Oral and transcutaneous pharmacologic agents in the treatment of impotence.

The pharmacologic treatment of erectile failure is now a reality. However, current agents have major drawbacks. Some require invasive administration, whereas others offer only marginal effect. The use of hormones should be limited to well-documented cases of endocrine dysfunction. Oral and transcutaneous agents remain experimental, but new drugs are under investigation and show early encouraging results.

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.

The pharmacokinetics of yohimbine in man.

The 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.

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 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.

Sub-nanogram analysis of yohimbine and related compounds by high-performance liquid chromatography.

A sensitive (50 pg/ml) method is described for the analysis of yohimbine in blood by high-performance liquid chromatography with fluorescence detection. The chromatographic behaviour of eserine (employed as internal standard), reserpine, corynanthine, yohimbinic acid, and yohimbine are examined on a series of reversed-phase and normal-phase chromatographic columns with methanol-water mobile phases.

Neuropsychological function in diabetic patients with neuropathy.

Psychometric examination of a group of diabetic patients and a group of age-matched controls failed to provide evidence of impaired intellectual functioning in the diabetic group. The cognitive status of the diabetics was not related to the duration of the illness, the age at diagnosis, or clinical ratings of peripheral or autonomic neuropathy.

Psychiatric aspects of diabetes mellitus.

A descriptive study of the psychiatric findings in 50 insulin--dependent diabetics is presented. Among the symptoms found were a marked reduction in energy level, increased fatigue and irritability, depression, and delayed psychosexual maturation. Diabetes mellitus is commonly considered to be a disease that, if properly controlled, allows the patient to lead a relatively normal life. We found, however, that these symptoms often made the patients' lives uncomfortable, reduced their functional capacity, disrupted their family life, and disturbed the adolescence of those who were affected at an early age.

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.

Functional correlates of reduced central conduction velocity in diabetic subjects.

In a previous publication, we presented evidence of slowed conduction speed in the central nervous systems of insulin-dependent diabetic subjects, manifest in a delay in the latency of the brainstem auditory-evoked response (BAER). In this article, we present the results of a multivariate study conducted on a larger sample of 50 insulin-dependent, adult diabetic subjects. The purpose of the study was to determine some of the functional correlates of the BAER delay; each patient received an assessment of the BAER, the late auditory-evoked potential (EP), the conduction velocities of the sural, median, and common peroneal nerves, and intellectual and emotional function, in addition to neurologic and audiologic examinations. A nondiabetic control group was matched with the diabetic group as to age and sex. The results indicated a delay in the latency of wave V, and in interpeak latencies I-III and I-V, of the BAER. The most reliable effect was on interpeak latency I-V; this suggested that the locus of the delay was in the central auditory projections, rather than in the acoustic nerve. In addition, BAER waves I, II, III, IV, and V were reduced in amplitude, as was the N1 component of the late auditory EP; the most reliable reduction in amplitude was in wave V. The effect was similar in magnitude for males and females, relative to their counterparts in the control group. The slowed BAER response appeared early in the disease and was not related to the duration of insulin treatment. It was correlated with a chronic loss of energy and the presence of sexual dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)

Penile elongation: a method for the screening of impotence.

Circumferentially assessed penile responses less than 10 per cent of maximal tumescence usually are regarded as random variation. However, several investigators have hypothesized that one of the initial responses to sexual stimulation is a lengthening of the penile shaft. Circumferential measurements detect this lengthening as a decrease in penile circumference. Two experiments were conducted to investigate this hypothesis. During the first experiment penile circumference changes were monitored at 2 levels of voltage sensitivity. A reliable voltage decrease was observed for all subjects immediately after the introduction of an erotic stimulus. In the second experiment the penis was videotaped to determine the magnitude of penile lengthening that occurred during the circumferential decrease. The results indicated that a substantial penile length change occurred (mean 34.5 per cent of the total erection length change) before any diameter increase was evident. A small number of impotent patients with a clear etiology were investigated using this new test. The results suggest that penile elongation occurs in the absence of full erections in patients with psychogenic impotence, while circumferential and longitudinal changes do not appear after visual erotic stimuli in organically impotent patients. The penile elongation test may prove useful in the etiological screening of impotent patients.

A new device for diagnostic screening of nocturnal penile tumescence.

An erectometer for the measurement of sleep erections is described. Comparative studies using simultaneously strain gauges and the new device indicate that it possesses a significant potential for valid measurement of the circumferential increase that may occur during sleep. Because of its reliability, simplicity and low cost the erectometer is proposed as a screening procedure or as a diagnostic alternative when sleep laboratory facilities are not feasible.

Delayed auditory brainstem responses in diabetes mellitus.

Diabetic patients have longer interpeak latencies in the brainstem auditory evoked responses than age-matched controls. The delay is not related to clinical hearing loss or blood glucose level at time of testing. Since waves I and II are normal in latency, the conduction velocity of the eighth nerve is not involved. The delay occurs between waves II and V, which would reflect altered transmission times in auditory brainstem and midbrain structures, and suggests the presence of a central neuropathy in patients with diabetes.