Abstract | Full Text | Full Text PDF | PubMed | Scopus (272) | Google ScholarSee all References Most adverse effects are mild and are related primarily to vasodilation (headache, flushing, nasal congestion), gastrointestinal disturbances (dyspepsia), or retinal effects such as vision changes.10x10Kloner, RA and Zusman, RM. Cardiovascular effects of sildenafil citrate and recommendations for its use. Am J Cardiol. 1999; 84: 11N–17N
Diabetes mellitus is associated with both decreased erectile function and increased cardiovascular risk. The MMAS found that the age-adjusted probability of complete impotence was 3 times higher in patients with diabetes mellitus than in those without the disease.6x6Kloner, RA. Erectile dysfunction and cardiovascular risk factors. Hosp Pract (Off Ed). 2001; 36: 41–44 (49-51.)
When it comes to scientific development, in Western medicine, an analytic approach is often used to identify and resolve medical challenges. A hypothesis is first derived through general observations of a phenomenon. A research plan is then carefully designed and data collected. Once sufficient data is collected, critical statistical evaluations are done and conclusions are drawn (4). Every aspects of a disease entity are studied from macroscopic to microscopic views, down to the cellular and molecular levels. The deep understanding of the role of cGMP-specific phosphodiesterase type 5 enzymes in ED and the use of phosphodiesterase-5 inhibitors in treatment of ED exemplifies the success of this approach.
Quassinoids isolated from Tongkat Ali have been reputed to be anti-tumor, anti-malarial, anti-amoebic and anti-inflammatory. Its leaves are used for washing itches, its fruits for the treatment of dysentery, its bark used as a vermifuge, the taproots used for treatment of hypertension and the root bark for treatment of diarrhea and fever. The roots extracts are used for sexual dysfunction, aging, malaria, cancer, diabetes, anxiety, aches, constipation, exercise recovery, fever, increased energy, increased strength, leukemia, osteoporosis, stress and syphilis. Animal studies done on middle age sex rats showed enhancement of the sexual qualities in terms of hesitation time among middle aged rats (46).
Most importantly, herbal supplements are not well regulated in the United States.  Studies have shown that 40-50% of herbal supplements do not even contain the supposed main ingredient, and many contain substances that are not listed which may have dangerous side effects2.  Another study found that over two thirds of the products tested had substituted other plant species for the plants listed on the label, and a third of products also contained other fillers or contaminants3.  A study by the New York State Attorney General of herbal products sold at GNC, Target, Walgreens, and Walmart found that four out of every five products didn’t contain the ingredient they claimed!  Fourteen US states and territories have petitioned Congress to regulate the herbal supplements industry.
PubMed | Google ScholarSee all References In comparison, a study of 132 patients evaluated by penile duplex ultrasonography after intracorporeal papaverine injection found that hypertension alone was not an independent risk factor for vasculogenic ED.34x34Shabsigh, R, Fishman, IJ, Schum, C, and Dunn, JK. Cigarette smoking and other vascular risk factors in vasculogenic impotence. Urology. 1991; 38: 227–231

The diagnosis of ED in a patient may affect its management in two ways.30 The first relates to the fact that the ED patient, irrespective of whether he has or has not established CVD, is ‘reclassified’ into a higher risk category for future CV events. Management in this case is altered in the sense that more aggressive treatment of risk factors, as well as a close follow-up, is warranted. Implementation of biomarkers in this setting is desirable.
Abstract | Full Text | Full Text PDF | PubMed | Scopus (53) | Google ScholarSee all References Erectile dysfunction is a common physiological disorder. According to estimates from the National Institutes of Health, ED affects 10 million to 20 million men in the United States; another 10 million men are affected by partial ED, defined as present but diminished erectile function.2x2NIH Consensus Development Panel on Impotence. NIH Consensus Conference: impotence. JAMA. 1993; 270: 83–90
The second way relates to the risk associated with the sexual activity in a patient with either overt or occult CVD. In this case, the diagnosis of ED should prompt an initial cardiovascular assessment based on the history and clinical examination in order to define the baseline risk according to (i) the likelihood of silent CAD18,31 (especially since ED patients have a high probability to have silent CAD) or to the stage of clinically evident CAD, (ii) other cardiovascular conditions either unrelated, or related to ED (e.g. heart failure, peripheral arterial disease).
Yohimbine is an indole alkaloid derived from the bark of the African yohimbe tree (33). Yohimbine has been noted to treat fatigue, depression, diabetes, and sexual dysfunction. A meta-analysis of seven placebo-controlled trials (34) deemed yohimbine superior to placebo for the treatment of ED with rare adverse events. The proposed mechanism of action (35) is via the inhibition of central alpha-2-adrenergic receptors, decreasing central inhibition of arousal, and increasing penile nerve stimulation resulting in increased NO. Common side effects include headache, sweating, agitation, hypertension and insomnia. Contraindications include patients on tricyclic antidepressants, anti-hypertensives and central nervous system stimulants.

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.

PubMed | Google ScholarSee all References Unlike sildenafil, vardenafil has been associated with a slight prolongation of the QT interval and thus should not be used by patients with a congenital QT prolongation or by any patient currently taking antiarrhythmic medications.67x67Vardenafil (levitra) for erectile dysfunction. Med Lett Drugs Ther. 2003; 45: 77–78
The views expressed in this article intend to highlight alternative studies and induce conversation. They are the views of the author and do not necessarily represent the views of hims, and are for informational purposes only, even if and to the extent that this article features the advice of physicians and medical practitioners. This article is not, nor is it intended to be, a substitute for professional medical advice, diagnosis, or treatment, and should never be relied upon for specific medical advice.
When antihypertensive medication comes to the fore, certain issues need to be carefully addressed. This is due to the fact that medically induced erectile dysfunction is one of the major reasons for non-adherence and treatment discontinuation, a reality that could have deleterious consequences on patient’s cardiovascular profile and health quality in the long term[38,39].
Crossref | PubMed | Scopus (72) | Google ScholarSee all References This study found that the mean PSV was a better predictor of the presence of cardiovascular disease than stratification by standard cardiac risk factors such as diabetes mellitus, hypertension, obesity, and smoking. The researchers recommended that persons with no history of prior perineal trauma and with a PSV lower than 35 mL/s should undergo exercise testing before receiving treatment of ED because these patients had a 42% risk of having ischemic heart disease. However, other investigators questioned the utility of using penile arterial flow to predict the presence of ischemic heart disease.18x18Chiu, AW, Chen, KK, Chen, MT, Chang, LS, and Chang, MS. Penile brachial index in impotent patients with coronary artery disease. Eur Urol. 1991; 19: 213–216
Most of the time, ED is the first symptom of poor cardiovascular health. Hypertension oftentimes doesn’t manifest outward symptoms of heart disease.  Some men go undiagnosed with high blood pressure for a long time. It can be troublesome for many men who feel uncomfortable discussing ED with their health providers. Many fail to seek medical advice and suffer from progressive worsening of their cardiovascular problems before deciding to undergo treatment.

The third Princeton Consensus (Expert Panel) Conference recommends assessing cardiovascular risk in all patients with ED and CVD. This refers to estimating the risk of mortality and morbidity associated with sexual activity. The current recommendations classify patients into low-, intermediate- and high-risk, based on their New York Heart Association class.57 The consensus also recommended that all patients with ED and CVD should undergo lifestyle changes, such as exercise, smoking cessation, healthy diet and weight reduction. These measures are likely to reduce cardiovascular risk and improve erectile function.58


Crossref | PubMed | Scopus (47) | Google ScholarSee all References Because of this perceived increase in risk, many couples are concerned about resuming sexual activity in the setting of cardiac disease. A study that monitored male patients after coronary artery bypass grafting found that 17% of patients and 35% of their partners were afraid of resuming sexual activity.1x1Muller, JE. Sexual activity as a trigger for cardiovascular events: what is the risk?. Am J Cardiol. 1999; 84: 2N–5N
At the same time, people with diabetes are susceptible to a type of blood vessel damage known as endothelial dysfunction. A recent study found that men with ED are at a greater risk of heart disease, which is also associated with endothelial dysfunction. If blood vessels aren't in good working order, the penis may not get enough blood for an erection.

Crossref | PubMed | Scopus (697) | Google ScholarSee all References Subsequent in vitro electrical stimulation of these tissue samples showed decreased neurogenic and endothelium-dependent smooth muscle relaxation in the tissue from the patients with diabetes. These effects persisted even after controlling for smoking and hypertension. Other studies have shown a heightened smooth muscle tone in patients with diabetes mellitus.24x24Christ, GJ, Stone, B, and Melman, A. Age-dependent alterations in the efficacy of phenylephrine-induced contractions in vascular smooth muscle isolated from the corpus cavernosum of impotent men. Can J Physiol Pharmacol. 1991; 69: 909–913


Neurological (nerve and brain) diseases: The nervous system plays a vital part in achieving and maintaining an erection. It is common for men with conditions such as stroke, multiple sclerosis (MS), Alzheimer’s disease, Parkinson’s disease, and spinal cord injuries to experience ED. This is due to an interruption in the transmission of nerve impulses between the brain and the penis.
Figure. Progression of atherosclerosis. Endothelial dysfunction occurs early in atherosclerosis and prevents blood vessels from dilating properly. When the blood vessels that supply the penis are not able to dilate during sexual stimulation because of endothelial dysfunction, the penis cannot fill with blood, and the man develops erectile dysfunction. As atherosclerosis progresses, plaques build up in blood vessels and blood flow is slowed, further worsening erectile function. A heart attack occurs when an atherosclerotic plaque in a coronary artery ruptures, a blood clot forms over the plaque, and blood flow to the heart muscle is completely blocked. Atherosclerotic risk factors (black arrows) worsen cardiovascular health; modification of these risk factors (red arrows) improves cardiovascular health.
DHEA. Testosterone is essential for a healthy libido and normal sexual function, and erectile dysfunction sufferers known to have low testosterone improve when placed on prescription testosterone replacement therapy. Similarly, studies have shown that taking over-the-counter supplements containing DHEA, a hormone that the body converts to testosterone and estrogen, can help alleviate some cases of ED. But DHEA can cause problems, including suppression of pituitary function, acne, hair loss and its long-term safety is unknown, says McCullough. For this reason, many experts discourage use of the supplements.
Crossref | PubMed | Scopus (539) | Google ScholarSee all References The MMAS found the total prevalence of minimal to severe ED to be 52% and estimated that more than 617,000 new cases were expected to occur annually in the United States.4x4Feldman, HA, Goldstein, I, Hatzichristou, DG, Krane, RJ, and McKinlay, JB. Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study. J Urol. 1994; 151: 54–61
A medical history focused on risk factors, such as cigarette smoking, hypertension, alcoholism, drug abuse, trauma, and endocrine problems including hypothyroidism, low testosterone levels, and hyperprolactinemia, is very important. Commonly used drugs that disrupt male sexual function are spironolactone (Aldactone), sympathetic blockers such as clonidine (Catapres), guanethidine (Islemin), methyldopa (Aldomet), thiazide diuretics, most antidepressants, ketoconazole (Nizoral), cimetidine (Tagamet), alcohol, methadone, heroin, and cocaine. Finally, assessment of psychiatric history will help identify emotional issues such as interpersonal conflict, performance anxiety, depression, or anxiety.
A deficiency of L-arginine, however, does not generally disrupt nitric oxide synthesis because L-arginine availability is not the rate-limiting step in this process. In fact, research over the past five years has identified an endogenous (occurs in the body naturally) inhibitor called “asymmetric dimethylarginine” or ADMA, an amino acid which blocks the production of nitric oxide. By acting as an L-arginine mimic, this damaging look-alike effectively elbows out L-arginine and pushes it off to the side in the biochemical pathway leading to the synthesis of nitric oxide. ADMA is relatively elevated in patients with hypertension, high levels of cholesterol, triglycerides, homocysteine and low-density lipoprotein (LDL), and low levels of high-density lipoprotein (HDL), as well as with aging itself. This inhibitor of nitric oxide synthesis may very well be the common factor shared by all of these abnormal conditions. Increased levels of this detrimental inhibitor (ADMA) block nitric oxide production, leading to endothelial dysfunction.
Sexual dysfunction is a common, underappreciated complication of diabetes. Male sexual dysfunction among diabetic patients can include disorders of libido, ejaculatory problems, and erectile dysfunction (ED). All three forms of male dysfunction can cause significant bother for diabetic patients and can affect their quality of life. Despite this, health care providers often do not specifically ask their male diabetic patients about sexual function. This results in considerable underdiagnosis because patients are often reluctant or embarrassed to initiate discussion of these issues themselves. By not recognizing sexual dysfunction as a common organic sequel-lae of diabetes that should be addressed and treated, providers are missing an important opportunity to improve their patients' daily existence and quality of life.

Older age. A man’s risk increases past the age of 40, as age is the variable most strongly associated with impotence. This is due to changing hormones, higher risk for heart problems and those affecting circulation, and decreased sexual desire that often occurs with increasing age. For example, based on findings from the National Health and Social Life Survey, it’s been found that “men between 50–60 years old are more than 3 times as likely to experience erection problems and to report low sexual desire compared to men aged 18 to 29 years.” (3)
Erectile dysfunction (ED), or impotence, is when a man has difficulty getting or maintaining a strong enough erection for sexual intercourse or other sexual activity. It can be caused by stress, anxiety or excessive alcohol consumption. But it can also be a symptom of an underlying condition such as atherosclerosis (narrowing of the arteries), diabetes or high blood pressure. Some medications can cause erectile dysfunction, for example beta-blockers and diuretics (commonly used to treat a variety of heart-related conditions such as high blood pressure and heart failure).
While all three forms of male sexual dysfunction can be found among diabetic men, this review will focus on the most common form, ED, because the literature is most mature in this area. Defined as the inability to achieve or maintain an erection sufficient for satisfactory sexual performance, ED is highly prevalent in diabetic men1 and is almost always organic in its etiology. Given that many patients feel that their ED is “in their heads” and that “their provider will dismiss any sexual problems they might bring up,”2 it may be a relief for patients to learn that their ED is physical, related to their diabetes, and treatable. To this end, the goal of this article is to review the epidemiology, pathophysiology, quality of life effect, and treatment of ED in men with type 2 diabetes.
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The bottom line is that nearly all men with diabetes who wish to have an erection adequate for sexual intercourse can do so with the therapies currently available. And with commitment and communication, the experience of erectile dysfunction can be changed from a potential personal tragedy to an opportunity for greater emotional intimacy in a couple.
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