Clinical evidence in men with erectile dysfunction (ED) shows that the phosphodiesterase type 5 (PDE5) inhibitors sildenafil citrate, tadalafil, and vardenafil hydrochloride have favorable safety and efficacy profiles. However, as mild vasodilators, the PDE5 inhibitors are also associated with hemodynamic effects that may be clinically significant, especially when treating men with ED who have comorbid cardiovascular disease. Hemodynamic studies have shown that therapeutic dosages of the PDE5 inhibitors produce only mild and transient changes in mean systolic and diastolic blood pressure and heart rate in healthy men as well as those with ischemic heart disease or chronic stable angina. Overall, PDE5 inhibitors are safe and effective in most patient populations, including men with ischemic cardiovascular disease or those receiving anti-hypertensive agents, and men with diabetes or those who have undergone nerve-sparing retropubic radical prostatectomy. With the entry of three novel PDE5 inhibitors into the therapeutic armamentarium for ED, differentiating properties of the new agents may confer clinical benefits that physicians as well as patients and their partners should consider when selecting a PDE5 inhibitor.
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BMC Urol
January 2025
Urology and Nephrology Research Center (UNRC), Research Institute for Urology and Nephrology, Center of Excellence in Urology, Shahid Labbafinejad Hospital, Shahid Beheshti University of Medical Sciences (SBMU), Tehran, Iran.
Background: Medical Expulsive Therapy (MET) has been recommended as an established modality for the treatment of distal ureteral stones due to its clearance rate, pain control, and patient satisfaction while having minimal morbidity in comparison to other urologic interventions. In some studies, a combination of medications has been used, which we assessed in this network meta-analysis (NMA).
Methods: We conducted systematic searches in PubMed, Scopus, and Web of Science to identify relevant trials published between 2001 and 2024.
Basic Clin Androl
January 2025
Chair of Endocrinology and Medical Sexology (ENDOSEX), Dept. of Systems Medicine, University of Rome Tor Vergata, via Montpellier 1, Rome, 00133, Italy.
The serendipitous discovery that inhibiting type 5 phosphodiesterase (PDE5) using sildenafil, a potent PDE5 inhibitor (PDE5i) initially developed for cardioprotection, introduced the possibility of orally managing erectile dysfunction (ED) led to an increase in research data, which are currently considered groundbreaking for the new discipline of sexual medicine. Findings from a number of laboratories and clinics around the world unanimously demonstrated the following: (i) the major cause of ED is directly or indirectly related to cardiovascular disease (CVD); (ii) ED and CVDs share the same risk factors, which are related mainly to lifestyle choices; (iii) the first therapeutic approach to both ED and CVDs is to transform harmful lifestyles into virtuous lifestyles; and (iv) PDE5is in general, particularly sildenafil, are very safe, if not protective, for use in CVD patients. However, the use of PDE5is has faced several challenges.
View Article and Find Full Text PDFCells
January 2025
Third Department of Urology, Attikon University Hospital, School of Medicine, National and Kapodistrian University of Athens, 12462 Athens, Greece.
Phosphodiesterases, particularly the type 5 isoform (PDE5), have gained recognition as pivotal regulators of male reproductive physiology, exerting significant influence on testicular function, sperm maturation, and overall fertility potential. Over the past several decades, investigations have expanded beyond the original therapeutic intent of PDE5 inhibitors for erectile dysfunction, exploring their broader reproductive implications. This narrative review integrates current evidence from in vitro studies, animal models, and clinical research to clarify the roles of PDEs in effecting the male reproductive tract, with an emphasis on the mechanistic pathways underlying cyclic nucleotide signaling, the cellular specificity of PDE isoform expression, and the effects of PDE5 inhibitors on Leydig and Sertoli cell functions.
View Article and Find Full Text PDFCells
January 2025
Department of Physiology, College of Medicine, Hallym University, Chuncheon 24252, Republic of Korea.
Phosphodiesterase (PDE) enzymes regulate intracellular signaling pathways crucial for brain development and the pathophysiology of neurological disorders. Among the 11 PDE subtypes, PDE4 and PDE5 are particularly significant due to their regulation of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) signaling, respectively, which are vital for learning, memory, and neuroprotection. This review synthesizes current evidence on the roles of PDE4 and PDE5 in neurological health and disease, focusing on their regulation of second messenger pathways and their implications for brain function.
View Article and Find Full Text PDFEClinicalMedicine
February 2025
Human Stem Cell and Genome Engineering Center, University of California Los Angeles David Geffen School of Medicine, UCLA - CHS 36 - 125/133/143 650 Charles E. Young Dr. South, Los Angeles, CA, 90095, USA.
Background: Phosphodiesterase 5 (PDE5) inhibitors, owing to their mechanism of action, have been gaining recognition as a potential case of drug repurposing and combination therapy for diabetes treatment. We aimed to examine the effect of long and short half-life PDE5 inhibitors have on Haemoglobin A1c (HbA1c) levels.
Methods: A systematic review and meta-analysis was conducted of randomised controlled trials (RCTs) in people with elevated HbA1c (>6%) to assess mean difference in HbA1c levels from baseline versus controls after any PDE5 inhibitor intervention of ≥4 weeks, excluding multiple interventions.
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