Safety and efficacy of sildenafil citrate in the treatment of male erectile dysfunction

Sildenafil citrate, an oral therapy for erectile dysfunction, is a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5), the predominant isozyme metabolizing cGMP in the corpus cavernosum. Chemically, it is a compound of the pyrazolo-pyrimidinyl-methylpiperazine class. Sildenafil has no direct relaxant effect on human corpus cavernosum but enhances the relaxant effect of nitric oxide (NO) on the corpus cavernosum by inhibiting PDE5, which is responsible for degradation of cGMP in this tissue. When sexual stimulation causes local release of NO, inhibition of PDE5 by sildenafil increases concentrations of cGMP in the corpus cavernosum, causing smooth muscle relaxation and blood flow into the penis, resulting in an erection. Sildenafil at recommended doses has no effect in the absence of sexual stimulation. The drug is rapidly absorbed after oral administration, with absolute bioavailability of 40%. Its pharmacokinetics are dose proportional over the recommended dosage range. Maximum plasma concentrations are reached within 30 to 120 minutes after oral dosing in the fasting state. Sildenafil is cleared predominantly by the hepatic microsomal isoenzymes CYP3A4 (major route) and CYP2C9 (minor route). Clinical studies assessed the effect of sildenafil on the ability of men with erectile dysfunction to engage in sexual activity and, specifically, to achieve and maintain an erection sufficient for satisfactory sexual intercourse. Sildenafil was evaluated at doses of 25, 50, and 100 mg in randomized, double-masked, placebo-controlled clinical trials of up to 6 months' duration. The drug was administered to hundreds of patients aged 19 to 87 years having erectile dysfunction of various etiologies for a mean duration of 5 years. Sildenafil was associated with statistically significant improvement in erectile function compared with placebo. Adverse effects reported at a rate of >2% were headache, flushing, dyspepsia, nasal congestion, urinary tract infection, abnormal vision, diarrhea, dizziness, and rash. No cases of priapism were reported. The use of sildenafil is contraindicated in men who are taking organic nitrates, because of the potential for a precipitous decrease in blood pressure. Postmarketing reports and surveillance have revealed at least 39 deaths with sildenafil use in men having a history of heart disease, men taking nitrate medications, and men in poor physical health due to lack of exercise. Many of the men who experienced serious adverse effects or death had a variety of concomitant diseases and were taking multiple medications.     

Alcoholic effect on male sexual function

Though an adequate volume of ethanol relieves nervousness and enhances sexual desire, acute administration of a great deal of ethanol suppresses central nervous system and causes sensory torpor and penile erectile dysfunction. Long term and excessive intake of ethanol causes central and/or peripheral neuropathy and sexual dysfunction; atrophy of testicles, low serum level of testosterone, impaired spermatogenesis and penile erectile dysfunction. It also invades various organs in digestive tract, cardiovascular system, central and peripheral nervous system and causes functional disorders in these organs. Successful treatment of patients with penile erectile dysfunction should be performed with treatment of these underlying and associated disease.     

A controlled trial of desmopressin and behavioral therapy for nocturnal enuresis

Erectile dysfunction may have psychological as well as a variety of organic causes. This necessitates in each case a careful medical evaluation. Various commonly used drugs, as well as alcohol and narcotics, may interfere with erection and should, whenever possible, be discontinued before starting treatment. Organic diseases should be identified and, if feasible, specially treated. In the remaining majority of afflicted men, psychological treatment and partner counseling may produce an improvement, but ultimately what is necessary remains an effective and safe medication. The drug, Sildenafil, introduces a new therapeutic principle. During sexual nerve stimulation, nitric oxide (NO) is released from nerves into the cells of the penile erectile bodies. NO activates in turn its "second messenger", the substance cyclic GMP, and the latter induces the vasorelaxation and blood filling of the erectile bodies. Orally administered Sildenafil competitively inhibits phosphodiesterase type 5, which physiologically inactivates cyclic GMP in the erectile bodies. Thus, Sildenafil increases in men with erectile dysfunction the NO-stimulated cyclic GMP concentration and, thereby, improves erection. This new therapy is attractive because 1. Sildenafil is the first pill (for oral use) with established efficacy that benefits most men with insufficient erection; 2. compared with previous therapeutic approaches (such as drug injections in the penis, instillations into the urinary duct, vacuum pumps or even prostheses), Sildenafil is at least as effective, is easy to take and appears well tolerated with no risk of a prolonged erection; 3. remarkably, this medication stimulates erection only during sexual arousal and, thus, has a rather "natural" effect, and 4. side effects (including headache, facial flushing and dyspepsia or epigastric discomfort) were mostly of mild degree and transient, so that only 4% of men interrupted treatment for this reason. Sildenafil does not need to be taken daily, but may be taken, when needed, 1 hour before a planned sexual activity. The new pill has the potential to enliven the boys "wunder horn" with fresh sound.     

Clinical guidelines panel on erectile dysfunction: summary report on the treatment of organic erectile dysfunction. The American Urological Association

PURPOSE: The American Urological Association convened the Clinical Guidelines Panel on Erectile Dysfunction to analyze the literature regarding available methods for treating organic erectile dysfunction and to make practice recommendations based on the treatment outcomes data. MATERIALS AND METHODS: The panel searched the MEDLINE data base for all articles from 1979 through 1994 on treatment of organic erectile dysfunction and meta-analyzed outcomes data for oral drug therapy (yohimbine), vacuum constriction devices, vasoactive drug injection therapy, penile prosthesis implantation and venous and arterial surgery. RESULTS: Estimated probabilities of desirable outcomes are relatively high for vacuum constriction devices, vasoactive drug injection therapy and penile prosthesis therapy. However, patients must be aware of potential complications. The outcomes data for yohimbine clearly indicate a therapy with marginal efficacy. For venous and arterial surgery, based on reported outcomes, chances of success do not appear high enough to justify routine use of such surgery. CONCLUSIONS: For the standard patient, defined as a man with acquired organic erectile dysfunction and no evidence of hypogonadism or hyperprolactinemia, the panel recommends 3 treatment alternatives: vacuum constriction devices, vasoactive drug injection therapy and penile prosthesis implantation. Based on the data to date, yohimbine does not appear to be effective for organic erectile dysfunction and, thus, it should not be recommended as treatment for the standard patient. Venous surgery and arterial surgery in men with arteriolosclerotic disease are considered investigational and should be performed only in a research setting with long-term followup available.     

Sexual dysfunction in male schizophrenic patients

BACKGROUND: Neuroleptic treatment in schizophrenic patients is associated with sexual dysfunction. However, it is not clear to what extent the psychiatric disorder and/or the pharmacologic treatment are responsible for the sexual impairment. The aim of the present study was to evaluate the sexual function of untreated and treated male schizophrenic patients in comparison with healthy subjects. METHOD: Participants included 122 male subjects: 20 drug-free schizophrenic patients, 51 neuroleptic-treated (depot form) schizophrenic patients, and 51 normal controls. A detailed structured interview was used to quantitatively and qualitatively assess sexual function. RESULTS: A high frequency of sexual dysfunction was reported by both schizophrenic groups of patients. Impairments in arousal items (erection) and orgasm during sex were reported mainly by the treated patients. Desire parameters were reduced in both schizophrenic groups, but reduction in the frequency of sexual thoughts was confined to the untreated one. The schizophrenic patients were more involved in masturbatory activity in comparison with the control subjects. Treated patients disclosed dissatisfaction with their sexual function. CONCLUSION: Untreated schizophrenic patients exhibit decreased sexual desire. Neuroleptic treatment is associated with restoration of sexual desire yet it entails erectile, orgasmic, and sexual satisfaction problems. Clinicians' awareness and open discussion of sexual problems with patients may improve comprehension and compliance.     

Sexual dysfunction in the male patients on hemodialysis

Several features of sexual dysfunction, such as infertility, decreased libido and potency, are frequently observed in male patients with uremia, and it usually worsens with time despite of hemodialysis(HD) therapy. Hormonal profile often demonstrates hypergonadotropic hypogonadism, and is suggestive of primary Leydig cell dysfunction. Hypotestosteronemia and hyperprolactinemia may partially participate in the pathogenesis of sexual dysfunction. Uremic toxins, renal anemia, hyperparathyroidism, zinc deficiency, vascular and neurologic abnormalities are also reported to be the causative factors of sexual dysfunction. Correction of anemia with recombinant human erythropoietin sometimes results in the amelioration of sexual potency, probably due to improvement of erectile performance by increased blood viscosity. Psychological derangement should be kept in mind as an another factor of sexual dysfunction.     

Efficacy and safety of transurethral alprostadil in patients with erectile dysfunction following radical prostatectomy

PURPOSE: A retrospective analysis of the MUSE clinical trial was performed to evaluate the efficacy and safety of transurethral alprostadil in patients with erectile dysfunction after radical prostatectomy. MATERIALS AND METHODS: Patients received doses of transurethral alprostadil in the clinic and those for whom a suitable dose was determined were treated at home with active drug or placebo for 3 months. Patients had undergone radical prostatectomy no less than 3 months before study entry. RESULTS: Of the 384 patients in whom radical prostatectomy was identified as a cause of erectile dysfunction 70.3% had an erection believed sufficient for intercourse in the clinic and 57.1% on active medication had sexual intercourse at least once at home. The product of clinic and home success rates (70.3 x 57.1%) was an overall success rate (the likelihood of active treatment to lead to intercourse at home) of 40.1%. The frequency of most adverse effects of radical prostatectomy was comparable to that of other organic etiologies of erectile dysfunction (1,127 patients). The percentage of patients with hypotension in the clinic was lower after radical prostatectomy compared to other erectile dysfunction etiologies (0.8 versus 4.2%, p < 0.001) but the percentage of patients with urethral pain/burning was higher (18.3 versus 10.4%, p = 0.027). No urinary tract infection, fibrosis or priapism occurred in the post-radical prostatectomy patients. CONCLUSIONS: Transurethral alprostadil is a well tolerated and efficacious method of treating erectile dysfunction after radical prostatectomy, although psychological changes associated with cancer and surgery may limit home response. The severe neurovascular deficit associated with prostatectomy neither limits the efficacy of transurethral alprostadil nor increases the risks.     

Nocturnal penile tumescence and rigidity monitoring in young potent volunteers: reproducibility, evaluation criteria and the effect of sexual intercourse

PURPOSE: We studied the reproducibility of nocturnal penile tumescence, rigidity evaluation criteria and the possible effects of sexual intercourse in young, healthy, potent male volunteers. MATERIALS AND METHODS: We recruited 12 male medical students 21 to 24 years old into the study. A disorder-free medical history, availability of a sexual partner and normal erectile function were the inclusion criteria. All subjects completed 3 sessions of 3 nights of recording using the RigiScan* device with at least a 3-day interval between recordings. During the last 3-night recording subjects were asked to have sexual intercourse at least once. Analysis of the recordings was focused on the best erectile event as well as on rigidity and tumescence activity units normalized per hour. RESULTS: The subjects completed 36, 3-night recordings. Of the total of 108 sessions 18 occurred after sexual intercourse. We analyzed 562 erectile episodes. All 3-night recordings included at least 1 episode of rigidity at the penile tip greater than 60% and more than 10 minutes in duration. Sexual intercourse did not significantly affect nocturnal penile tumescence and rigidity. When rigidity and tumescence activity unit values were normalized by the hour and expressed as mean values of the 3-night sessions, documented values became reproducible. CONCLUSIONS: At least 2 consecutive nights of recording are necessary to evaluate nocturnal penile tumescence and rigidity recordings. Nocturnal penile tumescence and rigidity with at least 1 erectile episode of tip penile rigidity greater than 60% and 10 minutes in duration may be associated with potency. Mean rigidity and tumescence activity unit values per hour of a recording may be used as objective parameters to measure overall erectile activity. In addition, sexual intercourse seems to decrease nocturnal penile tumescence and rigidity measurements, although not statistically significant. We anticipate that application of these criteria for nocturnal penile tumescence and rigidity evaluation will improve the diagnostic validity of the test. Future research will determine whether these criteria are too strict for the evaluation of aging men.     

Effects of femorofemoral grafts on postoperative sexual function: correlation with penile pulse volume recordings

Twenty-four male patients underwent 24 femorofemoral bypass graft procedures for severely limiting claudication or limb threat. These patients were assessed for sexual function preoperatively and postoperatively. Twenty-three patients reported impotence preoperatively. Eighteen patients were studied with sequential penile pulse volume recording (PVRS), and in each case of impotence an abnormal penile PVR curve was noted. Seventeen of these 23 patients regained satisfying sexual function after femorofemoral bypass, and in most cases this correlated with an improved PVR curve. This study demonstrates the effectiveness of femorofemoral bypass in preserving and restoring erectile function. Neural injury is avoided, pelvic-directed blood flow established, and atheroembolism avoided. The status of postoperatively sexual function can be quantified by the penile pulse volume recorder, noting pulse amplitude and curve contour. Transducer standardization should be accomplished in vascular laboratories with local populations and known control subjects. Under these circumstances an abnormal PVR appears to be a permanent record of a reliable, reproducible test assessing insufficient penile perfusion. Improved sexual function after femorofemoral bypass can be correlated with increased pelvic perfusion demonstrated by an improvement in penile PVR tracings.     

Radical surgery and conservation of erection in Peyronie's disease

The radical surgical option we propose for Peyronie's disease consists in removing the sclero-hyanolitic focus (plaque) and replacing it by an autologous dermal graft taken from the upper outer thigh area. Between 1981 and 1994, we operated 564 patients with Induration penis plastica (IPP), 418 of whom underwent plaque excision and dermal grafting. All could be assessed at two-year follow-up. Two main complications were observed: penile flexure relapse (71 Pts, 17% of cases), and erectile dysfunction with decreased corporal rigidity (84 Pts, 20% of cases). A mild deviation of the penis can occur some months after surgery and it is not due to disease progression (as it should have evolutive characteristics) but is mere scar retraction (44 Pts, 76% of examined relapsed flexures). The degree of this graft retraction is linked to the individual's histologic response and can be due to an idioptic tissular response or to an insufficient size of the patch. In some cases, the post-op penile flexure can result from a progression of disease (14 Pts, 24% of examined relapses flexures) and can be due either to a new "focus" or to an incomplete removal of the previous plaque. As the patient will date the onset of a possible postoperative erectile deficit from the time of the operation, it is advisable to assess preoperatively the real erectile ability of all patients. Furthermore, a post-op impaired erectile response (84 Pts, 20%) could result from a subalbuginear fibrosis of the erectile tissue that leads to a caverno-occlusive dysfunction (60%). In more than 35% of patients we found a psychogenic component, due to post-surgical stress, that involves an adrenergic hypertone with peripherical vasoconstriction. In few cases (4%) the post-op erectile dysfunction is the consequence of peroperative arterial damages that results in hypoaesthesia of the glans (injury of dorsal arteries) or in failure to obtaining corporal rigidity (damage of cavernosal arteries). A review of our experience involving plaque excision and dermal grafting led us to propose this option in case of mechanical disturbance during coitus and when the association of erectile dysfunction can be excluded.     

Follow-up of vacuum and nonvacuum constriction devices as treatments for erectile dysfunction

Of 20 men evaluated for erectile dysfunction (ED) for whom vacuum erection devices or constriction bands were recommended, only four experienced improvement of their erectile function by using the specific suggested method. Although use of a simple constriction band mechanism (e.g., a rubber band wound tightly around the penis) for men with brief erectile capacity has been described as a viable treatment, only one of five men who tried using it achieved any success. Three of six men who used a vacuum erection device were helped by it, particularly the men who suffered from only partial ED. Most patients did not follow through with the recommended treatment and stopped sexual activity, or belatedly returned for intracavernosal injections. The interviews revealed the pervasive influence of shame and demoralization regarding erectile problems, the importance of evaluation and treatment follow-up, and the necessity for careful, explicit, extensive, and concrete explanations and instructions regarding treatment options.     

Hip prostheses in women of fertile age. Consequences for sexuality and reproduction

About 6,000 patients undergo total hip replacement in Norway each year. 2.2% of them are women of fertile age, and 14% of them need hip replacement because of inflammatory rheumatic disease. Female patients may wish to know about possible consequences of hip arthroplasty on sexual activity or pregnancy and delivery. An inquiry on these issues was carried out among Norwegian orthopaedic surgeons and obstetricians. The results of the inquiry and a review of the literature can be summarized as follows: Uncomplicated total hip replacement does not preclude normal delivery nor interfere with sexual activity. Some restrictions as regards sexual activity may be advisable during the first three months after hip arthroplasty. Patients with widespread joint or muscle involvement due to inflammatory arthritis need individual counselling. As a rule, pre- and postoperative information to female patients undergoing total hip replacement should take up the possible consequences for sexual activity and reproduction.     

Impotence and its non-surgical management

Impotence is a common symptom which can cause considerable distress to both the sufferer and his partner. The use of pharmacotherapy to improve erectile function will continue to increase as safe and effective drugs are developed. However, restoring erectile function should not be the only treatment objective. It is also essential to address personal and emotional factors in the sufferer, conflicts in his relationship with his partner, and sexual problems in his partner, all of which may be instrumental in causing or maintaining the presenting impotence. We advocate a combined approach with appropriate medical treatment and sex and couple therapy.     

Effects of losartan on the sexual behavior of male rats

Many commonly used antihypertensive drugs such as diuretics and beta-blockers can interfere with sexual function in both sexes, causing loss of libido, impairment of erectile function and ejaculation in men, and delay or prevent orgasm in women. Newly developed antihypertensive drugs should ideally not interfere with the patients' quality of life including sexual function. This study examined the effects of losartan, a nonpeptide, specific antagonist for type I angiotensin II receptors, on the male sexual behavior of rats. Spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto (WKY) rats were treated with losartan 30 mg/ kg/day or saline control for 7, 30 and 90 days. Dark-cycle video recording was used to analyze the male sexual activities of the rats. No significant alteration in male sexual performance was observed after 7 and 30 days of treatment with losartan. In contrast, SHRs treated with propranolol 5 mg/kg/day showed increases in intromission latency, ejaculation latency and postejaculatory period indicating decreased libido and erectile and ejaculatory function. Upon completion of 90 days of losartan administration, the mount latency of the SHR was significantly increased, suggesting a decrease in libido although other parameters were unchanged and there was no effect in WKY rats. It is therefore concluded that losartan may have an advantage in preservation of sexual function when used clinically for the treatment of hypertensive disorders.     

Occult HIV infection: diagnosis and treatment of older patients

The decrease in immune status that accompanies normal aging leaves individuals age 50 and older increasingly susceptible to the two main modes of HIV infection: sexual activity and blood transfusions. Although therapy for older HIV patients is essentially the same as for younger patients, knowledge of appropriate drug dosages and nutritional issues that influence the care of the older HIV patient is essential for physicians treating this population. Physicians need to recognize the clinical features of HIV-related dementia and opportunistic infections that distinguish it from other age-related illnesses such as Alzheimer's and Parkinson's disease. Known risk factors that affect older patients should influence physicians to routinely include HIV in their differential diagnoses.     

The role of colour Doppler imaging in the management of Peyronie's disease

OBJECTIVE: To determine the role of colour Doppler imaging (CDI) in the investigation of erectile dysfunction in patients with Peyronie's disease. PATIENTS AND METHODS: Fifty consecutive patients (age 35-75 years) with Peyronie's disease who were considered suitable for surgical treatment were investigated using CDI to determine the haemodynamic variables of penile vasculature after an intracorporeal injection of 20 microg of alprostadil (with manual self-stimulation). A clinician independently recorded the quality of erection and the deformity. RESULTS: Twenty of 50 patients (40%) considered they had normal erectile function despite their penile deformity and all had normal responses, although they tended to exaggerate the degree of penile deformity. Of the 30 remaining patients, 21 who considered themselves to have erectile dysfunction had normal clinical and CDI haemodynamic responses to alprostadil. The remaining nine patients had a variety of erectile problems and whilst CDI showed altered haemodynamic values, in no case did CDI alter the proposed treatment based on the clinically apparent features of those patients. CONCLUSION: Colour Doppler imaging of the penis after pharmacologically induced erection gives anatomical and functional information in patients with Peyronie's disease but does not provide useful additional information to aid the selection of surgical treatment for the disease.     

Sexuality and sexual capacities of elderly people

Sexual behavior depends on biological and psychological factors. A gradual decline in interest and capacity may occur with advancing age. Sexual relationships have patterns that are influenced by prior degrees of sexual tension and outlet, physical and emotional status, and the mutual needs of the partners. In this article, the authors explore sexuality, psychosocial issues, and sexual capacities of elderly people, including issues of menopause and erectile dysfunction. The role of rehabilitation nurses in helping older adults understand and adjust to changes is addressed. Sexual counseling, already a part of rehabilitation nursing for younger patients, also should be provided for elderly patients. Nursing goals and strategies need to address identifying sexual problems and educating elderly rehabilitation patients about altered sexual needs and capacities. To do this, rehabilitation nurses must be knowledgeable about the physiology and sexual needs of older adults, be aware of myths about sexuality, and understand their own values and attitudes regarding sex and sexuality as well as the values and attitudes of individual patients.     

The pharmaco-erection test

Intracavernous administration of vasoactive drugs induces an erection in absence of erotic stimuli; we can use this property in the study of impotent patients, inducing the appearance on an erection to examine it in all its phases (FIC Test). In case of the appearance of a good erection, the test should rule out the presence of a penile arterial disease or of a corpora-veno-occlusive deficiency. When the administration of the drug does not cause complete tumescence, it is very probable that the erectile dysfunction is caused by arterial vascular alterations or by organic disorders of veno-occlusion mechanism, but we cannot exclude for a certainty a psychogenic dysfunction. In fact an excessive noradrenergic autonomic control, as during stress condition, may limit FIC Test response. Therefore we hope that more efficacious molecules will be available in a near future. Nevertheless, we consider the opportunity of enclosing tests in the diagnostic algorithm of impotent patients to reveal an excessive adrenergic tone, such as, for example, psychological tests, study of cavernous potential, or intracavernous catecholamine dosage.