Impotence and Blood Pressure in the Flaccid Penis:. Relationship To

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Impotence and Blood Pressure in the Flaccid Penis:. Relationship to Nocturnal Penile Tumescence Downloaded from https://academic.oup.com/sleep/article/1/2/125/2749493 by guest on 27 September 2021 Ismet Karacan, J. Catesby Ware, Baris Dervent, Attila Altinel, John I. Thornby, Robert L. Williams, Nusret Kaya, and F. Brantley Scott

Sleep Disorders Center, Department of Psychiatry, Baylor College of Medicine, and Sleep Laboratory, Veterans Administration Hospital, Houston, Texas

Summary: Evaluations of nocturnal penile tumescence (NPT) and penile blood pressure were performed on (1) a group of nondiabetics with normal NPT, (2) a group of nondiabetics with abnormally diminished NPT, and (3) a group of diabetics with abnormally diminished NPT. The 12 subjects in each group complained of impotence. Analysis of blood pressure data taken before the NPT evaluation suggests the possibility of selective low arterial blood pressure in impotent patients who show no obvious signs of other vascular disorders. Key Words: Nocturnal penile tumescence-Penile blood pressure-Sleep Impotence-Diabetes.

The recording of nocturnal penile tumescence (NPT) and other polysomno graphic parameters has led to the development of an evaluation technique that establishes the presence of organic factors contributing to erectile impotence (Karacan, 1970; Fisher et aI., 1975; Karacan et aI., 1977; Karacan et aI., 1978). Overall, it is still believed that approximately 90% of all cases of impotence have psychogenic etiologies (Sherman, 1975); however, our evaluations of more than 400 patients complaining of impotence suggest that a higher percentage of patients have contributing organic factors than is generally recognized. Systematic research has shown that normal males of all ages who have no sleep disturbance and no complaints of erectile dysfunction, and who take no alcohol or drugs, have regularly occurring periods of NPT in association with REM sleep (Fisher et aI., 1965; Karacan, 1965; Kahn and Fisher, 1969; Hursch et aI., 1972; Karacan et aI., 1972a ,b ,c, 1975, 1976). However, polysomnographic evaluations of men complaining of impotence (the inability to initiate or maintain penile erection)

Accepted for publication June 1978. Address reprint requests to Dr. Karacan, Sleep Disorders Center, Baylor College of Medicine, Houston, Texas 77030. .

125 126 1. KARACAN ET AL. reveal a subgroup with abnormal patterns of NPT (Karacan, 1970; Fisher et aI., 1975; Karacan et a!., 1975). We have found that these abnormal patterns generally consist of diminished expansion of circumference both at the tip and at the base of the penis during erection. Other abnormal patterns seen are diminished tip expan sion only, diminished base expansion only, and increased nonREM (NREM) tumescence with reduced REM tumescence time. To some extent, the type of NPT abnormality is indicative of specific factors contributing to impotence.

Those patients who complain of erectile impotence, but who have normal NPT, Downloaded from https://academic.oup.com/sleep/article/1/2/125/2749493 by guest on 27 September 2021 will often have psychological characteristics that are different and more sugges tive of psychogenic impotence than those with abnormally diminished tumescence (Beutler et aI., 1975); however, the presence of psychological factors does not preclude concomitant organic factors. Conversely, we have seen several patients who complained of impotence following an accident, but who had normal NPT. Later these patients have shown Clinical recovery. . Despite the ability to recognize the presence of general pathology, little is known of specific causes of erectile impotence. Of particular interest has been the relationship between penile blood pressure and impotence. The literature does not include arterial obstruction as a prominent cause of impotence, although there is evidence indicating that arterial obstruction is a factor in impotence. Gaskell (1971) measured penile blood pressure of normal subjects and of potent and impo tent patients with signs of occlusive diseases. In most of the impotent patients, even those with no symptoms of peripheral vascular disease, penile blood pres sure was well below brachial pressure. Malvar et a!. (1973) used a Doppler flowmeter to examine flaccid penile flow in 36 potent and impotent patients and found that flow was lower in the impotent patients. Finally, Abelson (1975) used an ultrasonic Doppler method to study normal subjects and impotent diabetics. He reported that in normal subjects penile systolic pressures were intermediate be tween arm and leg systolic pressures, and penile diastolic and mean pressures were significantly higher than were values for the arm or leg. Six of the 14 impotent patients exhibited an abnormally low penile blood pressure. To date, none of the studies reporting on penile blood pressure has differen tiated impotence in terms of NPT measurements. In order to evaluate the relation ship between complaints of impotence, the degree of erectile capability, and penile blood pressure, we examined three groups of patients: 1. Those with a complaint of impotence, but who had normal NPT (patient control group). 2. Those with a complaint of impotence who had abnormaIIy diminished NPT, but who were free of other physical problems (nondiabetic group). 3. Those with a complaint of impotence who had abnormaIIy diminished NPT, and who had diabetes (diabetic group). Our expectations were that the diabetic group would have the lowest penile blood pressure of any group, followed by the nondiabetic group, and finaIIyby the patient control (normal NPT) group. Since vascular damage to large and smaII vessels is characteristic of diabetics (Norris and Yunis, 1964; Warren et a!., 1966), it is logical to conclude that in some impotent diabetics damage to vessels that feed the penis may compromise adequate blood flow to the penis and therefore prevent

Sleep, Vol. I, No.2, 1978 NPT AND PENILE BLOOD PRESSURE 127 normal erection. Either simple occlusion of the vessels or more complex changes affecting the dynamic pattern of vascular events that take place during erection could produce erectile failure. Fournier and Huguet (1968) reported that arterio grams of the penis of impotent diabetics revealed areas of complete avasculariza tion in the cavernosus tissue. By contrast, nondiabetic patients who suffered from arteriosclerosis had good vascularization of the corpora cavernosa, in spite of large and diffuse arterial lesions. Downloaded from https://academic.oup.com/sleep/article/1/2/125/2749493 by guest on 27 September 2021 METHOD

Subjects Subjects were selected from the patients who had been referred to us for evalua tion of NPT. All patients were initially given a detailed explanation of the proce dure to be used and signed a written informed consent form. The last 260 patients we evaluated had also received a peripheral vascular evaluation. From this group, 36 subjects were selected for three different groups. Patients were not included if they were taking any medication other than insulin. Also, patients with medical disorders other than diabetes and impotence (e.g., hypertension, Peyronie's dis ease, spinal cord injury, or known cardiovascular problems) were excluded.

Procedure After a detailed interview, Minnesota MUltiphasic Personality Inventory (MMPI) , and general physical and neurological examinations, each patient was given an extensive blood pressure examination. Arterial blood pressures were measured by means of a Roche Doppler system, and recorded on a strip chart. Blood pressure was recorded from the following locations: left and right brachial (supine, sitting, standing); left and right finger (supine); left and right popliteal (supine); left and right toe (supine); and left, right, and midline dorsal flaccid penis (supine and standing). During all blood pressure measures, pulse volume was also reco~ded by means of a photoreflectance plethysmograph placed distally to the blood pressure cuff. The patients then went through a three-night polysomno graphic evaluation. The standard electroencephalographic-electrooculographic parameters were recorded (Williams et al., 1974) along with two penile circumfer ence channels. Penile circumference was monitored by means of mercury-filled strain gauges (Karacan, 1969) placed around the penis. One gauge was placed at the tip of the penis, just caudal to the glans, and the other was placed at the base. On one evaluation night the patient was awakened during a typical erection to measure the rigidity of the erection. After the three-night evaluation, the patient's NPT was categorized as normal, low-borderline normal, abnormally diminished, or absent in comparison to values for age-matched control subjects, by taking into account the number of NPT episodes, the change in circumference, the duration of each episode, and the rigidity of the erection (Karacan, 1977). This categoriza tion was made in case conferences following completion of the evaluation procedures. For this study, the subjects were then placed in one of three groups. Subject

Sleep, Vol. I. No.2, 1978 128 I. KARACAN ET AL.

grouping was "blind" with respect to knowledge of blood-pressure values. Except for knowing the categorization of NPT (normal, low-borderline normal, abnor mally diminished, absent), the grouping was done blind to exact NPT measures. Group I: Patient control group. These patients complained of impotence. The result of the NPT evaluation indicated normal NPT. (N = 12; mean age = 47.7; SD = 11.0). Group 2: Nondiabetic group. These patients complained of impotence. The

results of the NPT evaluation indicated abnormally diminished NPT (N = 12; Downloaded from https://academic.oup.com/sleep/article/1/2/125/2749493 by guest on 27 September 2021 mean age = 48.7; SD = 6.8). Group 3: Diabetic group. These patients complained of impotence. They were taking insulin daily for diabetes. The results of the NPT evaluation indicated abnormally diminished NPT (N = 12; mean age = 45.2; SD = 11.2). For this report the data recorded from the brachial, finger, and midline dorsal penis were analyzed.

RESULTS Mean values for systolic blood pressure, diastolic blood pressure, and mean blood pressure are illustrated in Figs. 1-3, respectively. Each graph shows blood pressure values at three different locations (i.e., average of left and right sides for brachial and finger blood pressures, and midline readings of the penile blood pressures), for the diabetic patients, nondiabetic patients, and patient control subjects. All points represent averages for 12 individuals. Clearly, the diabetic patients have lower blood pressures than do patient control subjects at all locations , but their readings closely approximate those of the non diabetic patients. It is also evident that the profiles of the three groups tended to differ more in their penile blood pressures than at the other two locations. For example, the differences between systolic blood pressures of control subjects and those of diabetics were 5.91 (brachial), 11.00 (finger), and 26.75 (penile). Pairwise comparisons were performed between groups at each location, using nominal Student's (-test criteria for statistical significance. These comparisons showed that diabetic patients had significantly lower penile systolic blood pres sures than patient control subjects (p < 0.01). Also, both diabetic and nondiabetic patients had lower brachial diastolic blood pressures than patient control subjects (p < 0.05 each). None of the other comparisons attained significance at the 5% level, although there were several comparisons with marginal differences. Since the diabetic and nondiabetic patients were generally comparable in their blood pressures, we compared their combined values with those of the control subjects, as above. The results were essentially the same as those obtained previ ously, and are summarized in Table 1. Note that the patients had lower blood pressures generally, and significantly lower penile (systolic and mean) and bra chial (diastolic and mean) blood pressures than control subjects. The MMPI suggested slightly more psychopathology for Group 1, the patient control group. Groups 2 and 3, the nondiabetic and diabetic groups, were similar.

Sleep, Vol. I, No.2, 1978 Downloaded from https://academic.oup.com/sleep/article/1/2/125/2749493 by guest on 27 September 2021

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t t I --T I t .----- , I B F P B F P B F P LOCATION LOCATION LOCATION FIG. 1. Systolic blood pressure in mm Hg at brachial FIG. 2. Diastolic blood pressure in mm Hg at brachial FIG. 3. Mean blood pressure (one-third pulse pressure (B), finger (F), and midline penis (P) locations. (B), finger (F), and midline penis (P) locations. plus diastolic) at brachial (B), finger (F), and midline penis (P) locations. 130 I. KARACAN ET AL.

TABLE 1. Blood pressure comparisons: All patients vs. controls

Mean ± SD

Combined diminished NPT groups Patient controls Significance Parameter Location (N = 24) (N = 12) t-value (p)

Systolic blood Brachial 113.7 ± 18.2 120.3 ± 15.7 -1.08 N.S.

pressure Finger 88.5 ± 22.1 99.8 ± 19.5 -1.50 N.S. Downloaded from https://academic.oup.com/sleep/article/1/2/125/2749493 by guest on 27 September 2021 Penile 79.8 ± 19.9 101.3 ± 23.8 -2.87 <0.01 Diastolic blood Brachial 56.7 ± 9.5 66.2 ± 9.1 -2.88 <0.01 pressure Finger 39.9 ± 16.4 41.1 ± 17.6 -0.20 N.S. Penile 43.6 ± 23.0 55.0 ± 19.3 -1.48 N.S. Mean blood Brachial 75.7 ± 11.6 84.3 ± 10.2 -2.19 <0.05 pressure Finger 56.1 ± 17.0 60.7 ± 14.8 -0.79 N.S. Penile 55.6 ± 21.3 70.4 ± 19.2 -2.03 <0.05

DISCUSSION In the flaccid penis, systolic blood pressure was lower in diabetic patients with abnormally diminished NPT than in nondiabetics with normal NPT. The non diabetic group, although not significantly different from either group, appears to have flaccid penile blood pressure closer to that of the diabetic group. In terms of the MMPI profile, the nondiabetic group also was closer to the diabetic group, which is counter to the possibility that psychosomatic factors contributed to the lowered penile blood pressure. The 12 subjects in each group were carefully selected in order to exclude patients with medical problems other than diabetes. Also, because of the exclusion of patients taking antihypertensive and other medi cations except for insulin, the groups are probably much closer in blood pressure readings than would be found in less carefully selected groups. The fact that in the compared groups penile blood pressure was selectively diminished in patients complaining of impotence suggests a specific pathophysiology which clinically may be seen as impotence. Impotence is occasionally the first symptom for which medical aid is sought resulting in the discovery of diabetes. The diabetes is often relatively mild, so that it is difficult to determine the probable time of its onset. Also, in the early stages, intermittent problems with erections can occur (Marble et al., 1971) which could mistakenly be used as evidence for psychogenic impo tence. Because the vascular network in the penis is unusual and complex, we expect that a variety of factors can contribute to penile vascular problems reflected in low penile blood pressure readings and diminished NPT. For example, in diabetes there are two, possibly neurogenic, factors which may be contributory: the inabil ity of small blood vessels to dilate (Handelsman et al., 1952), and the common absence of circulatory reflexes (Sharpey-Scharfer and Taylor, 1960). Since the penis can apparently be a target organ for vascular pathophysiology in otherwise healthy males, an incorrect diagnosis of psychogenic impotence is quite likely in those patients if they are not evaluated properly with NPT and blood pressure measurements.

Sleep, Vol. I, No.2, 1978 NPT AND PENILE BLOOD PRESSURE 131

For a complete analysis of penile blood pressures, comparisons between the patient controls and a normal control group and between the diminished NPT diabetic group and a group of potent diabetic patients would be advantageous. We have recorded penile blood pressure in normal controls, but of a much younger group of subjects than our patient control group; these results were similar to those obtained from the patient control group. Although we have not evaluated potent diabetics, it is doubtful that we would find low penile blood pressure since to date we have not recorded significantly low penile blood pressure in any patient Downloaded from https://academic.oup.com/sleep/article/1/2/125/2749493 by guest on 27 September 2021 able to achieve a normal full erection during NPT monitoring. It must be pointed out that many patients with normal blood pressure in the flaccid penis have abnormally diminished NPT. This emphasizes the fact that organic impotence can have varied etiologies. Research on psychological, neurophysiological, and neuroendocrine systems and their relationship to NPT will be important if the etiology of impotence is to be understood.

ACKNOWLEDGMENT This work was supported in part by the Public Information Section of the National Heart and Blood Vessel Research and Demonstration Center of Baylor College of Medicine and Research Funds from the Houston, Texas, Veterans Administration Hospital.

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Karacan J, Hursch CJ, Williams RL, and Thornby JI. Some characteristics of nocturnal penile tumescence in young adults. Arch Gen Psychiatry 26:351-356, 1972c. Karacan J, Salis PJ, Thornby JI, and Williams RL. The ontogeny of nocturnal penile tumescence. Waking and Sleeping 1:27, 1976. Karacan J, Salis PJ, Ware lC, Dervent B, Williams RL, and Scott FB. Nocturnal penile tumescence and diagnosis in diabetic impotence. Am J Psychiatry 135: 191-197, 1978. Karacan J, Scott FB, Salis Pl, Attia SL, Ware JC, Altinel A, and Williams RL. Nocturnal erections, differential diagnosis of impotence, and diabetes. Bioi Psychiatry 12:373-380, 1977. Karacan I, Williams RL, Thornby JI, and Salis PJ. Sleep-related tumescence as a function of age. Am J Psychiatry 132:932-937, 1975. Downloaded from https://academic.oup.com/sleep/article/1/2/125/2749493 by guest on 27 September 2021 Malvar R, Baron T, and Clark SS. Assessment of potency with the Doppler flowmeter. Urology 2:396-400, 1973. Marble A, White P, Bradley RF, and Krall LP (Eds). Joslin's Diabetes Mellitus. Lea and Febiger, Philadelphia, 1971. Norris HJ and Yunis E. Age changes of seminal vesicles and vasa deferentia in diabetics. Arch Pathol77:126-131,1964. Sharpey-Scharfer EP and Taylor PJ. Absent circulatory reflexes in diabetic neuritis. Lancet 1:559, 1960. Sherman FP. Impotence in patients with chronic renal failure on dialysis: Its frequency and etiol ogy. Ferti! Steril 26:221-223, 1975. Warren S, LeCompte PM, and Legg MA. The Pathology of Diabetes Mellitus. 4th Ed. Lea and Febiger, Philadelphia, 1966. Williams RL, Karacan J, and Hursch CJ. Electroencephalography (EEG) of Human Sleep: Clinical Applications. Wiley, New York, 1974.

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