Abstract | Full Text | Full Text PDF | PubMed | Scopus (95) | Google ScholarSee all References Originally evaluated as a mild preload reducer and antianginal agent in its early phases of development, sildenafil's effect on male and female genitalia became quickly apparent.10x10Kloner, RA and Zusman, RM. Cardiovascular effects of sildenafil citrate and recommendations for its use. Am J Cardiol. 1999; 84: 11N–17N
Yohimbe. Before Viagra and the other prescription erectile dysfunction drugs became available, doctors sometimes prescribed a derivative of the herb yohimbe (yohimbine hydrochloride) to their patients suffering from ED. But experts say the medication is not particularly effective, and it can cause jitteriness and other problems. "It's not a great drug," says McCullough. "And I suspect the herb is not as potent as the pharmaceutical version." What's more, evidence shows that yohimbe is associated with high blood pressure, anxiety, headache, and other health problems. Experts discourage its use.
A cold slice of watermelon can do more than just satisfy thirst and hunger during the warm summer months; it can help with bedroom satisfaction. Citrulline, the amino acid found in high concentrations of watermelon, is found to improve blood flow to the penis. A 2011 study revealed men who suffered from mild to moderate ED and took L-citrulline supplementation showed an improvement with their erectile function and were very satisfied. Natural watermelon juice, or “nature’s Viagra,” can also be easier on the stomach, since taking pills like Viagra can cause nausea and diarrhea.

Yohimbe. Before Viagra and the other prescription erectile dysfunction drugs became available, doctors sometimes prescribed a derivative of the herb yohimbe (yohimbine hydrochloride) to their patients suffering from ED. But experts say the medication is not particularly effective, and it can cause jitteriness and other problems. "It's not a great drug," says McCullough. "And I suspect the herb is not as potent as the pharmaceutical version." What's more, evidence shows that yohimbe is associated with high blood pressure, anxiety, headache, and other health problems. Experts discourage its use.
The discovery in 1992 of the second messenger of cavernosal smooth muscle relaxation was the critical step that led to the era of nonhormonal oral drug therapy for ED. In 1998, the multicenter trial of sildenafil in the treatment of ED was published in the New England Journal of Medicine, and the era of the phosphodiesterase type 5 (PDE-5) inhibitor began.1 For 5 years, sildenafil was the primary therapy for men with EDDM. Recently, 2 new PDE-5 inhibitors, vardenafil and tadalafil, were introduced.
The bad news: Men with diabetes are three times more likely to report having problems with sex than non-diabetic men. The most common sexual problem is Erectile Dysfunction, or ED, sometimes called impotence. Even worse, because ED is such a private issue, many men feel embarrassed to discuss the problem with their doctor, or even their partner, so the problem is never addressed.
The pathophysiological basis for the predictive ability of ED has been discussed above. It should be emphasized, however, that ED should not only be viewed as a manifestation of obstructive CAD that could be identified by ischaemia revealing tests. Owing to the inflammatory and pro-thrombotic activation of the disease,13 it should also be regarded as an early warning sign of an imminent acute event (mainly acute myocardial infarction)22 due to the rupture of a subclinical plaque, and thus identification of the risk should ideally include plaque vulnerability tests. Finally, an issue that has important clinical implications is by how long the clinical manifestation of ED precedes the clinical manifestation of CAD. According to studies, men with ED and no cardiac symptoms have an increased incidence of experiencing a cardiac event, both acute and chronic, in the ensuing 2–5 years, thus providing a ‘window of opportunity’ for risk reduction management in these patients.2
Testosterone therapy (TTh) should be reserved for patients who (i) are symptomatic (ED or reduced libido) of testosterone deficiency45 and (ii) they have biochemical evidence of low testosterone (TT <8 nmol/L or 2.3 ng/mL). In men with borderline TT (8–12 nmol/L or 2.3–3.5 ng/mL), a TTh trial (for 3–6 months and continuation if effective) may be envisaged. While adding a PDE5 inhibitor can be considered in men who have not improved with TTh, the usual clinical scenario is to add TTh in patients who have not responded to PDE5 inhibitors. Improvement is dependent on the testosterone levels with better results being obtained at lower levels of TT.45 Despite evidence of benefit in patients with pre-existing cardiovascular conditions (angina or heart failure), it should be emphasized that TTh is not a medication with cardiovascular indications.
Abstract | Full Text | Full Text PDF | PubMed | Scopus (30) | Google ScholarSee all References Increased cGMP levels cause intracellular calcium levels to decrease, resulting in relaxation of the corporeal smooth muscle, active dilatation of the penile arteries, arterioles, and sinusoids, and finally, increased arterial inflow and passive compression of penile venous outflow.10x10Kloner, RA and Zusman, RM. Cardiovascular effects of sildenafil citrate and recommendations for its use. Am J Cardiol. 1999; 84: 11N–17N
Low intracavernosal nitric oxide synthase levels are found in people with diabetes, smokers, and men with testosterone deficiency. Interference with oxygen delivery or nitric oxide synthesis can prevent intracavernosal blood pressure from rising to a level sufficient to impede emissary vein outflow, leading to an inability to acquire or sustain rigid erection. Examples include decreased blood flow and inadequate intracavernosal oxygen levels when atherosclerosis involves the hypogastric artery or other feeder vessels and conditions, such as diabetes, that are associated with suboptimal nitric oxide synthase activity.
In men without cardiovascular disease, erectile dysfunction (ED) pills are very safe. The three rivals -- Viagra, Cialis, and Levitra -- have similar side effects, including headache, facial flushing, nasal congestion, diarrhea, backache, and, in a few Viagra or Levitra users, temporary impaired color vision (men with retinitis pigmentosa, a rare eye disease, should check with their ophthalmologists before using these medications).
Abstract | Full Text | Full Text PDF | PubMed | Scopus (37) | Google ScholarSee all References It has been postulated that regular exercise can decrease or possibly eliminate the small risk of myocardial infarction associated with sexual intercourse in most patients.8x8Muller, JE, Mittleman, A, Maclure, M, Sherwood, JB, Tofler, GH, and Determinants of Myocardial Infarction Onset Study Investigators. Triggering myocardial infarction by sexual activity: low absolute risk and prevention by regular physical exertion. JAMA. 1996; 275: 1405–1409
Prescription drugs called “oral phosphodiesterase-5 (PDE5) inhibitors” are considered the “first-line non-invasive treatment” options for patients with ED. These include the drugs that go by brand names: Sildenafil, Vardenafil or Tadalafil. They work by helping the smooth muscle cells lining the blood vessels that supply the penis with blood to work properly. This allows a man to maintain an erection more easily.
Heart disease describes a range of conditions that affect your heart. Diseases under the heart disease umbrella include blood vessel diseases, such as coronary artery disease; heart rhythm problems (arrhythmias); and heart defects you’re born with (congenital heart defects), among others.The term “heart disease” is often used interchangeably with the term “cardiovascular disease.” Cardiovascular disease generally refers to conditions that involve narrowed or blocked blood vessels that can lead to a heart attack, chest pain (angina) or stroke. Other heart conditions such as those that affect your heart’s muscle, valves or rhythm, also are considered forms of heart disease.
This form of therapy has a response rate of well over 70%. The sympathetic nervous system normally maintains the penis in a flaccid or non-erect state. All of the vasoactive drugs, when injected into the corpora cavernosae, inhibit or override sympathetic inhibition to encourage relaxation of the smooth muscle trabeculae. The rush of blood engorges the penile corpora cavernosae sinusoidal spaces and creates an erection.
The term “heart disease” is often used interchangeably with the term “cardiovascular disease.” Cardiovascular disease generally refers to conditions that involve narrowed or blocked blood vessels that can lead to a heart attack, chest pain (angina) or stroke. Other heart conditions, such as those that affect your heart’s muscle, valves or rhythm, also are considered forms of heart disease.
Crossref | PubMed | Scopus (171) | Google ScholarSee all References Incidence increased notably with age in this patient cohort: only 1.1% of diabetic men aged 21 to 30 years had ED compared with 47.1% of all diabetic patients older than 43 years. Diabetic patients often have other cardiovascular risk factors that may play a role in the development of ED. However, in an analysis of the PBI in 441 patients with ED and various cardiovascular risk factors (diabetes mellitus, hypertension, hyperlipidemia, tobacco use), diabetes was the only risk factor that was significantly and independently associated with a decrease in the PBI.7x7Virag, R, Bouilly, P, and Frydman, D. Is impotence an arterial disorder? a study of arterial risk factors in 440 impotent men. Lancet. 1985; 1: 181–184
Abstract | Full Text | Full Text PDF | PubMed | Scopus (37) | Google ScholarSee all References It has been postulated that regular exercise can decrease or possibly eliminate the small risk of myocardial infarction associated with sexual intercourse in most patients.8x8Muller, JE, Mittleman, A, Maclure, M, Sherwood, JB, Tofler, GH, and Determinants of Myocardial Infarction Onset Study Investigators. Triggering myocardial infarction by sexual activity: low absolute risk and prevention by regular physical exertion. JAMA. 1996; 275: 1405–1409
80. Montorsi F, Briganti A, Salonia A, Rigatti P, Margonato A, Macchi A, Galli S, Ravagnani PM, Montorsi P. Erectile dysfunction prevalence, time of onset and association with risk factors in 300 consecutive patients with acute chest pain and angiographically documented coronary artery disease. Eur Urol. 2003;44:360–364; discussion 364-365. [PubMed]
Following the breakthrough in ED treatment using PDE5-inhibitors, Western medicine has now moved on to a new frontier of regenerative medicine, with stem cell and gene therapy leading the way (25). There is a practical need for novel therapy as a significant portion of diabetic or post-prostatectomy ED patients do not respond to oral pharmacotherapy. To date, stem cells derived from different sites including adipose tissue-derived stem cells, bone marrow mesenchymal stem cells and muscle-derived stem cells have been investigated using animal models for ED, to study their effects on neural, vascular, endothelial or smooth muscle regeneration (25,26).
Since 1998, when sildenafil (brand name Viagra) first came on the market, oral therapy has been successfully used to treat erectile dysfunction in many men with diabetes. (Sildenafil was followed in 2003 by the drugs tadalafil [Cialis], vardenafil [Levitra] and avanafil [Stendra], which work in much the same way.) Some 50% of men with Type 1 diabetes who try the drugs report improved erections, and some 60% men with Type 2 diabetes do, too. However, that leaves a large percentage of men with diabetes and erectile dysfunction who do not respond to therapy with one of these pills. This article takes a look at what can be done to treat those men who do not respond to oral therapy.
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