Centrally active compounds such as apomorphine have been used in men with ED whose cardiovascular comorbidity may prohibit PDE5i use, or in men who have concurrent apomorphine use for its anti-parkinsonian properties. Unfortunately, its side effect profile and poor effectiveness compared to other ED treatments have impaired its mainstream utilization (118). It is suspected that the side effects of apomorphine relate to its D2 receptor affinity. D4 receptor agonists, such as ABT-724 and azulenylmethylpiperazines, may not have the same associated side effects and show potent pro-erectile effects in animal models compared to apomorphine (32,119).
These oral medications reversibly inhibit penile-specific PDE5 and enhance the nitric oxide–cGMP pathways of cavernous smooth muscle relaxation; that is, all prevent the breakdown of cGMP by PDE5. It is important to emphasize to patients that these drugs augment the body’s natural erectile mechanisms, therefore the neural and psychoemotional stimuli typically needed for arousal still need to be activated for the drugs to be efficacious.
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Common medical conditions such as diabetes, heart disease, and high blood pressure are associated with an increased risk of developing erectile dysfunction. Thus, optimal management of these diseases may help prevent the development or progression of erectile dysfunction. Lifestyle modifications to improve vascular function, including smoking cessation, losing weight if overweight, and exercising regularly, may be helpful.

An analysis of 14 studies involving more than 90,000 patients with ED confirmed the relation between ED and an increased risk of cardiovascular events and mortality. [56] Compared with patients without ED, those with ED had a 44% increased risk of cardiovascular events, a 25% increased risk of all-cause mortality, a 62% increased risk of MI, and a 39% increased risk of cerebrovascular events. Treatment of ED, either through lifestyle interventions or by pharmacologic means, may improve prognosis and reduce risk.

Several pathways have been described to explain how information travels from the hypothalamus to the sacral autonomic centers. One pathway travels from the dorsomedial hypothalamus through the dorsal and central gray matter, descends to the locus ceruleus, and projects ventrally in the mesencephalic reticular formation. Input from the brain is conveyed through the dorsal spinal columns to the thoracolumbar and sacral autonomic nuclei.
The nerves and endothelium of sinusoids and vessels in the penis produce and release transmitters and modulators that control the contractile state of corporal smooth muscles. Although the membrane receptors play an important role, downstream signaling pathways are also important. The RhoA–Rho kinase pathway is involved in the regulation of cavernosal smooth muscle contraction. [12]
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).

Erectile problems can happen to men of any age.  There are many factors that contribute to ED including poor health, untreated medical problems, medications and pornography use.  Many men struggle with understanding when they are experiencing situational sexual dysfunction verses when is your erectile issue an ongoing problem that requires medical help.
Many reasonable nonsurgical erectile dysfunction (impotence) treatment options exist, including external vacuum devices, medications (oral and topical), hormonal therapy, penile injection therapy, and intraurethral pellet therapy. Sex counseling to further improve one's sexual health and sex life is another option and is discussed in Living With Erectile Dysfunction.

An occasional problem achieving an erection is nothing to worry about. But failure to do so more than 50% of the time at any age may indicate a condition that needs treatment. About 40% of men in their 40s report at least occasional problems getting and maintaining erections. So do more than half (52%) of men aged 40 to 70, and about 70% of men in their 70s.

Dr. Shiel received a Bachelor of Science degree with honors from the University of Notre Dame. There he was involved in research in radiation biology and received the Huisking Scholarship. After graduating from St. Louis University School of Medicine, he completed his Internal Medicine residency and Rheumatology fellowship at the University of California, Irvine. He is board-certified in Internal Medicine and Rheumatology.
Penile injection therapy, intracavernous injection, involves the injection of a vasodilator (a chemical that relaxes arteries to increase blood flow) into the penis. Penile injected therapy is recognized as the most effective nonsurgical treatment for erectile dysfunction. However, due to the invasive nature, it is often used in men who have failed or have contraindications to other treatments such as oral therapies.
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).
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

As with most other organ system in the human body, changes and loss of function is normal consequence of the ageing process. This is also true of the endocrine system, specifically the levels of testosterone production from the Leydig cells of the testicle. Accompanying the decrease in testosterone is a decrease in erections which also has a component in decrease in the blood supply to the penis making erection not as frequent and not as rigid compared with a young man’s erectile function. Although these changes are in itself not life threatening, they can impact a man’s relationship with his partner, and also ED may be a harbinger of other undiagnosed conditions such as coronary artery disease (CAD), hypercholesterolaemia or diabetes mellitus.6
"Medications that create blood flow to the penis can't help when an erection is blocked by the fear or anxiety of the fight-or-flight response,” says Feloney. “This type of erectile dysfunction probably has a lot to do with evolution — men didn't need an erection when a dinosaur was chasing them." The best way to treat erectile dysfunction caused by performance anxiety, depression, a poor relationship, or stress may be with a combination of ED drug treatment and sex therapy, individual therapy, or couples therapy from sexual health professionals.
Another tip is to make sure you communicate with your partner what you like during the process of sex.  Many men are not communicative about what really turns them on.  If you are not aroused by what is going on, then you might experience ED.  Make sure you tell your partner what turns you on.  Communicating about intimacy should also lead to feeling more connected with your partner aiding in relaxing when you are sexual together.
As men age they require more stimulation up front to get and maintain an erection firm enough for sex.  Engaging in some foreplay either on you or on your partner is a great way to get your arousal levels up and get an erection that is firm enough for sex.  Many men begin to rush the process of sex once they experience ED.  They worry that they will lose their erection so they rush rather than go slow understanding that rushing will only make the problem worse.
Physicians on the Ro platform use telemedicine technologies to diagnose ED in the same way they diagnose patients in-person. Doctors ask questions to evaluate your symptoms and make sure it’s safe and appropriate to prescribe ED medication. The physicians on the Ro platform use your answers to diagnose your condition and create a treatment plan. That’s why it’s vital you answer each question to the best of your knowledge and ensure that every communication with your physician is truthful, accurate, and thorough.
Erectile dysfunction (ED) is the inability to get and keep an erection firm enough for sexual intercourse. Estimates suggest that one of every 10 men will suffer from ED at some point during his lifetime. It is important to understand that in most cases, ED is a symptom of another, underlying problem. ED is not considered normal at any age, and may be associated with other problems that interfere with sexual intercourse, such as lack of desire and problems with orgasm and ejaculation.
A meta-analysis of 36 744 men with ED in 12 prospective cohort studies found that the presence of ED significantly increased the risk of CVD, CAD, stroke and all-cause mortality, and the presence of ED was an independent risk factor for CVD. Ponholzer et al found that men with moderate to severe ED had a 65% increased relative risk for developing symptomatic CAD compared with men who did not have ED.26
Oral ED medication is considered highly effective and studies show it works on the majority of men. But no medication works for everyone and ED medication is no exception. Everyone’s reaction to a medication is unique and anything potent enough to help is strong enough to have side effects. If the medication isn’t working, it is important to tell your doctor. Sometimes it is a matter of needing a higher dose. Also, it has been shown that it takes 6 to 8 tries using the medication to experience the best result.
ED usually has something physical behind it, particularly in older men. But psychological factors can be a factor in many cases of ED. Experts say stress, depression, poor self-esteem, and performance anxiety can short-circuit the process that leads to an erection. These factors can also make the problem worse in men whose ED stems from something physical.
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