IS IMPOTENCE AN ARTERIAL DISORDER?

Saturday 26 January

IS IMPOTENCE AN ARTERIAL DISORDER? A

Study of Arterial Risk Factors in 440 Impotent Men R. VIRAG

P. BOUILLY D. FRYDMAN

Centre d’Etudes

et

de Recherches de

l’Impuissance,

Paris, France The distribution of four main arterial risk factors (ARF) (diabetes, smoking, hyperlipidaemia (HLP), and hypertension) was investigated in 440 impotent men (mean age 46·8) in whom the penile bloodpressure index (PBPI) (ie, the ratio of the lowest systolic pressure in one of the four main arteries of the penis to the systolic pressure in the arm) was measured. In 222 the cause (organic or functional) of impotence was sought by further investigations, such as cavernosonography. 80% of this subgroup had organic impairment of erection. In 53% of these there was evidence of an arterial lesion. Smoking (64%), diabetes (30%), and HLP (34%) were all significantly more common in the 440 impotent men than in the general male population of a similar age. Whenever two or more ARFs were present mean PBPI was significantly lower. The frequency of organic impotence increased from 49% in the absence of any ARF to 100% in patients with 3 or 4 ARFs. It is concluded that increase in the frequency of impotence with age is mainly related to arteriosclerotic changes for the arteries of the penis and that the ARF and PBPI should be evaluated first in any patient complaining of impotence.

Summary

1985

Introduction ARTERIAL lesions are rarely cited as a cause of impotence, 1,2 despite the overriding importance of vascular function in the mechanism of erection.3,4 Any impairment of the arterial supply of the penis may result in some degree of arterial failure. The ratio of penile arterial pressure to the systolic pressure in the arm, known as the penile blood-pressure index (PBPI) is a useful test in assessing arterial impairment of erections and we have used this and other tests to investigate the aetiology of impotence in men in whom the presence of four major arterial risk factors (ARF) was determined.

Patients and Methods Between 1977 and 1981, 440 men in whom a history of erectile failure had been obtained by questionnaire were referred to us. The presence or absence of the following arterial risk factors was determined: smoking, raised serum triglyceride and/or cholesterol levels, diabetes, and hypertension. The four main arteries of the penis (left and right cavernosals and superficial arteries) were evaluated by continuous doppler ultrasonography at frequencies of 5 and 8 MHz. PBPI was determined in all 440 men. 222 men participated in a more detailed study6 to investigate the cause of their impotence. The following tests were performed: (1) nocturnal penile tumescence (NPT) during REM sleep; (2) artificial erection and cavernosography by infusion of the cavernous bodies with heparinised saline; (3) selective bilateral internal iliac angiography; (4) evaluation of bulbocavernous latency; (5) multiphasic Minnesota personality inventory (MMPI); (6) serum hormone levels, follicle-stimulating hormone, luteinising hormone, prolactin, testosterone, and oestradiol). In addition, normoglycaemic subjects had an oral glucose (75 g) tolerance test. 8422

182

Fig I-Age and arterial risk factors (ARF) in a group of 440 impotent men.

Heavy smoking was defined as tobacco consumption exceeding 15 cigarettes per day for at least 15 years. Hyperlipoproteinaemia was defined as a total serum cholesterol concentration exceeding 280 mg/dl and/or total cholesterol/high density lipoprotein (HDL) ratio greater than 5 and/or serum triglyceride concentration exceeding 140 mg/dl. There were 3 categories of diabetic patients: (a) insulin dependent; (b) non-insulin dependent; and (c) those with an abnormal fasting glucose test (ie, at least two samples with a blood

study the percentages of organic and non-organic impotence in the4 groups of ARF were determined. PBPIs in arterial, non-organic, and organic non-arterial groups were compared. Comparison of percentages and mean values was done by Fisher and Yates’ tests 05. and results were regarded as significant when p<0

glucose 20 mg/dl).

Hypertension was defined as a systolic pressure exceeding 160 mm/Hg and/or a diastolic pressure exceeding 90 mm/Hg. In addition, a history of coronary heart disease and/or intermittent claudication associated with arterial obstruction in the legs were noted.

Classification of Impotence Impotence was classified as organic or non-organic on the basis of investigations described above.7-9 Impotence was regarded as non-organic when all the examinations were normal including NPT. In these men the minimum increase of penile circumference required to produce the rigidity necessary for penetration was achieved during artificial erection as well as during REM sleep. Impotence was regarded as having an organic basis when the evaluation indicated an abnormality and NPT was impaired. Those

Results

Age (fig 1) The mean age of the 440 men was 46 -8± 11 -95years (range 21-73 years). The mean age in the sub-group with no ARF was 37’ 04 years and the mean age increased with the number of ARFs-ie, it was 45 in the 1 ARF group; 52 in the 2 ARF group; and 56 in the 3 and 4 ARF group.

the results of

men

in whom the PBPI

was

less than 0 - 91 and who had abnormal

arteriograms are termed the arterial group. In the remainder ("non arterial group") impotence had other venous, endocrine, and neurological causes.Patients were also divided into 3 groups on the basis

of PBPlS:>0-91,

0 91-0’ 65, and <0.

65.

Angiograms of both internal iliac arteries were available from 208 of the 220 patients. The findings were classified as normal, no significant abnormality, or abnormal. Statistical Analysis The main group of 440 men was divided into four according to the number of ARF present-ie, none, 1, 2, and a group for those with 3 or 4 ARF. The frequency of ARF in the impotent men was o 10 compared with that in French men with a similar age distribution. The distributions of age and PBPI within these 4 groups of ARF were determined. In the 222 men who took part in the more detailed ARF INCIDENCE AND PERCENTAGE OF IMPOTENCE DUE TO ORGANIC AND NON-ORGANIC CAUSES IN 222 MEN I

ARF Distribution The distribution of ARF cumulatively and in isolation is shown in fig 2. Fig 3 shows the distribution of ARF in various study groups. In the groups with organic impotence, men with hypertension were significantly more likely to have more than 1 ARF. All hypertensive patients had organic impairment of erection. Smoking, diabetes (including abnormal fasting glucose test), and hyperlipidaemia were significantly more common in the impotent men than in French men of the same aged The frequencies of hypertension in the total group of impotent men and the general population were not significantly different. 12% of the impotent men had a history of CHD, and 10% had claudication related to arteriosclerosis in the aorto-iliac artery and/or arteries in the leg.

of ARFs According to NPT Findings, PBPI, and Arteriography (table) In 19 - 8% of the patients NPT was in the normal range and non-organic impotence was diagnosed. 32% of these patients Distribution

were

smokers, 1407o had abnormal

serum

cholesterol

or

triglyceride concentrations, 4’5% had an abnormal fasting glucose test, and none was hypertensive. Only 3 -6% of these patients had two or more ARFs and 51% had no ARFs. 42 of these patients had selective bilateral arteriography and 2 had unilateral lesion of one pudendal artery. The mean PBPI in this group was 1 -. 02±005. Selective arteriograms in 178 men

with abnormal NPT, demonstrated arterial lesions

ii,

183

organic impotence, and involvement of pudendal arteries, reduced PBPI, and frequency of ARF.

correlations between the

Nunaber

of ARF and Organic Basis of Impotence The table and figs 4 and 5 show the correlations between increasing numbers of ARF and organic aetiology and reduced PBPI. Fig 4 shows the relation between reduced PBPI and arterial involvement. Fig 5 presents additional data on the frequency of individual ARFs and when one or more of the remaining three ARFs is present. It shows the mean value and limits of highest and lowest PBPI for each ARF, isolated

Fig 3-Percentage of ARFs in sub-groups of impotent men and comparison with percentages of ARF in general male age-matched

and associated with one or more of the other ARFs. Clinical diabetes is the only condition which is always associated with a reduced PBPI. PBPI values tended to be less abnormal in the groups with the other ARFs in isolation.

population. Discussion The

organic

causes

of

impotence

are now more

widely

recognised. 1- 3,6 Karacan 11found that erections during REM sleep were impaired in 75% of his patients complaining of impotence. Varying degrees of organic impotence were demonstrated in 80% of men in our study. This did not necessarily imply that the organic defect detected was the major cause of the impotence; it could merely have acted as a triggering factor. An increase in intracavernous pressure of at least mm Hg is required for erection with full rigidity.4 Changes in the cavernosal arteries and their branches produce this pressure change. In studies of intravenous injection of papaverine,12,13 it was demonstrated than an impaired arterial supply to the cavernous bodies, impeded erection of increased the time taken to achieve full erection, compared with patients with normal arteries.9 Even a minor degree of stenosis (25%) of the internal pudendal artery in the3 flaccid penis may become critical during penile erection.3 Other factors such as stress and performance anxiety, and drugs such as antihypertensive medications, may result in the release of vasoconstrictors which exacerbate the effects of arteriosclerosis.9Smoking may have a direct vasoconstrictive effect on small penile arteries. 14 Major arterial diseases, such as myocardial infarction, stroke, and arterial obstruction affecting the legs 15 are associated with ARFs. Impotence has been reported in patients with arterial occlusion of the aortic bifurcation, 16 and 87% of patients with claudication related to aorto-iliac obstruction also had partial or complete failure of erectionY In the present study, only 10-29% of impotent men had unrelated claudication. Arteriosclerotic changes have been found at necropsy in the penile arterial bed of men with normal aorto-iliac arteries.18 Ginestie and Romieu19 and Michal and Pospichal,2O found arteriographic evidence of lesions affecting the pudendal bed but the frequency of impotence due to arteriosclerosis of the penile arteries in their patients was not known. We have attempted to obtain information on the frequency of impotence with an arterial aetiology in a large group of men. Abelson21 first proposed the use ofPBPI to assess the severity of arterial impairment. 5,8,1,22 A PBPI of more than 0 - 91 is not generally accompanied by any significant arterial abnormalities, whereas a PBPI of less than 0- 65tends to be associated with severe disease of the arteries of the penis and inadequate rigidity. Between these two limits, a variable degree of arterial impairment increases the time taken to achieve erection and weakens the rigidity obtained. 75

Fig 4-PBPI and ARF for whole group, sub-group with impotence due to arterial causes, sub-group with non organic impotence, and that with organic, non-arterial impotence.

Figures indicate

number of ARF present.

118 (67-8%). ARFs were most common in the group with abnormal arteriograms (86% smokers, 54% diabetes, 55% hypercholesterolaemia, and 907o hypertension); none of these patients was without ARFs. The group mean PBPI was 0-77±0-12. 36 patients had non-arterial, organic impotence. They had normal NPT and arteriograms and had a mean PBPI of 1’01±0’06. The frequency of ARFs (except for hypertension) was significantly lower in this group than in the group with arterial disease and resembled that in men with non-organic impotence (fig 3). There were significant

5-Relation of PBPI to ARF in isolation (first column), or associated with one other ARF (second column) or with more than one other ARF (third column).

Fig

184

In 97% of the impotent men with 2 or more ARFs, an organic aetiology was believed to be the major cause of impotence or a triggering factor. When 2 or more ARFs were present, the PBPI was alwaysless than 0 - 91 and the mean PBPI

significantly

was

presenting

with

lower in these men than in patients impotence with a non-organic basis.

Clinical diabetes

was

the

only risk factor which in isolation

significantly reduced the PBPI. The other ARFs lowered the PBPI significantly only in the presence of other ARFs. However, 50% of the patients with smoking

their only ARF and 51 % of those with HLP as their only ARF had PBPI values of below 0 - 91. In isolation, hypertension did not affect the PBPI. 92% of impotent men aged over 40 (fig 1) had at least one and usually had two ARFs.

Kinsey

et

a123 reported

a

as

considerable increase in the

impotence after the age of 50. 34% of 1108 middle aged men in an outpatient clinic were impotent. 24 Our results indicate that much of the increase in impotence with age is associated with arteriosclerotic changes in the arteries

occurrence

of

tissue. We suggest that the PBPI could be index of arteriosclerotic changes in patients regarded free of both coronary disease and other apparently obstructive peripheral arterial disease.

and

cavernous

as an

Even when impotence is an apparently isolated symptom, arteriosclerotic changes should be sought in the penile arteries, especially if one or more ARF is present. Impotent patients should follow the regimens recommended to patients with more severe arteriosclerosis of other sites.

EFFECTS OF MANIPULATION OF DIETARY FATTY ACIDS ON CLINICAL MANIFESTATIONS OF RHEUMATOID ARTHRITIS

JOEL M. KREMER ANN V. MICHALEK LLOYD LININGER CHRISTOPHER HUYCK

JEAN BIGAUOETTE MARY ANN TIMCHALK RICHARD I. RYNES JOHN ZIEMINSKI

LEE E. BARTHOLOMEW

of Rheumatology and Department of Clinical Nutrition, Albany Medical College; and Department of Mathematics and Statistics, State University of New York, Albany, New York, USA Division

The effects of manipulation of dietary fatty acids in patients with rheumatoid arthritis were investigated in a 12-week, prospective, double-blind, controlled study. 17 patients took an experimental diet high in polyunsaturated fat and low in saturated fat, with a daily supplement (1· 8 g) of eicosapentaenoic acid. 20 patients took a control diet with a lower polyunsaturated to saturated fat ratio and a placebo supplement. Compliance was monitored

Summary

by plasma lipid gas-chromatographic analysis, Ivy bleeding time, and diet diaries. Results favoured the experimental group at 12 weeks for morning stiffness and number of tender joints. On follow-up evaluation 1-2 months after stopping the diet, the experimental group had deteriorated significantly in patient and physician global evaluation of disease activity, pain assessment, and number of tender joints. The control group had improved in morning stiffness and number of tender joints on follow-up.

REFERENCES

Introduction 1.

Wagner G,

Green R.

Impotence physiological psychological, surgical diagnosis

and

treatment New York Plenum Press, 1981. 2 Bennet AH The management of male impotence Baltimore Williams and Wilkins, 1982 3 Michal V Arterial disease as a cause of impotence Clin Endocrinol Metab 1982; 11: 725-48 4. Virag R Arterial and venous hemodynamics in male impotence In: Bennet AH. The management of male impotence. Baltimore Williams and Wilkins 1982: 108-25 5. Kempczinski RF. Role of the vascular diagnostic laboratory in the evaluation of impotence Am J Surg 1979, 138: 278-82. 6 Virag R, Zwang G, Dermange H, Legman M Vasculogenic impotence: review of 92 cases with 54 surgical operations Vasc Surg 1981, 15: 9-17. 7. Virag R, Frydman D. L’exploration multidisciplinaire de l’impuissance. Contraception, Fertilité, Sexualité 1982; 10: 873-78. 8 Virag R. L’Exploration Doppler de l’impuissance Angéiologie 1980, 32: 117-23. 9. Virag R. Hemodynamic value of arterial and venous lesions as a cause of impotence. Int Angiol 1984; 3: 241-45. 10. Bouilly P. Impuissance sexuelle et facteurs de risques artériels: Une étude statistique de 440 cas Thèse pour le Doctorat en Médecine, Paris 1983. 11. Karacan I. Evaluation of noturnal penile tumescence and impotence. In: Guilleminault G Sleeping and waking disorders. indications and techniques. Menlo Park, California: Addison Wesley Publishing Company, 1982: 343-71. 12. Virag R Intracavernous injection of papaverine for erectile failure Lancet 1982; ii: 938. 13 Virag R, Frydman D, Legman M, Virag H. Intracavernous injection of papaverine as a diagnostic and therapeutic method in erectile failure Angiology 1984; 35: 79-87. 14 Forsberg L, Olson C. Impotence, smoking and &bgr; blocking drugs. Fertil Steril 1979 31: 589-91. 15 Gordon R, Kannel WB The Framingham man study twenty years later. In: The community as an epidemiological laboratory. a case book of community studies. Baltimore: Johns Hopkins Press, 1970 123-46. 16. Leriche R. Des oblitérations artérielles hautes comme cause d’une insuffisance circulatoire des membres inférieurs. Bull Soc Chirurgie 1923, 49: 1404. 17. Virag R, Frydman D, Cadre N. Hémodynamique de la circulation artérielle pénienne avant et après reconstruction aorto iliaque pour artériopathie des membres inférieurs Angéiologie 1981; 33: 269-74 18 Rusbarsky I, Michal V. Morphologic changes in the arterial bed of the penis with aging Invest Urology 1977, 15: 194-99. 19 Ginestie JF, Romieu A L’exploration radiologique de l’impuissance. Paris: Maloine, 1976. 20 Michal V, Pospichal J Phallo arteriography in the diagnosis of impotence. World J Surg 1978, 2: 239-48 21. Abelson D. Diagnostic value of the penile pulse and blood pressure A Doppler study in impotence in diabetics J Urol 1975, 113: 636-39. 22 Karacan I, Aslan G, Moore C, et al. Penile blood pressure index criterion based on NPT monitoring of erectile capacity Int Angiography 1984, 3: 233-39. 23. Kinsey A, Pomeroy W, Martin C Sexual behaviour in the human male Philadelphia W B Saunders, 1948. 24 Slag MF, Morley JE, Eison MK. et al Impotence in medical clinical outpatient. JAMA 1983, 249: 1736-40.

THE influence of diet on the clinical manifestations of rheumatoid arthritis is controversial. Panush et al found that a. diet popular in the lay press had no significant benefit.’ There is growing evidence, however, that manipulation of fatty acids in the diet can be beneficial in animal models of inflammatory disease. The types of fatty acid in the diet strongly influence the fatty-acid composition of tissue and serum lipids,6-8 and prostaglandin metabolism is largely dependent on the amount and types of fatty-acid precursor in the diet.9 High dietary levels of eicosapentaenoic acid (EPA) would provide a substrate for prostaglandin metabolism that would lead to higher levels of prostaglandins of the 3 series (eg, E3), which are less active than the inflammatory prostaglandins of the 2 series (eg, E2) derived from arachidonic acid. A change in prostaglandin concentrations can effect the immune response through various mechanisms affecting lymphocyte and macrophage reactivity.3,1O,11 Wesought to examine the effect of manipulation of dietary fatty acids on rheumatoid arthritis by comparing a diet high in polyunsaturated fat and low in saturated fat, with a supplement of EPA, and the typical American diet high in saturated fat.

Patients and Methods Patients with rheumatoid arthritis with onset after age 16 who were stage ii-iii, class 11-111 by American Rheumatism Association criterial’ were eligible for the study. They had to have active disease shown by at least three of the following: six or more tender or painful joints; three or more swollen joints; morning stiffness of 45 min duration; and Westergren erythrocyte sedimentation rate (ESR) of >28 mm/h. All patients were taking a slow-acting antirheumatic drug (hydroxychloroqume, gold, or penicillamine) and a non-steroidal anti-inflammatory drug. Ten patients were also receiving low-dose prednisone.