Male lower urinary tract symptoms (LUTS), previously known as prostatism, are common in aging men. LUTS include storage symptoms like urgency, frequency, and nocturia as well as voiding symptoms like weak stream and incomplete emptying. While LUTS were traditionally attributed to benign prostatic hyperplasia (BPH), it is now recognized that storage symptoms are similar to overactive bladder (OAB) seen in women. Medical therapy for LUTS has evolved from surgery to treat obstruction to current use of alpha-blockers, 5-alpha-reductase inhibitors, and antimuscarinic medications to treat both storage and voiding symptoms, with or without BPH. Proper evaluation
This document discusses overactive bladder (OAB), including its definition, symptoms, prevalence, impact, and treatment options. It defines OAB as a syndrome characterized by urgency, with or without urge incontinence, usually accompanied by frequency and nocturia. It notes that OAB is very common, affecting 11-22% of adults over 40, and is more prevalent in older individuals and females. While over half of females with OAB seek treatment, far fewer males do. Non-pharmacological treatments discussed include behavior modification, diet and fluid management, and pelvic floor exercises.
This document summarizes the evidence-based approach to managing male benign prostatic enlargement. It discusses the terminology, natural history, and management of lower urinary tract symptoms. The main treatment options for LUTS/BPO that are supported by evidence include alpha-1 adrenoceptor antagonists, 5-alpha reductase inhibitors, and combination therapy with both. Guidelines aim to guide best practice and provide consensus based on evidence.
This document provides an overview of benign prostatic hyperplasia (BPH), including its epidemiology, terminology, evaluation, medical and surgical treatment options, and pathophysiology. Some key points include:
- BPH is a histological diagnosis defined as nonmalignant hyperplasia of the prostate gland. It often presents clinically as lower urinary tract symptoms and prostate enlargement.
- Evaluation involves assessment of symptoms, physical exam including DRE, urinalysis, and consideration of PSA. Objective tests like flow rate and residual urine may be used depending on symptom severity.
- Medical therapy options aim to reduce bladder outlet obstruction and include alpha-blockers which relax smooth muscle, and 5-alpha
This document provides an overview of benign prostatic hyperplasia (BPH), including its epidemiology, terminology, evaluation, medical and surgical treatment options, and pathophysiology. Some key points include:
- BPH is a histological diagnosis defined as nonmalignant hyperplasia of the prostate gland. It often presents clinically as bothersome lower urinary tract symptoms and an enlarged prostate.
- Evaluation involves medical history, physical exam including DRE, urinalysis, and symptom assessment. Additional tests like flow rate and residual urine may be used if symptoms are moderate to severe.
- Medical therapy options are alpha-blockers which target the dynamic component of obstruction, and 5-alpha-re
The document discusses pharmacotherapy for overactive bladder. It provides an overview of overactive bladder terminology, prevalence, diagnosis, and differential diagnosis. It then focuses on the rationale for pharmacologic treatment of overactive bladder, including the use of antimuscarinic drugs which are the mainstay of treatment by inhibiting involuntary bladder contractions. Clinical trials demonstrate the efficacy of drugs like tolterodine in reducing overactive bladder symptoms and improving quality of life.
This document provides an update on research into Fabry disease. Some key points:
- Fabry disease is an X-linked lysosomal storage disease caused by a deficiency in the enzyme alpha-galactosidase A. Symptoms typically appear in childhood and include pain, fatigue, and kidney, heart, and neurological problems.
- Current treatments include enzyme replacement therapies which require intravenous infusions. Research is exploring oral treatments, biomarkers to monitor treatment effectiveness, and ways to target tissues not reached by current therapies.
- Studies show symptoms often appear earlier than previously thought, and early initiation of treatment may help prevent organ damage. However, most patients still start treatment after significant disease progression.
- Research is
This document discusses obesity, systemic lupus erythematosus (SLE), thyroid disease, and in vitro fertilization (IVF). It summarizes that obesity is associated with lower clinical pregnancy and live birth rates after IVF due to factors like insulin resistance and inflammation. For SLE patients undergoing IVF, aggressive ovarian stimulation should be avoided to prevent thrombosis, and immunosuppressants may be increased. Thyroid disorders must be controlled before conception, and levothyroxine doses may need adjustment during ovarian stimulation due to changes in hormone levels. Screening for thyroid disease is recommended for those with risk factors prior to IVF to optimize treatment.
Mens urological health cme bph-luts- final- nov 13 2013Ihsaan Peer
The document provides guidance on evaluating patients with benign prostatic hyperplasia and lower urinary tract symptoms (BPH-LUTS). It recommends obtaining a medical history, physical exam including digital rectal exam and urinalysis, and using validated symptom assessment tools. PSA testing should be offered to men over 50 according to Canadian guidelines, and storage symptoms persisting after treatment may indicate conditions like overactive bladder requiring further evaluation.
This document discusses overactive bladder (OAB), including its definition, symptoms, prevalence, impact, and treatment options. It defines OAB as a syndrome characterized by urgency, with or without urge incontinence, usually accompanied by frequency and nocturia. It notes that OAB is very common, affecting 11-22% of adults over 40, and is more prevalent in older individuals and females. While over half of females with OAB seek treatment, far fewer males do. Non-pharmacological treatments discussed include behavior modification, diet and fluid management, and pelvic floor exercises.
This document summarizes the evidence-based approach to managing male benign prostatic enlargement. It discusses the terminology, natural history, and management of lower urinary tract symptoms. The main treatment options for LUTS/BPO that are supported by evidence include alpha-1 adrenoceptor antagonists, 5-alpha reductase inhibitors, and combination therapy with both. Guidelines aim to guide best practice and provide consensus based on evidence.
This document provides an overview of benign prostatic hyperplasia (BPH), including its epidemiology, terminology, evaluation, medical and surgical treatment options, and pathophysiology. Some key points include:
- BPH is a histological diagnosis defined as nonmalignant hyperplasia of the prostate gland. It often presents clinically as lower urinary tract symptoms and prostate enlargement.
- Evaluation involves assessment of symptoms, physical exam including DRE, urinalysis, and consideration of PSA. Objective tests like flow rate and residual urine may be used depending on symptom severity.
- Medical therapy options aim to reduce bladder outlet obstruction and include alpha-blockers which relax smooth muscle, and 5-alpha
This document provides an overview of benign prostatic hyperplasia (BPH), including its epidemiology, terminology, evaluation, medical and surgical treatment options, and pathophysiology. Some key points include:
- BPH is a histological diagnosis defined as nonmalignant hyperplasia of the prostate gland. It often presents clinically as bothersome lower urinary tract symptoms and an enlarged prostate.
- Evaluation involves medical history, physical exam including DRE, urinalysis, and symptom assessment. Additional tests like flow rate and residual urine may be used if symptoms are moderate to severe.
- Medical therapy options are alpha-blockers which target the dynamic component of obstruction, and 5-alpha-re
The document discusses pharmacotherapy for overactive bladder. It provides an overview of overactive bladder terminology, prevalence, diagnosis, and differential diagnosis. It then focuses on the rationale for pharmacologic treatment of overactive bladder, including the use of antimuscarinic drugs which are the mainstay of treatment by inhibiting involuntary bladder contractions. Clinical trials demonstrate the efficacy of drugs like tolterodine in reducing overactive bladder symptoms and improving quality of life.
This document provides an update on research into Fabry disease. Some key points:
- Fabry disease is an X-linked lysosomal storage disease caused by a deficiency in the enzyme alpha-galactosidase A. Symptoms typically appear in childhood and include pain, fatigue, and kidney, heart, and neurological problems.
- Current treatments include enzyme replacement therapies which require intravenous infusions. Research is exploring oral treatments, biomarkers to monitor treatment effectiveness, and ways to target tissues not reached by current therapies.
- Studies show symptoms often appear earlier than previously thought, and early initiation of treatment may help prevent organ damage. However, most patients still start treatment after significant disease progression.
- Research is
This document discusses obesity, systemic lupus erythematosus (SLE), thyroid disease, and in vitro fertilization (IVF). It summarizes that obesity is associated with lower clinical pregnancy and live birth rates after IVF due to factors like insulin resistance and inflammation. For SLE patients undergoing IVF, aggressive ovarian stimulation should be avoided to prevent thrombosis, and immunosuppressants may be increased. Thyroid disorders must be controlled before conception, and levothyroxine doses may need adjustment during ovarian stimulation due to changes in hormone levels. Screening for thyroid disease is recommended for those with risk factors prior to IVF to optimize treatment.
Mens urological health cme bph-luts- final- nov 13 2013Ihsaan Peer
The document provides guidance on evaluating patients with benign prostatic hyperplasia and lower urinary tract symptoms (BPH-LUTS). It recommends obtaining a medical history, physical exam including digital rectal exam and urinalysis, and using validated symptom assessment tools. PSA testing should be offered to men over 50 according to Canadian guidelines, and storage symptoms persisting after treatment may indicate conditions like overactive bladder requiring further evaluation.
This document discusses the medical management of benign prostatic hyperplasia (BPH). It describes the pathology and pathophysiology of BPH, including the hyperplastic process that leads to nodule formation and bladder outlet obstruction. Clinical definitions related to BPH and lower urinary tract symptoms are provided. Assessment tools for lower urinary tract symptoms like the International Prostate Symptom Score are discussed. The document reviews differential diagnoses, treatments including watchful waiting, medications like alpha blockers and 5-alpha reductase inhibitors, and procedures. Side effects of medications and evidence for various treatment options are also summarized.
Updates in Prostatic enlargement Management by Dr.Wadah CeifoDr.wadah Ceifo
Silodosin is a highly selective alpha-1A adrenergic receptor blocker that is effective for treating lower urinary tract symptoms associated with benign prostatic hyperplasia. It has several advantages compared to other alpha blockers, including greater improvement in bladder outlet obstruction, higher selectivity for the alpha-1A receptor subtype found in the prostate, and a safer cardiovascular profile with fewer side effects like dizziness and orthostatic hypotension. Silodosin is considered a first-line treatment for moderate to severe LUTS according to EAU guidelines due to its rapid onset of action, good efficacy, and low rates of adverse events.
Ejaculation involves three phases - emission, bladder neck contraction, and expulsion. Premature ejaculation (PE) is defined as ejaculation occurring within about 1 minute of penetration that the man has little control over, causing distress. The pathophysiology of PE is not fully understood but may involve genetic, psychological, hormonal, penile sensitivity, and prostatic factors. PE is diagnosed based on history and can be evaluated using tools like the Premature Ejaculation Diagnostic Tool. Treatment includes behavioral therapies like stop-start and squeeze techniques as well as pharmacotherapies.
The document summarizes benign prostatic hyperplasia (BPH). It describes the anatomy of the prostate gland and discusses terminology related to BPH. BPH involves benign enlargement of the prostate, which can obstruct the urethra and cause urinary symptoms. Risk factors include increasing age, genetics, and metabolic conditions. Evaluation of BPH involves medical history, physical exam including digital rectal exam, and may include urinalysis, blood tests, questionnaires, ultrasound, and urodynamic studies.
Overactive bladder, DR Sharda Jain Lifecare Centre Lifecare Centre
OAB OAB is not synonymous with detrusor overactivity as the former is a symptom based diagnosis whilst the latter is an urodynamic diagnosis.
It has been estimated that 64% of patients with OAB have urodynamically proven detrusor overactivity and that 83% of patient with detrusor overactivity have symptoms suggestive of OAB.
This document summarizes key aspects of primary biliary cholangitis (PBC), formerly known as primary biliary cirrhosis. It discusses the epidemiology, risk factors, natural history, presentation, diagnosis and management of PBC. If left untreated, PBC progresses through several clinical phases over many years, eventually leading to liver failure and death in some patients. Prognosis is generally better in asymptomatic patients than in those with symptoms.
Common Urological Problems in Geriatric PopulationRamayya Pramila
Common urological problems in the geriatric population significantly affect quality of life. These include lower urinary tract symptoms from benign prostatic hyperplasia and overactive bladder, urinary tract infections, erectile dysfunction, and prostate cancer. Treatment involves addressing underlying causes, medications like alpha blockers and antimuscarinics, and procedures for severe cases. Managing incontinence, infections, and other issues in elderly patients requires close monitoring, tailored treatment, and attention to their unique needs.
This document discusses the consequences of cancer treatment and late effects. It notes that late effects currently affect 400,000 people in the UK and have a significant impact on survivors' daily lives. Late effects are underappreciated and can be managed through early intervention to prevent long-term impacts. The risks of late effects depend on treatment factors like radiation dose and chemotherapy drugs, as well as individual patient factors. Common late effects include scarring, functional disability, lymphedema, cardiac issues, and gastrointestinal problems. The document calls for improved assessment, management, and services to address late effects.
This document discusses urinary incontinence (UI) in older adults. It covers the prevalence of UI increasing with age, especially in women and those in long-term care. Risk factors include obesity, functional impairment, and medications. Age-related changes to the lower urinary tract are described for both men and women. The pathophysiology of different types of UI is explained. Screening, evaluation, treatments including lifestyle changes, behavioral therapies, and medications are outlined.
Benign enlargement of prostate . medical therapy Dr Pralhad Patki
This document discusses benign prostatic hyperplasia (BPH), including:
1. BPH is a common condition in aging men that causes lower urinary tract symptoms. The prevalence increases with age from around 8% in men in their 40s to over 80% in men in their 80s.
2. BPH is caused by both static enlargement of the prostate and dynamic obstruction of the bladder neck. Medical management focuses on reducing smooth muscle tone in the prostate and bladder neck using alpha-blockers.
3. Evaluation of BPH involves assessing symptoms, digital rectal exam, urinalysis, and tests like uroflowmetry. Treatment is based on symptom severity and includes watchful waiting
1. The document discusses erectile dysfunction (ED), including its anatomy, physiology, etiology, evaluation, and treatment. It defines ED and describes the neurovascular processes underlying erection.
2. Common organic, psychogenic, and mixed causes of ED are outlined. Evaluation involves history, physical exam, and investigations.
3. Treatment options discussed include lifestyle modifications and first-line oral phosphodiesterase type 5 inhibitors like sildenafil, tadalafil, and vardenafil. Guidelines on their use and dosing are provided.
There I go again, a Western guy giving a lecture to an Eastern crowd. What team do I play on, you ask? In fact, I am honored to give a keynote at the First Integrative Fertility Symposium in Vancouver. Ok, call me a “swingman,” but the Easterners have a lot up their medical sleeves too. Ask Western medicine how to help a guy relax, and they’ll say, “don’t work so hard and take this pill.” Ask an Easterner, and they might suggest acupuncture, mindfulness and meditation. Which approach is better: a patch or a fix? You decide. Read more on my blog at > http://bit.ly/1EMuRFF
Family Physician's Approach to Erectile DysfunctionSiewhong Ho
This document discusses the approach to treating erectile dysfunction. It defines erectile dysfunction and outlines its diagnosis and investigations. It describes how erectile dysfunction is often associated with other medical conditions like diabetes, cardiovascular disease, and depression. The document then discusses current treatment options for erectile dysfunction like PDE5 inhibitors, testosterone replacement therapy, and surgery. It provides details on the effectiveness, safety profiles, and proper use of PDE5 inhibitors.
Overactive bladder (OAB) is a common condition characterized by urinary urgency, usually accompanied by increased daytime frequency and/or nocturia, with or without urinary incontinence. OAB affects a significant portion of the global population but often goes untreated due to underdiagnosis and patients adapting to symptoms. Untreated OAB can negatively impact patients' quality of life, relationships, and productivity. Guidelines recommend behavioral therapies and pharmacologic treatments such as antimuscarinics and mirabegron as first-line options for managing OAB.
This document provides an overview of benign prostatic hyperplasia (BPH). It defines key terms related to BPH and lower urinary tract symptoms. It describes the histopathology and molecular etiology of BPH, risk factors such as aging and genetics, and the pathophysiology whereby BPH causes bladder outlet obstruction and changes in bladder function. It also discusses complications of BPH, correlations with severity measures, and a staging system for determining appropriate treatment.
This document discusses SLE (systemic lupus erythematosus) and infertility. It notes that SLE commonly affects women of childbearing age and can impact fertility through several mechanisms, including disease activity, medications like cyclophosphamide that may cause ovarian failure, and hormonal or renal issues. The document provides details on evaluating and managing infertility risks for SLE patients, such as using lower doses of cyclophosphamide or gonadotropin-releasing hormone agonists to protect fertility, and outlines fertility preservation and assisted reproduction options while controlling lupus disease activity and other risks. The conclusion emphasizes the need to consider how to minimize all factors that may increase infertility risk when managing reproductive-aged women with SLE.
1) The document discusses erectile dysfunction (ED) and low testosterone levels (hypogonadism) as men age, and current treatment options.
2) Common treatments for ED include oral PDE5 inhibitor tablets like Viagra, Cialis, and Levitra, which are effective in 80% of cases; testosterone replacement therapy; and other options like injections or surgery.
3) Low testosterone levels (hypogonadism) are another cause of ED, and testosterone replacement therapy has been shown to effectively treat ED symptoms and other effects of low testosterone. Monitoring of treatment is important to ensure safety.
Cell Therapy Expansion and Challenges in Autoimmune DiseaseHealth Advances
There is increasing confidence that cell therapies will soon play a role in the treatment of autoimmune disorders, but the extent of this impact remains to be seen. Early readouts on autologous CAR-Ts in lupus are encouraging, but manufacturing and cost limitations are likely to restrict access to highly refractory patients. Allogeneic CAR-Ts have the potential to broaden access to earlier lines of treatment due to their inherent cost benefits, however they will need to demonstrate comparable or improved efficacy to established modalities.
In addition to infrastructure and capacity constraints, CAR-Ts face a very different risk-benefit dynamic in autoimmune compared to oncology, highlighting the need for tolerable therapies with low adverse event risk. CAR-NK and Treg-based therapies are also being developed in certain autoimmune disorders and may demonstrate favorable safety profiles. Several novel non-cell therapies such as bispecific antibodies, nanobodies, and RNAi drugs, may also offer future alternative competitive solutions with variable value propositions.
Widespread adoption of cell therapies will not only require strong efficacy and safety data, but also adapted pricing and access strategies. At oncology-based price points, CAR-Ts are unlikely to achieve broad market access in autoimmune disorders, with eligible patient populations that are potentially orders of magnitude greater than the number of currently addressable cancer patients. Developers have made strides towards reducing cell therapy COGS while improving manufacturing efficiency, but payors will inevitably restrict access until more sustainable pricing is achieved.
Despite these headwinds, industry leaders and investors remain confident that cell therapies are poised to address significant unmet need in patients suffering from autoimmune disorders. However, the extent of this impact on the treatment landscape remains to be seen, as the industry rapidly approaches an inflection point.
This document discusses the medical management of benign prostatic hyperplasia (BPH). It describes the pathology and pathophysiology of BPH, including the hyperplastic process that leads to nodule formation and bladder outlet obstruction. Clinical definitions related to BPH and lower urinary tract symptoms are provided. Assessment tools for lower urinary tract symptoms like the International Prostate Symptom Score are discussed. The document reviews differential diagnoses, treatments including watchful waiting, medications like alpha blockers and 5-alpha reductase inhibitors, and procedures. Side effects of medications and evidence for various treatment options are also summarized.
Updates in Prostatic enlargement Management by Dr.Wadah CeifoDr.wadah Ceifo
Silodosin is a highly selective alpha-1A adrenergic receptor blocker that is effective for treating lower urinary tract symptoms associated with benign prostatic hyperplasia. It has several advantages compared to other alpha blockers, including greater improvement in bladder outlet obstruction, higher selectivity for the alpha-1A receptor subtype found in the prostate, and a safer cardiovascular profile with fewer side effects like dizziness and orthostatic hypotension. Silodosin is considered a first-line treatment for moderate to severe LUTS according to EAU guidelines due to its rapid onset of action, good efficacy, and low rates of adverse events.
Ejaculation involves three phases - emission, bladder neck contraction, and expulsion. Premature ejaculation (PE) is defined as ejaculation occurring within about 1 minute of penetration that the man has little control over, causing distress. The pathophysiology of PE is not fully understood but may involve genetic, psychological, hormonal, penile sensitivity, and prostatic factors. PE is diagnosed based on history and can be evaluated using tools like the Premature Ejaculation Diagnostic Tool. Treatment includes behavioral therapies like stop-start and squeeze techniques as well as pharmacotherapies.
The document summarizes benign prostatic hyperplasia (BPH). It describes the anatomy of the prostate gland and discusses terminology related to BPH. BPH involves benign enlargement of the prostate, which can obstruct the urethra and cause urinary symptoms. Risk factors include increasing age, genetics, and metabolic conditions. Evaluation of BPH involves medical history, physical exam including digital rectal exam, and may include urinalysis, blood tests, questionnaires, ultrasound, and urodynamic studies.
Overactive bladder, DR Sharda Jain Lifecare Centre Lifecare Centre
OAB OAB is not synonymous with detrusor overactivity as the former is a symptom based diagnosis whilst the latter is an urodynamic diagnosis.
It has been estimated that 64% of patients with OAB have urodynamically proven detrusor overactivity and that 83% of patient with detrusor overactivity have symptoms suggestive of OAB.
This document summarizes key aspects of primary biliary cholangitis (PBC), formerly known as primary biliary cirrhosis. It discusses the epidemiology, risk factors, natural history, presentation, diagnosis and management of PBC. If left untreated, PBC progresses through several clinical phases over many years, eventually leading to liver failure and death in some patients. Prognosis is generally better in asymptomatic patients than in those with symptoms.
Common Urological Problems in Geriatric PopulationRamayya Pramila
Common urological problems in the geriatric population significantly affect quality of life. These include lower urinary tract symptoms from benign prostatic hyperplasia and overactive bladder, urinary tract infections, erectile dysfunction, and prostate cancer. Treatment involves addressing underlying causes, medications like alpha blockers and antimuscarinics, and procedures for severe cases. Managing incontinence, infections, and other issues in elderly patients requires close monitoring, tailored treatment, and attention to their unique needs.
This document discusses the consequences of cancer treatment and late effects. It notes that late effects currently affect 400,000 people in the UK and have a significant impact on survivors' daily lives. Late effects are underappreciated and can be managed through early intervention to prevent long-term impacts. The risks of late effects depend on treatment factors like radiation dose and chemotherapy drugs, as well as individual patient factors. Common late effects include scarring, functional disability, lymphedema, cardiac issues, and gastrointestinal problems. The document calls for improved assessment, management, and services to address late effects.
This document discusses urinary incontinence (UI) in older adults. It covers the prevalence of UI increasing with age, especially in women and those in long-term care. Risk factors include obesity, functional impairment, and medications. Age-related changes to the lower urinary tract are described for both men and women. The pathophysiology of different types of UI is explained. Screening, evaluation, treatments including lifestyle changes, behavioral therapies, and medications are outlined.
Benign enlargement of prostate . medical therapy Dr Pralhad Patki
This document discusses benign prostatic hyperplasia (BPH), including:
1. BPH is a common condition in aging men that causes lower urinary tract symptoms. The prevalence increases with age from around 8% in men in their 40s to over 80% in men in their 80s.
2. BPH is caused by both static enlargement of the prostate and dynamic obstruction of the bladder neck. Medical management focuses on reducing smooth muscle tone in the prostate and bladder neck using alpha-blockers.
3. Evaluation of BPH involves assessing symptoms, digital rectal exam, urinalysis, and tests like uroflowmetry. Treatment is based on symptom severity and includes watchful waiting
1. The document discusses erectile dysfunction (ED), including its anatomy, physiology, etiology, evaluation, and treatment. It defines ED and describes the neurovascular processes underlying erection.
2. Common organic, psychogenic, and mixed causes of ED are outlined. Evaluation involves history, physical exam, and investigations.
3. Treatment options discussed include lifestyle modifications and first-line oral phosphodiesterase type 5 inhibitors like sildenafil, tadalafil, and vardenafil. Guidelines on their use and dosing are provided.
There I go again, a Western guy giving a lecture to an Eastern crowd. What team do I play on, you ask? In fact, I am honored to give a keynote at the First Integrative Fertility Symposium in Vancouver. Ok, call me a “swingman,” but the Easterners have a lot up their medical sleeves too. Ask Western medicine how to help a guy relax, and they’ll say, “don’t work so hard and take this pill.” Ask an Easterner, and they might suggest acupuncture, mindfulness and meditation. Which approach is better: a patch or a fix? You decide. Read more on my blog at > http://bit.ly/1EMuRFF
Family Physician's Approach to Erectile DysfunctionSiewhong Ho
This document discusses the approach to treating erectile dysfunction. It defines erectile dysfunction and outlines its diagnosis and investigations. It describes how erectile dysfunction is often associated with other medical conditions like diabetes, cardiovascular disease, and depression. The document then discusses current treatment options for erectile dysfunction like PDE5 inhibitors, testosterone replacement therapy, and surgery. It provides details on the effectiveness, safety profiles, and proper use of PDE5 inhibitors.
Overactive bladder (OAB) is a common condition characterized by urinary urgency, usually accompanied by increased daytime frequency and/or nocturia, with or without urinary incontinence. OAB affects a significant portion of the global population but often goes untreated due to underdiagnosis and patients adapting to symptoms. Untreated OAB can negatively impact patients' quality of life, relationships, and productivity. Guidelines recommend behavioral therapies and pharmacologic treatments such as antimuscarinics and mirabegron as first-line options for managing OAB.
This document provides an overview of benign prostatic hyperplasia (BPH). It defines key terms related to BPH and lower urinary tract symptoms. It describes the histopathology and molecular etiology of BPH, risk factors such as aging and genetics, and the pathophysiology whereby BPH causes bladder outlet obstruction and changes in bladder function. It also discusses complications of BPH, correlations with severity measures, and a staging system for determining appropriate treatment.
This document discusses SLE (systemic lupus erythematosus) and infertility. It notes that SLE commonly affects women of childbearing age and can impact fertility through several mechanisms, including disease activity, medications like cyclophosphamide that may cause ovarian failure, and hormonal or renal issues. The document provides details on evaluating and managing infertility risks for SLE patients, such as using lower doses of cyclophosphamide or gonadotropin-releasing hormone agonists to protect fertility, and outlines fertility preservation and assisted reproduction options while controlling lupus disease activity and other risks. The conclusion emphasizes the need to consider how to minimize all factors that may increase infertility risk when managing reproductive-aged women with SLE.
1) The document discusses erectile dysfunction (ED) and low testosterone levels (hypogonadism) as men age, and current treatment options.
2) Common treatments for ED include oral PDE5 inhibitor tablets like Viagra, Cialis, and Levitra, which are effective in 80% of cases; testosterone replacement therapy; and other options like injections or surgery.
3) Low testosterone levels (hypogonadism) are another cause of ED, and testosterone replacement therapy has been shown to effectively treat ED symptoms and other effects of low testosterone. Monitoring of treatment is important to ensure safety.
Cell Therapy Expansion and Challenges in Autoimmune DiseaseHealth Advances
There is increasing confidence that cell therapies will soon play a role in the treatment of autoimmune disorders, but the extent of this impact remains to be seen. Early readouts on autologous CAR-Ts in lupus are encouraging, but manufacturing and cost limitations are likely to restrict access to highly refractory patients. Allogeneic CAR-Ts have the potential to broaden access to earlier lines of treatment due to their inherent cost benefits, however they will need to demonstrate comparable or improved efficacy to established modalities.
In addition to infrastructure and capacity constraints, CAR-Ts face a very different risk-benefit dynamic in autoimmune compared to oncology, highlighting the need for tolerable therapies with low adverse event risk. CAR-NK and Treg-based therapies are also being developed in certain autoimmune disorders and may demonstrate favorable safety profiles. Several novel non-cell therapies such as bispecific antibodies, nanobodies, and RNAi drugs, may also offer future alternative competitive solutions with variable value propositions.
Widespread adoption of cell therapies will not only require strong efficacy and safety data, but also adapted pricing and access strategies. At oncology-based price points, CAR-Ts are unlikely to achieve broad market access in autoimmune disorders, with eligible patient populations that are potentially orders of magnitude greater than the number of currently addressable cancer patients. Developers have made strides towards reducing cell therapy COGS while improving manufacturing efficiency, but payors will inevitably restrict access until more sustainable pricing is achieved.
Despite these headwinds, industry leaders and investors remain confident that cell therapies are poised to address significant unmet need in patients suffering from autoimmune disorders. However, the extent of this impact on the treatment landscape remains to be seen, as the industry rapidly approaches an inflection point.
Rasamanikya is a excellent preparation in the field of Rasashastra, it is used in various Kushtha Roga, Shwasa, Vicharchika, Bhagandara, Vatarakta, and Phiranga Roga. In this article Preparation& Comparative analytical profile for both Formulationon i.e Rasamanikya prepared by Kushmanda swarasa & Churnodhaka Shodita Haratala. The study aims to provide insights into the comparative efficacy and analytical aspects of these formulations for enhanced therapeutic outcomes.
Histololgy of Female Reproductive System.pptxAyeshaZaid1
Dive into an in-depth exploration of the histological structure of female reproductive system with this comprehensive lecture. Presented by Dr. Ayesha Irfan, Assistant Professor of Anatomy, this presentation covers the Gross anatomy and functional histology of the female reproductive organs. Ideal for students, educators, and anyone interested in medical science, this lecture provides clear explanations, detailed diagrams, and valuable insights into female reproductive system. Enhance your knowledge and understanding of this essential aspect of human biology.
Muktapishti is a traditional Ayurvedic preparation made from Shoditha Mukta (Purified Pearl), is believed to help regulate thyroid function and reduce symptoms of hyperthyroidism due to its cooling and balancing properties. Clinical evidence on its efficacy remains limited, necessitating further research to validate its therapeutic benefits.
- Video recording of this lecture in English language: https://youtu.be/kqbnxVAZs-0
- Video recording of this lecture in Arabic language: https://youtu.be/SINlygW1Mpc
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Integrating Ayurveda into Parkinson’s Management: A Holistic ApproachAyurveda ForAll
Explore the benefits of combining Ayurveda with conventional Parkinson's treatments. Learn how a holistic approach can manage symptoms, enhance well-being, and balance body energies. Discover the steps to safely integrate Ayurvedic practices into your Parkinson’s care plan, including expert guidance on diet, herbal remedies, and lifestyle modifications.
2. Topics Discussed
Population demographics
Evolution of medical therapy for LUTS and BPH
Male overactive bladder OAB &LUTS/BPH
Treatment of male LUTS/OAB with antimuscarinics – alone or in
combination
The TIMES trial and its analyses
Are antimuscarinics safe in men with presumed BPH ?
Algorithms, Guidelines and some suggestions
3. A New Term for prostatism
LUTS is a recent term for what used to be known as
prostatism
4. LUTS
Abnormal voiding sensations that occur with a
frequency or severity that affects quality of life.
Common LUTS include:
Urinary frequency,
Urgency,
Nocturia,
Intermittency,
Incomplete emptying, and
Weak stream.
Nocturia is the most prevalent - half to two-thirds.
6. Epidemiology
In the aging male, LUTS are common and can have a
significant effect on quality of life.
Two-thirds to three-quarters of men experience some
degree of urinary symptoms
Most symptoms occur with greater frequency and
severity with increasing age.
20% to 30% of men reported having:
Weak stream, hesitancy, urgency, incomplete emptying, or
postvoid incontinence at least sometimes.
5% to 15% of men reported these same symptoms often.
9. BPH and Ca Prostate:
common conditions in ageing men
0
10
20
30
40
50
60
70
80
90
100
Prevalence (% men)
Age (years)
3140 4150 5160 6170 7180 80+
Histological Hyperplasia or BPH
Prostate cancer
Berry SJ et al. J Urol. 1984;132:474479;
Bulletin of the World Health Organization 2002;80:622-628
11. Evolution of LUTS Timeline
Surgical treatment of obstruction to
relieve LUTS
Research initiated to examine
medical treatments
TURP introduced in the late
1920’s by pioneer advocates:
Davis, Alcock, Stern, McCarthy,
and Nesbit
Obstruction
12. Evolution of LUTS Timeline
Pharmacologic treatment of
symptoms of “BPH” to relieve LUTS
Alpha-blockers
• Caine M. J Urol. 1986;136:1.
• Lepor H. J Urol. 1989;141:1283.
• Hedlund H, Andersson KE.
J Urol. 1989;141:1283.
13. Evolution of LUTS Timeline
Finasteride was the first 5-ARI proven to
reduce obstructive symptoms in men
Prostate size was reduced along with
symptoms in men with large prostates
5-ARI’s maybe beneficial in
men with large prostates
Gormley GJ, Stoner E, et al.
N Engl J Med. 1992;327:1185.
5-Alpha Reductase Inhibitors
14. Evolution of LUTS Timeline
Combination pharmacologic therapy
examined to treat “BPH” symptoms
and relieve obstructive symptoms
Alpha blockers better at reducing
obstructive symptoms
5-ARI’s no beneficial effect
to treat symptoms
VA COOP
Lepor H et al. NEJM. 1996;335:533.
MTOPS initiated
Combination Therapy
15. VA COOP Trial –
Changes at 1 Year
Lepor H et al. NEJM. 1996;335:533-539
placebo-controlled, multi-center study in 1,229 men with BPH in US VA system
-3.2
-6.1 -6.2
-2.6
-7
-6
-5
-4
-3
-2
-1
0
AUASI
Mean
Change
(Points)
Finasteride Terazosin Combination Placebo
1.6
2.7
3.2
1.4
0
0.5
1
1.5
2
2.5
3
3.5
Qmax
Mean
Change
(ml/sec)
16. Evolution of LUTS Timeline
Treatment with 5-ARI’s
slow/reverse prostatic disease
progression
5-ARI’s more beneficial in
larger prostates
PLESS
McConnell et al. N Engl J Med.
1998;338:557
Prostate Disease Progression
17. Adapted from: McConnell et al. N Engl J Med. 1998;338:557; Data available, Merck & Co., Inc. DA-PRO19(1).
Finasteride in BPH:
PLESS—Acute Urinary Retention
8
2
4
0
6
0 4 8 12 16 20 24 28 32 36 40 44 48
%
of
Patients
Months
Placebo (n = 1503)
6.6
P < 0.001
Finasteride (n = 1513)
2.8
18. Finasteride in BPH:
PLESS - BPH-Related Surgery
0
Months
12
10
8
2
4
0
6
4 8 12 16 20 24 28 32 36 40 44 48
10.1
Adapted from: McConnell et al. N Engl J Med. 1998;338:557; Data available, Merck & Co., Inc. DA-PRO19(1).
%
of
Patients
Placebo (n = 1503)
P < 0.001
4.6
Finasteride (n = 1513)
19. Evolution of LUTS Timeline
Precedence of combination therapy
set in MTOPS
Pharmacologic therapy targeted to
relieve LUTS, including OAB
Response by prostate size
& PSA
MTOPS
TIMES
ADAM
Bladder vs Prostate
20. Evolution of LUTS Timeline
Symptom clusters
Metabolic syndrome
Inflammation
Central obesity
Role of sexual dysfunction
as a component of LUTS?
3 agonist
PDE-5 inhibitors
EpiLUTS
BACH
Scientific research
Future Concepts
Optimize Diagnosis,
Treatment, and
Patient Outcomes
21. Evolution of Medical Therapy for
LUTS/BPH/BOO/BPE
In recent years the recognition grew that some men with
“LUTS” actually suffer from the same symptoms as
women with OAB, thus creating the term “male OAB”
While previously viewed as contraindicated, the use of
antimuscarinics is now being seriously investigated in
many studies
The term BPH is reserved to describe the histological
presence of hyperplasia in the prostate
23. Prevalence of LUTS in Men Is High
6 of 10 men in the general population
(N = 5460) reported at least 1 type of LUTS
38.7%
61.3%
Men without LUTS
Men with LUTS
Post-
micturition
Total
16.5%
Voiding
Total
25.7%
Storage
Total
49.7%
Percentage of men in the general male
population who report at least 1 symptom
representative of a particular type of LUTS
Irwin DE et al. Eur Urol. 2006;50:1306-1315.
24. Prevalence of Individual LUTS in Men
Irwin DE et al. Abstract presented at EAU 2006.
EPIC Study. Data on file. Pfizer Inc.
Storage Voiding
Post-
micturition
Prevalence,
%
20.8
14.8 13.3
11.1
8.9
5.1
6.4 6.4
5.1
2.8
0
5
10
15
20
25
30
35
40
45
50
Nocturia: waking to void ≥2 times per night.
Frequency: subject feels he/she urinates too often during the day.
25. Storage
Symptoms Relate
to the Bladder
• Urgency
• Frequency
• Nocturia
• Urgency urinary
incontinence
• Other incontinence
OAB is defined as urgency, with or without urgency incontinence,
usually with frequency and nocturia (ICS definition).
Irwin DE et al. Eur Urol. 2006;50:1306-1315.
Abrams P et al. Urology. 2003;61:37-49.
OAB = overactive bladder.
Most Men with LUTS Have Both Storage
and Voiding/Post-micturition Symptoms
67%
of Men
Experience
Symptoms of both
OAB and BPH
Voiding/Post-
micturition
Symptoms Relate
to the Prostate
• Slow stream
• Intermittency
• Straining
• Terminal dribble
• Post-micturition dribble
• Incomplete emptying
26. OAB Symptoms Are as Prevalent in Men as
in Women and Increase with Age
Comparison of Data from the SIFO Study 1997
and the EPIC Study 2005
Prevalence,
%
0
5
10
15
20
25
30
35
40
Age, years
18-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70+
Men – SIFO 1997
Men – 2005
Women – SIFO 1997
Women ̶ 2005
16.6
11.8
Milsom I et al. BJU Int. 2001;87:760-766.
Irwin DE et al. Eur Urol. 2006;50:1306-1315.
27. OAB Has a Considerable
Impact on Quality of Life
Kobelt G et al. BJU Int. 1999;83:583-590.
Komaroff AL et al. Am J Med. 1996;101:281-290.
Healthy
Diabetes
Depression
OAB
SF-36
Score
0
10
40
50
60
70
80
90
28. Men with OAB Report a Greater Degree
of Impairment in HRQL
EQ-5D: Percentage of Respondents
Reporting Any Problems—Men
OAB without UI OAB with UI
Control male
*
*
*
*
*
*
0
5
10
15
20
25
30
35
40
45
Mobility Self-care Usual
activities
Pain/
discomfort
Anxiety
depression
Patients,
%
The EQ-5D is a 5-item generic QOL instrument used to measure overall QOL.
*P ≤ .05 OAB with UI vs controls and OAB without UI vs controls.
HRQL = health-related quality of life; QOL = quality of life; UI = urinary incontinence. Irwin DE. ICS 2006.
29. Men with LUTS Are Treated Predominantly
with BPH Agents Rather than OAB Agents
OAB Rx
only
BPH Rx
only
OAB &
BPH Rx
No Rx
Patients
Receiving
Treatment,
%
0
10
20
30
40
50
60
70
OAB & BPH (n = 4806)
9 11
36
22
8
6
47
61 Diagnosis
Type of Treatment
Data were obtained from medical and pharmacy claims database of diverse managed care plans.
BPH prescriptions include all alpha-blockers and 5-ARIs; OAB prescriptions include all antimuscarinics.
OAB & No BPH (n = 12,192)
Jumadilova Z et al. Abstract. ICS 2005.
30. Patient Bother Is High;
Treatment Rates Are Low
Although symptoms are bothersome, OAB often remains under-
diagnosed and under-treated
In a survey of patients who informed their physicians about OAB
symptoms, only 27% were treated with medication
Patient- and physician-related barriers exist, making recognition and
treatment of OAB in men challenging
Complex clinical presentation of OAB symptoms in combination with other
LUTS (voiding symptoms)
Complex terminology
Significant regional and country differences
Alternative potential pathophysiology
Bladder dysfunction or prostate conditions, or both
Concerns about safety
Clinical effect of a significant increase in PVR
Presumed increased risk for AUR Elinoff V et al. Int J Clin Pract. 2006;60:745-751.
Ricci JA et al. Clin Ther. 2001;23:1245-1259.
Milsom I et al. BJU Int. 2001;87:760-766.
Chapple CR et al. Eur Urol. 2006;49:651-659.
Steers WD. Rev Urol. 2002;4:S7-S18.
AUR = acute urinary retention;
PVR = post-void residual.
31. Symptoms of OAB May Be Associated
with Several Possible Etiologies
Ouslander J. N Engl J Med. 2004;350:786-799.
Myogenic
Unknown
Neurogenic
Combination
32. Increased electrical
coupling between cells
Hypertrophy/hyperplasia
Instability of membrane
potential
Altered intracellular
Ca2+ regulation
OAB/
Detrusor Overactivity
Detrusor
muscle
Outlet
Obstruction
Ischaemia
Supersensitivity to
acetylcholine
Reduced response to
intramural nerve
stimulation
Partial
denervation
OAB/
Detrusor Overactivity
Outlet
Obstruction
Re-organization of
spinal micturition reflex
(C-fibre–mediated)
Altered Na+ channel
expression/function
Hypertrophy of
afferent and efferent
neurons
Expression of
nerve
growth factor
OAB/
Detrusor Overactivity
Outlet
Obstruction
Male OAB Symptoms/DO May be Primary
or May Develop Secondary to BOO
BOO = bladder outlet obstruction; DO = detrusor overactivity. Steers WD. Rev Urol. 2002;4:S7-S18.
Potential Etiology of OAB/DO in Men with BOO
33. Evaluation of Symptoms
OAB
No. micturition
episodes/24 h
No. urge
incontinence
episodes
Nocturnal voids
Effect on urgency
LUTS in men
IPSS
Flow rate
Postvoid residual
(PVR)
36. Bladder Diaries
Patient-completed instrument capturing time and
number of micturitions, urgency, and urgency
incontinence episodes, as well as voided volume
over at least 3 days
Urgency is recorded according to the ICS definition
and can be classified using a five-point urinary
sensation scale
The scale helps patients interpret various sensations
associated with a micturition, by grading urgency from 0
(no urgency) to 5 (urgency resulting in a leak)
Rackley R et al. Urology. 2006;67:731-736.
Recommendations of the ISC: Evaluation and Treatment of LUTS in
Older Men 6th International Consultation on New Developments in
Prostate Cancer and Prostate Diseases: June 24-28, 2005; Paris,
France
37. Bladder Diary: Assessment of Urgency
During Micturition
Date:
What time did you start your day today (time
arose)?
What time did you go to bed for the night?
Urinary Sensation Scale*
Urinary urgency is defined as an intense and/or sudden
need to urinate. Please rate the feeling of urinary urgency
that was associated with this urination using the following
scale:
1. No feeling of urgency: I could continue activities until I
chose to use the bathroom
2. Mild feeling of urgency: I could feel the need to urinate,
but it was easily tolerated. I could finish my activity or task
before going to the bathroom
3. Moderate feeling of urgency: My urgency caused
discomfort. I needed to stop my activity or task and go to
the bathroom.
4. Severe feeling of urgency: My urgency cause much
discomfort. I had difficulty holding my urine. I had to stop
my activity or task and hurry to the bathroom to avoid a
wetting accident
5. Unable to hold; leak urine: I had a wetting accident before
arriving to the bathroom
BLADDER
38. Complex Clinical Presentation:
Male LUTS Can Be Associated with the Bladder, the Prostate, or
Both
Bladder Condition:
OAB
Urgency, with or without
urgency incontinence,
usually with frequency
and nocturia
Pharmacological Therapy
for OAB:
Antimuscarinics
Prostate Condition:
BPH
Term used and reserved
for the typical histological
pattern that defines
the disease
Pharmacological Therapy
for BPH:
alpha-Blockers
5-ARIs
5-ARI = 5-alpha-reductase inhibitor. Abrams P et al. Urology. 2003;61:37-49.
39. Treatment Response May Vary in Men with
LUTS Because of Different Pathologies
LUTS (n = 144; 100%)
Urodynamic Evaluation
Doxazosin 3 mo
BOO (n = 76; 52.8%)
Improved
n = 60
79%
NOT Improved
n = 16
21%
Doxazosin 3 mo
BOO and DO (n = 68; 47.2%)
Improved
n = 24
35%
NOT
Improved
n = 44
65%
Lee JY et al. BJU Int. 2004;94:817-820.
Patients with DO had involuntary detrusor contractions 10 cm H2O.
Improvement was defined as at least a 3-point reduction in International
Prostate Symptom Score (IPSS).
40. Tolterodine Alone or in Combination
with alpha-Blockers for the Treatment
of Men with OAB and Other LUTS
Evaluated Urodynamically
42. Athanasopoulos A et al. 2002 Neurourol Urod 19; 308-309.
• Randomised, controlled trial
• 50 men
• mild/moderate BOO on UDS
• concomitant idiopathic detrusor overactivity
• Study design
• complete QoL9 UROLIFE questionnaire prior to
study onset
• 1 week tamsulosin 0.4 mg qd, then randomly
assigned to receive concomitant tolterodine 2 mg
bid or continue tamsulosin monotherapy
• repeat QoL9 and UDS at 12 weeks
Antimuscarinic and -Adrenergic Blocking
Combination Therapy in Men with BOO
43. 542.2
525
548.2
628.4
0
480
500
520
540
560
580
600
620
640
Tamsulosin Tamsulosin + Tolterodine
Baseline
12 Weeks
Mean
Score
(QoL
9
UROLIFE)
P = NS
P =
0.0003
(n = 25) (n = 25)
Improved
QoL
Athanasopoulos A et al. 2002 Neurourol Urodyn. 19;308-309.
Antimuscarinic and -Adrenergic Blocking Combination
Therapy in Men with BOO: Effects on QoL
44. Effect on Urodynamic Parameters
Tamsulosin
(n = 25)
Tamsulosin +
Tolterodine (n = 25)
Mean Change
from Baseline
P value
Mean Change
from Baseline
P value
Maximum detrusor
pressure (cm H2O)
–5.2 0.0827 –8.24 0.0082
Maximum flow rate
(mL/second)
+1.16 0.0001 +1.32 0.0020
Pressure at maximum
overactivity (cm H2O)
–2.16 0.05690 –11.16 0.0001
Volume at first overactive
contraction (mL)
+30.40 0.0190 +100.40 0.0001
Athanasopoulos A et al.2002 Neurourol Urodyn 19; 308-309.
45. Safety and Efficacy of tolterodine extended release in men with
overactive bladder symptoms and presumed non-obstructive
benign prostatic hyperplasia
Hoefner et al: World J Urol 25:627, 2007
• Patients with presumed non-obstructive BPH (Qmax¸ 15
ml/s) treated with tolterodine ER 4 mg/day for OAB
symptoms, alone or added to unsuccessful alphablocker
treatment of 6 weeks duration, were observed for 12 weeks
• The study was completed by 926 patients of the safety
set (85.7%).
• In the FAS, 661 (89.2%) subjects completed the study. Of
80 (10.9%) who discontinued prematurely, in 59 (8.0%)
the cause was treatment related:
• 1.1% due to adverse events,
• 1.6% due to lack of efficacy and
• 5.3% for complete response.
46. Safety and Efficacy of tolterodine extended release in men with
overactive bladder symptoms and presumed non-obstructive
benign prostatic hyperplasia
Hoefner et al: World J Urol 25:627, 2007
47. Well-Designed, Double-Blind,
Placebo-Controlled Trials
• Efficacy and safety of tolterodine ER
4 mg in men with LUTS that include
OAB symptoms
• 4-arm study (200 patients/arm)
– Placebo
– Tamsulosin
– Tolterodine ER
– Tolterodine ER + Tamsulosin
• Efficacy and safety of tolterodine
ER 4 mg in men with persistent
OAB symptoms undergoing stable
alpha-blocker therapy
• 2 arms (304 patients/arm)
– Placebo + alpha-blocker
(stable dose for ≥1 month)
– Tolterodine ER + alpha-blocker
(stable dose for ≥1 month)
Studies collect OAB end points, IPSS, and data on PSA, PVR, flow rate, and prostate volume
Ongoing Trial Completed Trial
PSA = prostate-specific antigen. Kaplan SA et al. JAMA. 2006;296:2319-2328.
49. Study Objectives
• Primary objective
– Evaluate the effect of tolterodine ER plus
tamsulosin versus placebo on patient perception
of treatment benefit at week 12
• Secondary objective
– Evaluate the effect on efficacy, safety, patient
perception, and health-related quality of life
(HRQL) among the various treatment groups
Kaplan SA et al. JAMA. 2006;296:2319-2328.
BOO = bladder outlet obstruction; ER = extended release; UUI =
urgency urinary incontinence.
50. Study Design
• Design
– 12-week, randomised, double-blind, active- and placebo-controlled, 4-
arm (placebo, tolterodine ER, tamsulosin, and tolterodine ER plus
tamsulosin) multi-centre study
– 876 adult male subjects (≥40 years of age)
• Setting
– 95 centres (urology offices/clinics) throughout the US
• Treatment
– Equally randomised into 4 groups with night-time dosing
• Placebo
• Tolterodine ER 4mg
• Tamsulosin 0.4 mg
• Tolterodine ER plus tamsulosin
Kaplan SA et al. JAMA. 2006;296:2319-2328.
51. TIMES: Study Timeline
Week 1 Week 6 Week 12
Visit 1 Visit 3
Visit 2 Visit 4 Visit 5
Screen
Placebo
Tolterodine ER
Tamsulosin
Combination
Week –1
Kaplan SA et al. JAMA. 2006;296:2319-2328.
52. 652 Excluded:
Did not meet inclusion/exclusion criteria: 481
Lost to follow
-
Other: 29
Refusal to participate further: 118
879 Randomized
tolterodine ER = 217 Tamsulosin = 215
Discontinued: 27
Adverse event: 5
Lack of efficacy: 8
Consent withdrawn: 9
Protocol deviation: 2
Lost to follow
-up: 1
Death: 1
Other: 1
Discontinued: 29
Adverse event: 7
Protocol deviation: 4
Lost to follow
-up: 4
Other: 5
tolterodine ER /
Tamsulosin = 225
Discontinued: 34
Adverse event: 20
Lack of efficacy: 4
Consent withdrawn: 2
Lost to follow
-up: 6
Other: 2
Efficacy Analysis = 217
Placebo = 222
Discontinued: 32
Adverse event : 7
Lack of efficacy: 7
Consent withdrawn: 5
Protocol deviation: 4
Lost to follow
-up: 4
Other: 5
Safety Analysis = 216 Safety Analysis = 215 Safety Analysis = 225
1531 Assessed for Eligibility
652 Excluded:
Did not meet inclusion/exclusion criteria: 481
Lost to follow
- up: 24
Other: 29
Refusal to participate further: 118
879 Randomized
tolterodine ER = 217 Tamsulosin = 215
Discontinued: 27
Adverse event: 5
Lack of efficacy: 8
Consent withdrawn: 9
Protocol deviation: 2
Lost to follow: 1
-
Death: 1
Other: 1
Discontinued: 29
Adverse event: 7
Consent withdrawn: 9
Protocol deviation: 4
Lost to follow: 4
-
Other: 5
Efficacy Analysis = 210 Efficacy Analysis = 209
tolterodine ER /
Tamsulosin = 225
Discontinued: 34
Adverse event: 20
Lack of efficacy: 4
Consent withdrawn: 2
Lost to follow: 6
-
Other: 2
Efficacy Analysis = 217
Placebo = 222
Discontinued: 32
Adverse event : 7
Lack of efficacy: 7
Consent withdrawn: 5
Protocol deviation: 4
Lost to follow: 4
-
Other: 5
Efficacy Analysis = 215
Safety Analysis = 216 Safety Analysis = 215 Safety Analysis = 225
Safety Analysis = 220
Disposition of Study
Participants
53. Measurement Instruments Used
• Patient perception of treatment benefit (PPTB,
primary outcome)
– The following questions were asked to capture patient
perception of treatment benefit
• Have you had any benefit from your treatment?
• If yes, have you had little benefit or much benefit?
• Bladder diary (3-day)
– Patient-recorded micturitions and episodes of urgency
and UUI
• International Prostate Symptom Score IPSS (0-35
score)
– Storage (0-15) and voiding (0-20) sub-scores
Data on file. Pfizer Inc.
54. Baseline Characteristics Suggest Subjects Had
Moderate-Severe Storage and Voiding Symptoms
Placebo
(n = 215)
Tolterodine ER
(n = 210)
Tamsulosin
(n = 209)
Tolterodine ER/
Tamsulosin
(n = 217)
Diary variables, mean
UUI episodes/24 h* 1.0 0.0 0.7 1.4
Urgency
episodes/24 h
7.3 7.6 7.1 6.7
Micturitions/24 h 11.9 11.8 12.1 11.9
Micturitions/night 2.0 2.0 1.7 2.1
Total IPSS score† 20.0 19.5 20.0 20.1
Storage IPSS 10.2 9.9 10.3 10.2
Voiding IPSS 9.9 9.6 9.7 9.9
IPSS QOL 4.6 4.6 4.6 4.6
Mean Qmax , ml/s 12.2 13.3 13.4 12.7
Mean PVR, ml 47.1 50.5 56.5 58.8
*Patients who had incontinence at baseline.
PVR = post-void residual; Qmax = maximum flow rate. Kaplan SA et al. JAMA. 2006;296:2319-2328.
†Total IPSS score: 0-7, mildly symptomatic; 8-19, moderately symptomatic; 20-35, severely symptomatic.
55. Baseline Characteristics Suggest Subjects Had
Moderate-Severe Storage and Voiding Symptoms
Placebo
(n = 215)
Tolterodine ER
(n = 210)
Tamsulosin
(n = 209)
Tolterodine ER/
Tamsulosin
(n = 217)
Diary variables, mean
UUI episodes/24 h* 1.0 0.0 0.7 1.4
Urgency
episodes/24 h
7.3 7.6 7.1 6.7
Micturitions/24 h 11.9 11.8 12.1 11.9
Micturitions/night 2.0 2.0 1.7 2.1
Total IPSS score† 20.0 19.5 20.0 20.1
Storage IPSS 10.2 9.9 10.3 10.2
Voiding IPSS 9.9 9.6 9.7 9.9
IPSS QOL 4.6 4.6 4.6 4.6
Mean Qmax , ml/s 12.2 13.3 13.4 12.7
Mean PVR, ml 47.1 50.5 56.5 58.8
*Patients who had incontinence at baseline.
PVR = post-void residual; Qmax = maximum flow rate. Kaplan SA et al. JAMA. 2006;296:2319-2328.
†Total IPSS score: 0-7, mildly symptomatic; 8-19, moderately symptomatic; 20-25, severely symptomatic.
10 of possible 15 Storage
Vs
10 of possible 20 Voiding
56. Baseline Characteristics Suggest Subjects Had
Moderate-Severe Storage and Voiding Symptoms
Placebo
(n = 215)
Tolterodine ER
(n = 210)
Tamsulosin
(n = 209)
Tolterodine ER/
Tamsulosin
(n = 217)
Diary variables, mean
UUI episodes/24 h* 1.0 0.0 0.7 1.4
Urgency
episodes/24 h
7.3 7.6 7.1 6.7
Micturitions/24 h 11.9 11.8 12.1 11.9
Micturitions/night 2.0 2.0 1.7 2.1
Total IPSS score† 20.0 19.5 20.0 20.1
Storage IPSS 10.2 9.9 10.3 10.2
Voiding IPSS 9.9 9.6 9.7 9.9
IPSS QOL 4.6 4.6 4.6 4.6
Mean Qmax , ml/s 12.2 13.3 13.4 12.7
Mean PVR, ml 47.1 50.5 56.5 58.8
*Patients who had incontinence at baseline.
PVR = post-void residual; Qmax = maximum flow rate. Kaplan SA et al. JAMA. 2006;296:2319-2328.
†Total IPSS score: 0-7, mildly symptomatic; 8-19, moderately symptomatic; 20-25, severely symptomatic.
Due to the exclusion of pts who score
“delighted”, “very pleased” or
“pleased” to this question
57. Baseline Characteristics Suggest Subjects Had
Moderate-Severe Storage and Voiding Symptoms
Placebo
(n = 215)
Tolterodine ER
(n = 210)
Tamsulosin
(n = 209)
Tolterodine ER/
Tamsulosin
(n = 217)
Diary variables, mean
UUI episodes/24 h* 1.0 0.0 0.7 1.4
Urgency
episodes/24 h
7.3 7.6 7.1 6.7
Micturitions/24 h 11.9 11.8 12.1 11.9
Micturitions/night 2.0 2.0 1.7 2.1
Total IPSS score† 20.0 19.5 20.0 20.1
Storage IPSS 10.2 9.9 10.3 10.2
Voiding IPSS 9.9 9.6 9.7 9.9
IPSS QOL 4.6 4.6 4.6 4.6
Mean Qmax , ml/s 12.2 13.3 13.4 12.7
Mean PVR, ml 47.1 50.5 56.5 58.8
*Patients who had incontinence at baseline.
PVR = post-void residual; Qmax = maximum flow rate. Kaplan SA et al. JAMA. 2006;296:2319-2328.
†Total IPSS score: 0-7, mildly symptomatic; 8-19, moderately symptomatic; 20-25, severely symptomatic.
No upper threshold for Qmax
had to be > 5 ml/sec
This likely prevented an effect of Rx
on Qmax
58. *P < .001 between-group comparisons.
†P = .001 between-group comparisons.
‡P < .05 between-group comparisons.
Treatment with Tolterodine ER plus Tamsulosin Resulted in
Significant Treatment Benefit at Week 12
‡
†
*
62
65
35
71
30
80
20
38
0
10
20
30
40
50
60
70
80
90
100
Placebo Tolterodine ER Tamsulosin Tolterodine ER /
Tamsulosin
Patients,
%
Benefit No Benefit
Kaplan SA et al. JAMA. 2006;296:2319-2328.
Only Combination Therapy
Was superior to Placebo!
59. –1.24
–1.75 –1.75
Treatment with Tolterodine ER plus Tamsulosin
Significantly Reduced Frequency
*P < .05 versus placebo.
†P < .01 versus placebo.
‡P < .001 versus placebo.
LS = least squares. Kaplan SA et al. JAMA. 2006;296:2319-2328.
0
–3.0
–2.5
–2.0
–1.5
–1.0
–0.5
0.0
Week 0 Week 1 Week 6 Week 12
Episodes,
n
per
day
(LS
mean)
Tamsulosin (n = 209, baseline: 12.1) Tolterodine ER / Tamsulosin (n = 217, baseline: 11.92)
Tolterodine ER (n = 210, baseline: 11.79)
Placebo (n = 215, baseline: 11.86)
Change in Micturition Frequency per 24 Hours
–0.8*
–1.41
–1.46
–0.51
–1.67
–1.42
–1.41†
–2.36‡
–2.54‡
60. Treatment with Tolterodine ER plus Tamsulosin
and Tolterodine ER Alone Significantly Reduced UUI
Kaplan SA et al. JAMA. 2006;296:2319-2328.
* Only those patients with UUI at baseline
UUI = urgency urinary incontinence
Placebo (n = 48, baseline: 0.98)
0
–0.26
–0.13
–0.38
–0.35
–0.85*
–0.83*
–0.39
–0.78*
–0.70
–0.63
–0.81*
–0.88*
Tolterodine ER (n = 53, baseline: 0.84)
Tamsulosin (n = 50, baseline: 0.71) Tolterodine ER / Tamsulosin (n = 52, baseline: 1.4)
Change in Urgency Incontinence Episodes / 24 Hours*
Week 0 Week 1 Week 6 Week 12
*P < .01 vs placebo.
Episodes,
n
per
day
(LS
mean)
–1.0
–0.9
–0.8
–0.7
–0.6
–0.5
–0.4
–0.3
–0.2
–0.1
0.0
61. TIMES: Efficacy Summary
Tolterodine ER Tamsulosin
Tolterodine ER/
Tamsulosin
Patient perception of treatment benefit ++
Frequency/24 h ++
Night-time frequency +
Urgency incontinence/24 h ++ ++
Urgency episodes/24 h +
IPSS total ++ ++
IPSS storage ++
IPSS voiding ++
IPSS QOL ++
PPBC +
OAB-q/Symptom Severity score ++
OAB-q/HRQL total score +
++P < .01 versus placebo.
+P < .05 versus placebo.
62. TIMES: Efficacy Summary
• In bothered male patients with LUTS, including diary-
documented OAB
– Tolterodine ER and tamsulosin were used according to
their indications
• Tolterodine is indicated for the treatment of OAB with symptoms
of UUI, urgency, and frequency
• Tamsulosin is indicated for the treatment of signs and symptoms
of BPH
– Tolterodine ER, administered with tamsulosin, was an
efficacious treatment
– Tolterodine ER or tamsulosin therapy alone was not
sufficient to show significant clinical efficacy
63. Conclusions
• In this stratified analysis of the TIMES study,
tolterodine ER alone was an effective therapy
for OAB in men with smaller glands and lower
PSA
• Tolterodine ER administered with an alpha-
blocker was an effective treatment for OAB
symptoms in men with larger glands and
higher PSA
64. Are antimuscarinics safe in men with presumed
BPH and possible bladder outlet obstruction?
In the past there had been concerns that the use of
antimuscarinic agents might negatively affect
detrusor muscle function and result in:
Increased postvoid residual urine (PVR)
Worsening of voiding efficiency
Episodes of acute urinary retention (AUR)
Need for BPH related surgery
65. Can MOA of Antimuscarinics Aggravate Voiding
Difficulties?
Antimuscarinics inhibit detrusor contractions
Theoretical risk for AUR
However, it is postulated that
Antimuscarinics inhibit detrusor contractions during the filling
phase and are displaced during the emptying phase
During normal voiding, massive release of acetylcholine occurs from
parasympathetic nerves, displacing antimuscarinics via competitive
binding (resulting in normal voiding)
At therapeutic doses of antimuscarinics, there is no effect on
normal voiding and no increased occurrence of AUR
This hypothesis is supported by clinical evidence on the
urinary safety of antimuscarinics at recommended doses
Andersson KE et al. Eur Urol. 2003;43:1-5.
Reynard JM. Cur Opin Urol. 2004,14:13-16.
MOA = mechanism of action.
66. In Men with Symptoms of OAB and BOO, Tolterodine IR
Was Not Associated with Increased Incidence of AUR
≤12-Week Studies in Men Evaluated Urodynamically for
BOO and DO
AUR, % (n/N)
Abrams et al study (N = 221)
Tolterodine IR*
Placebo
0.0 (0/149)
1.4 (1/72)
Lee et al study (N = 144)
Doxazosin + Tolterodine IR*
Doxazosin†
3.3 (2/60) ‡
0.0 (0/84)
Athanasopoulos et al study (N = 50)
Tamsulosin + Tolterodine IR*
Tamsulosin†
0.0 (0/25)
0.0 (0/25)
Abrams P et al. J Urol. 2006;175:999-1004.
Lee JY et al. BJU Int. 2004;94:817-820.
Athanasopoulos A et al. J Urol. 2003;169:2253-2256.
Data on File. Pfizer Inc.
*Tolterodine IR 2 mg 2 times daily (BID).
†Doxazosin 4 mg/d or tamsulosin 0.4 mg/d.
‡An erratum submitted to the journal stated that only 1 of the 2 patients
who experienced AUR was taking tolterodine IR + doxazosin, whereas
the other received doxazosin monotherapy.
IR = immediate release.
67. Safety of Tolterodine® IR in Men with OAB/DO and
BOO: AEs
Urinary Symptom AEs
Placebo n = 72
Tolterodine IR
n = 149
n % n %
Micturition disorder 2 2.8 7 4.7
Urinary tract infection 3 4.2 6 4.0
Dysuria 1 1.4 3 2.0
Micturition frequency 2 2.8 3 2.0
Micturition urgency 1 1.4 2 1.3
Strangury 0 – 2 1.3
Acute urinary retention 1 1.4 0 0.0
Bladder discomfort 0 – 1 0.7
Urethral disorder 0 – 1 0.7
Urinary incontinence 2 2.8 0 –
Overall 9 12.5 19 12.8
Abrams P et al. J Urol. 2006;175:999-1004.
AE = aderse event; IR = immediate release.
68. Safety of Tolterodine® IR in Men with OAB/DO and
BOO: Conclusions
Abrams P et al. J Urol. 2006;175:999-1004.
Tolterodine IR did not affect urinary function in men with OAB/DO
and BOO
No difference between Tolterodine IR and placebo on Qmax and PdetQmax
Tolterodine IR did not adversely affect urinary flow or detrusor
muscle function
27-ml increase in median PVR for Tolterodine IR over placebo
No subjects in the Tolterodine IR–treated group reported AUR
1 (1.4%) of 74 patients reported AUR in the placebo-treated group
Results suggest Tolterodine IR is safe in men with OAB/DO and mild
to severe BOO
Tolterodine was well tolerated and did not aggravate voiding difficulties or
increase the incidence of AUR
69. TIMES: Safety and Tolerability Profile Furthers Evidence
for Urinary Safety in Men with OAB and Other LUTS
Treated with Tolterodine®
In this study population, Tolterodine SR, administered with or without
tamsulosin, was well tolerated, and the risk for AUR was low
LUTS/OAB patients with PVR <200 ml and Qmax >5 ml/s
No increase in PVR
No decrease of Qmax
Low incidence of AUR
70. Longer term studies with antimuscarinics
Abrams P, Malone-Lee J, Jacquetin B, et al. Twelve-month treatment
of overactive bladder: efficacy and tolerability of tolterodine. Drugs
Aging 2001;18:551-60
Van Kerrebroeck P. Long-term (12-months) efficacy and tolerability of
tolterodine once daily in the treatment of overactive bladder. ICS
2001. Neurourol Urodyn 2001;20:401-2 (Abstr)
Appell RA, Diokno A, Antoei J, Labasky RF for the Ditropan XL Study
Group. One-year prospective, open-label trial of controlled-release
oxybutynin for overactive bladder in a community- based population.
Neurol Urodyn 2000;19:528-9 (Abstr)
71. Practical guide to the evaluation and treatment of male lower
urinary tract symptoms in the primary care setting.
Rosenberg
et
al:
International
Journal
of
Clinical
Practice
61
(9),
1535-1546
72. New Guidelines on Treatment of LUTS
in Older Men
Recommendations of the ISC: Evaluation and Treatment of LUTS in Older Men 5th International
Consultation on New Developments in prostate Cancer and Prostate Diseases: June 24-28, 2005
73. Specialized Management for Persistent
Bothersome LUTS after Basic Management
OAB
(Overactive Bladder)
(Storage Symptoms)
No Evidence
of BOO
• Lifestyle
Intervention
• Behavioral
Therapy
• Antimuscarinics
Recommended Tests:
• Validated Questionnaires
• FVC (Frequent Volume Chart)
• Flowrate Recording
• Residual Urine
Evidence of BOO
Discuss Rx Options
Shared Decision
Medical Therapy Option
Predominant BOO
MIST
(Minimally Invasive
Surgical Treatment)
OR
Surgery Option
Mixed OAB
And BOO
Failure
Reassess and
Consider Invasive
Therapy of OAB
Antimuscarinic*
&
α-Blockers
Small Gland and/or
Low PSA
α-Blockers
Larger Gland and/or Higher
PSA
α-Blockers +
5α-Reductase Inhibitors
Failure
Offer MIST or Surgery to Patient
Evaluation clearly suggestive of
Obstruction? (Qmax < 10 ml/s)
Pressure-Flow Studies
Obstruction?
NO YES
NO YES
Proceed with
selected technique
Treat appropriately. If interventional therapy is
pursued, patients need to be informed of possible
higher failure rates
OAB: Overactive Bladder
MIST: Minimally Invasive
Surgical Treatment
BOO: Bladder Outlet
Obstruction