Ageing men's sexual functions decline and the erectile dysfunction (ED) increase

Association between ageing men's progressive falling of circulating androgen levels and ED is not clearly demonstrated. The analysis of all what have been written about this subject clearly proves that an androgenomodulation of erectile function exists. Indeed, the androgens seem to have an action on penile tissue innervation, on the structure and function of penile trabecular smooth muscle, on the penile endothelial function, as well as on the fibroelastic properties of the penile corpus cavernous. The addition of testosterone improves a great number of androgen deficiency in the aging male (ADAM). Recent studies demonstrated that all hypogonadal patients cannot successfully benefit of phosphodiesterase type 5 (PDE5) inhibitors. With these patients, the prescription of testosterone replacement therapy may improve the response of PDE5 inhibitors.

Male reproductive health--what is the GP's role?

BACKGROUND: Male reproductive health issues cause considerable morbidity, as well as mortality, in our community. Although 'women's health' has been a separate and important subject of medical interest for many years, it is only recently that the study of male health, andrology, has gained impetus as an area of research and clinical importance. OBJECTIVE: This article outlines the current issues and recent advances in men's reproductive health. DISCUSSION: Despite publicity in the popular press about erectile dysfunction it remains an under treated, treatable condition, with close association with increased cardiovascular risk. The advent of intracytoplasmic sperm injection has significantly improved the management of male infertility. Testicular cancer now has an excellent prognosis and, while screening for prostate cancer remains a controversial area, prostate cancer mortality appears to be declining. As general practitioners we need to keep abreast of developments in male reproductive health, know how to sensitively question our male patients about their concerns and to deal effectively with the answers we receive.

Diabetic autonomic neuropathy.

Diabetic autonomic neuropathy (DAN) is a serious and common complication of diabetes. Despite its relationship to an increased risk of cardiovascular mortality and its association with multiple symptoms and impairments, the significance of DAN has not been fully appreciated. The reported prevalence of DAN varies widely depending on the cohort studied and the methods of assessment. In randomly selected cohorts of asymptomatic individuals with diabetes, approximately 20% had abnormal cardiovascular autonomic function. DAN frequently coexists with other peripheral neuropathies and other diabetic complications, but DAN may be isolated, frequently preceding the detection of other complications. Major clinical manifestations of DAN include resting tachycardia, exercise intolerance, orthostatic hypotension, constipation, gastroparesis, erectile dysfunction, sudomotor dysfunction, impaired neurovascular function, "brittle diabetes," and hypoglycemic autonomic failure. DAN may affect many organ systems throughout the body (e.g., gastrointestinal [GI], genitourinary, and cardiovascular). GI disturbances (e.g., esophageal enteropathy, gastroparesis, constipation, diarrhea, and fecal incontinence) are common, and any section of the GI tract may be affected. Gastroparesis should be suspected in individuals with erratic glucose control. Upper-GI symptoms should lead to consideration of all possible causes, including autonomic dysfunction. Whereas a radiographic gastric emptying study can definitively establish the diagnosis of gastroparesis, a reasonable approach is to exclude autonomic dysfunction and other known causes of these upper-GI symptoms. Constipation is the most common lower-GI symptom but can alternate with episodes of diarrhea. Diagnostic approaches should rule out autonomic dysfunction and the well-known causes such as neoplasia. Occasionally, anorectal manometry and other specialized tests typically performed by the gastroenterologist may be helpful. DAN is also associated with genitourinary tract disturbances including bladder and/or sexual dysfunction. Evaluation of bladder dysfunction should be performed for individuals with diabetes who have recurrent urinary tract infections, pyelonephritis, incontinence, or a palpable bladder. Specialized assessment of bladder dysfunction will typically be performed by a urologist. In men, DAN may cause loss of penile erection and/or retrograde ejaculation. A complete workup for erectile dysfunction in men should include history (medical and sexual); psychological evaluation; hormone levels; measurement of nocturnal penile tumescence; tests to assess penile, pelvic, and spinal nerve function; cardiovascular autonomic function tests; and measurement of penile and brachial blood pressure. Neurovascular dysfunction resulting from DAN contributes to a wide spectrum of clinical disorders including erectile dysfunction, loss of skin integrity, and abnormal vascular reflexes. Disruption of microvascular skin blood flow and sudomotor function may be among the earliest manifestations of DAN and lead to dry skin, loss of sweating, and the development of fissures and cracks that allow microorganisms to enter. These changes ultimately contribute to the development of ulcers, gangrene, and limb loss. Various aspects of neurovascular function can be evaluated with specialized tests, but generally these have not been well standardized and have limited clinical utility. Cardiovascular autonomic neuropathy (CAN) is the most studied and clinically important form of DAN. Meta-analyses of published data demonstrate that reduced cardiovascular autonomic function as measured by heart rate variability (HRV) is strongly (i.e., relative risk is doubled) associated with an increased risk of silent myocardial ischemia and mortality. The determination of the presence of CAN is usually based on a battery of autonomic function tests rather than just on one test. Proceedings from a consensus conference in 1992 recommended that three tests (R-R variation, Valsalva maneuver, and postural blood pressure testing)or longitudinal testing of the cardiovascular autonomic system. Other forms of autonomic neuropathy can be evaluated with specialized tests, but these are less standardized and less available than commonly used tests of cardiovascular autonomic function, which quantify loss of HRV. Interpretability of serial HRV testing requires accurate, precise, and reproducible procedures that use established physiological maneuvers. The battery of three recommended tests for assessing CAN is readily performed in the average clinic, hospital, or diagnostic center with the use of available technology. Measurement of HRV at the time of diagnosis of type 2 diabetes and within 5 years after diagnosis of type 1 diabetes (unless an individual has symptoms suggestive of autonomic dysfunction earlier) serves to establish a baseline, with which 1-year interval tests can be compared. Regular HRV testing provides early detection and thereby promotes timely diagnostic and therapeutic interventions. HRV testing may also facilitate differential diagnosis and the attribution of symptoms (e.g., erectile dysfunction, dyspepsia, and dizziness) to autonomic dysfunction. Finally, knowledge of early autonomic dysfunction can encourage patient and physician to improve metabolic control and to use therapies such as ACE inhibitors and beta-blockers, proven to be effective for patients with CAN.

Combination therapy in benign prostatic hyperplasia (BPH)

Because of the constant progress in our understanding of the physiopathology of benign prostatic hyperplasia, it is now possible to propose a more rational use of combination therapy, which is often used empirically, though not recommended, in routine practice. This chronic disorder, which is in fact more complex than it appears, may benefit in theory from a combination of molecules with different complementary action mechanisms. Prostatic obstruction may be treated either by alphablockers with their peripheral muscle-relaxant action on the smooth muscle fibers of the prostate and bladder neck, or by 5-alpha-reductase inhibitors for their reducing effect on gland volume. Irritative bladder symptoms involving the detrusor may be treated by antimuscarinics and to a lesser extent by alphablockers. Currently available data from recent studies suggest that a combination of an alphablocker and a 5-alpha-reductase inhibitor may be useful in patients with symptomatic BPH and a prostate of more than 40 grams with PSA > 1.6 ng/ml. Combinations including an antimuscarinic are effective in patients with BPH with marked irritative symptoms. Finally, the combination of an alphablocker and a phosphodiesterase type 5 inhibitor may be useful in patients with lower urinary tract symptoms (LUTS) associated with erectile dysfunction. erectile dysfunction Central mechanisms of erectile dysfunction: what a clinician may want to know.

The interplay between peripheral and central mechanisms of erectile function are not fully elucidated although basic science is moving ahead in this area. It is important from a clinical point of view to understand these mechanisms so that we may begin to make further therapeutic advances in the treatment of erectile dysfunction (ED). It is now widely understood that central disinhibition plays a crucial role in the induction of erectile responses and this has led to the development of the central initiator, apomorphine SL (Ixense ) [apo SL]. Apo SL acts in the paraventricular nucleus of the hypothalamus as a dopamine receptor agonist. It works as a proerectile conditioner at this level to increase the responses of the erectile pathway following appropriate sexual stimulation. This unique central mode of action of apo SL has thus proved efficacious in approximately 70% of ED patients although persistence may be required to produce a robust effect for the maximum number of patients.

The urological management of the patient with acquired immunodeficiency syndrome.

In people infected with the human immunodeficiency virus (HIV) both the CD4 T-cell count and the viral load are used to monitor disease progression to acquired immunodeficiency syndrome (AIDS). CD4 counts of <500/mm(3) are associated with opportunistic infections and certain malignancies, so-called 'AIDS-defining' conditions. Highly active antiretroviral therapy, using combinations of reverse transcriptase inhibitors and/or protease inhibitors, can improve considerably the prognosis of people who are HIV-positive, but such therapy is not yet widely available in many developing countries. People with AIDS are predisposed to urinary tract infection (UTI) by uncommon bacteria and pathogens, e.g. fungi, parasites and viruses, which may affect any urogenital organ; treatment should be culture-specific and long-term, because there is a tendency to recurrence, infection with multiple organisms and resistant isolates. Voiding dysfunction in patients with AIDS is usually a result of neurological complications caused by opportunistic infections, and has a poor prognosis. Of patients with AIDS, 30-50% develop a cancer, especially Kaposi's sarcoma (KS) and non-Hodgkin's lymphoma (NHL). KS may involve any urogenital organ, but is usually part of systemic disease. Small lesions on the external genitalia can be treated with laser, cryotherapy or surgical excision, larger lesions with radiotherapy, and disseminated or visceral KS with multidrug chemotherapy. NHL may involve the kidneys, testes and retroperitoneal lymph nodes, thus obstructing the ureters, which may require ureteric stenting or percutaneous nephrostomy. NHL can be treated with radiotherapy and combination chemotherapy. Urolithiasis in patients with AIDS may be caused by indinavir, a protease inhibitor, but the more common types of stones may also occur. Fluid-electrolyte and acid-base disturbances are common in patients with advanced AIDS, secondary to vomiting, diarrhoea, malnutrition or septicaemia. HIV-associated nephropathy occurs in 10-30% of patients, and often leads to renal failure. Testicular atrophy is common, leading to infertility, erectile dysfunction (ED) and decreased libido. Treatment for ED must include counselling about strategies to reduce the transmission of HIV. The risk of HIV transmission after parenteral exposure to blood from an HIV-positive patient is relatively low (0.2-0.4%); the urologist can reduce the risk of transmission during surgery by adopting certain precautions. After occupational exposure to HIV, chemoprophylaxis with antiretroviral medication can significantly reduce the probability of HIV transmission.

Gene therapy for erectile dysfunction: where is it going?

PURPOSE OF REVIEW: This review will summarize the most recent preclinical data from the leading US laboratories regarding the application of gene therapy to the treatment of erectile dysfunction. The implications of these findings in the field of gene therapy in general, and more specifically to the treatment of non-life threatening disorders such as erectile dysfunction, will be outlined. RECENT FINDINGS: The preclinical work of several laboratories has clearly documented 'proof-of-concept' for the utility of gene therapy for the treatment of erectile dysfunction. A variety of vectors and several distinct molecular targets have been successfully leveraged. Such observations suggest that numerous potential strategies may exist for gene-based treatments of erectile dysfunction. SUMMARY: The apparent preclinical success of most, if not all, gene-based strategies for the treatment of erectile dysfunction is consistent with the multifactorial regulatory mechanisms governing the erectile process. The bottleneck in the gene therapy clinical development process therefore apparently will not lie in the ability to identify relevant molecular targets that are amenable to gene therapy for erectile dysfunction, but rather in the safety, specificity and longevity of those targets. That is, the next technical hurdle is to find the strategy(ies) that has the best safety profile, the greatest specificity for altering (increasing) intracavernous pressure 'on demand' and, furthermore, the most appropriate (longest?) half-life. While these criteria may correspond to intuition, finding molecular targets that clear these clinical hurdles may place restrictions on the molecular choices for gene transfer.

The potential value of erectile dysfunction inquiry and management.

Erectile dysfunction (ED) is a serious condition that becomes more common as men age. Many older men, however, report satisfactory erectile capacity and enjoy satisfying sexual relationships. Physicians have been slow to discuss ED with patients even in the presence of multiple risk factors. New information provides strong reasons for ED inquiry and management in the primary care physician's office. The presence of ED can reveal as yet undiscovered neurovascular and psychological disorders including diabetes, hypertension, dyslipidaemia, depression and anxiety as well as early neuromuscular disorders. By inquiring about ED, physicians can better decrease iatrogenic sexual dysfunction caused by certain commonly used medications. The successful management of ED, made much easier by the development of phosphodiesterase type 5 inhibitors, has additional potential benefits including improvement of quality of life for both the patient and his partner; decreasing the symptoms of depression in depressed men who also have ED; improving relationships, a significant factor related to good health; and enhancing overall patient health. Other potential values for the physician include a better clinician-patient and increased physician work satisfaction. Primary care physicians need to recognise the value of ED inquiry and management and integrate these activities into practice.