Materiały źródłowe

• #1 Benign Prostatic Hyperplasia – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK558920/

  Benign prostatic hyperplasia (BPH) refers to the nonmalignant growth or hyperplasia of prostate tissue and is a common cause of lower urinary tract symptoms (LUTS) in older men. Disease prevalence has been shown to increase with advancing age. The histological prevalence of BPH at autopsy is as high as 50% to 60% for males in their 60s, increasing to 80% to 90% of those older than 70 years of age. […] The development of BPH is characterized by stromal and epithelial cell proliferation in the prostate transition zone, which surrounds the urethra. This leads to urethral compression and bladder outflow obstruction, which can result in clinical manifestations of LUTS, urinary retention, or infections due to incomplete bladder emptying. Long-term, untreated disease can lead to the development of chronic high-pressure retention (a potentially life-threatening condition) and long-term or permanent changes to the bladder detrusor muscle.

• #2 Benign Prostatic Hyperplasia: Etiology, Pathophysiology, Epidemiology, and Natural History | Abdominal Key

  https://abdominalkey.com/benign-prostatic-hyperplasia-etiology-pathophysiology-epidemiology-and-natural-history/

  Benign prostatic hyperplasia (BPH) is a pathologic process that contributes to, but is not the sole cause of, lower urinary tract symptoms (LUTS) in aging men. Despite intense research efforts in the past 5 decades to elucidate the underlying etiology of prostatic growth in older men, cause-and-effect relationships have not been established. For example, androgens are a necessary but not a clearly causative aspect of BPH. […] Previously held ideas that the clinical symptoms of BPH (prostatism) are simply due to a mass-related increase in urethral resistance are too simplistic. It is now clear that a significant portion of LUTS is due to age-related detrusor dysfunction and other conditions such as polyuria, sleep disorders, and a variety of systemic medical conditions unrelated to the prostate-bladder unit.

• #3 A genetic study to identify pathogenic mechanisms and drug targets for benign prostatic hyperplasia: a multi-omics Mendelian randomization study | Scientific Reports

  https://www.nature.com/articles/s41598-024-73466-w

  Benign prostatic hyperplasia (BPH) as a common geriatric disease in urology, the incidence and prevalence are rapidly increasing with the aging society, prompting an urgent need for effective prevention and treatment of BPH. […] The unclear pathogenic mechanism also hampers further exploration of therapeutic approaches for BPH. […] BPH is considered a chronic inflammatory disease, and immune pathways contribute significantly to BPH. […] Understanding the immune pathways and the causal relationship between circulating metabolites and BPH offers hope for the development of new therapeutic strategies. […] The pathogenic mechanisms of BPH remain poorly understood, the biomolecules associated with BPH remain elusive, and the relative scarcity of molecular data has hampered further exploration of the pathogenic mechanisms of BPH, resulting in the slow development of pharmacological therapeutic research.

• #4 Benign Prostatic Hyperplasia – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK558920/

  BPH arises due to the loss of homeostasis between prostatic cellular proliferation and apoptosis or cell death. This imbalance favors cellular proliferation without intervention. The result is increased numbers of prostatic periurethral epithelial and stromal cells, which can be seen histopathologically. The etiology of BPH is influenced by a wide variety of risk factors, in addition to the direct hormonal effects of testosterone on prostate tissue. […] Testicular androgens are required to develop BPH as dihydrotestosterone (DHT) promotes tissue growth and cellular proliferation by interacting directly with prostatic epithelium and stroma. DHT directly influences prostatic stromal and adjacent cells, which affect cellular proliferation and apoptosis. […] The development of LUTS and bladder outlet obstruction in men with BPH can be attributable to static and dynamic components. Static obstruction is a direct consequence of prostate enlargement, resulting in periurethral compression and bladder outlet obstruction. Prostate enlargement distorts the bladder outlet, causing urinary obstruction, while periurethral compression requires increasing voiding pressures to overcome flow resistance.

• #5 Prostate BPH- pathophysiology | PPT

  https://www.slideshare.net/slideshow/prostate-bph-pathophysiology/248946103

  5) BPH is characterized by an increased number of epithelial and stromal cells in the periurethral area of the prostate. […] 6) The aging process blocks maturation process progression to terminally differentiated cells rate of cell death. […] 7) Hormones may exert their influence over the stem cell population advancing age, during embryonic and neonatal development. […] 8) The Role of Androgens: Androgens do not cause BPH, the development of BPH requires the presence of testicular androgens during prostate development, puberty, and aging. […] 9) Despite the importance of androgens in normal prostatic development and secretory physiology, no evidence that either testosterone or DHT serves as the direct mitogen for growth of the prostate in older men. […] 10) The prostate maintains its ability to respond to androgens throughout life.

• #6 Benign Prostatic Hyperplasia: Etiology, Pathophysiology, Epidemiology, and Natural History | Abdominal Key

  https://abdominalkey.com/benign-prostatic-hyperplasia-etiology-pathophysiology-epidemiology-and-natural-history/

  The precise molecular etiology of this hyperplastic process is uncertain. The observed increase in cell number may be due to epithelial and stromal proliferation or to impaired programmed cell death leading to cellular accumulation. Androgens, estrogens, stromal-epithelial interactions, growth factors, and neurotransmitters may play a role, either singly or in combination, in the etiology of the hyperplastic process. […] Although androgens and growth factors stimulate cell proliferation in experimental models, the relative role of cell proliferation in human BPH is questioned because there is no clear evidence of an active proliferative process. […] Androgens not only are required for normal cell proliferation and differentiation in the prostate but also actively inhibit cell death. […] The aging process induces a block in this maturation process so that the progression to terminally differentiated cells is reduced, reducing the overall rate of cell death.

• #7 Prostate BPH- pathophysiology | PPT

  https://www.slideshare.net/slideshow/prostate-bph-pathophysiology/248946103

  5) BPH is characterized by an increased number of epithelial and stromal cells in the periurethral area of the prostate. […] 6) The aging process blocks maturation process progression to terminally differentiated cells rate of cell death. […] 7) Hormones may exert their influence over the stem cell population advancing age, during embryonic and neonatal development. […] 8) The Role of Androgens: Androgens do not cause BPH, the development of BPH requires the presence of testicular androgens during prostate development, puberty, and aging. […] 9) Despite the importance of androgens in normal prostatic development and secretory physiology, no evidence that either testosterone or DHT serves as the direct mitogen for growth of the prostate in older men. […] 10) The prostate maintains its ability to respond to androgens throughout life.

• #8 Benign Prostatic Hyperplasia (BPH) Guideline – American Urological Association

  https://www.auanet.org/guidelines-and-quality/guidelines/benign-prostatic-hyperplasia-(bph)-guideline

  BPH is likely the result of a multifactorial process, the exact etiology of which is unknown. […] What is clearly necessary for the development of BPH, however, is the presence of functioning testes. […] The mechanism by which testosterone exerts many of its physiological effects on the prostate gland is through dihydrotestosterone (DHT). […] Androgens, including testosterone, are produced by the Leydig cells of the testes and the adrenal glands. […] Once intracytoplasmic, testosterone is converted to its active metabolite DHT by the enzyme 5-reductase, type 2. […] DHT forms a complex with androgen receptors that is then transported to the nucleus. […] Within the nucleus, this complex exerts its effects on the transcription of DNA. […] These effects are necessary for the normal development of the prostate gland as well as the normal growth and hyperplasia of the prostate.

• #9 Benign prostatic hyperplasia: pathogenesis and the role of medical management | SpringerLink

  https://link.springer.com/chapter/10.1007/978-94-011-1822-4_55

  Two factors, critical for the development of benign prostatic hyperplasia (BPH), are androgen production by the testes and aging. […] Thus, these clinical observations strongly suggest that androgen production by the testes plays a major role in the development of BPH in man.

• #10 Benign Prostatic Hyperplasia (BPH) Guideline – American Urological Association

  https://www.auanet.org/guidelines-and-quality/guidelines/benign-prostatic-hyperplasia-%28bph%29-guideline

  BPH is likely the result of a multifactorial process, the exact etiology of which is unknown. […] The mechanism by which testosterone exerts many of its physiological effects on the prostate gland is through dihydrotestosterone (DHT). […] Androgens, including testosterone, are produced by the Leydig cells of the testes and the adrenal glands. […] Once intracytoplasmic, testosterone is converted to its active metabolite DHT by the enzyme 5-reductase, type 2. […] DHT forms a complex with androgen receptors that is then transported to the nucleus. […] Within the nucleus, this complex exerts its effects on the transcription of DNA. […] These effects are necessary for the normal development of the prostate gland as well as the normal growth and hyperplasia of the prostate.

• #11 Benign Prostatic Hyperplasia – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK558920/

  BPH arises due to the loss of homeostasis between prostatic cellular proliferation and apoptosis or cell death. This imbalance favors cellular proliferation without intervention. The result is increased numbers of prostatic periurethral epithelial and stromal cells, which can be seen histopathologically. The etiology of BPH is influenced by a wide variety of risk factors, in addition to the direct hormonal effects of testosterone on prostate tissue. […] Testicular androgens are required to develop BPH as dihydrotestosterone (DHT) promotes tissue growth and cellular proliferation by interacting directly with prostatic epithelium and stroma. DHT directly influences prostatic stromal and adjacent cells, which affect cellular proliferation and apoptosis. […] The development of LUTS and bladder outlet obstruction in men with BPH can be attributable to static and dynamic components. Static obstruction is a direct consequence of prostate enlargement, resulting in periurethral compression and bladder outlet obstruction. Prostate enlargement distorts the bladder outlet, causing urinary obstruction, while periurethral compression requires increasing voiding pressures to overcome flow resistance.

• #12 Prostate BPH- pathophysiology | PPT

  https://www.slideshare.net/slideshow/prostate-bph-pathophysiology/248946103

  11) DHT and 5-Reductase: Intraprostatic DHT concentrations are maintained same/elevated in BPH. […] 12) The Role of Estrogens: Serum estrogen levels increased in aging men. […] 13) Regulation of Programmed Cell Death: Programmed cell death (apoptosis) is a physiologic mechanism crucial to the maintenance of normal glandular homeostasis. […] 14) Stromal-Epithelial Interaction: Prostatic stromal and epithelial cells maintain a sophisticated paracrine type of communication. […] 15) Growth factors are small peptide molecules that stimulate, or inhibit cell division and differentiation processes. […] 16) Genetic and Familial Factors: BPH – inheritable genetic component. […] 17) Anatomic Features: BPH first develops in the periurethral transition zone of the prostate. […] 18) Histologic Features: BPH – true hyperplastic process – an increase in the cell number. […] 19) Importance of Prostatic Smooth Muscle: Prostatic smooth muscle represents a significant volume of the gland. […] 20) The Bladder’s Response to Obstruction: The bladder’s response to obstruction – an adaptive one. […] 21) Summary: The exact etiology of BPH is yet to be elucidated.

• #13 The Etiology and Pathogenesis of Benign Prostatic Hyperplasia: The Roles of Sex Hormones and Anatomy

  https://pmc.ncbi.nlm.nih.gov/articles/PMC11430843/

  The pathogenesis is defined as the process and factors associated with the perpetuation or progression of a disease. […] It has been known that both prostate volume ( 30 g) and age ( 62 years old) are two baseline predictors for an increase in risk of BPH progression, and a histological hallmark of BPH progression is enlargement of the prostate that is caused by nodular proliferation of epithelial and/or stromal cells in the TZ. […] However, the exact mechanisms by which the testicular function mediates the progression of BPH remain unclear. […] Taken together, these studies at least imply that a high level of serum T may be not required for BPH progression, and, in some cases, T may not be needed at all for the pathogenesis of BPH. […] The central role of DHT in the development of BPH has been further verified by successful clinical use of finasteride (an inhibitor of SRD5-2, 3) or dutasteride (an inhibitor of SRD5-1, 2, 3) in the management of BPH, showing that dutasteride at a dosage of 0.5 mg/day or finasteride at 5 mg/day significantly reduces serum or intraprostatic DHT of over 70% and prostate volume of approximately 30%.

• #14 The etiology and pathogenesis of benign prostatic hyperplasia：The ro | RRU

  https://www.dovepress.com/the-etiology-and-pathogenesis-of-benign-prostatic-hyperplasia-the-role-peer-reviewed-fulltext-article-RRU

  The pathogenesis is defined as the process and factors associated with the perpetuation or progression of a disease. […] It has been known that both prostate volume ( 30 g) and age ( 62 years old) are two baseline predictors for an increase in risk of BPH progression, and a histological hallmark of BPH progression is enlargement of the prostate that is caused by nodular proliferation of epithelial and/or stromal cells in the TZ. […] However, the exact mechanisms by which the testicular function mediates the progression of BPH remain unclear. […] The central role of DHT in the development of BPH has been further verified by successful clinical use of finasteride (an inhibitor of SRD5-2, 3) or dutasteride (an inhibitor of SRD5-1, 2, 3) in the management of BPH, showing that dutasteride at a dosage of 0.5 mg/day or finasteride at 5 mg/day significantly reduces serum or intraprostatic DHT of over 70% and prostate volume of approximately 30%. […] A complete understanding of DHT-mediating molecular pathways by which BPH is developed is required for development of any new therapeutic approaches to treat BPH.

• #15 Benign Prostatic Hyperplasia – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK558920/

  BPH arises due to the loss of homeostasis between prostatic cellular proliferation and apoptosis or cell death. This imbalance favors cellular proliferation without intervention. The result is increased numbers of prostatic periurethral epithelial and stromal cells, which can be seen histopathologically. The etiology of BPH is influenced by a wide variety of risk factors, in addition to the direct hormonal effects of testosterone on prostate tissue. […] Testicular androgens are required to develop BPH as dihydrotestosterone (DHT) promotes tissue growth and cellular proliferation by interacting directly with prostatic epithelium and stroma. DHT directly influences prostatic stromal and adjacent cells, which affect cellular proliferation and apoptosis. […] The development of LUTS and bladder outlet obstruction in men with BPH can be attributable to static and dynamic components. Static obstruction is a direct consequence of prostate enlargement, resulting in periurethral compression and bladder outlet obstruction. Prostate enlargement distorts the bladder outlet, causing urinary obstruction, while periurethral compression requires increasing voiding pressures to overcome flow resistance.

• #16 Benign Prostatic Hyperplasia – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK558920/

  Dynamic components include the prostatic smooth muscle tension (hence using five alpha-reductase inhibitors to reduce prostate volume and alpha-blockers to relax prostatic smooth muscle). This is explained by decreased elasticity and collagen in the prostatic urethra in men with BPH, which exacerbates symptoms of bladder outlet obstruction due to loss of compliance and increased flow resistance. […] Although BPH can increase prostate-specific antigen levels (PSA), it is not a risk factor for prostate cancer. BPH occurs primarily in the central/transitional portion of the prostate, while malignancies typically form in the prostatic periphery.

• #17 Benign Prostatic Hyperplasia: Evaluation and Medical Management in Primary Care

  https://consultqd.clevelandclinic.org/benign-prostatic-hyperplasia-evaluation-and-medical-management-in-primary-care

  BPH is a histologic diagnosis of proliferation of smooth muscle, epithelium, and stromal cells within the transition zone of the prostate, which surrounds the proximal urethra. […] Symptoms arise through two mechanisms: static, in which the hyperplastic prostatic tissue compresses the urethra; and dynamic, with increased adrenergic nervous system and prostatic smooth muscle tone. Both mechanisms increase resistance to urinary flow at the level of the bladder outlet. […] Chronic bladder outlet obstruction can lead to bladder decompensation and detrusor underactivity, manifesting as incomplete emptying, urinary hesitancy, intermittency (starting and stopping while voiding), a weakened urinary stream and urinary retention. […] Finasteride and dutasteride are believed to mitigate the static obstructive component of BPH, with similar improvements in urinary flow rate and symptom score in men with an enlarged prostate.

• #18 Benign Prostatic Hyperplasia (BPH): Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/9100-benign-prostatic-hyperplasia

  One theory is that, as you age, the amount of testosterone in your body decreases (low testosterone). At the same time, your estrogen levels remain the same. These hormone changes may cause your prostate cells to grow. However, people who take supplemental testosterone may develop or worsen BPH. […] Older males also have higher levels of dihydrotestosterone (DHT). DHT is a more potent form of testosterone that increases the size of your prostate. […] There isnt a cure for BPH. However, treatment options are available to help alleviate your symptoms. […] The most commonly prescribed medications relax the muscle in your prostate, which reduces tension on your urethra. […] Some medications decrease the production of the hormone DHT, which can slow the growth of your prostate gland. […] Several different types of surgery can remove prostate tissue that blocks your urethra.

• #19 Benign Prostatic Hyperplasia (BPH) – Life Extension

  https://www.lifeextension.com/protocols/male-reproductive/benign-prostatic-hyperplasia?srsltid=AfmBOopOFO0lflxMyJwSAZvY1_-HkVwPuP_W_EZRFg3bDgtDkWCIpWmb

  Furthermore, ethnic differences have been reported, such as lower rates of BPH and prostate surgery among Asian men relative to Caucasian men. […] Estrogens appear to contribute to prostate tissue growth and may represent an underappreciated piece of the BPH puzzle. […] Aging in men is associated with an increase in the activity of an enzyme called aromatase, which converts testosterone into estrogen. Some research suggests increased estrogen levels in prostate tissue may promote hyperplasia. […] This breakdown in cellular regulation that occurs with aging allows prostate cells to proliferate and promote the formation of additional tissue. This additional tissue is smooth muscle, and this tends to increase the overall muscle tone of the prostate, which can contribute to blockage of the urinary tract.

• #20 Epidemiology and treatment modalities for the management of benign prostatic hyperplasia – Lokeshwar – Translational Andrology and Urology

  https://tau.amegroups.org/article/view/30514/html

  Benign prostatic hyperplasia (BPH) is defined by the American Urological Association (AUA) as a histologic diagnosis referring to the proliferation of smooth muscle and epithelial cells within the prostatic transition zone. […] The pathophysiology of BPH has been linked to many factors including sex hormones, neurotransmitters, inflammation, diet, microorganisms and cellular effects on epithelial as well as stromal tissue. […] Although androgen levels have long been studied as one of the largest influencers on prostatic growth, estrogen may also play a role. […] Estrogen signaling increases the level of androgen receptors in the prostatic gland leading to signal amplification and stimulation of hyperplasia, even with reducing levels of androgen. […] Additionally, estradiol has been found to induce epithelial-to-mesenchymal transition in benign prostatic epithelial cells.

• #21 Epidemiology and treatment modalities for the management of benign prostatic hyperplasia – Lokeshwar – Translational Andrology and Urology

  https://tau.amegroups.org/article/view/30514/html

  Benign prostatic hyperplasia (BPH) is defined by the American Urological Association (AUA) as a histologic diagnosis referring to the proliferation of smooth muscle and epithelial cells within the prostatic transition zone. […] The pathophysiology of BPH has been linked to many factors including sex hormones, neurotransmitters, inflammation, diet, microorganisms and cellular effects on epithelial as well as stromal tissue. […] Although androgen levels have long been studied as one of the largest influencers on prostatic growth, estrogen may also play a role. […] Estrogen signaling increases the level of androgen receptors in the prostatic gland leading to signal amplification and stimulation of hyperplasia, even with reducing levels of androgen. […] Additionally, estradiol has been found to induce epithelial-to-mesenchymal transition in benign prostatic epithelial cells.

• #22 Epidemiology and treatment modalities for the management of benign prostatic hyperplasia – Lokeshwar – Translational Andrology and Urology

  https://tau.amegroups.org/article/view/30514/html

  Epithelial-to-mesenchymal transition causes prostatic hyperplasia, and is evidenced by the loss of E-cadherin, increased pSmad3 and high Snail markers in BPH samples. […] This affirmed the notion that the accumulation of mesenchymal-like cells derived from prostatic epithelium causes BPH rather than prostatic stromal proliferation.

• #23 Estrogen and G protein-coupled estrogen receptor accelerate the progression of benign prostatic hyperplasia by inducing prostatic fibrosis | Cell Death & Disease

  https://www.nature.com/articles/s41419-022-04979-3

  Moreover, mechanism dissection suggested the CYP19/estrogen/G protein-coupled estrogen receptor (GPER)/Gi signaling pathway may be involved in the regulation of stromal cell proliferation and prostatic fibrosis, which may function to accelerate the clinical progression of patients with BPH. […] The results revealed the expression of SRD5A2 and AR in the early-progressed BPH group was slightly lower than in the other two groups. In contrast, higher CYP19 expression was found in the early-progressed BPH group in both the epithelium and stroma, which was confirmed by the IOD analysis of CYP19 intensity. […] This result suggests that more androgen can be converted to estrogen, and the elevated estrogen levels may be involved in the pathologic modification of prostatic stroma in patients with BPH with accelerated clinical progression.

• #24 Estrogen and G protein-coupled estrogen receptor accelerate the progression of benign prostatic hyperplasia by inducing prostatic fibrosis | Cell Death & Disease

  https://www.nature.com/articles/s41419-022-04979-3

  We found that the increased stromal components, and prostatic fibrosis may be the key factor for the rapid clinical progression of BPH/LUTS. […] The CYP19/estrogen/GPER pathway modulates EGFR/ERK and HIF-1/TGF-1 signaling, all of which have key roles in the proliferation and fibrogenesis of prostatic stromal cells in patients with accelerated clinical progression of BPH.

• #25 Oxidative Stress in Benign Prostatic Hyperplasia: Mechanisms, Clinical Relevance and Therapeutic Perspectives

  https://www.mdpi.com/2079-9721/13/2/53

  Chronic inflammation and oxidative stress (OS) constitute critical, yet underexplored, facets of BPH pathogenesis. […] Histological analyses of resected BPH tissue frequently reveal moderate to marked inflammatory cell infiltrates, suggesting that inflammation is an active driver of aberrant prostatic growth rather than an incidental finding. […] OS, a condition defined by excessive ROS relative to antioxidant defense systems, is increasingly regarded as a critical factor in BPH. […] Chronic inflammation intensifies local ROS levels as immune cells release reactive oxygen and nitrogen intermediates in their attempt to neutralize pathogens or remove damaged tissues. […] The synergy among decreased antioxidant capacity, excess ROS, and chronic prostatic inflammation creates a vicious cycle that perpetuates hyperplastic changes. […] Findings indicate that OS and inflammation are key contributors to BPH progression. Incorporating antioxidant and anti-inflammatory strategies alongside conventional treatments holds promise for improving clinical outcomes and patient quality of life.

• #26 Lesson: Managing Benign Prostatic Hyperplasia

  https://journalce.powerpak.com/ce/managing-benign-prostatic-hyperplasia?utm_source=uspharmacist&utm_medium=banner&utm_content=article_ce_banner&utm_campaign=moreCE

  Benign prostatic hyperplasia (BPH) is a histologic diagnosis that refers to the proliferation of smooth muscle, glandular epithelial cells, and connective tissue within the transition zone of the prostate. […] The pathogenesis of BPH is multifactorial. Among the proposed etiological factors that are associated with the development of BPH are inflammation, changes in the prostatic microbiota, toxic exposures, vitamin D polymorphism, and alterations in telomere length. […] Chronic inflammation is considered a key component of benign prostatic obstruction (BPO) in BPH and underlies several of the other proposed mechanisms. Inflammation can be initiated by the presence of infection such as prostatitis, by hormonal alterations, autoimmune disorder, immunological defects, urinary reflux, and even by diet and lifestyle.

• #27

  https://journals.lww.com/imna/fulltext/2024/09000/research_progress_on_the_mechanism_of_chinese.12.aspx

  Benign prostatic hyperplasia (BPH) is one of the most common benign diseases in middle-aged and elderly men. […] Prostatic inflammation is considered a key factor in the pathogenesis and progression of BPH. […] Studies have shown that inflammatory responses can promote the occurrence and progression of BPH through various pathways. […] When inflammation persists or occurs excessively in prostate tissue, it leads to local vasodilation and increased permeability, resulting in congestion and edema of the prostate tissue, thereby promoting its hyperplasia. […] The release of inflammatory cells and inflammatory mediators can cause damage to tissue cells and induce cell apoptosis, leading to abnormal proliferation of prostate tissue. […] Local inflammation, possibly triggered by viral or bacterial infections, can lead to the secretion of growth factors, thereby promoting the growth of prostate epithelial and stromal cells.

• #28 Benign Prostatic Hyperplasia: Epidemiology, Pathophysiology, and Clinical Manifestations | IntechOpen

  https://www.intechopen.com/chapters/81872

  Interestingly, there is a close relationship between GFs and steroid hormones in the development of BPH; the activation of the AR leads to the increase of the GFs responsible for cell proliferation. […] Recently, evidence has emerged on the participation of inflammatory processes in BPH development. […] The initial stimulus causes the activation of T lymphocytes, as well as the release of cytokines and interleukins (IL) responsible for cell damage, as well as a cascade activation of different factors, among which are the increase in the expression of IL-15 in stromal cells; IL-17 on T cells; interferon- in basal and stromal cells and IL-8 in epithelial cells; events that promote a process of chronic inflammation whose consequence is the increase in the volume of the prostate gland. […] Therefore, inflammatory processes are decisive in developing BPH.

• #29 Mechanism of Androgen-Independent Stromal Proliferation in Benign Prostatic Hyperplasia

  https://www.mdpi.com/1422-0067/24/14/11634

  Inflammation in prostate tissues has been implicated as having the greatest role in the androgen-independent pathways in the BPH proliferative process. In the last decades, a potentially important role of inflammation in BPH proliferation has emerged. A relationship between inflammation and increase in prostate volume has been reported in several clinical studies. The presence of inflammation is involved in increased prostate volumes and risk of acute urinary retention. This relationship was even more pronounced when stratified by the severity of histological markers of inflammation. […] Chronic inflammation in BPH has been implicated in tissue remodeling through the wound healing process. Generally, injured tissues convert their biology of priority from differentiated function to a biology directed toward an expedient and effective healing process that involves an acute response, and when unresolved, chronic responses. These responses include inflammation, immune reaction, extracellular matrix remodeling, angiogenesis, and the formation of reactive stroma. Some researchers consider that tissue injury related to inflammation and subsequent chronic tissue healing processes may be an important factor in the inflammatory proliferation of BPH prostate tissues.

• #30 Frontiers | Immune Cell Proinflammatory Microenvironment and Androgen-Related Metabolic Regulation During Benign Prostatic Hyperplasia in Aging

  https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.842008/full

  Inflammation causes cell and DNA damage, promotes cell replacement and creates a tissue microenvironment rich in cytokines and growth factors, thereby promoting cell proliferation and causing hyperplasia during tissue repair. […] While inflammation promotes the occurrence and development of BPH, the presence of BPH cells can also promote the occurrence of inflammation and make inflammation continue to expand. […] The latest research also shows that BPH may be an immunoinflammatory disease. […] The immune disorder response in BPH may occur through increased expression of proinflammatory IL-17, and the autoimmune response associated with T cells may induce abnormal proliferation of epithelial cells and stromal cells. […] In summary, inflammation plays a vital role in the pathogenesis and disease development of BPH. Inflammation can independently affect the development of BPH in a variety of ways, and it can also interact with androgens. At the same time, BPH can also promote inflammation to expand its scope and aggravate the situation. Therefore, in the treatment process, early intervention in the occurrence and development of inflammation in prostate tissue can slow down the progression of BPH. The combination of standard therapies and anti-inflammatory measures may provide valuable new ideas for the treatment of BPH.

• #31 Mechanism of Androgen-Independent Stromal Proliferation in Benign Prostatic Hyperplasia

  https://www.mdpi.com/1422-0067/24/14/11634

  The immune response in BPH proliferation might be caused by an autoimmune reaction that responds to autoantigens in prostatic tissues. An interesting study of the involvement of autoimmune reactions in the prostate was published in 1987. In that study, a mouse model involving removal of the thymus immediately after birth was created. Thymectomy inhibits central immune tolerance and produces T cells and antibodies that react to autoantigens, inducing autoimmune prostatitis. However, what this autoantigen associated with BPH development was not clarified. Therefore, since these reports, there have been numerous studies attempting to identify the autoantigens in the BPH proliferative process. […] The activation of complement classical and lectin pathways is reported to be involved in tissue regeneration, angiogenesis, and amplification of inflammation in addition to the well-appreciated properties of defending against foreign pathogens. In addition, the complement classical pathway is known to be activated by an antigen-antibody reaction triggered by an autoantigen. From the above, autoimmune reactions might be involved in BPH proliferation including epithelial and stromal cells through the activation of the complement classical pathway.

• #32 Frontiers | Immune Cell Proinflammatory Microenvironment and Androgen-Related Metabolic Regulation During Benign Prostatic Hyperplasia in Aging

  https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.842008/full

  Inflammation causes cell and DNA damage, promotes cell replacement and creates a tissue microenvironment rich in cytokines and growth factors, thereby promoting cell proliferation and causing hyperplasia during tissue repair. […] While inflammation promotes the occurrence and development of BPH, the presence of BPH cells can also promote the occurrence of inflammation and make inflammation continue to expand. […] The latest research also shows that BPH may be an immunoinflammatory disease. […] The immune disorder response in BPH may occur through increased expression of proinflammatory IL-17, and the autoimmune response associated with T cells may induce abnormal proliferation of epithelial cells and stromal cells. […] In summary, inflammation plays a vital role in the pathogenesis and disease development of BPH. Inflammation can independently affect the development of BPH in a variety of ways, and it can also interact with androgens. At the same time, BPH can also promote inflammation to expand its scope and aggravate the situation. Therefore, in the treatment process, early intervention in the occurrence and development of inflammation in prostate tissue can slow down the progression of BPH. The combination of standard therapies and anti-inflammatory measures may provide valuable new ideas for the treatment of BPH.

• #33 Autophagy in benign prostatic hyperplasia: insights and therapeutic potential | BMC Urology | Full Text

  https://bmcurol.biomedcentral.com/articles/10.1186/s12894-024-01585-7

  In this review, we will elucidate the process and regulatory mechanisms of autophagy and analyze its various specific mechanisms of action in BPH. […] The PI3K-AKT-mTOR pathway is considered one of the main pathways regulating autophagy, exerting a negative regulatory effect on cellular autophagy. […] In androgen-induced BPH rats, testosterone can inhibit autophagy by activating the PI3K/Akt/mTOR pathway, reducing the expression of Beclin1 and LC3-II. […] Studies have also shown that the use of the autophagy inducer rapamycin can enhance autophagy by inhibiting mTOR, thereby suppressing the testosterone-induced proliferation of prostate tissue in rats. […] In BPH patients treated with 5-ARIs, the expression of Beclin-1 and LC3 is significantly higher than in untreated control groups. This suggests that autophagy is promoted during 5-ARI treatment.

• #34 Mechanism of RhoA regulating benign prostatic hyperplasia: RhoA-ROCK-β-catenin signaling axis and static & dynamic dual roles | Molecular Medicine | Full Text

  https://molmed.biomedcentral.com/articles/10.1186/s10020-023-00734-2

  In our current study, we concluded that RhoA was an important factor in the development of BPH. RhoA was found to be up-regulated in hyperplastic human prostate tissue and rat prostate tissue. Further knockdown and overexpression of RhoA in human prostate cell lines identified potential static dynamic dual roles of RhoA in BPH, including cell proliferation, apoptosis, fibrosis, EMT, and cell contraction. More importantly, we found that RhoA-ROCK and the -catenin-dependent canonical Wnt pathway constituted a signaling axis that mediated multiple phenotypic changes in the development of BPH. […] RhoA-ROCK is up-regulated in human prostate tissues and increases the tension of human prostate strips. […] RhoA promotes the cell proliferation of WPMY-1 and BPH-1 cells. […] RhoA inhibits the cell apoptosis of WPMY-1 and BPH-1 cells, but do not affect the cell cycle.

• #35

  https://www.ics.org/2020/abstract/160

  Gene and protein expression levels of C5a, NLRP3, Caspase-1, IL-1, and IL-18 was significantly up-regulated in BPH tissues compared to normal prostate tissues respectively, and showed an increase time-dependently. […] In IHC analysis, significant deposition of NLRP3 was observed abundantly in stromal area. […] The expression and function analysis of C5a, NLRP3, Caspase-1, IL-1, and IL-18 indicated that the pathway of NLRP3 inflammasome by C5a was activated in the growth process of BPH. […] In addition, this activation of inflammasome was located in the stromal area of BPH, describing that NLRP3 inflammasome system had an important role for the proliferation of BPH stromal area. […] These results suggested that resveratrol effectively suppressed the NLRP3 inflammasome activation during the BPH growth process in model rats. […] The activation of NLRP3 inflammasome by complement component C5a promotes IL-1 and IL-18 production via Caspase-1 and amplifies inflammation during the growth process of BPH. […] Our results suggested that inflammasome might be a therapeutic target during the growth process of BPH.

• #36

  https://insight.jci.org/articles/view/176479

  Here, by spatial transcriptomics of human BPH nodules, we identify secreted factors expressed in the presumptive inductive stroma adjacent to hyperplastic branching ducts. […] The topmost gene transcripts enriched in the inner stroma were insulin-like growth factor 1 (IGF1) and CXC chemokine ligand 13 (CXCL13). […] IGF1 has previously been linked to prostate development and has been implicated, among many other growth factors, in BPH pathogenesis. […] Our finding of high stromal IGF1 expression adjacent to BPH hubs is notable, but equally striking is what we did not find. […] Our studies identified only IGF1 (and IGF2) as top enriched genes. […] Our results may also explain why hyperinsulinemia is a risk factor for BPH; high insulin levels can crossactivate the IGF1R. […] Our studies also have several therapeutic implications. […] Our findings suggest the potential efficacy of IGF1R inhibitors as a disease-targeted approach in preventing or managing BPH and its associated lower urinary tract symptoms.

• #37 Autophagy in benign prostatic hyperplasia: insights and therapeutic potential | BMC Urology | Full Text

  https://bmcurol.biomedcentral.com/articles/10.1186/s12894-024-01585-7

  Autophagy is a cellular homeostatic mechanism characterized by cyclic degradation. It plays an essential role in maintaining cellular quality and survival by eliminating dysfunctional cellular components. This process is pivotal in various pathophysiological processes. Benign prostatic hyperplasia (BPH) is a common urological disorder in middle-aged and elderly men. It frequently presents as lower urinary tract symptoms due to an increase in epithelial and stromal cells surrounding the prostatic urethra. The precise pathogenesis of BPH is complex. […] In recent years, research on autophagy in BPH has gained significant momentum, with accumulating evidence indicating its crucial role in the onset and progression of the disease. […] Autophagy is widely present in the prostate tissues of BPH patients. Additionally, as a survival mechanism, autophagy helps human prostatic stromal cells survive in mildly hypoxic environments caused by reduced blood flow to the prostate. However, the ultimate outcome of autophagy’s role remains controversial. Some believe that the continuous progression of BPH is due to the upregulation of autophagy. Conversely, others have found that autophagy in BPH tissue cells decreases under both basal and inducible conditions.

• #38 Autophagy in benign prostatic hyperplasia: insights and therapeutic potential | BMC Urology | Full Text

  https://bmcurol.biomedcentral.com/articles/10.1186/s12894-024-01585-7

  Research has also indicated that long-term use of 5-ARIs reduces the secretion of IGF-1 by prostate stromal cells, thereby inducing autophagy in prostate epithelial cells. […] Autophagy plays a crucial role in maintaining cell survival while also being decisive in the process of cell death. […] Some studies indicate that the increase in prostate volume is not due to excessive proliferation of prostate tissue but is related to reduced apoptosis of prostate cells caused by crosstalk between autophagy and apoptosis. […] Autophagy and apoptosis are tightly regulated biological processes that play a central role in tissue homeostasis, development, and disease. […] Studies have pointed out that under AD conditions, silencing Beclin-1 leads to blocked autophagy and activated apoptosis. […] This suggests that AD and autophagy inhibition may have a synergistic effect, potentially treating BPH by further enhancing apoptosis levels.

• #39 Autophagy in benign prostatic hyperplasia: insights and therapeutic potential | BMC Urology | Full Text

  https://bmcurol.biomedcentral.com/articles/10.1186/s12894-024-01585-7

  In this review, we will elucidate the process and regulatory mechanisms of autophagy and analyze its various specific mechanisms of action in BPH. […] The PI3K-AKT-mTOR pathway is considered one of the main pathways regulating autophagy, exerting a negative regulatory effect on cellular autophagy. […] In androgen-induced BPH rats, testosterone can inhibit autophagy by activating the PI3K/Akt/mTOR pathway, reducing the expression of Beclin1 and LC3-II. […] Studies have also shown that the use of the autophagy inducer rapamycin can enhance autophagy by inhibiting mTOR, thereby suppressing the testosterone-induced proliferation of prostate tissue in rats. […] In BPH patients treated with 5-ARIs, the expression of Beclin-1 and LC3 is significantly higher than in untreated control groups. This suggests that autophagy is promoted during 5-ARI treatment.

• #40 Prostate BPH- pathophysiology | PPT

  https://www.slideshare.net/slideshow/prostate-bph-pathophysiology/248946103

  11) DHT and 5-Reductase: Intraprostatic DHT concentrations are maintained same/elevated in BPH. […] 12) The Role of Estrogens: Serum estrogen levels increased in aging men. […] 13) Regulation of Programmed Cell Death: Programmed cell death (apoptosis) is a physiologic mechanism crucial to the maintenance of normal glandular homeostasis. […] 14) Stromal-Epithelial Interaction: Prostatic stromal and epithelial cells maintain a sophisticated paracrine type of communication. […] 15) Growth factors are small peptide molecules that stimulate, or inhibit cell division and differentiation processes. […] 16) Genetic and Familial Factors: BPH – inheritable genetic component. […] 17) Anatomic Features: BPH first develops in the periurethral transition zone of the prostate. […] 18) Histologic Features: BPH – true hyperplastic process – an increase in the cell number. […] 19) Importance of Prostatic Smooth Muscle: Prostatic smooth muscle represents a significant volume of the gland. […] 20) The Bladder’s Response to Obstruction: The bladder’s response to obstruction – an adaptive one. […] 21) Summary: The exact etiology of BPH is yet to be elucidated.

• #41 Benign Prostatic Hyperplasia (BPH): Practice Essentials, Background, Anatomy

  https://emedicine.medscape.com/article/437359-overview

  This increased sensitivity (detrusor overactivity), even with small volumes of urine in the bladder, is believed to contribute to urinary frequency and LUTS. […] In the bladder, obstruction leads to smooth-muscle-cell hypertrophy. Biopsy specimens of trabeculated bladders demonstrate evidence of scarce smooth-muscle fibers with an increase in collagen. The collagen fibers limit compliance, leading to higher bladder pressures upon filling.

• #42 Benign Prostatic Hyperplasia: Etiology, Pathophysiology, Epidemiology, and Natural History | Abdominal Key

  https://abdominalkey.com/benign-prostatic-hyperplasia-etiology-pathophysiology-epidemiology-and-natural-history/

  Hormones may exert their influence over the stem cell population not only with advancing age but also during embryonic and neonatal development. […] Although androgens do not cause BPH, the development of BPH requires the presence of testicular androgens during prostate development, puberty, and aging. […] The potential role of AR mutations, polymorphisms, or other alterations in the pathogenesis of BPH is unclear. […] The type 2 isoform is critical to normal development of the prostate and hyperplastic growth later in life. […] The stromal cell plays a central role in androgen-dependent prostatic growth and that type 2 5-reductase within the stromal cell is the key androgenic amplification step. […] Prostatic hyperplasia increases urethral resistance, resulting in compensatory changes in bladder function. However, the elevated detrusor pressure required to maintain urinary flow in the presence of increased outflow resistance occurs at the expense of normal bladder storage function. Obstruction-induced changes in detrusor function, compounded by age-related changes in both bladder and nervous system function, lead to urinary frequency, urgency, and nocturia, the most bothersome BPH-related complaints.

• #43 Benign Prostatic Hyperplasia (BPH): Practice Essentials, Background, Anatomy

  https://emedicine.medscape.com/article/437359-overview

  This increased sensitivity (detrusor overactivity), even with small volumes of urine in the bladder, is believed to contribute to urinary frequency and LUTS. […] In the bladder, obstruction leads to smooth-muscle-cell hypertrophy. Biopsy specimens of trabeculated bladders demonstrate evidence of scarce smooth-muscle fibers with an increase in collagen. The collagen fibers limit compliance, leading to higher bladder pressures upon filling.

• #44 Benign Prostatic Hyperplasia – Genitourinary Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/genitourinary-disorders/benign-prostate-disease/benign-prostatic-hyperplasia

  Benign prostatic hyperplasia (BPH) is nonmalignant adenomatous overgrowth of the periurethral prostate gland. […] The etiology is unknown but probably involves hormonal changes associated with aging. […] Multiple fibroadenomatous nodules develop in the periurethral region of the prostate, probably originating within the periurethral glands rather than in the true fibromuscular prostate (surgical capsule), which is displaced peripherally by progressive growth of the nodules. […] As the lumen of the prostatic urethra narrows and lengthens, urine outflow is progressively obstructed. Increased pressure associated with micturition and bladder distention can progress to hypertrophy of the bladder detrusor, trabeculation, cellule formation, and diverticula. Incomplete bladder emptying causes stasis and predisposes to calculus formation and infection. Prolonged urinary tract obstruction, even if incomplete, can cause hydronephrosis and compromise renal function.

• #45 Benign prostatic hyperplasia – Wikipedia

  https://en.wikipedia.org/wiki/Benign_prostatic_hyperplasia

  Benign prostatic hyperplasia (BPH), also called prostate enlargement, is a noncancerous increase in size of the prostate gland. […] The cause is unclear. Risk factors include a family history, obesity, type 2 diabetes, not enough exercise, and erectile dysfunction. […] The underlying mechanism involves the prostate pressing on the urethra thereby making it difficult to pass urine out of the bladder. […] Most experts consider androgens (testosterone and related hormones) to play a permissive role in the development of BPH. […] Dihydrotestosterone (DHT), a metabolite of testosterone, is a critical mediator of prostatic growth. […] The importance of DHT in causing nodular hyperplasia is supported by clinical observations in which an inhibitor of 5-reductase such as finasteride is given to men with this condition.

• #46 Benign Prostatic Pathology | Radiology Key

  https://radiologykey.com/benign-prostatic-pathology/

  Benign prostatic hyperplasia (BPH) represents the most commonly diagnosed urological disease in men after the fifth decade. […] Although BPH etiology remains uncertain in some aspects, several mechanisms have been proposed to be involved in the pathogenesis and progression of BPH. First, aging represents the most significant risk factor for the development of BPH and the compliant of lower urinary tract symptoms (LUTS). In aging men, an interference in growth factor pathway occurs and a significant tissue-remodeling process takes place, leading to prostatic enlargement. […] Second, hormonal alterations have been proposed to be involved in BPH pathogenesis and progression. Indeed, the development of BPH requires the presence of testicular androgens, and BPH tissue has higher dihydrotestosterone activity than normal prostate gland tissue.

• #47 Benign prostatic hyperplasia – Wikipedia

  https://en.wikipedia.org/wiki/Benign_prostatic_hyperplasia

  Benign prostatic hyperplasia (BPH), also called prostate enlargement, is a noncancerous increase in size of the prostate gland. […] The cause is unclear. Risk factors include a family history, obesity, type 2 diabetes, not enough exercise, and erectile dysfunction. […] The underlying mechanism involves the prostate pressing on the urethra thereby making it difficult to pass urine out of the bladder. […] Most experts consider androgens (testosterone and related hormones) to play a permissive role in the development of BPH. […] Dihydrotestosterone (DHT), a metabolite of testosterone, is a critical mediator of prostatic growth. […] The importance of DHT in causing nodular hyperplasia is supported by clinical observations in which an inhibitor of 5-reductase such as finasteride is given to men with this condition.

• #48 Benign prostatic hyperplasia – Wikipedia

  https://en.wikipedia.org/wiki/Benign_prostatic_hyperplasia

  Benign prostatic hyperplasia (BPH), also called prostate enlargement, is a noncancerous increase in size of the prostate gland. […] The cause is unclear. Risk factors include a family history, obesity, type 2 diabetes, not enough exercise, and erectile dysfunction. […] The underlying mechanism involves the prostate pressing on the urethra thereby making it difficult to pass urine out of the bladder. […] Most experts consider androgens (testosterone and related hormones) to play a permissive role in the development of BPH. […] Dihydrotestosterone (DHT), a metabolite of testosterone, is a critical mediator of prostatic growth. […] The importance of DHT in causing nodular hyperplasia is supported by clinical observations in which an inhibitor of 5-reductase such as finasteride is given to men with this condition.

• #49 Benign prostatic hyperplasia – Wikipedia

  https://en.wikipedia.org/wiki/Benign_prostatic_hyperplasia

  Benign prostatic hyperplasia (BPH), also called prostate enlargement, is a noncancerous increase in size of the prostate gland. […] The cause is unclear. Risk factors include a family history, obesity, type 2 diabetes, not enough exercise, and erectile dysfunction. […] The underlying mechanism involves the prostate pressing on the urethra thereby making it difficult to pass urine out of the bladder. […] Most experts consider androgens (testosterone and related hormones) to play a permissive role in the development of BPH. […] Dihydrotestosterone (DHT), a metabolite of testosterone, is a critical mediator of prostatic growth. […] The importance of DHT in causing nodular hyperplasia is supported by clinical observations in which an inhibitor of 5-reductase such as finasteride is given to men with this condition.

• #50 Benign prostatic hyperplasia – Wikipedia

  https://en.wikipedia.org/wiki/Benign_prostatic_hyperplasia

  Benign prostatic hyperplasia (BPH), also called prostate enlargement, is a noncancerous increase in size of the prostate gland. […] The cause is unclear. Risk factors include a family history, obesity, type 2 diabetes, not enough exercise, and erectile dysfunction. […] The underlying mechanism involves the prostate pressing on the urethra thereby making it difficult to pass urine out of the bladder. […] Most experts consider androgens (testosterone and related hormones) to play a permissive role in the development of BPH. […] Dihydrotestosterone (DHT), a metabolite of testosterone, is a critical mediator of prostatic growth. […] The importance of DHT in causing nodular hyperplasia is supported by clinical observations in which an inhibitor of 5-reductase such as finasteride is given to men with this condition.

• #51 Benign prostatic hyperplasia – Wikipedia

  https://en.wikipedia.org/wiki/Benign_prostatic_hyperplasia

  Benign prostatic hyperplasia (BPH), also called prostate enlargement, is a noncancerous increase in size of the prostate gland. […] The cause is unclear. Risk factors include a family history, obesity, type 2 diabetes, not enough exercise, and erectile dysfunction. […] The underlying mechanism involves the prostate pressing on the urethra thereby making it difficult to pass urine out of the bladder. […] Most experts consider androgens (testosterone and related hormones) to play a permissive role in the development of BPH. […] Dihydrotestosterone (DHT), a metabolite of testosterone, is a critical mediator of prostatic growth. […] The importance of DHT in causing nodular hyperplasia is supported by clinical observations in which an inhibitor of 5-reductase such as finasteride is given to men with this condition.

• #52 Benign Prostatic Pathology | Radiology Key

  https://radiologykey.com/benign-prostatic-pathology/

  Additionally, insulin resistance with secondary hyperinsulinemia has been proposed to be involved in the development of BPH. […] Third, a role of increased sympathetic nerve activity has also been proposed. […] Finally, in the last few years, the role of prostatic inflammation as a crucial part of BPH pathogenesis and progression has emerged. The chronic inflammatory condition may contribute to tissue injury, activating cytokine release and increasing the concentration of growth factors, creating a local vicious cycle. […] In this context, the upregulation of proinflammatory cytokines has been widely reported in prostatic tissues of patients with BPH. […] Concluding, all these data support the hypothesis that tissue damage, hypoxia, and chronic process of wound healing lead to a persistent process of stimulation of stromal and epithelial prostatic tissues, potentially resulting in BPH. […] Interestingly, it has been hypothesized that inflammatory infiltrate leads to tissue damage and to a chronic process of wound healing that might subsequently determinate prostatic enlargement.

• #53 Benign Prostatic Hyperplasia (BPH): Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/9100-benign-prostatic-hyperplasia

  New BPH treatments are less invasive and damaging to healthy tissue than surgery. […] TURP is the most effective treatment for most cases of BPH. […] The best ways to reduce your risk of developing BPH are to make lifestyle changes that improve your prostate and heart health and take supplements. […] The outlook for people with BPH is very good. BPH doesnt have a cure, but treatments can help alleviate your symptoms. Mild symptoms may not require treatment. Medications, surgery and minimally invasive treatments can treat more severe cases.

• #54 Medical management of benign prostatic hyperplasia | Cleveland Clinic Journal of Medicine

  https://www.ccjm.org/content/91/3/163

  An enlarged prostate gland, while not in itself pathologic, can result in lower urinary tract symptoms, either by directly obstructing the bladder outlet as enlargement changes the shape of the gland, or by increasing smooth muscle tone and resistance to flow within the enlarged gland.2 […] The goal of treatment for lower urinary tract symptoms associated with BPH has long been to maximize quality of life and minimize bothersome symptoms. More recently, focus on preventing side effects or treatment complications has been growing. […] Androgens are essential to prostatic growth.16 The conversion of testosterone to dihydrotestosterone, a more potent ligand for the androgen receptor and arbiter of prostatic growth, is central to this process.1417,22 Inhibiting the conversion of testosterone to dihydrotestosterone with 5-alpha reductase inhibitors (5ARIs) can reduce prostate growth and tip the scales toward prostatic cellular apoptosis and atrophy.

• #55 Diagnosis and Management of Benign Prostatic Hyperplasia | AAFP

  https://www.aafp.org/pubs/afp/issues/2008/0515/p1403.html

  Benign prostatic hyperplasia (BPH) is a common condition in older men. Histologically, it is characterized by the presence of discrete nodules in the periurethral zone of the prostate gland. Clinical manifestations of BPH are caused by extrinsic compression of the prostatic urethra leading to impaired voiding. Chronic inability to completely empty the bladder may cause bladder distension with hypertrophy and instability of the detrusor muscle. […] The prevalence of BPH increases with age. One study suggests that the prevalence is 20 percent in 40-year-old men and increases to 90 percent in men in their seventies. […] Prostate growth is stimulated by androgenic hormones, especially dihydrotestosterone. Finasteride and dutasteride inhibit the conversion of testosterone to dihydrotestosterone, suppressing prostate growth. These agents appear to be most beneficial when the prostate volume is 40 mL or greater. The 5-alpha reductase inhibitors do not provide immediate symptom relief, and approximately six months of therapy is required to achieve clinical benefit. Unlike alpha blockers, 5-alpha reductase inhibitors have been shown to affect the clinical course of BPH, reducing the risk of acute urinary retention and surgical intervention four years after therapy.

• #56 Medical management of benign prostatic hyperplasia | Cleveland Clinic Journal of Medicine

  https://www.ccjm.org/content/91/3/163

  5ARIs for prostate cancer prevention have been studied for some time, with the evidence showing these medications reduce overall prostate cancer rates, particularly low-grade cancers. […] Phosphodiesterase-5 (PDE5) inhibitors increase intracellular cyclic guanosine monophosphate, causing nitric oxide-mediated relaxation of smooth muscle throughout the prostate, detrusor muscle (bladder), and urethra.27 It is thought that this is the beneficial mechanism of action of PDE5 inhibitors on patients with BPH and lower urinary tract symptoms. […] Beta-3 agonists, including mirabegron and vibegron, work via the sympathetic pathway to cause relaxation of the detrusor muscle and increase bladder capacity. […] Combination pharmacotherapy has been shown to be more effective than monotherapy or placebo, specifically in patients with larger prostates who meet criteria for 5ARIs and can be offered alpha-blockers simultaneously.

• #57 Medical management of benign prostatic hyperplasia | Cleveland Clinic Journal of Medicine

  https://www.ccjm.org/content/91/3/163

  5ARIs for prostate cancer prevention have been studied for some time, with the evidence showing these medications reduce overall prostate cancer rates, particularly low-grade cancers. […] Phosphodiesterase-5 (PDE5) inhibitors increase intracellular cyclic guanosine monophosphate, causing nitric oxide-mediated relaxation of smooth muscle throughout the prostate, detrusor muscle (bladder), and urethra.27 It is thought that this is the beneficial mechanism of action of PDE5 inhibitors on patients with BPH and lower urinary tract symptoms. […] Beta-3 agonists, including mirabegron and vibegron, work via the sympathetic pathway to cause relaxation of the detrusor muscle and increase bladder capacity. […] Combination pharmacotherapy has been shown to be more effective than monotherapy or placebo, specifically in patients with larger prostates who meet criteria for 5ARIs and can be offered alpha-blockers simultaneously.

• #58 Medical management of benign prostatic hyperplasia | Cleveland Clinic Journal of Medicine

  https://www.ccjm.org/content/91/3/163

  5ARIs for prostate cancer prevention have been studied for some time, with the evidence showing these medications reduce overall prostate cancer rates, particularly low-grade cancers. […] Phosphodiesterase-5 (PDE5) inhibitors increase intracellular cyclic guanosine monophosphate, causing nitric oxide-mediated relaxation of smooth muscle throughout the prostate, detrusor muscle (bladder), and urethra.27 It is thought that this is the beneficial mechanism of action of PDE5 inhibitors on patients with BPH and lower urinary tract symptoms. […] Beta-3 agonists, including mirabegron and vibegron, work via the sympathetic pathway to cause relaxation of the detrusor muscle and increase bladder capacity. […] Combination pharmacotherapy has been shown to be more effective than monotherapy or placebo, specifically in patients with larger prostates who meet criteria for 5ARIs and can be offered alpha-blockers simultaneously.

• #59 Newer Medications for Lower Urinary Tract Symptoms (LUTS) Associated with Benign Prostatic Hyperplasia (BPH) | Effective Health Care (EHC) Program

  https://effectivehealthcare.ahrq.gov/products/prostatic-hyperplasia-medications/research-protocol

  The AUA guideline also lists AB/5-ARI combinations as appropriate and effective treatment options for men with LUTS/BPH and prostate enlargement. […] Recently, newer drugs and other drug classes have shown promise in treating LUTS/BPH. A new AB, silodosin, was approved for the treatment of BPH in 2008. Several anticholinergics drugs approved for overactive bladder (OAB) have the potential to alleviate symptoms of LUTS/BPH due to the similarity of symptoms such as urgency, frequency, and nocturia, which may or may not be causally related. […] A new class of drugs, beta-3 adrenoceptor agonists, was recently developed to treat OAB. The proposed advantages over anticholinergics include potentially lower rates of adverse effects and potentially smaller risk of urinary retention. […] Tadalafil, a phosphodiesterase (PDE-5) inhibitor (FDA-approved for the treatment of erectile dysfunction [ED] since 2003) was approved by the FDA for the treatment of BPH in 2011.

• #60 Review and update of benign prostatic hyperplasia in general practice

  https://www1.racgp.org.au/ajgp/2018/july/benign-prostatic-hyperplasia

  5-ARIs inhibit the conversion of testosterone to dihydrotestosterone (DHT) to reduce prostate growth and prostate volume. […] The most common side effects of 5-ARIs are erectile dysfunction, decreased libido, decreased ejaculate and decreased sperm count. […] Transurethral resection of the prostate (TURP) is the gold standard surgical treatment for symptomatic BPH.

• #61 Autophagy in benign prostatic hyperplasia: insights and therapeutic potential | BMC Urology | Full Text

  https://bmcurol.biomedcentral.com/articles/10.1186/s12894-024-01585-7

  In this review, we will elucidate the process and regulatory mechanisms of autophagy and analyze its various specific mechanisms of action in BPH. […] The PI3K-AKT-mTOR pathway is considered one of the main pathways regulating autophagy, exerting a negative regulatory effect on cellular autophagy. […] In androgen-induced BPH rats, testosterone can inhibit autophagy by activating the PI3K/Akt/mTOR pathway, reducing the expression of Beclin1 and LC3-II. […] Studies have also shown that the use of the autophagy inducer rapamycin can enhance autophagy by inhibiting mTOR, thereby suppressing the testosterone-induced proliferation of prostate tissue in rats. […] In BPH patients treated with 5-ARIs, the expression of Beclin-1 and LC3 is significantly higher than in untreated control groups. This suggests that autophagy is promoted during 5-ARI treatment.

• #62 Frontiers | Immune Cell Proinflammatory Microenvironment and Androgen-Related Metabolic Regulation During Benign Prostatic Hyperplasia in Aging

  https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.842008/full

  Inflammation causes cell and DNA damage, promotes cell replacement and creates a tissue microenvironment rich in cytokines and growth factors, thereby promoting cell proliferation and causing hyperplasia during tissue repair. […] While inflammation promotes the occurrence and development of BPH, the presence of BPH cells can also promote the occurrence of inflammation and make inflammation continue to expand. […] The latest research also shows that BPH may be an immunoinflammatory disease. […] The immune disorder response in BPH may occur through increased expression of proinflammatory IL-17, and the autoimmune response associated with T cells may induce abnormal proliferation of epithelial cells and stromal cells. […] In summary, inflammation plays a vital role in the pathogenesis and disease development of BPH. Inflammation can independently affect the development of BPH in a variety of ways, and it can also interact with androgens. At the same time, BPH can also promote inflammation to expand its scope and aggravate the situation. Therefore, in the treatment process, early intervention in the occurrence and development of inflammation in prostate tissue can slow down the progression of BPH. The combination of standard therapies and anti-inflammatory measures may provide valuable new ideas for the treatment of BPH.

• #63 A new mechanism to explain benign prostatic hyperplasia – Baylor College of Medicine Blog Network

  https://blogs.bcm.edu/2016/10/14/a-new-mechanism-to-explain-benign-prostatic-hyperplasia/

  Our result that disruption of androgen receptor signaling in luminal cells can drive inflammation is consistent with the observation that luminal cells of inflamed human prostate glands have fewer androgen receptors than luminal cells from non-inflamed prostates. […] This research has clinical implications related to the treatment of BPH with androgen-targeting therapy, the goal of which is to deplete androgen to starve proliferating cells that require androgen to survive. […] Our results may explain why some BPH patients respond to androgen-targeting therapies, such as finasteride, while in other patients the disease continues to progress, said Xin. We suggest that treatment for BPH might be more effective if patients received androgen-targeting therapy together with drugs that target inflammation.

• #64 The Etiology and Pathogenesis of Benign Prostatic Hyperplasia: The Roles of Sex Hormones and Anatomy

  https://pmc.ncbi.nlm.nih.gov/articles/PMC11430843/

  Benign prostatic hyperplasia (BPH) mainly causes lower urinary tract symptoms in ageing men, but its exact etiology and pathogenesis have not been established. […] The objective of this review was to design an update on the advances of human BPH research. […] No evidence for the role of testosterone (T) or dihydrotestosterone (DHT) is found in BPH initiation. […] After cellular damage and subsequent inflammation generated, the intraprostatic DHT produced mainly from T by 5-reductase promotes BPH development. […] The confounding of BPH may attenuate the development of prostate tumor in the TZ. […] In conclusion, evidence in literature suggests that androgens are not etiological factors for BPH, and intraprostatic DHT along with chronic inflammation are mainly responsible for nodular proliferation of stromal and/or epithelial cells in prostatic TZ.

• #65 Mechanism of Androgen-Independent Stromal Proliferation in Benign Prostatic Hyperplasia

  https://www.mdpi.com/1422-0067/24/14/11634

  Benign prostatic hyperplasia (BPH) is a chronic proliferative disease showing stromal-dominant proliferation. However, the detailed proliferation mechanism has remained unclear. Although aging and androgen have been reported as definitive risk factors for BPH, recent studies have focused on the involvement of androgen-independent factors. Androgen-independent factors include ischemia, oxidative stress, metabolic syndrome, infection, autoimmune reactions, and inflammation, with inflammation in BPH tissues playing a central role in the BPH proliferative process. Inflammation in BPH tissues by various factors finally leads to tissue remodeling and stromal proliferation through the wound healing process of the prostate. To elucidate the proliferative mechanism of BPH, a study using whole-genome gene expression analysis in a stromal-dominant BPH rat model was performed and showed that immune response-related pathways and complement classical pathways are activated. Furthermore, expression analysis using this BPH rat model showed that the autoimmune reaction triggered complement pathway activation in the proliferative process of BPH. BPH is a multifactorial disease, and understanding the role of androgen-independent factors including immune responses contributes to elucidating the pathogenesis of BPH. Androgen-independent factors may lead to new therapeutic targets for BPH, and further development of this research is expected.

• #66 Benign Prostatic Hyperplasia: Evaluation and Medical Management in Primary Care

  https://consultqd.clevelandclinic.org/benign-prostatic-hyperplasia-evaluation-and-medical-management-in-primary-care

  BPH is a histologic diagnosis of proliferation of smooth muscle, epithelium, and stromal cells within the transition zone of the prostate, which surrounds the proximal urethra. […] Symptoms arise through two mechanisms: static, in which the hyperplastic prostatic tissue compresses the urethra; and dynamic, with increased adrenergic nervous system and prostatic smooth muscle tone. Both mechanisms increase resistance to urinary flow at the level of the bladder outlet. […] Chronic bladder outlet obstruction can lead to bladder decompensation and detrusor underactivity, manifesting as incomplete emptying, urinary hesitancy, intermittency (starting and stopping while voiding), a weakened urinary stream and urinary retention. […] Finasteride and dutasteride are believed to mitigate the static obstructive component of BPH, with similar improvements in urinary flow rate and symptom score in men with an enlarged prostate.

• #67 A genetic study to identify pathogenic mechanisms and drug targets for benign prostatic hyperplasia: a multi-omics Mendelian randomization study | Scientific Reports

  https://www.nature.com/articles/s41598-024-73466-w

  We also used druggable gene data to identify 30 promising therapeutic target genes, including BTN3A2 and C4A. […] Our study identified a potential pathogenic pathway for BPH, that lower cg14345882 levels upregulated BTN3A2 expression, which increased the risk of BPH. […] Our study suggests that the C4A gene mediates the development of BPH through hyperactivation of the complement system. […] Our study identified many BPH-related traits, from genes to immune pathways to circulating metabolites, laying a solid foundation for BPH research and providing directions for basic and translational research on therapeutic drugs. […] In conclusion, our study lays a solid foundation for future studies on the pathogenic mechanisms of BPH, explores new directions for the therapeutic approach of BPH, and provides a new method for differential diagnosis between BPH and early PCA.

• #68

  https://insight.jci.org/articles/view/176479

  Here, by spatial transcriptomics of human BPH nodules, we identify secreted factors expressed in the presumptive inductive stroma adjacent to hyperplastic branching ducts. […] The topmost gene transcripts enriched in the inner stroma were insulin-like growth factor 1 (IGF1) and CXC chemokine ligand 13 (CXCL13). […] IGF1 has previously been linked to prostate development and has been implicated, among many other growth factors, in BPH pathogenesis. […] Our finding of high stromal IGF1 expression adjacent to BPH hubs is notable, but equally striking is what we did not find. […] Our studies identified only IGF1 (and IGF2) as top enriched genes. […] Our results may also explain why hyperinsulinemia is a risk factor for BPH; high insulin levels can crossactivate the IGF1R. […] Our studies also have several therapeutic implications. […] Our findings suggest the potential efficacy of IGF1R inhibitors as a disease-targeted approach in preventing or managing BPH and its associated lower urinary tract symptoms.

Zobacz więcej