intervention studies. However, if verified, it carries the important message that BPH can be limited or even avoided by controlling very common modifiable risk factors, such as dyslipidemia, obesity, and insulin resistance. In addition, treating hypogonadism, which frequently accompanies MetS, not only is not detrimental for the prostate, but also could even be a therapeutic resource for relieving urinary symptoms and limiting the inflammatory process in the prostate.
Giulia Rastrelli, MD, PhD, Linda Vignozzi, MD, PhD, Giovanni Corona, MD, PhD, and Mario Maggi, MD
ABSTRACT
Introduction: Benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS) are frequent in aging. Nonetheless, their pathogenesis is largely unknown. The androgen dependence of the first phases of prostate development have inspired the historical view that higher testosterone (T) may be involved in BPH occurrence; however, recent evidence suggests a different scenario.
Aim: To review the available knowledge on the pathogenesis of BPH particularly concerning the role of T and the possible connections with metabolic impairments.
Methods: Relevant records were retrieved by an extensive search in Medline, including the following keywords ("testosterone"[MeSH Terms] OR "testosterone"[All Fields]) AND ("prostatic hyperplasia"[MeSH Terms] OR ("prostatic"[All Fields] AND "hyperplasia"[All Fields]) OR "prostatic hyperplasia"[All Fields] OR ("benign"[All Fields] AND "prostatic"[All Fields] AND "hyperplasia"[All Fields]) OR "benign prostatic hyperplasia"[All Fields]). There were no limitations in terms of publication date or study design.
Main outcome measures: Preclinical and clinical studies have been reported, with special emphasis on our contribution and interpretation.
Results: Inflammation is a key aspect of BPH development. Along with infectious agents, prostate inflammation can be triggered by metabolic stimuli, such as dyslipidemia, an important component of metabolic syndrome (MetS). Low T and hyperestrogenism frequently occur in MetS. Mounting evidence shows that low, rather than high, T and hyperestrogenism may favor prostate inflammation. Considering these data as a whole, we postulate that BPH is the result of the action of multiple factors, which reinforce their mutual detrimental effects.
Conclusion: T is not detrimental for the prostate, and treating hypogonadism could even produce relief from LUTS and limit prostatic inflammation, which generates and maintains the process leading to BPH.
CONCLUSION: A JOINT HYPOTHESIS FOR PATHOGENESIS OF BPH
The pathogenesis of BPH remains incompletely understood. Inflammation is a key aspect of this process; however, how this mechanism is initiated is a subject for further research. Along with infectious agents, metabolic stimuli, such as dyslipidemia, are emerging as pivotal elements in the development of prostatic enlargement. MetS is often accompanied by low T and a relative hyperestrogenism. Mounting evidence shows that low, rather than high, T levels favor prostate inflammation and that hyperestrogenism also may play a role. Considering all these data, we postulate that BPH results from the actions of multiple factors occurring together or at different time points, which can reinforce and favor their mutual detrimental effects. The initial steps in this process are likely to occur early in life with an overt or subclinical prostatitis, probably influenced by infectious agents. The resulting prostatic inflammation could be amplified and maintained by metabolic derangements occurring in such conditions as MetS. Low T and the relative hyperestrogenism secondary to MetS could further exacerbate the immune process, leading to a chronic inflammation. When prostatitis becomes chronic, a number of cytokines are produced that act in the tissue to maintain the pathological condition. On the other hand, several growth factors are secreted, and their elevated concentrations lead to prostate remodeling and enlargement. The resulting mechanical obstruction and inflammatory damage are the basis of BPH and its associated urinary symptoms.
This hypothesis, based on existing experimental evidence, remains to be proven with ad hoc intervention studies. However, if verified, it carries the important message that BPH can be limited or even avoided by controlling very common modifiable risk factors, such as dyslipidemia, obesity, and insulin resistance. In addition, treating hypogonadism, which frequently accompanies MetS, not only is not detrimental for the prostate, but also could even be a therapeutic resource for relieving urinary symptoms and limiting the inflammatory process in the prostate.
