David Surridge

DOUBLE-BLIND TRIAL OF YOHIMBINE IN TREATMENT OF PSYCHOGENIC IMPOTENCE

48 subjects meeting strict diagnostic criteria for psychogenic impotence took part in a 10 week placebo-controlled, double-blind, partial crossover trial of yohimbine (18 mg a day) for restoring erectile function. At the end of the first arm of the trial 62% of the yohimbine group and 16% of the placebo group reported some improvement in sexual function (chi 2 = 10.41, df = 2, p less than 0.05). 21% of the originally placebo-treated group noticed some improvement over pre-treatment levels when they were put on yohimbine in the second arm of the trial. Overall 46% of those who received yohimbine reported a positive response to the drug, a response rate very similar to that observed in a previous study of patients with organic impotence. Response to yohimbine thus seems to be unrelated to current groupings of the cause of impotence. Yohimbine is a safe treatment for psychogenic impotence that seems to be as effective as sex and marital therapy for restoring satisfactory sexual functioning.

Is Yohimbine Effective in the Treatment of Organic Impotence? Results of a Controlled Trial

Yohimbine is an alpha-adrenoceptor blocker that has been used in the treatment of erectile dysfunction. Adequate trials of this substance in a clearly defined organically impotent population are not available. We conducted a randomized, controlled study with partial cross-over of yohimbine versus placebo in 100 organically impotent men. The first phase of the study showed a positive response in 42.6 per cent of the patients receiving yohimbine versus 27.6 per cent in the placebo group. Although favorable to the test medication these values did not reach statistical significance (p equals 0.42). A similar pattern was noted in the second phase of the study. The over-all response rate of 43.5 per cent was consistent with a previous noncontrolled trial but it was much lower than previous studies. The response rate of organically impotent patients to yohimbine is at best marginal. Owing to its ease of administration, safety and modest effect it still is used in those patients who do not accept more invasive methods. Adrenoceptors are involved in the erectile process, although other neurotransmitter systems also are putative modulators of penile erection, including cholinergic, dopaminergic and vasoactive intestinal polypeptide pathways. It is beyond reasonable expectation that a single agent be of value for all cases of organic impotence. However, yohimbine has shown modest effectiveness at the doses used in this trial (18 mg. per day). Higher doses or a different route of administration may produce different effects.

Nonhormonal Pharmacological Treatment of Organic Impotence

AbstractA pilot study was conducted to assess the effect of the alpha-adrenergic antagonist, yohimbine, in a group of patients with organic impotence. The results suggest that the drug may be beneficial in selected cases but the number of satisfactory results is inferior to previous reports. The need for controlled trials is emphasized.

Topical nitroglycerin: a potential treatment for impotence.

The effect of 2 per cent nitroglycerin paste applied to the penile shaft of impotent subjects was evaluated in a placebo controlled double-blind study under laboratory conditions. After application of nitroglycerin paste or a placebo ointment base, penile tumescence was recorded through a strain gauge transducer while subjects viewed an erotic video presentation. Relative to the placebo paste the number of subjects demonstrating an increase in penile circumference after nitroglycerin (18 of 26) was significantly different than all other outcome possibilities (p less than 0.05). Noninvasive vascular assessment by ultrasonography demonstrated an increase in diameter and blood flow in the cavernous arteries after application of nitroglycerin paste. Nitroglycerin paste increases blood flow in the cavernous arteries and improves tumescence after erotic stimulation. This agent may represent a new therapy for impotence.

Endocrine dysfunction in impotence: incidence, significance and cost-effective screening

A comprehensive evaluation of impotence includes assessment of the functional integrity of the hypothalamic-pituitary-gonadal axis. However, little is known about the incidence or significance of hormonal abnormalities in an unselected group of men with erectile failure. A systematic multidisciplinary, multidimensional assessment of 256 impotent men showed clearly an organic etiology in 35.9 per cent, psychogenic in 38.3 per cent and mixed or uncertain in 25.8 per cent. The incidence of hypothalamic-pituitary-gonadal axis abnormalities in the entire group was 17.5 per cent but in only 12.1 per cent did they contribute clearly to erectile dysfunction. A cost-effective screening of the endocrine system in impotent men includes a thorough history and physical examination, and a serum testosterone determination. More sophisticated and expensive investigations should be reserved for patients with a history of drug use known to induce hormonal abnormalities or with somatic evidence of hypogonadism and a depressed serum testosterone level.

Prevalence and significance of tobacco smoking in impotence.

We investigated the incidence of cigarette smoking in a sample of patients and compared these figures with estimates of smoking among males in the general population. Among 178 impotent patients the number of current smokers (58.4%) and current ex-smokers combined (81%) was significantly higher than would be expected among males in the general population. In each age group, and at all levels of tobacco use, impotent patients smoked more than would be expected from population estimates. Smoking and nonsmoking impotent patients did not differ in terms of their hormonal profile; however, mean penile blood pressure (PBI) was lower among patients who smoked than among those who did not. A significantly higher proportion (20.9%) of impotent patients with a history of smoking showed abnormally low PBI compared with nonsmoking patients (8.8%). This study adds to preliminary evidence that smoking may be a significant risk factor in impotence, and its effects are evident in the small vasculature.

The pharmacokinetics of yohimbine in man.

SummaryThe kinetic disposition of yohimbine was examined in eight young male subjects following a single oral dose of 10 mg yohimbine hydrochloride. The drug was rapidly absorbed (absorption half-time 0.17±0.11 h) and rapidly eliminated from the plasma (elimination half-life 0.60±0.26 h).This clearance of yohimbine from plasma was constant over approximately 10 elimination half-lives, suggesting that distribution into a second pharmacokinetically distinct compartment was not responsible for the rapid decline in plasma yohimbine levels.Urinary excretion and the partitioning of the drug into red blood cells (RBC) was investigated. In the 24 h following oral administration of the drug, virtually no yohimbine was eliminated in the urine (0.35±0.50% of the administered dose). Furthermore, only 20% of blood-borne yohimbine was located in RBC.These results suggest that yohimbine is eliminated primarily through metabolism since the rapid plasma clearance of yohimbine was not the result of renal elimination or sequestration by RBC.

The role of nocturnal penile tumescence in differentiating between organic and psychogenic impotence: the first stage of validation.

A study was conducted to assess the validity of nocturnal penile tumescence (NPT) as a means of distinguishing between psychogenic and organic erectile failure (impotence). On the basis of independent clinical criteria, patients were assigned to one of four diagnostic categories—organic impotence, psychogenic impotence, mixed etiology, and uncertain etiology. The NPT characteristics of the patients in the organic and psychogenic groups were compared and decision rules formulated in order to provide optimal discrimination between the two diagnostic categories. A decision rule based on the maximum erectile response observed for each patient led to the correct diagnosis in 80% of cases. Accuracy was increased to 95% when a decision rule based on the maximum frequency of nocturnal erections was employed. The clinical value and limitations of NPT as a diagnostic procedure are discussed.

The Unreliability of Nocturnal Penile Tumescence Recording as an Outcome Measurement in the Treatment of Organic Impotence

We investigated the degree of congruence between outcome measures used to evaluate pharmacological treatment of impotence. After a comprehensive multidisciplinary assessment 17 patients were treated with an adrenergic blocker during an 8-week interval. Nocturnal penile tumescence recordings were made before treatment (as part of the assessment procedure) and at its conclusion. As part of a larger study the use of nocturnal penile tumescence monitoring has been examined as a possible outcome measure. Patient and partner self-reports also were used to evaluate treatment outcome. A comparison of patient and partner self-reports with nocturnal penile tumescence records showed little agreement between the 2 measures. These findings suggest that despite its intuitive appeal as an index of erectile function nocturnal penile tumescence recording is not a reliable index of therapeutic effectiveness. Furthermore, these findings lend support to the hypothesis that nocturnal penile tumescence and sexual erections may be separate phenomena, perhaps under the control of different mechanisms.

Diagnostic significance of penile erections during sleep

The evidence for the validity of nocturnal penile tumescence as a means of differentiating between psychogenic and organic impotence is reviewed. Five necessary stages in the validation process are described, and the relevance of the research literature to each stage is examined. Problems and issues in the clinical application of NPT recording are discussed, including (1) the need to validate NPT against independent diagnostic criteria; (2) the high probability of misdiagnosis when the absolute magnitude of NPT is used to determine cause; and (3) the need for follow-up studies to establish that NPT can be of value in the diagnoses of those patients who do not clearly belong to either the psychogenic or organic categories. We conclude that further validation studies are required before the clinical utility of NPT can be determined.