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BMJ (Clinical Research Ed.) Dec 2023To investigate the association of genetically proxied (using a surrogate biomarker) inhibition of phosphodiesterase 5 (PDE5), an established drug target for erectile...
OBJECTIVE
To investigate the association of genetically proxied (using a surrogate biomarker) inhibition of phosphodiesterase 5 (PDE5), an established drug target for erectile dysfunction, with fertility, sexual behaviour, and subjective wellbeing.
DESIGN
Two sample cis-mendelian randomisation study.
SETTING
Summary data on genetic associations obtained from the International Consortium for Blood Pressure and UK Biobank.
PARTICIPANTS
Individuals of European ancestry from the International Consortium for Blood Pressure (n=757 601) for estimating PDE5 inhibition (using the surrogate biomarker of diastolic blood pressure reduction), and UK Biobank (n=211 840) for estimating the fertility, sexual behaviour, and subjective wellbeing outcomes in male participants.
INTERVENTION
Genetically proxied PDE5 inhibition.
MAIN OUTCOME MEASURES
Number of children fathered, number of sexual partners, probability of never having had sexual intercourse, and subjective wellbeing.
RESULTS
Genetically proxied PDE5 inhibition was associated with male participants having 0.28 (95% confidence interval 0.16 to 0.39) more children (false discovery rate corrected P<0.001). This association was not identified in female participants. No evidence was found of an association between genetically proxied PDE5 inhibition and number of sexual partners, probability of never having had sexual intercourse, or self-reported wellbeing in male participants.
CONCLUSIONS
The findings of this study provide genetic support for PDE5 inhibition potentially increasing the number of children fathered by male individuals. Absence of this association in female participants supports increased propensity for sustained and robust penile erections as a potential underlying mechanism. Further studies are required to confirm this, however, and these findings should not promote indiscriminate use of PDE5 inhibitors, which can also have harmful adverse effects.
Topics: Child; Male; Humans; Female; Erectile Dysfunction; Sexual Behavior; Penile Erection; Fertility; Biomarkers
PubMed: 38086555
DOI: 10.1136/bmj-2023-076197 -
Journal of Clinical Medicine Jun 2021Several hormones contribute to ensure penile erection, a neurovascular phenomenon in which nitric oxide plays a major role. Erectile dysfunction (ED), which is defined... (Review)
Review
Several hormones contribute to ensure penile erection, a neurovascular phenomenon in which nitric oxide plays a major role. Erectile dysfunction (ED), which is defined as the persistent inability to obtain or maintain penile erection sufficient for a satisfactory sexual performance, may be due to arteriogenic, neurogenic, iatrogenic, but also endocrinological causes. The hypothalamus-pituitary axis plays a central role in the endocrine system and represents a fundamental link between the brain and peripheral glands, including gonads. Therefore, the hormonal production of the hypothalamic-pituitary axis can control various aspects of sexual function and its dysregulation can compromise erectile function. In addition, excess and deficiency of pituitary hormones or metabolic alterations that are associated with some pituitary diseases (e.g., Cushing's disease and acromegaly, hypopituitarism) can determine the development of ED with different mechanisms. Thus, the present review aimed to explore the relationship between hypothalamic and pituitary diseases based on the most recent clinical and experimental evidence.
PubMed: 34207687
DOI: 10.3390/jcm10122551 -
The World Journal of Men's Health Jul 2021Peyronie's disease (PD), a fibrotic disorder of the tunica albuginea fully described in 1793 by French physician Francois de la Peyronie, is characterized by pain,... (Review)
Review
Peyronie's disease (PD), a fibrotic disorder of the tunica albuginea fully described in 1793 by French physician Francois de la Peyronie, is characterized by pain, plaque formation, penile deformity, and ultimately sexual function decline. The epidemiological data on PD vary considerably across previous studies, with recent evidence reporting a prevalence of up to 9%. PD is generally divided into two different phases: active or acute and stable or chronic. Plaque formation generally occurs during the acute phase, while during chronic phase pain usually tends to complete resolution and penile deformity stabilizes. PD's pathophysiology is still subject of great discussion. Tunical mechanical stress and microvascular trauma are major contributory factors. However, better understanding of the molecular pathophysiology of this condition remains paramount towards an in-depth comprehension of the disorder and the development of newer and more effective disease-targeted interventions. In this review we provide a detailed overview of natural history of PD, specifically focusing on clinical manifestations and the underlying molecular regulation patterns.
PubMed: 32648381
DOI: 10.5534/wjmh.200065 -
American Journal of Men's Health 2022We conducted a meta-analysis to evaluate the efficacy of low-intensity extracorporeal shock wave therapy (LI-ESWT) in the treatment of erectile dysfunction (ED). From... (Meta-Analysis)
Meta-Analysis
Systematic Review and Meta-Analysis of 16 Randomized Controlled Trials of Clinical Outcomes of Low-Intensity Extracorporeal Shock Wave Therapy in Treating Erectile Dysfunction.
We conducted a meta-analysis to evaluate the efficacy of low-intensity extracorporeal shock wave therapy (LI-ESWT) in the treatment of erectile dysfunction (ED). From July 2011 to June 2021, we finally selected 16 randomized controlled trials (RCTs) including 1,064 participants to evaluate the efficacy of LI-ESWT in the treatment of ED from PubMed, EMBASE, and Cochrane databases. The data are analyzed by Review Manager Version 5.4. Fifteen articles mentioned International Index of Erectile Function (IIEF), in the follow-up of 1 month (mean difference [MD] = 3.18, 95% confidence interval [CI] = [1.38, 4.98], = .0005), 3 months (MD = 3.01, 95% CI = [2.04, 3.98], < .00001), and 6 months (MD = 3.20, 95% CI = [2.49, 3.92], < .00001). After treatment, the improvement of IIEF in the LI-ESWT group was better than that in the control group. Besides, eight of the 16 trials provided data on the proportion of patients with baseline Erectile Hardness Score (EHS) ≤ 2 improved to EHS ≥ 3. The LI-ESWT group was also significantly better than the placebo group (odds ratio [OR] = 5.07, 95% CI = [1.78, 14.44], = .002). The positive response rate of Questions 2 and 3 of the Sexual Encounter Profile (SEP) was not statistically significant (SEP2: OR = 1.27, 95% CI = [0.70, 2.30], = .43; SEP3: OR = 4.24, 95% CI = [0.67, 26.83], = .13). The results of this meta-analysis suggest that treatment plans with an energy density of 0.09 mJ/mm and pulses number of 1,500 to 2,000 are more beneficial to IIEF in ED patients. In addition, IIEF improvement was more pronounced in patients with moderate ED after extracorporeal shockwave therapy.
Topics: Erectile Dysfunction; Extracorporeal Shockwave Therapy; Humans; Male; Penile Erection; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 35319291
DOI: 10.1177/15579883221087532 -
Future Journal of Pharmaceutical... 2021A plethora of chemicals exists in human body which can alter physiology in one way or other. Scientists have always been astounded by such abilities of chemicals but as... (Review)
Review
BACKGROUND
A plethora of chemicals exists in human body which can alter physiology in one way or other. Scientists have always been astounded by such abilities of chemicals but as the technology advances, even the chemical which was once expected to be well known changes its status to not really well known. Adenosine is one of the chemicals which is in consonance with the aforementioned statements, although previous articles have covered vast information on role of adenosine in cardiovascular physiology, bacterial pathophysiology and inflammatory diseases. In this review we have discussed adenosine and its congeners as potential promising agents in the treatment of Huntington's disease, post-traumatic stress disorder, erectile dysfunction, viral infections (SARS-CoV) and anxiety.
MAIN TEXT
Adenosine is a unique metabolite of ATP; which serves in signalling as well. It is made up of adenine (a nitrogenous base) and ribo-furanose (pentose) sugar linked by β-N9-glycosidic bond. Adenosine on two successive phosphorylation forms ATP (Adenosine Triphosphate) which is involved in several active processes of cell. It is also one of the building blocks (nucleotides) involved in DNA (Deoxy-ribonucleic Acid) and RNA (Ribonucleic Acid) synthesis. It is also a component of an enzyme called S-adenosyl-L-methionine (SAM) and cyano-cobalamin (vitamin B-12). Adenosine acts by binding to G protein-coupled receptor (GPCR: A1, A2A, A2B and A3) carries out various responses some of which are anti-platelet function, hyperaemic response, bone remodelling, involvement in penile erection and suppression of inflammation. On the other hand, certain microorganisms belonging to genus utilize adenosine in order to escape host immune response (phagocytic clearance). These microbes evade host immune response by synthesizing and releasing adenosine (with the help of an enzyme: adenosine synthase-A), at the site of infection.
CONCLUSION
With the recent advancement in attribution of adenosine in physiology and pathological states, adenosine and its congeners are being looked forward to bringing a revolution in treatment of inflammation, viral infections, psychiatric and neurodegenerative disorders.
PubMed: 34697594
DOI: 10.1186/s43094-021-00353-w -
Current Cardiology Reviews 2022Cardiovascular diseases are the most common cause of death worldwide, with cardiovascular medications being amongst the most common medications prescribed. These... (Review)
Review
Cardiovascular diseases are the most common cause of death worldwide, with cardiovascular medications being amongst the most common medications prescribed. These medications have diverse effects on the heart, vascular system, as well as other tissues and organ systems. The extra cardiovascular effects have been found to be of use in the treatment of non-cardiovascular diseases and pathologies. Minoxidil is used to manage systemic hypertension with its well-known side effect of hirsutism used to treat alopecia and baldness. Sildenafil was originally investigated as a treatment option for systemic hypertension; however, its side effect of penile erection led to it being widely used for erectile dysfunction. Alpha-1 blockers such as terazosin are indicated to treat systemic hypertension but are more commonly used for benign prostatic hyperplasia and post-traumatic stress disorder. Beta blockers are the mainstay treatment for congestive heart failure and systemic hypertension but have been found useful to help in patients with intention tremors as well as prophylaxis of migraines. Similarly, calcium channel blockers are indicated in medical expulsion therapy for ureteric calculi in addition to their cardiovascular indications. Thiazides are commonly used for treating systemic hypertension and as diuretics. Thiazides can cause hypocalciuria and hypercalcemia. This side effect has led to thiazides being used to treat idiopathic hypercalciuria and associated nephrolithiasis. Spironolactone is commonly utilized in treating heart failure and as a diuretic for edema. It's well described anti-androgen side effects have been used for acne vulgaris and hirsutism in polycystic ovarian syndrome. This review article discusses how the various extracardiovascular effects of commonly used cardiovascular medications are put to use in managing non-cardiovascular conditions.
Topics: Adrenergic beta-Antagonists; Cardiovascular Diseases; Diuretics; Heart Failure; Hirsutism; Humans; Hypertension; Male; Thiazides
PubMed: 34779371
DOI: 10.2174/1573403X17666211015145132 -
International Braz J Urol : Official... 2022Total corpora mobilization (TCM) is a novel technique that is used for penile reconstruction in cases of micropenis and penile amputation. Its principle is based on...
PURPOSE
Total corpora mobilization (TCM) is a novel technique that is used for penile reconstruction in cases of micropenis and penile amputation. Its principle is based on Kelly's procedure for bladder exstrophy (1). In contrast to the Kelly procedure, TCM is performed entirely through the perineum with the patient in the lithotomy position.
MATERIALS AND METHODS
TCM was performed on three patients. The first was a boy who suffered trauma from a dog bite at an age of eight months. At 23 years old he underwent TCM. The second patient had genital self-amputation induced by psychiatric disorder. After treatment, at 27 years old, he desired surgery for penile reconstruction. The third patient had partial androgen insensitivity syndrome (PAIS) with a micropenis and at 23 years old had TCM procedure. The patients were placed in the lithotomy position with a perineal incision in the midline. A subperiosteal incision was made and the corpora cavernosa were detached from the pubic arch and the ischial rami. The periosteum and the neurovascular bundles were preserved. Subsequently the corpora cavernosa was mobilized upward and the periosteum that was left attached to them was sutured to the pubis.
RESULTS
At twenty-four, nine, and six months, respectively, in the follow-up process, all patients expressed satisfaction with the final cosmetic appearance, penile length, and erectile function.
CONCLUSION
TCM may prove to be an alternative for patients with a functional disturbance because of small penile length, though a higher number of cases and a more extended follow-up are needed to draw a more definitive conclusion.
Topics: Animals; Bladder Exstrophy; Dogs; Genital Diseases, Male; Humans; Male; Penile Diseases; Penile Erection; Penis
PubMed: 35838516
DOI: 10.1590/S1677-5538.IBJU.2022.0177