NO is produced by the enzyme NO synthase (NOS).  NOS plays many roles, ranging from homeostasis to immune system regulation. To date, 3 subtypes have been identified: nNOS, iNOS, and eNOS, which are produced by the genes NOS1, NOS2, and NOS3, respectively. This nomenclature is derived from the sources of the original isolates: neuronal tissue (nNOS), immunoactivated macrophage cell lines (iNOS), and vascular endothelium (eNOS). The subtypes are not, however, limited to the tissues from which they were first isolated.
Martha K Terris, MD, FACS is a member of the following medical societies: American Cancer Society, American College of Surgeons, American Institute of Ultrasound in Medicine, American Society of Clinical Oncology, American Urological Association, Association of Women Surgeons, New York Academy of Sciences, Society of Government Service Urologists, Society of University Urologists, Society of Urology Chairpersons and Program Directors, and Society of Women in Urology
With sex therapy, your counselor looks at the sexual problems you and your partner are having. Sex therapy works with problems such as performance anxiety, which means that you worry so much about whether you will be able to have sex that you are not able to. It also helps when you have erection problems that are not due to physical or drug problems, or premature ejaculation (you come too quickly). It may help you to reach orgasm or to learn to relax enough to avoid pain during sex. Counseling can help you to adjust to the treatment you and your doctor choose.
In a prospective study from the Prostate Cancer Prevention Trial database, Thompson et al reported that men presenting with ED had a significantly higher chance of developing a cardiovascular event over a 7-year follow-up period.  The hazard ratio was 1.45, which is in the range of risk associated with current smoking or a family history of MI.
Qaseem, A., Snow, V., Denberg, T. D., Casey, D. E., Forciea, M. A., Owens, D. K., & Shekelle, P. (2009). Hormonal testing and pharmacologic treatment of erectile dysfunction: A clinical practice guideline from the American College of Physicians. Annals of internal medicine, 151(9), 639-649. Retrieved from http://annals.org/aim/article/745155/hormonal-testing-pharmacologic-treatment-erectile-dysfunction-clinical-practice-guideline-from
Penis pumps produce erections by drawing blood, via air suction, into the penis. The devices consist of a cylindrical tube, 12 to 18 inches long, connected by a small air hose to a hand pump (on many models this resembles the squeeze mechanism on a blood pressure monitor). Users place the tube over the penis then pump to produce an erection. They must then place an elastic band around the base of the penis to keep the blood there and maintain the erection.
Before pursuing ED treatments, though, bear in mind that improving heart health by losing weight, eating a healthier diet, exercising more and quitting smoking typically enhances erectile performance as well as one’s overall health. In addition, sex therapy counseling sessions can often ease or eradicate ED symptoms, if the underlying cause is psychological in nature, says Drogo Montague, M.D., director of the Center for Genitourinary Reconstruction at the Cleveland Clinic.
Men with a rare heart condition known as long QT syndrome should not take vardenafil since this may lead to abnormal heart rhythms. The QT interval is the time it takes for the heart's muscle to recover after it has contracted and is measured on an electrocardiogram (EKG). In addition, vardenafil is not recommended for men taking medications that can affect the QT interval such as quinidine, procainamide, amiodarone, and sotalol.
…have traditionally been classified as impotence (inability of a man to achieve or maintain penile erection) and frigidity (inability of a woman to achieve arousal or orgasm during sexual intercourse). Because these terms—impotence and frigidity—have developed pejorative and misleading connotations, they are no longer used as scientific classifications, having been…
The American Urological Association Guideline on the Management of ED states oral PDE5i are considered first line therapy for the treatment of ED, unless contraindicated (57). Sildenafil, the first oral PDE5i, was introduced in 1998 and has revolutionized ED therapy due to its broad applicability, effectiveness and safety profile. PDE5i work by preventing hydrolysis of cGMP by the PDE5 enzyme in the smooth muscle of the corpora cavernosa. cGMP degradation typically leads to smooth muscle contraction and detumescence prevented by PDE5i administration. Two other PDE5i, vardenafil and tadalafil are other PDE5i with different pharmacokinetics, PDE receptor selectivity and side effect profiles.
A common and important cause of ED is vasculogenic. Many men with ED have comorbid conditions such as hyperlipidemia, hypercholesterolemia, tobacco abuse, diabetes mellitus, or coronary artery disease (CAD).  The Princeton III Consensus recommends screening men who present with ED for cardiovascular risk factors; ED may be the earliest presentation of atherosclerosis and vascular disease. 
Psychosocial problems are important and may cause erectile dysfunction by themselves or together with other causes of erectile dysfunction, such as diabetes and heart disease. Relationships are complicated and many factors cause tensions, which can affect sexual relations. For some men, these problems can become ongoing and it can help to talk through the issue with a skilled counsellor. It is important to know that the longer erectile dysfunction is left untreated, the greater the effect on relationships. This is another reason why early treatment of erectile dysfunction is important.
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.
Vardenafil and tadalafil belong to the same group of chemical compounds as sildenafil, namely phos-phodiesterase type 5 (PDE-5) inhibitors. Some men cannot benefit from sildenafil or the two newer PDE-5 inhibitors because they have low levels of nitric oxide. British investigators reported in late 2002 that three different types of compounds are being studied as possible medications for men with low levels of nitric oxide. They are Rho-kinase inhibitors, soluble guanylate cyclase activators, and nitric oxide-releasing PDE-5 inhibitors.
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
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
PDE5 inhibitors, the primary second-line therapy, have been the mainstay of ED treatment since the release of sildenafil (Viagra) in 1998, with the subsequent development of many others, and still more in the development stage. These medications do improve erectile quality for the majority of men, and they work by enhancing blood flow in the corpora cavernosa. These medications are generally used on demand and need to be taken about an hour before sexual intimacy. Tadalafil (Cialis) is longer acting and does come in a daily preparation potentially eliminating the ‘on-demand’ need. The daily dosing of tadalafil, 2.5–5 mg\day, has also been approved by the FDA for treatment of symptoms of BPH.41 PDE5 inhibitors are contraindicated in men taking nitrates, but otherwise PDE5 inhibitors are very safe and effective. When PDE5 inhibitors are coadministered with nitrates, pronounced systemic vasodilation and severe hypotension are possible. Many patients with ED are elderly and have the same risk factors as patients with CAD, so these drug combinations are commonly considered or encountered in clinical practice.42
Several medications can interfere with the chemical processing of PDE5i medications by the liver. These can include ketoconazole (an antifungal medication known by the brand name Nizoral), erythromycin (an antibiotic), and cimetidine (also known as Tagamet, for reducing stomach acid). A lower dose of PDE5i medications should be used if one is taking any of these medications.
If you can't take one of these oral medications, your physician may have you try Caverject (alprostadil for injection), a hormone that you inject into your penis using a fine needle, or Muse (alprostadil urogenital), a tiny suppository that you insert into the tip of the penis. Both of these will bring on an erection within five to 15 minutes without sexual stimulation.
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Some men say certain alternative medicines taken by mouth can help them get and maintain an erection. However, not all “natural” medicines or supplements are safe. Combinations of certain prescribed and alternative medicines could cause major health problems. To help ensure coordinated and safe care, discuss your use of alternative medicines, including use of vitamin and mineral supplements, with a health care professional. Also, never order a medicine online without talking with your doctor.
The most common treatment for erectile dysfunction is drugs known as phosphodiesterase-5 (PDE-5) inhibitors. These include tadalafil (Cialis), vardenafil (Levitra), and sildenafil citrate (Viagra). These are effective for about 75% of men with erectile dysfunction. They are tablets that are taken around an hour before sex, and last between 4 and 36 hours. Sexual stimulation is required before an erection will occur. The PDE-5 inhibitors cause dilation of blood vessels in the penis to allow erection to occur, and help it to stay rigid. Men using nitrate medication (e.g. GTN spray or sublingual tablets for angina) should not use PDE-5 inhibitors.
Nerve or spinal cord damage: Damage to the spinal cord and nerves in the pelvis can cause erectile dysfunction. Nerve damage can be due to disease, trauma, or surgical procedures. Examples include injury to the spinal cord from automobile accidents, injury to the pelvic nerves from prostate surgery for cancer (prostatectomy), and some surgeries for colorectal cancer, radiation to the prostate, surgery for benign prostatic enlargement, multiple sclerosis (a neurological disease with the potential to cause widespread damage to nerves), and long-term diabetes mellitus.
The penis is composed of three cylinders, two on the top and one on the underside of the penis. The top two cylinders are involved in the erectile process. The urethra, the tube that urine and semen pass through, is on the underside of the penis. The top two penile cylinders, the corpora cavernosa, are composed of tissue that is analogous to a sponge, containing spaces that can fill with blood and expand. These two cylinders are surrounding by a strong layer of tissue, like Saran wrap, the tunica albuginea. For an erection to occur, there must be properly functioning nerves, arteries, veins, and normal penile tissues.
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.
Infection is a concern after placement of a prosthesis and is a reported complication in 8%-20% of men undergoing placement of a penile prosthesis. If a prosthesis becomes infected (redness, pain, and swelling of the penis and sometimes purulent drainage are signs of infection), the prosthesis must be removed. Depending on the timing and severity of the infection and your surgeon's preference, the area can be irrigated extensively with antibiotic solutions and a new prosthesis placed at the same time or removal of the infected prosthesis and an attempt to place a new prosthesis made at a later time when the infection is totally cleared.
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 somatosensory pathways for erections originate in the penile skin, glans and urethra. Glans afferent sensory free nerve endings are 10-fold more than their corpuscular receptors, and are derived from Aδ and unmyelinated C fibers. The nerve endings coalesce to form the dorsal penile nerve along with other sensory nerve fibers. Through the pudendal nerve they enter the S2-4 nerve roots to terminate on spinal neurons and interneurons. The dorsal nerve is not purely somatic, however. Nerve bundles within the dorsal nerve contain nitric oxide (NO) synthase, found typically in autonomic nerves, and stimulation of the sympathetic chain can leak to evoked potentials from the dorsal nerve and vice versa (10-12).
Acupuncture may help treat psychological ED, though studies are limited and inconclusive. You’ll likely need several appointments before you begin to notice any improvements. When choosing an acupuncturist, look for a certified practitioner who uses disposable needles and follows U.S. Food and Drug Administration guidelines for needle disposal and sterilization.
The primary nerve fibers to the penis are from the dorsal nerve of the penis, a branch of the pudendal nerve. The cavernosal nerves are a part of the autonomic nervous system and incorporate both sympathetic and parasympathetic fibers. They travel posterolaterally along the prostate and enter the corpora cavernosa and corpus spongiosum to regulate blood flow during erection and detumescence. The dorsal somatic nerves are also branches of the pudendal nerves. They are primarily responsible for penile sensation. 
All of these medicines work by relaxing smooth muscles and increasing blood flow in the penis during sexual stimulation. You should not take any of these medicines to treat ED if you are taking nitrates to treat a heart condition. Nitrates widen and relax your blood vessels. The combination can lead to a sudden drop in blood pressure, which may cause you to become faint or dizzy, or fall, leading to possible injuries.
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
Can’t or don’t want to take ED drugs? The vacuum pump method is the next most common choice among men with erectile dysfunction who pass on pills, says Dr. Bennett. To create an erection, you place a plastic cylinder over the penis and pump the air out of the cylinder to force blood to flow into the penis. An elastic ring that you slide onto the base of your penis holds the erection. This ED treatment device is effective for about 75 percent of men. Side effects include numbness, bruising, and weak ejaculation — and the ring must be removed after 30 minutes.
En español | If you watch TV or read magazines, you could easily conclude that men seeking treatment for erectile dysfunction (ED) have but one option: pills. The three dominant brands — Cialis, Levitra and Viagra — are locked in an expensive battle for men’s allegiances, and have, through their suggestive advertising, triggered both satire and controversy in the 14 years since the Food and Drug Administration approved Viagra.
In later chapters, the book delves into the specific branch of Ayurveda known as Vajikarana. It holds such a powerful imagery in its meaning, “to be like a horse”. Ayurveda sustains balance in the body, mind and consciousness. Nutrition plays an important role and the author offers dietary suggestions and a handful of easily found herbs to complement the program.
3. An intact, anatomically correct penis; 25% of impotence may be psychologic or 'partner-specific', 25% has an organic component and 50% of impotence is organic in nature; in organic impotence, nocturnal penile tumescence is absent Management-surgical Microvascular surgery to bypass occluded vessels–most effective in younger ♂, penile prosthesis Management-medical Combined therapy with phentolamine and papaverine–self-injected by the Pt, wielding an erection of 1 hr's duration is useful for arterial, neurologic, psychogenic impotence; other therapies–zinc, bromocriptine–Parlodel, isoxsuprine-Vasodilan, Voxsuprine, nitroglycerine, yohimbine–Yocon, Yohimex Etiology Smoking, CAD, HTN, DM, medications–hypoglycemic agents, vasodilators, cardiac drugs, antihypertensives, anger and depression; it is inversely correlated to dehydroepiandrosterone, HDL-C, and an index of dominant personality Primary impotence Complete absence of successful sexual coupling Secondary impotence Priapism, penile plaques, Peyronie's disease; drugs linked to impotence: antihypertensives–eg, methyldopa, guanethidine, reserpine, clonidine, due to ↓ BP, antidepressants–eg, phenelzine, isocarboxazide, amitriptyline–causing altered moods and decreased libido, tranquilizers–eg, chlordiazepoxide and lorazepam, and the muscle-relaxing diazepam, cimetidine, which ↑ prolactin, and is associated with impotence and loss of libido. Cf Infertility, Orgasmic dysfunction.
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).
Penile implants - are generally used if physical damage (like an accident) makes the anatomical parts needed for an erection not work. These are inserted by surgery and can provide a permanent treatment choice if others fail to work. The implants can be semi-rigid or inflatable. They can be pretty expensive and are not usually available on the NHS.
Multiple combinations of intracavernosal therapy exist and the effectiveness of them varies based on patient characteristics and varying dosing strength (Table 1). Combination therapy have been extremely effective in the SCI population, and have several advantages including a reduction in cost per dose and side effects base on the lowered dose of each component (101,102). Effectiveness of combination therapy in the spinal cord population is well established, but no specific dose recommendations can be made based on the data (103-106). The use of combination therapy on other forms of neurogenic ED have not been well studied, but there use can be trialed as second-line therapy, or for populations were the side effects of PDE5i may preclude use such as in MSA due to hypotension.
The Food and Drug Administration (FDA) does not recommend alternative therapies to treat sexual dysfunction. Many products are advertised as "herbal viagra" or "natural" sexual enhancement products, but no clinical trials or scientific studies support the effectiveness of these products for the treatment of ED, and synthetic chemical compounds similar to sildenafil have been found as adulterants in many of these products. The FDA has warned consumers that any sexual enhancement product that claims to work as well as prescription products is likely to contain such a contaminant.
Erythrocytosis has been noted in men on TRT, and should be monitored every 6–12 months depending upon the patients’ response to changes in haematocrit levels. For mild elevations, the dosage of testosterone can be decreased or the interval of using the medication can be increased. With the haematocrit greater than 50%, decisions to temporarily discontinue the medication or periodic phlebotomy may be indicated.38
These are not currently approved by the FDA for ED management, but they may be offered through research studies (clinical trials). Patients who are interested should discuss the risks and benefits (informed consent) of each, as well as costs before starting any clinical trials. Most therapies not approved by the FDA are not covered by government or private insurance benefits.