Crossref | PubMed | Google ScholarSee all References These hormonal findings were supported by a study of 1132 men aged 30 to 79 years that found an inverse relationship between blood pressure and serum testosterone levels.32x32Khaw, KT and Barrett-Connor, E. Blood pressure and endogenous testosterone in men: an inverse relationship. J Hypertens. 1988; 6: 329–332
The natural history of ED in people with diabetes is normally gradual and does not occur overnight. Both vascular and neurological mechanisms are most commonly involved in people with diabetes. Atherosclerosis in the penile and pudendal arteries limits the blood flow into the corpus cavernosum. Because of the loss of compliance in the cavernous trabeculae, the venous flow is also lost. This loss of flow results in the inability of the corpora cavernosae to expand and compress the outflow vessels.
Erection is a neurovascular event that involves spinal and supra spinal pathways. The final common pathway involves the release of nitric oxide (NO) from both endothelial cells and neurons, which acts as a vasodilator causing penile engorgement and erection. NO is degraded by the enzyme phosphodiesterase (PDE) type 5 in the penis. Erectile dysfunction (ED), defined as the persistent inability to achieve and/or maintain an erection sufficient for satisfactory sexual performance, results when the neurovascular pathway is interrupted by medical conditions or drugs. A 15-item self-administered questionnaire, the International Index of Erectile Function (IIEF), is one of the most useful tools to evaluate erectile function (EF) in clinical trials, although of much less use in routine clinical practice. The MMAS (Massachusetts Male Aging Study) was the first major epidemiological investigation to study the prevalence of ED. The study found that ED was three times more common in patients with diabetes mellitus. The aetiopathogenesis of ED in diabetes is multifactorial, with vascular and neural factors being equally implicated. Hyperglycaemia is believed to give rise to biochemical perturbations that lead to these microvascular changes. In the MMAS, ED in diabetes was strongly correlated with glycaemic control, duration of disease and diabetic complications. The incidence increased with increasing age, duration of diabetes and deteriorating metabolic control, and was higher in individuals with type 2 diabetes than those with type 1.ED in men with diabetes often affects their quality of life and, as patients are often reluctant to come forward with their symptoms, a carefully taken history is one of the most useful approaches in identifying affected individuals. The PDE inhibitors have revolutionised the management of ED and oral drug therapy is currently first-line therapy for the condition. These agents act by potentiating the action of intracavernosal NO, thereby leading to a more sustained erection. Sildenafil was the first PDE5 inhibitor to undergo evaluation and has been studied extensively. More recently two other agents, vardenafil and tadalafil, have been introduced. All the drugs have been shown to be effective across a wide range of aetiologies of ED, including diabetes. The drugs have been shown to improve EF domain scores, penetration and maintenance of erection, resulting in more successful intercourse. Their effects are greater at higher doses. Sildenafil and vardenafil are shorter-acting agents, while tadalafil has a longer half-life allowing the user more flexibility in sexual activity. Common adverse effects include headache, nasal congestion and dyspepsia, all actions related to inhibition of PDE5. The drugs are generally well tolerated and withdrawal from the clinical studies as a result of drug-related adverse effects were rare. The use of PDE5 inhibitors in the presence of oral nitrates is absolutely contraindicated. The clinical studies to date have not evaluated the use of one drug in the case of treatment failure with another agent. Sublingual apomorphine, which stimulates central neurogenic pathways, is a new agent and may be a suitable alternative in those patients in whom PDE5 inhibitors are ineffective or contraindicated. In clinical trials, all IIEF domains except sexual desire were found to have improved after apomorphine. The median times to erection in these studies were 18.9 and 18.8 minutes for the 2 and 3mg doses, respectively. Intraurethral and intracavernosal alprostadil may be a useful alternative when oral drug therapy is ineffective or contraindicated. The management of ED in the diabetic patient may often involve a multidisciplinary approach where psychosexual counselling and specialist urologist advice is required in addition to the skills and expertise of the diabetologist. Finally, the introduction of the new oral agents have completely revolutionised the management of ED and allowed more individuals to come forward for treatment.
The initial event for normal erectile function is sexual stimulation. Subsequent to processing in the central nervous system neural impulses are conveyed along the spinal cord, exiting through the pelvic parasympathetic preganglionic nerves. These pelvic nerves form the pelvic plexus and send their message through first messenger, acetyl choline, to the cavernosal nerves. The cavernosal nerves enter erectile bodies (corpora cavernosa) (Figure 1). Here, their nerve endings release a second messenger, nitric oxide. Nitric oxide activates the enzyme guanylyl cyclase, which lyses guanosine triphosphate (GTP) to produce a third messenger, the intracellular cyclic guanosine monophosphate (cGMP). Ultimately, the result is a decrease of intracellular calcium and an opening of potassium channels with the resultant relaxation of vascular smooth muscle in the arteries, aterioles, and sinusoids of the corpora cavernosa. The sinusoids open and rapidly fill with blood. Finally, the distended sinusoids compress their drainage pathways (venules) against the fibroelastic covering of the cavernosal bodies (tunica albuginea) and trap the blood in cavernosal bodies. The combination of an increased inflow of blood into the penis and coincident markedly diminished outflow results in rapidly increasing intracavernosal pressure that ultimately approximates systolic pressure. At this pressure the penis has sufficient axial rigidity to permit vaginal penetration.
While additional investigation is usually necessary, the medical and sexual history is essential and frequently the most revealing aspect of the ED assessment process. Questionnaires are an integral part of the history. The International Index of Erectile Function (IIEF), a 15-item, self-evaluation questionnaire is a validated instrument for assessing erectile function, orgasmic function, desire and satisfaction after sexual relations.8 An abridged version of the IIEF is a 5-item questionnaire the Sexual Health Inventory for Men (SHIM) or IIEF-5 (Table 2). Responses to the five questions range from 1 (worst) to 5 (best). Questions 2 to 4 may be graded 0 (if there is no sexual activity, or no sexual intercourse attempt) and the final score ranges from 1 to 25 points; a descending score indicates worsening of erectile function, with values ≤21 being diagnostic of ED.8 Importantly, validated questionnaires correlate with the extend of CAD9 and improve the predictive value of ED for total cardiovascular events compared with a single-question ED diagnosis.5 It cannot be overemphasized that the SHIM can be effectively used not only by andrologists and urologists but by a wide array of medical specialists, such as cardiologists, diabetologists, primary care physicians, etc.
There are no studies specifically assessing the effectiveness of intraurethral suppositories of prostaglandin E1 (PGE-1) in diabetic men. A single randomized clinical trial of the effectiveness of this agent in the general population of men with ED documented that 60% of those who tried this agent were able to achieve successful sexual intercourse.53 Unfortunately, in clinical practice, this agent appears to be considerably less effective.54
In particular, patients are classified into three categories (low, intermediate, high) depending on their CV risk profile. Individuals with controlled hypertension belong to the low-risk group where sexual dysfunction can be safely managed with the approved medical therapies regardless of the number or class (with the exception of b-blockers and diuretics) of agents of the patient’s antihypertensive regime. Moreover, patients of this group can safely initiate or reinstitute sexual activity without any need for additional cardiovascular evaluation.
Three longitudinal studies have estimated incidence rates of ED in men with diabetes. Unfortunately, none of these studies specifically examined men with type 2 disease. In a cohort of 278 diabetic men with type 1 or type 2 diabetes potent at study entry, the proportion of patients reporting ED at 5-year follow-up was 28%.7 A follow-up analysis of the Massachusetts Male Aging Study, a community-based cohort of men between 40 and 70 years of age, found that the incidence of ED in the diabetic men was 51/1,000 population-years.8 This figure was similar to the 68/1,000 person-years crude incidence rate of ED reported in a study of 1,010 men with diabetes.5 However, new studies need to be carried out in well-characterized populations of men with diabetes in order to better determine the incidence of ED and potential effects of interventions to reduce complications.
Luckily, awareness of ED as a significant and common complication of diabetes has increased in recent years, mainly because of increasing knowledge of male sexual function and the rapidly expanding armamentarium of novel treatments being developed for impotence. Studies of ED suggest that its prevalence in men with diabetes ranges from 35–75% versus 26% in general population. The onset of ED also occurs 10–15 years earlier in men with diabetes than it does in sex-matched counterparts without diabetes.
Erectile dysfunction usually precedes cardiovascular events by 3 to 5 years. Therefore, sexual function should be incorporated into cardiovascular disease risk assessment for all men. Recently, algorithms for the management of patients with erectile dysfunction according to the risk for sexual activity and future cardiovascular events were proposed. A comprehensive approach to cardiovascular risk reduction (comprising of both lifestyle changes and pharmacological treatment) will result in significant benefits on overall vascular health, including sexual function. Proper sexual counselling will exert beneficial effects on the quality of life of hypertensive patients with erectile dysfunction and will improve adherence to antihypertensive drug therapy.
Yohimbine: The main component of an African tree bark, yohimbine is probably one of the most problematic of all natural remedies for ED. Some research suggests that yohimbine can improve a type of sexual dysfunction that is linked with a drug used to treat depression. However, studies have linked yohimbine to a number of side effects, which can include anxiety, increased blood pressure, and a fast, irregular heartbeat. Like all natural remedies, yohimbine should only be used after advice and under supervision from a doctor.
Despite the existing controversies, available data so far imply the old generation b-blockers (e.g., propranolol) as the major culprits for sexual dysfunction with the newer ones (carvedilol, celiprolol) to exert a less pronounced negative effect[21-24]. A luminous exception to the rule, nebivolol, is a newer agent of its class which significantly ameliorates erectile dysfunction through increased nitric oxide generation, an effect consistently demonstrated in recent studies[25,26]. Diuretics, even on adjunct therapy, constitute another antihypertensive agent negatively associated with sexual function[27-29]. On the other hand, calcium antagonists and angiotensin converting enzyme inhibitors seem to demonstrate a neutral effect[30-32]. Interestingly, angiotensin receptor blockers (ARBs) by blocking the vasoconstrictive action of angiotensin II seem to positively affect erectile function and are thus regarded as a first-line treatment in hypertensive patients with erectile dysfunction[22,25,33-35].
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.
Considering the fact that CV disease presents with higher incidence in patients with erectile dysfunction while at the same time sexual activity by itself poses potential CV risks, the appropriate management of those complex conditions is of utmost importance. Accordingly, the working group of the third Princeton Consensus Conference developed practical guidelines and a simplified algorithm in order to manage sexual dysfunction and sexual activity implementation issues in patients with different levels of CV risk, including hypertensive patients.
To reduce the risk of side effects from these medications, including sexual problems, take medications exactly as prescribed. If you still have side effects, talk to your doctor about other possible medications that may have fewer side effects. On the other hand, you should not take any medication that promotes and erection while on medication to lower blood pressure.
• Blood Vessels: Diabetes damages blood vessels, especially the smallest blood vessels such as those in the penis. Diabetes can also cause heart disease and other circulatory problems. Proper blood flow is absolutely crucial to achieving erection. “Erection is a hydraulic phenomenon that occurs involuntarily,” says Arturo Rolla, MD, of Harvard University School of Medicine. “Nobody can will an erection!” Anything that limits or impairs blood flow can interfere with the ability to achieve an erection, no matter how strong one’s sexual desire.