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Prostaglandins as a Topical Therapy for Erectile Dysfunction: A Comprehensive Review (2022)
Mohammadsadegh Hamzehnejadi, PharmD, Marziye Ranjbar Tavakoli, PharmD, Fatemeh Homayouni, PharmD, Zahra Jahani, PharmD, Masoud Rezaei, PharmD, Mohammad Amin Langarizadeh, PharmD, and Hamid Forootanfar, PhD
ABSTRACT
Introduction: Erectile dysfunction (ED) is a substantial cause of dissatisfaction among many men. This discontentment has led to the emergence of various drug treatment options for this problem.
Objectives: Unfortunately, due to various interactions, contraindications, and side effects, systemic therapies such as phosphodiesterase-5 inhibitors (including sildenafil, tadalafil, vardenafil, avanafil, etc.) are not welcomed in many patients. These problems have led researchers to look for other ways to reduce these complications.
Methods: This article holistically reviews the efficacy of topical prostaglandins and their role in treating ED. We sought to provide a comprehensive overview of recent findings on the current topic by using an extensive literature search to identify the latest scientific reports on the topic.
Results: In this regard, topical and transdermal treatments can be suitable alternatives. In diverse studies, prostaglandins, remarkably PGE1 (also known as alprostadil), have been suggested to be an acceptable candidate for topical treatment.
Conclusion: Numerous formulations of PGE1 have been used to treat patients so far. Still, in general, with the evolution of classical formulation methods toward modern techniques (such as using nanocarriers and skin permeability enhancers), the probability of treatment success also increases.
INTRODUCTION
According to the definition, erectile dysfunction (ED) is the persistent inability to create or maintain a penile erection with sufficient quality.1 Adequate erections are essential for penetration and durability of sex, and there is a clear connection between ED and infertility in men.2 The issues of sex, primarily related to a man's strength, may cause embarrassment and stress, leading to frustration in the person relative to this subject.3 This problem causes mental health problems such as depression and loss of confidence by reducing patients' quality of life.3 ED remains untreated because the patient is reluctant to report it.1 That is why the physician should examine the patients at risk.4 The physician should talk to the patient about psychosocial issues, sexual records, and psychological factors.1 Appropriate and timely intervention to return earlier to sexual performance provides a higher quality of life.1 ED treatment improves patient and partner satisfaction and improves overall health.5
*Erectile Function
*Etiology
*Management
*Lifestyle Modifications
*Oral Treatment
*Intracavernousal Injection (ICI)
*Vacuum Erection Devices (VED)
*Testosterone Therapy
*Penis Prosthesis
*History of ED's Topical Therapy
Phosphodiesterase-5 (PDE5) Inhibitors
Tadalafil
Sildenafil
Vasodilators
Papaverine
Minoxidil
Nitroglycerin
*Testosterone
Topical Prostaglandins Applications
Alopecia and Eyelash Changes
Vitiligo
Psoriasis
Oral Mucositis
Glaucoma
Ulcers
RESULTS AND DISCUSSION
Prostaglandins as a Topical Therapy for ED
Prostaglandins have shown significant positive effects in the treatment of ED. Unlike PDE5Is, this class of drugs exerts its effects directly. After binding to PGE1 receptors, Alprostadil activates the cyclic adenosine monophosphate pathway, inducing an erection into smooth muscle.64,102 This pathway further leads to the activation of protein kinase A, which leads to the relaxation of smooth muscles by stopping the flow of intracellular potassium and calcium. Following smooth muscle relaxation, the cavernosal arteries dilate. Alprostadil can also achieve this goal by acting as a norepinephrine antagonist.103 PGE1 increases intracellular cAMP after binding to E-prostaglandin receptors through adenylate cyclase activity bound to the cortex. Activation of Maxi K channels (neuronal calcium sensors) changes the flow of calcium ions, resulting in cell polarity, and finally inhibits noradrenaline and angiotensin II secretion.43,104,105
CONCLUSION
ED is a prevalent problem often caused by a patient's medical condition. Despite being the first line of treatment for ED, phosphodiesterase inhibitors do not provide an acceptable response in half of their users and have numerous systemic side effects and contraindications. PDE5Is and other drugs, such as vasodilators and testosterone, seem to be topically effective in individuals. In some people, topical prostaglandin increases cavernous artery diameter, which leads to effective intercourse when ED improves. Notably, prostaglandins' potential to improve ED diminishes as people get older. Topical prostaglandins are well tolerated, have few side effects, and have no drug-drug and food-drug interactions. Painful erections, urinary tract pain, syncope, erythema, and unusual partner side effects like weight gain and itching are all rare side effects.
Alprostadil formulations depend on penetration and would affect better when combined with penetration enhancers such as DDAIP and SEPA. Lipophile ethylene glycol and alcoholic hydrogel formulations with limonene or cineole, as well as liposomes, particularly liposomes from phosphatidylcholine with methyl salicylates, positively affect the penetration. Furthermore, a formulation including prostaglandin E1 ethyl ester enhances the penetration and action of prostaglandin E1. In general, the effectiveness of topical prostaglandins in the treatment of ED can be reported as moderate but acceptable. Prostaglandins are more efficacious than monotherapy when administered orally or topically alongside other medications such as minoxidil, nitroglycerin, phosphodiesterase inhibitors, prazosin, herbal medicines, etc. However, due to their expensive cost and lower stability at room temperature, several studies have preferred alternative medications such as papaverine over prostaglandins. To achieve this therapeutic goal, more research and new types of prostaglandin medication formulations will be required in the future. Also, some formulations are needed to be investigated in the future, including a combination of prostaglandins and herbal medicines that are useful in treating ED orally or topically.
Mohammadsadegh Hamzehnejadi, PharmD, Marziye Ranjbar Tavakoli, PharmD, Fatemeh Homayouni, PharmD, Zahra Jahani, PharmD, Masoud Rezaei, PharmD, Mohammad Amin Langarizadeh, PharmD, and Hamid Forootanfar, PhD
ABSTRACT
Introduction: Erectile dysfunction (ED) is a substantial cause of dissatisfaction among many men. This discontentment has led to the emergence of various drug treatment options for this problem.
Objectives: Unfortunately, due to various interactions, contraindications, and side effects, systemic therapies such as phosphodiesterase-5 inhibitors (including sildenafil, tadalafil, vardenafil, avanafil, etc.) are not welcomed in many patients. These problems have led researchers to look for other ways to reduce these complications.
Methods: This article holistically reviews the efficacy of topical prostaglandins and their role in treating ED. We sought to provide a comprehensive overview of recent findings on the current topic by using an extensive literature search to identify the latest scientific reports on the topic.
Results: In this regard, topical and transdermal treatments can be suitable alternatives. In diverse studies, prostaglandins, remarkably PGE1 (also known as alprostadil), have been suggested to be an acceptable candidate for topical treatment.
Conclusion: Numerous formulations of PGE1 have been used to treat patients so far. Still, in general, with the evolution of classical formulation methods toward modern techniques (such as using nanocarriers and skin permeability enhancers), the probability of treatment success also increases.
INTRODUCTION
According to the definition, erectile dysfunction (ED) is the persistent inability to create or maintain a penile erection with sufficient quality.1 Adequate erections are essential for penetration and durability of sex, and there is a clear connection between ED and infertility in men.2 The issues of sex, primarily related to a man's strength, may cause embarrassment and stress, leading to frustration in the person relative to this subject.3 This problem causes mental health problems such as depression and loss of confidence by reducing patients' quality of life.3 ED remains untreated because the patient is reluctant to report it.1 That is why the physician should examine the patients at risk.4 The physician should talk to the patient about psychosocial issues, sexual records, and psychological factors.1 Appropriate and timely intervention to return earlier to sexual performance provides a higher quality of life.1 ED treatment improves patient and partner satisfaction and improves overall health.5
*Erectile Function
*Etiology
*Management
*Lifestyle Modifications
*Oral Treatment
*Intracavernousal Injection (ICI)
*Vacuum Erection Devices (VED)
*Testosterone Therapy
*Penis Prosthesis
*History of ED's Topical Therapy
Phosphodiesterase-5 (PDE5) Inhibitors
Tadalafil
Sildenafil
Vasodilators
Papaverine
Minoxidil
Nitroglycerin
*Testosterone
Topical Prostaglandins Applications
Alopecia and Eyelash Changes
Vitiligo
Psoriasis
Oral Mucositis
Glaucoma
Ulcers
RESULTS AND DISCUSSION
Prostaglandins as a Topical Therapy for ED
Prostaglandins have shown significant positive effects in the treatment of ED. Unlike PDE5Is, this class of drugs exerts its effects directly. After binding to PGE1 receptors, Alprostadil activates the cyclic adenosine monophosphate pathway, inducing an erection into smooth muscle.64,102 This pathway further leads to the activation of protein kinase A, which leads to the relaxation of smooth muscles by stopping the flow of intracellular potassium and calcium. Following smooth muscle relaxation, the cavernosal arteries dilate. Alprostadil can also achieve this goal by acting as a norepinephrine antagonist.103 PGE1 increases intracellular cAMP after binding to E-prostaglandin receptors through adenylate cyclase activity bound to the cortex. Activation of Maxi K channels (neuronal calcium sensors) changes the flow of calcium ions, resulting in cell polarity, and finally inhibits noradrenaline and angiotensin II secretion.43,104,105
CONCLUSION
ED is a prevalent problem often caused by a patient's medical condition. Despite being the first line of treatment for ED, phosphodiesterase inhibitors do not provide an acceptable response in half of their users and have numerous systemic side effects and contraindications. PDE5Is and other drugs, such as vasodilators and testosterone, seem to be topically effective in individuals. In some people, topical prostaglandin increases cavernous artery diameter, which leads to effective intercourse when ED improves. Notably, prostaglandins' potential to improve ED diminishes as people get older. Topical prostaglandins are well tolerated, have few side effects, and have no drug-drug and food-drug interactions. Painful erections, urinary tract pain, syncope, erythema, and unusual partner side effects like weight gain and itching are all rare side effects.
Alprostadil formulations depend on penetration and would affect better when combined with penetration enhancers such as DDAIP and SEPA. Lipophile ethylene glycol and alcoholic hydrogel formulations with limonene or cineole, as well as liposomes, particularly liposomes from phosphatidylcholine with methyl salicylates, positively affect the penetration. Furthermore, a formulation including prostaglandin E1 ethyl ester enhances the penetration and action of prostaglandin E1. In general, the effectiveness of topical prostaglandins in the treatment of ED can be reported as moderate but acceptable. Prostaglandins are more efficacious than monotherapy when administered orally or topically alongside other medications such as minoxidil, nitroglycerin, phosphodiesterase inhibitors, prazosin, herbal medicines, etc. However, due to their expensive cost and lower stability at room temperature, several studies have preferred alternative medications such as papaverine over prostaglandins. To achieve this therapeutic goal, more research and new types of prostaglandin medication formulations will be required in the future. Also, some formulations are needed to be investigated in the future, including a combination of prostaglandins and herbal medicines that are useful in treating ED orally or topically.
