The pathogenesis of organic ED is related to dysfunction of the endothelium. Endothelial cells can become injured through a variety of mechanisms, most of which cause oxidative stress on the tissues. Many of these causes of oxidative stress are related to lifestyle issues which lead to hypertension, diabetes and dyslipidaemia (figure 1). Endothelial cell dysfunction results in reduction of endothelium-dependent vasorelaxation as well as increased adhesion of leukocytes to the endothelium. Endothelial cell injury then leads to a variety of sequelae, including ED, other types of vasoconstriction, atherosclerosis and thrombus formation.18
There are so many potential reasons a man might develop erectile dysfunction (ED), it's nearly impossible to generalize the best ways to treat it. What works for one man may not work for another simply because they are having problems for different reasons. That said, it may encouraging to hear that there are a variety of options that may be considered, from psychological counseling to lifestyle changes, medications to treatments and devices.
Recently, the US Food and Drug Administration (FDA) has issued a safety announcement regarding TRT. In part it reads ‘The benefit and safety of these medications have not been established. We are also requiring these manufacturers to add information to the labeling about a possible increased risk of heart attacks and strokes in patients taking testosterone.’37
Erectile dysfunction is defined as the persistent inability to achieve or maintain penile erection sufficient for satisfactory sexual performance. The Massachusetts Male Aging Study surveyed 1,709 men aged 40–70 years between 1987 and 1989 and found there was a total prevalence of erectile dysfunction of 52 percent. It was estimated that, in 1995, over 152 million men worldwide experienced ED. For 2025, the prevalence of ED is predicted to be approximately 322 million worldwide.

Inside the cell, NOS catalyzes the oxidation of L-arginine to NO and L-citrulline. Endogenous blockers of this pathway have been identified. The gaseous NO that is produced acts as a neurotransmitter or paracrine messenger. Its biologic half-life is only 5 seconds. NO may act within the cell or diffuse and interact with nearby target cells. In the corpora cavernosa, NO activates guanylate cyclase, which in turn increases cyclic guanosine monophosphate (cGMP). Relaxation of vascular smooth muscles by cGMP leads to vasodilation and increased blood flow.
Alprostadil (also known as prostaglandin E1 [PGE1]) is the prominent known smooth-muscle dilator of the corpus cavernosum. Its mechanism of action is believed to be the promotion of intracellular accumulation of cyclic adenosine monophosphate, thereby causing decreased intracellular accumulation of calcium and resulting smooth muscle relaxation. Alprostadil can be delivered to the erectile tissue either via an intraurethral suppository that is massaged and then absorbed across the corpus spongiosum of the urethra to the corpora cavernosa, or directly injected into the corpora cavernosa. When administered urethrally, doses are substantially higher than when directly injected (typical dosing is 500 mcg to 1 mg intraurethral compared with 2.5 mcg to 20 mcg intracavernosal).
Take an ED drug. Such drugs can help men maintain erections for several hours at a time. They work by enhancing the effect of nitric oxide, which the body produces naturally to relax and increase blood flow to the penis.[9] If you're interested in taking a drug specifically geared toward treating ED, talk with your doctor about getting a prescription.
There are hundreds of medications that have the side effect of ED and/or decreased libido. Examples of drugs implicated as a cause of ED include hydrochlorothiazides and beta-blocking agents. Medications used to treat depression, particularly the SSRIs such as citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac, Prozac Weekly, Sarafem), fluvoxamine (Luvox, Luvox CR), paroxetine (Paxil, Paxil CR, Pexeva) and sertraline (Zoloft), may also contribute to ED.9 Bupropion (Wellbutrin) which has a predominant effect on blocking the reuptake of dopamine is an antidepressant with lower incidence of ED.10 The side effects of 5ARIs occurring in fewer than 5% of patients can include gynaecomastia, ED, loss of libido and ejaculatory dysfunction.11
Having erection trouble from time to time isn't necessarily a cause for concern. If erectile dysfunction is an ongoing issue, however, it can cause stress, affect your self-confidence and contribute to relationship problems. Problems getting or keeping an erection can also be a sign of an underlying health condition that needs treatment and a risk factor for heart disease.
Alprostadil, a drug also discussed in Penile Injection Therapy, has been formulated into a small suppository. This applicator is inserted into the urethra (the canal through which urine and semen are excreted), and with compression of the applicator, the small suppository is released into the urethra. With massage/rubbing of the penis, the suppository dissolves in the urethra and the medication is absorbed into the penis where it acts to increase blood flow into the penis. One cannot use any form of lubricant (for example, K-Y jelly, Vaseline, etc) to help with the insertion of the suppository. Urinating prior to inserting the applicator will help moisten/lubricate the urethra.
Prior to the introduction of PDE5i in 1998, intracavernosal vasoactive medications and penile implant surgery were the mainstays of treatment. Penile implant surgery involves placement of inflatable or malleable rods within the corpora cavernosa to provide rigidity for intercourse. Choice of which implant to place usually depends upon manual dexterity and function of the patient, patient anatomy, physician preference and surgical approach.
Robbins, C. L., Schick, V., Reece. M., Herbenick, D., Sanders, S. A. Dodge, B., & Fortenberry J. D., (2011, December 1). Prevalence, frequency, and associations of masturbation with partnered sexual behaviors among US adolescents. JAMA Pediatrics, 165(12), 1087–1093. Retrieved from https://jamanetwork.com/journals/jamapediatrics/fullarticle/1107656
ED can also occur among younger men. A 2013 study found that one in four men seeking their first treatment for ED were under the age of 40. The researchers found a stronger correlation between smoking and illicit drug use and ED in men under 40 than among older men. That suggests that lifestyle choices may be a main contributing factor for ED in younger men.

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Impotence is the inability to get and keep an erection hard enough to have sex. Many men experience difficulties getting an erection when they are tired or stressed. This is normal and it doesn’t require treatment. However, if you encounter problems that persist, you may be suffering with a degree of impotence. Impotence is a very treatable condition and help is available either when you visit your local GP or an online doctor.
Neurogenic erectile dysfunction (NED) is a traditional classification of erectile dysfunction (ED) encompassing disorders impairing erections via neurologic compromise or dysfunction. The disorders compromising erections may act centrally, peripherally or both. The prevalence of neurogenic ED has been suspected to be between 10% and 19% of all causes of ED (1,2). However, several classically defined neurogenic processes may affect several components of the normal pathway to achieve erection e.g., multiple sclerosis (MS), diabetes mellitus, iatrogenic surgical and spinal cord injury. Each disease state has its own unique characteristics that require acknowledgement to fully understand their effect on ED.

Robbins, C. L., Schick, V., Reece. M., Herbenick, D., Sanders, S. A. Dodge, B., & Fortenberry J. D., (2011, December 1). Prevalence, frequency, and associations of masturbation with partnered sexual behaviors among US adolescents. JAMA Pediatrics, 165(12), 1087–1093. Retrieved from https://jamanetwork.com/journals/jamapediatrics/fullarticle/1107656
Knowing about your history of ED will help your health provider learn if your problems are because of your desire for sex, erection function, ejaculation, or orgasm (climax). Some of these questions may seem private or even embarrassing. However, be assured that your doctor is a professional and your honest answers will help find the cause and best treatment for you.
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