3. Testosterone replacement. Before oral medications like Viagra, testosterone was routinely used to treat erectile dysfunction as it is central in the male sexual response, including the desire for sex and the process of getting an erection. Testosterone can be administered in a number of ways, for example orally, by means of an injection, skin patch, or subcutaneous (under the skin) pellet. 
ED can be caused by a handful of things, but one thing’s for sure: You need a healthy supply of the neurotransmitter nitric oxide (NO) to get and maintain an erection. NO is produced in nerve tissue and helps jolt your Johnson by relaxing the smooth muscle so blood can fill the penis. After the initial release of NO, your body releases a cascade of chemicals—including more of the neurotransmitter—to help keep you hard and happy, according to a study in the Proceedings of the National Academy of Sciences.
^Effects of Korean ginseng berry extract on sexual function in men with erectile dysfunction: a multicenter, placebo-controlled, double-blind clinical study. - Author: Department of Urology and Urological Science Institute, Yonsei University College of Medicine, Seoul, and R&D Center, Amorepacific Corporation, Gyeonggi-do, South Korea (20 Dec 2012)
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Dr. Niket Sonpal is the Associate Program Director of the Internal Medicine Residency at Brookdale Hospital Medical Center in Brooklyn and an Associate Professor at Touro College of Osteopathic Medicine. He's a practicing Gastroenterologist and Hepatologist with a focus on Men's and Women's Health, and a regular contributor to Women's health, Shape and Prevention Magazine.
There’s no bedroom bummer quite like having to fly at half mast, but your penis problems are likely more common than you think: As many as 30 million American men suffer from erectile dysfunction, and one in four who seek treatment for ED are actually under the age of 40, according to a study in The Journal of Sexual Medicine. We all know there’s a little blue pill that can fix the failure to launch—but you don’t necessarily have to fill a ‘script to save your stiffy.
Currently, there are four orally active drugs are available to treat ED. These include: sildenafil citrate (Viagra [Pfizer, USA]), vardenafil hydrochloride (Levitra [Bayer, Germany]), tadalafil (Cialis [Eli Lilly, USA]) and avanafil (Stendra, Spedra [Vivus Inc, USA]). These drugs inhibit the enzyme phosphodiesterase type 5 (PDE-5), which is responsible for the hydrolysis of cGMP. PDE-5 inhibitors and cGMP act as effectors of dilation of smooth muscle of cavernosal bodies. PDE-5 inhibitors are contraindicated in patients taking any kind of nitrate therapy for angina, and may not be appropriate for men with certain health conditions, such as severe heart disease, heart failure, history of stroke or heart attack, uncontrolled high blood pressure or diabetes, and patients with pigmental retinopathy. PDE-5 inhibitors are less effective in men with diabetes and men who have been treated for prostate cancer. PDE-5 inhibitors are also not effective in men with retinitis pigmentosa, a genetic disease involving PDE-5 deficiency. The common side effects of PDE-5 inhibitors include gastrointestinal upset, headache, nasal congestion, back pain and dizziness. The PDE-5 inhibitors may interact with other medications including antihypertension drugs. Nonetheless, the PDE-5 inhibitors are generally safe and effective for most men. The primary mechanism of action of these drugs is through the mediation of NO. NO is one of the key molecules involved in ED. It is a short-lived, highly permeable, pleiotropic, gaseous molecule, secreted from the postganglionic cavernosal parasympathetic nerves, endothelium of the cavernosal blood vessels, platelets in the cavernosal sinuses and phagocytic cells (monocytes, macrophages and neutrophils). NO acts on platelets to inhibit platelets adhesion and aggregation. NO causes relaxation of the smooth muscle of the cavernosal blood vessels of the penis, leading to vasodilation, tumescence and stimulation. Release of NO in the corpus cavernosum of the penis during stimulation activates the enzyme guanylate cyclase, which results in increased levels of cGMP, producing smooth muscle relaxation in the corpus cavernosum and resulting in increased blood flow (5). NO is mainly produced from cavernosal nerves, which are nonadrenergic, noncholinergic nerves within the penis, and acting via its second messenger cGMP. It has been suggested that maintaining normal body weight and mild exercise, as well as dietary supplementation of folic acid, zinc, calcium, vitamin C, vitamin E and L-arginine, a precursor of NO, can support the biochemical pathway leading to NO release [6]. NO is an effector molecule that is involved in a number of intracellular functions such as vasorelaxation, endothelial regeneration, inhibition of leukocyte chemotaxis and platelet adhesion [7]. A small proportion of autonomic nerves do not release either Ach or norepinephrine [8]. For example, the cavernous nerves predominantly release NO in the penis. The exact mechanism is not known, but it is believed to be through increased intracellular calcium. Another gaseous molecule produced in the corpora cavernosa is hydrogen sulphide (H2S), which is also known to be involved in erectile function [9]. H2S activates ATP-sensitive potassium channels in smooth muscle cells. Some reports indicate that NO acts in large vessels and H2S in small vessels. A high level of tumour necrosis factor-alpha has been shown in ED patients [10]. Although current ED therapies using PDE-5 inhibitors are safe and effective, approximately 40% of ED patients do not respond to currently available treatment [11,12]. For these patients, herbal therapy may be useful.
L-arginine, or arginine, is an amino acid found in red meat, poultry, fish, and dairy products that helps expand blood vessels and increase blood flow. “The body uses this semi-essential amino acid as the primary building block for nitric oxide,” explains Harry Fisch, M.D., clinical professor of urology and reproductive medicine at Weill Cornell Medical College/New York Presbyterian Hospital.
A study published in May 2014 in The Journal of Sexual Medicine found that some men can reverse erectile dysfunction with healthy lifestyle changes, such as exercise, weight loss, a varied diet, and good sleep. The Australian researchers also showed that even if erectile dysfunction medication is required, it's likely to be more effective if you implement these healthy lifestyle changes.
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