Melissa Conrad Stöppler, MD, is a U.S. board-certified Anatomic Pathologist with subspecialty training in the fields of Experimental and Molecular Pathology. Dr. Stöppler's educational background includes a BA with Highest Distinction from the University of Virginia and an MD from the University of North Carolina. She completed residency training in Anatomic Pathology at Georgetown University followed by subspecialty fellowship training in molecular diagnostics and experimental pathology.

Exercise and lifestyle modifications may improve erectile function. Weight loss may help by decreasing inflammation, increasing testosterone, and improving self-esteem. Patients should be educated to increase activity, reduce weight, and stop smoking, as these efforts can improve or restore erectile function in men without comorbidities. Precise glycemic control in diabetic patients and pharmacologic treatment of hypertension may be important in preventing or reducing sexual dysfunction. [49]

Her remark was entirely destructive of poetry, since it was to the effect that poetry had nothing whatever to do with her; all her friends spent their lives in making up phrases, she said; all his feeling was an illusion, and next moment, as if to taunt him with his impotence, she had sunk into one of those dreamy states which took no account whatever of his existence.


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.

One study by Palmer and colleagues evaluated sildenafil use in SB males with thoracic lesions (76). A prospective, blinded, randomized, placebo-controlled, dose-escalation, crossover study in 17 patients with SB and ED was performed. All study participates took sets of tablet in groups, two sets of placebo, one of 25 mg, and the last 50 mg. Overall response to the tablet sets was measured by IIEF response and self-report of erectile rigidity. Patients reported that taking 50 mg of sildenafil led to improved erections, duration of erections, frequency of erections and level of confidence compared to sildenafil 25 mg and more significantly compared to placebo. Of the five patients who reported side effects, two experienced mild hematological changes that reverted to baseline after study completion.
The role of the endothelium in erectile function became clearer with the observation that the phosphodiesterase type 5 (PDE5) inhibitor, sildenafil, enhanced erectile function. Erection occurs with the release of nitric oxide (NO) from the vascular endothelial cells.17 The reduction in endothelial cell production of NO results in the negative impact on the smooth muscles in the corporal bodies and results in less relaxation of the smooth muscle cells with decrease in blood supply and resulting ED. A similar phenomenon is well known to impact the coronary arterial system resulting in CVD.
The downside to these prostheses includes the standard risks of surgery, the very low risk of infection — less than 2 percent in most patients, slightly higher in diabetics — and a slight drop in penis length versus a natural erection or other ED treatments. Also, unlike with other methods, any hope for a natural erection is abolished once a pump is implanted. The cost for surgical options varies, and insurance coverage is typically good.
Injection therapy involves injecting a substance into the penis to enhance blood flow and cause an erection. The Food and Drug Administration (FDA) approved a drug called alprostadil (Caverject) for this purpose in July of 1995. Alprostadil relaxes smooth muscle tissue to enhance blood flow into the penis. It must be injected shortly before intercourse. Another, similar drug that is sometimes used is papaverine—not yet been approved by the FDA for this use. Either drug may sometimes cause painful erections or priapism (uncomfortable, prolonged erections) that must be treated with a shot of epinephrine.
The obvious risks are the same that accompany any surgery: infection, pain, bleeding, and scarring. If for some reason the prosthesis or parts become damaged or dislocated, surgical removal may be necessary. With a general success rate of about 90 percent, any of the devices will restore erections, but they will not affect sexual desire, ejaculation, or orgasm.
However, a review of a United Kingdom medical record database found no evidence that the use of 5-alpha reductase inhibitors independently increase the risk for ED. In 71,849 men with benign prostatic hyperplasia (BPH), the risk of ED was not increased with the use of finasteride or dutasteride only (odds ratio [OR] 0.94), or a 5-alpha reductase inhibitor plus an alpha blocker (OR 0.92) compared with an alpha blocker only. In addition, the risk of ED was not increase in 12 346 men prescribed finasteride 1 mg for alopecia, compared with unexposed men with alopecia (OR 0.95). The risk of ED did increase with longer duration of BPH, regardless of drug exposure. [48]
All studies demonstrate a strong association with age, even when data are adjusted for the confounding effects of other risk factors. The independent association with aging suggests that vascular changes in the arteries and sinusoids of the corpora cavernosa, similar to those found elsewhere in the body, are contributing factors. Other risk factors associated with aging include depression, sleep apnea, and low HDL levels.
Parasympathetic pathways originate from the intermediolateral cell columns of the 2nd, 3rd and 4th sacral spinal cord segments. Preganglionic fibers pass through the pelvic plexus where they coalesce with sympathetic fibers from the superior hypogastric plexus. The cavernous nerves that innervate the penis arise from the portion of the pelvic plexus. The pelvic plexus also contains nerves that innervate the rectum, bladder and urinary sphincter and the nerve projections can be damaged during radical excision of the bladder, prostate and rectum, leading to iatrogenic ED (4).

Since the advent of PDE5i, many other selective and non-selective peripheral acting compounds have been developed or are in development. Avanafil has shown promising results in treating ED in post-prostatectomy patients with suspected cavernous nerve injury (111). Other PDE5i marked in Asia such as udenafil, and mirodenafil also effective at treating ED may minimize side effects due to shorter half-lives (112-114). Soluable guanylate-cyclase inhibitors and potassium channel activators are compounds that have induced erections in animal models but remain experimental requiring further investigation (115-117).
If a trial of oral ED therapy and withdrawal of offending medications prove to be ineffective in restoring erectile function, it is appropriate for most primary care practitioners to consider referral to a specialist for additional evaluation and discussion of alternative treatment options. These include intracavernous injection therapy, vacuum constriction devices, intraurethral therapy, and possible surgery.
Many factors can contribute to sexual dysfunction in older men, including physical and psychological conditions, comorbidities and the medications used to treat them. Aspects of an ageing man’s lifestyle and behaviour and androgen deficiency, most often decreasing testosterone levels, may affect sexual function as well. A study of men between the ages of 30 and 79 years showed that 24% had testosterone levels below 300 ng/dL and 5.6% had symptomatic androgen deficiency.2
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).
Metabolism (breakdown) of vardenafil can be slowed by aging, liver disease, and concurrent use of certain medications (such as erythromycin [an antibiotic], ketoconazole [Nizoral, a medication for fungal/yeast infections], and protease inhibitors [medications used to treat AIDS]). Slowed breakdown allows vardenafil to accumulate in the body and potentially increase the risk for side effects. Therefore, in men over 65 years of age with liver disease, or who are also taking medication(s) that can slow the breakdown of vardenafil, the doctor will initiate vardenafil at low doses to avoid its accumulation. For example,
The neurovascular events that ultimately occur result in the inhibition of adrenergic tone and the release of the nonadrenergic, noncholinergic neurotransmitter, nitric oxide. Nitric oxide is believed to be released from nonadrenergic, noncholinergic nerves and endothelial cells. It subsequently stimulates the guanylate cyclase enzyme system in penile smooth muscle. This results in increased levels of cyclic guanosine monophosphate (cGMP) and ultimately in smooth muscle relaxation, enhancement of arterial inflow, and veno-occlusion, producing adequate firmness for sexual activity.
ED is defined as the inability to achieve a full erection or the inability to maintain an erection adequate for sexual intimacy. Other types of sexual dysfunction such as premature ejaculation and low libido may occur; however, the most common and disruptive problem in men is ED. Although most men will experience periodic episodes of ED, these episodes tend to become more frequent with advancing age.

Experts often treat psychologically based impotence using techniques that decrease anxiety associated with intercourse. The patient's partner can help apply the techniques, which include gradual development of intimacy and stimulation. Such techniques also can help relieve anxiety during treatment of physical impotence. If these simple behavioral methods at home are ineffective, a doctor may refer an individual to a sex counselor.
Another potential new treatment consists of penile low-intensity shock wave lithotripsy. This consists of 1500 shocks twice a week for 3–6 weeks. The purpose is to stimulate neovascularisation to the corporal bodies with improvement in penile blood flow and endothelial function. The use of low-intensity shock wave lithotripsy may convert PDE5 inhibitor non-responders to responders.47
Stress is your body responding to your environment. And it’s a good thing—in limited doses. When you get stressed out your body makes chemicals like adrenaline that make you stronger, faster, fitter, and even able to think more clearly. Most people call this reaction the “fight-or-flight” response, and it’s a life-saver in dangerous situations. In a very real sense, adrenaline makes you a part-time superhero. The problems happen when your body deals with constant stress.
When lifestyle changes alone don’t work, drug therapy (Viagra®, Cialis®, Levitra®, etc.) is normally the next step. Most of these medications work similarly to enhance a natural chemical in your body that relaxes the muscles in your penis. The goal of this medication is to increase your response to sexual stimulation by increasing the blood flow in your penis allowing you to get an erection.22
The prostaglandin E1 is contained in a small suppository located at the tip of an applicator. You should urinate first as this lubricates the urethra and makes it easier to insert the applicator into the tip of the urethra (urethral meatus, the opening at the tip of the penis that urine passes through). A patient can release the suppository into urethra by gently wiggling the applicator and pressing the button at the end. Rubbing the penis allows the suppository to dissolve, and the prostaglandin is absorbed through the tissue of the urethra into the penis. It takes 15 to 30 minutes for this occur. Once into the penis, the prostaglandin causes increased blood flow into the penis. The prostaglandin can be present in the ejaculate, and thus doctors recommend that men use a condom when having intercourse with a pregnant partner. Men may need to use a condom if vaginal irritation occurs in female partner.

The main surgical treatment of ED involves insertion of a penile implant (also called penile prostheses). Because penile vascular surgery is not recommended for aging males who have failed oral PDE5 inhibitors, ICI or IU therapies, implants are the next step for these patients. Although placement of a penile implant is a surgery which carries risks, they have the highest rates of success and satisfaction among ED treatment options.
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