All NOS subtypes produce NO, but each may play a different biologic role in various tissues. nNOS and eNOS are considered constitutive forms because they share biochemical features: They are calcium-dependent, they require calmodulin and reduced nicotinamide adenine dinucleotide phosphate for catalytic activity, and they are competitively inhibited by arginine derivatives. nNOS is involved in the regulation of neurotransmission, and eNOS is involved in the regulation of blood flow.
Hello everyone my name is john Scott,i was heartbroken because i had very small penis, not nice to satisfy a woman, i had so many relationship called off because of my situation, i have used so many product which i found online but none could offer me the help i searched for. i saw some few comments about this specialist called Dr Austin and decided to email him on DRaustinenlargementhome
In prescribing sildenafil, a doctor considers the age, general health status, and other medication(s) the patient is taking. The usual starting dose for most men is 50 mg, however, the doctor may increase or decrease the dose depending on side effects and effectiveness. The maximum recommended dose is 100 mg every 24 hours. However, many men will need 100 mg of sildenafil for optimal effectiveness, and some doctors are recommending 100 mg as the starting dose.

Erectile dysfunction, also known as ED or impotence, is the inability to attain or maintain an erection of the penis adequate for the sexual satisfaction of both partners. It can be devastating to the self-esteem of a man and of his partner. As many as 30 million American men are afflicted on a continuing basis, and transient episodes affect nearly all adult males. But nearly all men who seek treatment find some measure of relief.
This penile tumescence monitor is placed at the base and near the corona of the penis. It is connected to a monitor that records a continuous graph depicting the force and duration of erections that occur during sleep. The monitor is strapped to the leg. The nocturnal penile tumescence test is conducted on several nights to obtain an accurate indication of erections that normally occur during the alpha phase of sleep.
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
The availability of phosphodiesterase-5 (PDE5) inhibitors—sildenafil, vardenafil, tadalafil, and avanafil—has fundamentally altered the medical management of ED. In addition, direct-to-consumer marketing of these agents over the last 15 years has increased the general public’s awareness of ED as a medical condition with underlying causes and effective treatments.
ED exists in approximately 75% of men with SB and is dependent upon the level of the neurologic lesion (54). The level of the neurologic lesions usually corresponds to sensation and penile sensation indicates pudendal nerve signaling. With absent sacral reflexes ED is variable. Furthermore, Diamond et al. reported that 64% of men with lesions below T10 obtained erections versus 14% with a lesion above T10 (55). It has also been suggested that ED may be underreported due to lack of sexual education even in men without associated cognitive impairment (56).
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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]
Hormone deficiency or hypogonadism, whether primary or secondary, has been thought to impact erectile function. Approximately a third of men in the European Male Aging Study demonstrated low testosterone, suggesting that hypogonadism is overrepresented among men with ED.11 Hormone deficiency, however, is less frequently the cause of ED than diabetes or vascular disease. Many entities with a strong relationship to ED also diminish bioavailable testosterone, including obesity, diabetes, and opioid use. Other hormones involved in testosterone metabolism or availability, like thyroid stimulating hormone and gonadotropins, also may impact erectile quality, presumably through regulating bioavailable testosterone. Understanding the relationship between testosterone and ED has been impaired by a lack of standardized measurement of this hormone and the cyclic nature of its release and consumption.

Erectile dysfunction (ED) affects 50% of men older than 40 years, [4] exerting substantial effects on quality of life. [5] This common problem is complex and involves multiple pathways. Penile erections are produced by an integration of physiologic processes involving the central nervous, peripheral nervous, hormonal, and vascular systems. Any abnormality in these systems, whether from medication or disease, has a significant impact on the ability to develop and sustain an erection, ejaculate, and experience orgasm.


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
In their extensive review, Bassil and coworkers summarise the benefits and risks, with benefits such as improvement of sexual function, bone density, muscle strength, cognition and overall improvement in quality of life. Among the risks that have been suggested include erythrocytosis, liver toxicity, worsening of sleep apnoea and cardiac function, possibly increasing symptoms of benign prostatic hyperplasia (BPH). They also note that although a possibility of stimulation of prostate cancer has been hypothesised, no scientific or clinical evidence exists to this possible risk.38
The information shared on our websites is information developed solely from internal experts on the subject matter, including medical advisory boards, who have developed guidelines for our patient content. This material does not constitute medical advice. It is intended for informational purposes only. No one associated with the National Kidney Foundation will answer medical questions via e-mail. Please consult a physician for specific treatment recommendations.
Both ED and low testosterone (hypogonadism) increase with age. The incidence of the latter is 40% in men aged 45 years and older. [15] Testosterone is known to be important in mood, cognition, vitality, bone health, and muscle and fat composition. It also plays a key role in sexual dysfunction (eg, low libido, poor erection quality, ejaculatory or orgasmic dysfunction, reduced spontaneous erections, or reduced sexual activity). [16]
The physical examination can reveal clues for physical causes of erectile dysfunction. A doctor will perform an assessment of BMI and waist circumference to evaluate for abdominal obesity. A genital examination is part of the evaluation of erectile dysfunction. The examination will focus on the penis and testes. The doctor will ask you about penile curvature and will examine the penis to see if there are any plaques (hard areas) palpable. The doctor will examine the testes to make sure they are in the proper location in the scrotum and are normal in size. Small testicles, lack of facial hair, and enlarged breasts (gynecomastia) can point to hormonal problems such as hypogonadism with low testosterone levels. A health care provider may check pulses in your groin and feet to determine if there is a suggestion of hardening of the arteries that could also affect the arteries to the penis.
If PDE-5 inhibitors are not suitable or don’t work, other therapies include injections into the base of the penis, which cause flow of blood into the penis and a fairly immediate erection that lasts around an hour. The drugs injected are alprostadil (Caverject and Erectile dysfunctionex) and Invicorp (VIP and phentolamine). Alprostadil may also be inserted as a gel into the opening of the penis. This is not suitable if your partner is pregnant.
In 1983, Brindley injected the corpora of several SCI men with phentolamine (85). Two out of the three men had a sufficient erection produced. Since then multiple reports on the efficacy of intracavernosal therapy have been published using, phentolamine, papaverine, prostaglandin, vasoactive intestinal peptide (VIP), and these medications in combination (86-90). These medications have been found to be extremely effective for neurogenic ED due to their ability act locally and essentially bypassing neuronal pathways. Local therapies are usually considered second-line after PDE5i fail to elicit a desired response which can occur in about 25–30% of men with ED, in general (91). Furthermore, the locally delivered medications can be quite dangerous if not used appropriately as priapism and significant pain with injections can occur. These specific occurrences have been suggested as a reason for high discontinuation rates with intracavernosal therapy (92).
Modern drug therapy for ED made a significant advance in 1983, when British physiologist Giles Brindley dropped his trousers and demonstrated to a shocked Urodynamics Society audience his papaverine-induced erection.[35] The drug Brindley injected into his penis was a non-specific vasodilator, an alpha-blocking agent, and the mechanism of action was clearly corporal smooth muscle relaxation. The effect that Brindley discovered established the fundamentals for the later development of specific, safe, and orally effective drug therapies.[36][better source needed][37][better source needed]
Much of the emphasis on erectile pathophysiology has been placed on penile smooth muscle function and cavernosal hemodynamics. The neuroanatomy and neurophysiology of erection can be characterized but its full extent is poorly understood. Neurologic disease does not always reproducibly affect erections in a uniform manner compared to other types of sexual dysfunction (SD). This offers many obstacles to understanding the role the nervous systems plays in SD and consequently obscures what treatment options readily optimize erections specific to the neurologic insult.
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
The vascular processes that produce an erection are controlled by the nervous system and certain prescription medications may have the side effect of interfering with necessary nerve signals. Among the possible culprits are a variety of stimulants, sedatives, diuretics, antihistamines, and drugs to treat high blood pressure, cancer, or depression. But never stop a medication unless your doctor tells you to. In addition, alcohol, tobacco, and illegal drugs, such as marijuana, may contribute to the dysfunction.
Treatment depends on the underlying cause. In general, exercise, particularly of the aerobic type, is effective for preventing ED during midlife. Exercise as a treatment is under investigation.[22]:6, 18–19 For tobacco smokers, cessation often results in a significant improvement.[23] Oral pharmacotherapy and vacuum erection devices are first-line treatments,[22]:20, 24 followed by injections of drugs into the penis, as well as penile implants.[22]:25–26 Vascular reconstructive surgeries are beneficial in certain groups.[24]

Oral therapies via the PDE5i sildenafil, vardenafil, and tadalafil have been proven to be generally safe and effective in select NED populations. The majority of the treatment effectiveness data has been generated in the SCI population. Data regarding the use of PDE5i outside of the SCI population is lacking (58). Furthermore, the ED that exists in the population with neurologic disorders is often multifactorial and may be caused by psychogenic, psychosocial, hormonal, medication-related and disability-related factors. A careful evaluation of each patient must be performed to isolate these factors prior to initiating vasoactive therapy.

Medical conditions, such as hypertension, diabetes mellitus, and cardiovascular disease (CVD), and psychological conditions, such as depression and anxiety, also contribute to sexual dysfunction in middle-aged or elderly men. CVD and hypertension cause a narrowing and hardening of the arteries, leading to reduced blood flow to the corporal bodies, which is essential for achieving an erection. Diabetes is a common aetiology of sexual dysfunction, because it can affect both the blood vessels and the nerves that supply the penis. Men with diabetes are four times more likely to experience ED, and on average, experience ED 15 years earlier than men without diabetes.7 Obesity is also correlated to the development of several types of dysfunction, including a decrease in sex drive and an increase in episodes of ED.8
In one study, 9.6% reported ‘occasional’ erectile dysfunction, 8.9% reported erectile dysfunction occurring ‘often’, and 18.6% reported erectile dysfunction occurring ‘all the time’. Of these, only 11.6% had received treatment.In another study, only 14.1% of men reported that they had received treatment, despite experiencing erectile dysfunction for longer than 12 months.
It appears that testosterone has NOS-independent pathways as well. In one study, castrated rats were implanted with testosterone pellets and then divided into a group that received an NOS inhibitor (L-nitro-L-arginine methyl ester [L-NAME]) and a control group that received no enzyme. [24] The castrated rats that were given testosterone pellets and L-NAME still had partial erections, a result suggesting the presence of a pathway independent of NOS activity.
Penile prostheses are very effective, and most patients who have a prosthesis placed are satisfied with the prosthesis. However, placement of a prosthesis causes scarring of the tissue within the corpora cavernosa, and if the prosthesis requires removal, other forms of therapy, except for the vacuum device, are often not effective. Thus, most physicians reserve placement of a prosthesis for men who have tried and failed or have contraindications to other therapies.
Herbal supplements such as ginkgo biloba, saw palmetto, and yohimbe have been touted as sexual enhancers, and some men have been tempted to try them to treat erectile dysfunction. Bennett warns, however, that none has been approved by the FDA or even shown by any reliable studies to prevent, treat, or improve erectile dysfunction. Moreover, supplements are unregulated and can have many side effects or interfere with prescribed medications you’re already taking. Don’t jeopardize your health by taking a supplement to treat erectile dysfunction without first talking with your doctor.
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 first line and by far the most common treatment today is with the prescription drug sildenafil citrate, sold under the brand name Viagra. An estimated 20 million prescriptions for the pill have been filled since it was approved by the FDA in March 1998. It is also the most effective treatment with a success rate of more than 60%. The drug boosts levels of a substance called cyclic GMP, which is responsible for widening the blood vessels of the penis. In clinical studies, Viagra produced headaches in 16% of men who took it, and other side effects included flushing, indigestion, and stuffy nose.
Besides PDE5 inhibitors and among second-line therapies are VCDs which are clear plastic chambers placed over the penis, tightened against the lower abdomen with a mechanism to create a vacuum inside the chamber. This directs blood into the penis. If an adequate erection occurs inside the chamber, the patient slips a small constriction band off the end of the VCD and onto the base of the penis. An erection beyond 30 min is not recommended. These devices can be a bit cumbersome, but are very safe.40
Taking one of these tablets will not automatically produce an erection. Sexual stimulation is needed first to cause the release of nitric oxide from your penile nerves. These medications amplify that signal, allowing some men to function normally. Oral erectile dysfunction medications are not aphrodisiacs, will not cause excitement and are not needed in men who get normal erections.
A physical exam checks your total health. Examination focusing on your genitals (penis and testicles) is often done to check for ED. Based on your age and risk factors, the exam may also focus on your heart and blood system: heart, peripheral pulses and blood pressure. Based on your age and family history your doctor may do a rectal exam to check the prostate. These tests are not painful. Most patients do not need a lot of testing before starting treatment.
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