From the New England Research Institutes, Watertown, MA.
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ABSTRACT |
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aging; anger; depression; dominance-subordination; impotence; incidence; longitudinal studies; psychology
Abbreviations: CES-D, Center for Epidemiologic Studies Depression [Scale]; ED, erectile dysfunction
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INTRODUCTION |
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Although ED was once thought to be primarily a condition of psychogenic origin, recent work suggests that medical or physical influences may be of greater import. ED may be related to a wide range of factors, including age (6), smoking (7
, 8
), side effects of therapeutic agents (especially antihypertensive and antidepressant medications) (9
, 10
), atherogenesis (11
14
), or neuropathy of diabetic (15
, 16
), surgical (17
), or other origin (e.g., bicycling) (18
). However, the importance of psychosocial risk factors for ED should not be dismissed. Several cross-sectional studies have reported an association between ED and depression (19
21
), anger (3
, 22
), and the personality trait of dominance (3
). Whether these factors are prospectively associated with the risk of ED has yet to be established. Thus, the purpose of this investigation was to use longitudinal data from the Massachusetts Male Aging Study to examine whether depressive symptoms, anger expression, or dominance independently contribute to the risk of ED after other established ED risk factors are taken into account.
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MATERIALS AND METHODS |
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The follow-up phase of the Massachusetts Male Aging Study was conducted from 1995 to 1997 (average follow-up interval = 8.8 years). During this phase, men who were alive, had not moved out of the country, and were not seriously ill were eligible for interview. Of the original 1,709 respondents to the baseline survey, 180 were confirmed to be deceased, five were residing outside of the United States, and 28 were seriously ill, which left 1,496 men eligible for the follow-up interview. Of these 1,496 eligible men, 1,156 completed a follow-up interview (a follow-up response rate of 77 percent).
Measures used
The field protocol for the Massachusetts Male Aging Study has been previously described (23, 24
). Briefly, a trained field technician/phlebotomist visited each subject in his home, administered a health questionnaire and psychological assessment instruments, and obtained two nonfasting blood samples. Height, weight, and blood pressure (two measurements) were measured according to standard research protocols developed for large scale fieldwork (25
). Age, education, income level, and marital and employment status were noted. This study received institutional review board approval, and written informed consent was given by all study participants.
The presence of medical conditions, including heart disease, diabetes mellitus, and hypertension, was ascertained through self-report. The field technician inventoried all current prescription and nonprescription medications, noting the subject's stated reason for use of each. Medications were then coded according to the American Hospital Formulary Service classification (26).
Main outcome variable: incident ED.
A self-administered questionnaire on sexual activity was given to each subject for completion in private. The questionnaire was then returned to the interviewer in a sealed envelope. The baseline sexual activity questionnaire included questions related to erectile function, but it concentrated on specific items (e.g., frequency and quality of erections) rather than on the global subjective self-assessment which later became the method of choice in this field of research (1). The follow-up questionnaire included the specific items related to erectile function plus an additional single-question global subjective self-assessment whereby men classified themselves into one of four levels of ED: none, minimal, moderate, or complete.
To maintain a consistent definition of ED status at baseline and follow-up, discriminant analysis was applied to the follow-up data to assess the relation between the specific responses and the global self-assessment (27). This resulted in functions that determined the probability that an individual with a given set of responses would fall into a particular ED category. Once the functions were constructed, they were applied to both baseline and follow-up questionnaires, and subjects were then assigned to the category of ED for which they had the greatest probability of membership. The four-category ED status variable was dichotomized into absence or presence of ED, the latter defined as moderate or complete ED. New cases of ED were those identified as cases of moderate or complete ED at follow-up among men who were free of ED at baseline.
Baseline psychosocial risk factors for incident ED.
Baseline depressive symptomatology was measured using the Center for Epidemiologic Studies Depression (CES-D) Scale (28). This instrument measures current levels of depressive symptomatology in community populations and does not indicate a diagnosis of clinical depression. Scores can range from 0 to 60, with higher scores indicating more depressive symptomatology. For the present analysis, the presence of depressive symptomatology was indicated by a score greater than or equal to 16 on the CES-D Scale (29
).
Dominance was measured using the Jackson dominance scale, a subscale of the Jackson Personality Research Form E (30). This scale consists of 16 items regarding the frequency of attempts to control one's environment, influence others, and express opinions forcefully. The response set for this scale includes "false," "true," and "don't know," coded as 0, 1, and 0.5, respectively. Scores can range from 0 to 16, with higher scores indicating a higher degree of dominance. For the present analysis, dominance was measured at baseline and was categorized into tertiles (low dominance (a score of 09), moderate dominance (9.512.5), and high dominance (1316)).
The Anger-In and Anger-Out subscales of the Spielberger Anger Expression Scale (31) were used to measure the frequency with which anger was experienced but not expressed (Anger-In) and expressed (Anger-Out). Each subscale consists of eight questions pertaining to feelings of anger, addressing how often the subject generally reacts or behaves in the manner described. Each item is scored from 1 ("almost never") to 4 ("almost always"). Scores for each subscale can range from 8 to 32, with higher scores indicating a tendency to experience but not express anger (Anger-In) and a tendency to express oneself when angry (Anger-Out). For the present analysis, each subscale was administered at baseline, and scores were then categorized into tertiles (low Anger-In (a score of 713), moderate Anger-In (1416), and high Anger-In (1729) and low Anger-Out (812), moderate Anger-Out (1314), and high Anger-Out (1525)).
Other baseline risk factors for incident ED.
ED classification at baseline was categorized as none or minimal. Overweight was defined as a body mass index (weight (kg)/height (m)2) of 27.8 or more (32). Physical activity was estimated from recall of the past 7 days' activities (both work-related and leisure), including frequency and duration. Sedentary behavior was indicated when a subject's energy expenditure was less than 200 kcal/day, aligning with the recent recommendation from the Centers for Disease Control and Prevention and the American College of Sports Medicine that individuals accumulate at least 30 minutes of moderate-intensity physical activity per day (33
). Subjects' customary alcohol intake was estimated by self-report of beer, wine, and liquor consumption, accounting for frequency, quantity, and binge drinking using the formula of Khavari and Farber (34
).
Exposure to cigarette smoke was ascertained through self-report. Subjects were classified as unexposed, passively exposed to smoke in the home, and actively exposed (35). Nutritional intake was measured using the semiquantitative 1-year food frequency questionnaire of Willett et al. (36
). A high fat diet was indicated when a subject obtained more than 30 percent of his calories from fat (37
). Hypertension at baseline was indicated if one or more of the following four conditions were met: 1) the subject reported being treated for high blood pressure; 2) an inventory of medications revealed use of antihypertensive medication; 3) the subject's systolic blood pressure (second reading) was greater than or equal to 140 mmHg (38
); or 4) the subject's diastolic blood pressure (second reading) was greater than or equal to 90 mmHg (38
).
Nonfasting blood samples were drawn from the antecubital space within 4 hours of the subject's awakening, to control for diurnal variation in hormone levels (). Blood was kept in an ice-cooled container for transport and was centrifuged within 6 hours. Serum was stored in 5-ml scintillation vials at -20°C, shipped to the laboratory within 1 week by same-day courier, and stored at -70°C until the time of assay. One tube of blood was taken for lipid assays (conducted at Miriam Hospital in Providence, Rhode Island). Total cholesterol was measured by standard techniques (40
). High blood cholesterol in this analysis was defined as a blood cholesterol level greater than or equal to 200 mg/dl (37
). Two additional tubes of blood were drawn for hormone assays (conducted at the University of Massachusetts in Worcester, Massachusetts). These tubes of blood were drawn 30 minutes apart, and serum was pooled for analysis in equal aliquots in order to smooth out episodic secretion (41
). Total testosterone level was measured by radioimmunoassay (42
).
Follow-up characteristics.
Age at follow-up was treated as a three-category variable (<60, 6069, and 70 years). Follow-up total testosterone level (ng/dl) and antihypertensive medication use were tested as mediators of the relation between psychosocial risk factors and ED, based on their potential concurrent influence on ED.
Statistical analysis
The relation of psychosocial and other risk factors and follow-up characteristics to risk of ED was evaluated using simple and multiple logistic regression.
Analysis sample
Of the 1,156 men interviewed at follow-up, 125 failed to provide sufficient sexual activity data and were not assigned an ED scoring. To determine the sample at risk for developing ED, we excluded 184 men who either were missing information on baseline ED status or had moderate or complete ED at baseline. This left 847 men at risk of developing ED. Thirteen men who had undergone radical prostatectomy between the baseline and follow-up phases of the Massachusetts Male Aging Study were excluded, because of the strong association of this procedure with ED. In addition, we excluded 21 men who reported having diabetes or using related medications at baseline and 35 men who reported having heart disease or using related medications at baseline. After these exclusions, 778 men remained eligible for the analysis sample. Two men who were missing data on smoking status were excluded from the final regression model.
The exclusion of men with diabetes or heart disease at baseline was based on results indicating potential effect modification of the ED-dominance relation in these groups. In men with diabetes or use of related medications at baseline (n = 21), the percentage of men with ED increased with increasing dominance scores. By contrast, in men without diabetes, the percentage of men with ED decreased as dominance scores increased. In men with heart disease or use of related medications (n = 37; two of the 21 men with diabetes also had heart disease), an identical pattern emerged. Thus, including these groups in the analysis sample could have distorted the relation between ED and dominance. Stratification according to heart disease and diabetes was not possible because of small sample sizes in both groups; thus, men with heart disease or diabetes at baseline were excluded from the analysis sample.
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RESULTS |
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Overall, 163 of the 778 men in the analysis sample (21 percent) were classified as having moderate or complete ED at follow-up. The distributions of the main psychosocial risk factors and outcome are presented in table 1. The prevalence of depressive symptoms (CES-D score 16) in the analysis sample was 9 percent at baseline; the mean baseline CES-D score was 5.81 (not shown). Mean baseline scores for dominance, Anger-In, and Anger-Out were 10.51, 14.81, and 13.73, respectively (not shown).
The analysis sample was similar to the baseline and follow-up samples with regard to most study variables presented, most notably with respect to the main predictors of interest. Small differences between samples were observed with respect to ED, age, education, income, high blood pressure, and cigarette smoke exposure.
The occurrence of ED at follow-up according to the baseline psychosocial risk factors is presented in table 2. The presence of depressive symptoms at baseline was not a significant predictor of incident ED (p = 0.12). The percentage of persons developing ED was actually lower in men with baseline depressive symptoms than in those without them (13.2 percent vs. 21.3 percent). The percentage of men with new ED tended to decrease as baseline dominance score increased (p < 0.001), falling from 30.1 percent among those with low dominance scores to 16.4 percent and 15.4 percent among those with moderate and high scores, respectively. Neither baseline Anger-In nor baseline Anger-Out was a significant predictor of ED at the bivariate level (p > 0.50).
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DISCUSSION |
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In interpreting these findings, some limitations of the study should be noted. It is possible that dominant men respond differently to questions about sexual function, and thus the findings could be partly due to self-reporting bias. Another limitation is the extent to which the analysis sample differed from the original baseline sample, restricting the generalizability of the results. Furthermore, a number of subjects with baseline diabetes or heart disease were excluded from the analysis sample on the basis of results indicating possible effect modification of the ED-dominance relation in these groups. However, these exclusions were not related to the main predictors of interest (see table 1), and thus the chance that bias was introduced by these exclusions is minimal. Despite these limitations, we believe that the results of this study are important in that no other studies (to our knowledge) have examined the prospective relation between psychosocial risk factors and ED.
The risk of ED in this sample was inversely related to subjects' level of dominance. Men scoring moderate or high in dominance were approximately two times less likely to develop ED at follow-up than men with low dominance scores; this finding is in line with previous cross-sectional findings from the Massachusetts Male Aging Study in terms of magnitude, strength, and direction (3). We know of no other study that has examined dominance in relation to ED. However, dominance has been studied in relation to various other health outcomes. Contrary to the findings presented herein, dominance has been positively related to such outcomes as peripheral atherosclerotic disease (43
), coronary artery disease (44
), cardiovascular reactivity (45
), and mortality (46
). On the other hand, research has also shown dominant individuals to be at lower risk for poor health outcomes (47
, 48
).
Hamm et al. (48) suggested that the mechanism for dominance may be a function of the long term stress experienced by submissive individuals in response to stressful circumstances; dominant individuals presumably respond better. This stress may lead to neurocardiovascular changes (e.g., transient increases in cardiac output, damaging cardiac arteries directly or indirectly via the release of catecholamines into the bloodstream, and chronic activation of the autonomic nervous system) which may increase susceptibility to coronary artery atherosclerosis (49
). Given that some have heralded ED as a possible sentinel for subclinical cardiovascular disease (13
, 14
, 50
), a similar physiologic mechanism may explain the prospective relation between ED and dominance. That is, this association may be due to submissive individuals' inability to cope with stress, resulting in neurocardiovascular changes that could play a role in their subsequent development of ED. If a submissive behavioral tendency is a contributing factor in the etiology of ED, psychosocial or behavioral counseling addressing this issue might be useful, especially in men for whom treatment with Viagra (Pfizer, Inc., New York, New York) (51
) is contraindicated, such as those taking cardiac drugs (52
).
Neither Anger-In nor Anger-Out predicted incident ED in this sample. In previous studies, the prevalence of ED has been shown to be associated with anger. Bozman and Beck (22) found that penile tumescence was lower when a man was in an angry condition than when he was in a controlled condition. In the baseline phase of the Massachusetts Male Aging Study, anger suppression and anger expression were both positively correlated with ED (3
). Given the lack of a prospective relation between ED and anger, it is possible that the effects of anger are more short-lived. The literature on the relation between anger and cardiovascular disease supports this possibility, since anger may be associated only with transient risk of myocardial infarction (53
).
The presence of depressive symptoms was not associated with new cases of ED in this study sample. This finding could be explained in three different ways. First, depression may not be a cause of ED. If this were true, the previously demonstrated cross-sectional association of ED with depression might indicate either that ED causes depression or that the two conditions coexist simultaneously. Second, it may not be a preponderance of depressive symptoms that leads to ED but rather the more endogenous and severe forms of depression. If this were so, the measure of depressive symptoms in this study would be inadequate to detect an association with ED. Third, it could be that the presence of depressive symptoms is not a long term risk factor for ED. In other words, the effect that depressive symptoms have on ED may be transient, lasting only while someone is in the depressed state. This would have been undetectable in the current study, given the length of follow-up. Conversely, major depression may be more longstanding, affecting the autonomic nervous system, increasing vagal and sympathetic tone and platelet aggregability, and leading to poor adherence to medical regimens (31, 54
). Thus, it is possible that only these chronic effects of major depression are associated with ED over the long term.
The question of whether ED leads to depression, depression leads to ED, or each affects the other is of great interest to the urologic community and remains unresolved. Despite the longitudinal nature of these data, we were unable to clarify this issue. A study including both clinical measures of depression and epidemiologic measures of depressive symptoms evaluated at repeated, regular intervals would be able to address the question more rigorously.
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ACKNOWLEDGMENTS |
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NOTES |
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REFERENCES |
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