International Journal of Impotence Research (2000) 12, Suppl 4, S6±S11 ß 2000 Macmillan Publishers Ltd All rights reserved 0955-9930/00 $15.00 www.nature.com/ijir
The worldwide prevalence and epidemiology of erectile dysfunction JB McKinlay1* 1New
England Research Institutes Inc., Watertown, Massachusetts, USA This paper: (i) describes the worldwide prevalence of erectile dysfunction (ED); (ii) presents agespeci®c incidence rates for ED in the US; (iii) summarizes some key epidemiologic correlates of ED in the general population; and (iv) considers the possibility that ED may be a biobehavioral marker (sentinel event) of subsequent cardiovascular disease in men. Clinical, anthropometric, life style and hormonal data are presented from the milestone Massachusetts Male Aging Study (MMAS), a large (over 1000) prospective cohort of randomly sampled community-dwelling, normally aging men. Newly updated population prevalence and (more importantly) age-speci®c incidence rates are reported. We also estimate the likely magnitude of ED that will accompany the worldwide globalization of aging. Key correlates (predictors) of incident ED, especially vasculogenic in¯uences, are identi®ed and discussed. In conclusion, ED is a common biobehavioral phenomenon and there are strong physiological and epidemiological reasons for considering it a major marker (or predictor) of subsequent cardiovascular disease in men. International Journal of Impotence Research (2000) 12, Suppl 4, S6±S11. Keywords: incidence; prevalence; questionnaire; depression; cardiovascular risk; impotence
Introduction There was very little reliable information on erectile dysfunction (ED) available until the very end of the twentieth century.1 Pioneering contributions during the 1950s were not extended into later decades and half-century-old ®ndings had little relevance to very different subsequent cohorts. That situation has changed dramatically Ð more has been learned about ED (a medical condition formerly termed `impotence') during the past decade than was known during the rest of the twentieth century combined. Prior to about 1985, most information on ED was based on clinical impressions and studies of convenience samples of atypical patients. The Massachusetts Male Aging Study (MMAS) was the ®rst major epidemiologic investigation of ED2,3 and it is the largest population-based study to date with information on the prevalence, incidence and etiology of ED. The overall research design of the MMAS is summarized in Figure 1. The MMAS is a random-sample prospective study of health and aging in middle-aged men, addressing speci®c conditions of importance to older men (prostate cancer (PCa), hormone status, and erectile function) in the context of comprehensive information on physiology, behavior, illness, medication, anthropometrics, sexual activity, psychology and lifestyle.4 It *Correspondence: JB McKinlay, New England Research Institutes Inc., 9 Galen Street, Watertown, Mass, USA. E-mail:
[email protected]
is the only large random sample study to provide longitudinal data regarding the epidemiology of ED and other aspects of sexual function in men over the age of 60. The MMAS baseline study (1987 ± 1989) established a cohort of 1709 men aged 40 ± 70, of whom 1156 were re-interviewed in 1995 ± 1997. The study has provided important new cross-sectional and longitudinal information regarding changes in hormone status and sexual function with respect to aging, the relation of these changes to ED and prostate cancer, and preliminary evidence for a relation between ED and cardiovascular disease.
Prevalence and worldwide burden The prevalence of minimal, moderate and complete ED from the baseline (T1) MMAS (1987 ± 1989) is summarized in Figure 2. It should be noted that these estimates improve upon and re®ne our earlier published estimates,2 mainly as a result of a better method (a new discriminant function) for estimating ED in a population-based epidemiological study.5 Our new approach is less susceptible to selection bias, results in less missing data and has greater construct validity than our earlier widely accepted method.2 The prevalence and degree of ED (minimal, moderate and complete) clearly increases with age. While 8% of men in their forties report either moderate or complete ED, this approaches 40% in men aged 60 ± 69 y. In short, men between the ages
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Figure 1 Description of MMAS cohorts: MMAS-1 (1987 ± 1989); MMMAS-2 (1995 ± 1997), and a proposed MMAS-3 (2001 ± 2003).
Figure 2 Prevalence of erectile dysfunction: Massachusetts Male Aging Study, 1987 ± 1989 (n 1626); source Kleinman et al. J Clin Epidemiol 2000.5
of 60 and 69 y experience more than four times the level of moderate or complete ED compared to their 40 ± 49-y-old counterparts. Using recent MMAS estimates, Figure 3 shows the likely worldwide (age-adjusted) prevalence of ED between 1995 and 2025 (employing the most conservative, ie lowest, United Nations population projections).6 The worldwide prevalence of ED will probably increase from 152 million men in 1995 to 322 million men with ED in 2025, representing an increase of 170 million.7 Much of this increase will occur in the developing world and is associated with the aging of the world's population. Other related factors (secular increases in weight, dietary changes, smoking behavior and an emerging diabetes pandemic) are also contributing to the increase. The MMAS has provided the ®rst incidence rates for ED (Table 1). Incidence rates, which comprise new cases of a condition, or a transition from a
Table 1 Estimated number of new cases of ED annually in the US; MMAS rates and 1990 US Census data (men, aged 40 ± 69)
Age
Number of men at risk
Age-speci®c incidence rate for ED=1000
Expected number of new ED cases
40 ± 49 50 ± 59 60 ± 69
11 928 664 7 540 415 5 282 236
12.4 29.8 46.4
147 915 224 704 245 096
Total
24 751 351
617 715
nondiseased to a diseased state, obviously require prospective data for their calculation. Prior to the MMAS, the only published estimate of the incidence of ED was from a convenience sample of 3250 men aged 26 ± 83 y visiting a preventive medicine clinic in Texas between 1987 and 1991.8 Johannes et al 9 has recently reported age-category speci®c incidence rates for ED and shows how they differ International Journal of Impotence Research
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Figure 3 Prevalence of erectile dysfunction: between 1995 and 2025, the world total increase 169,932,786. Source: World Population Prospects: the 1996 Revision. New York: United Nations, 1997. The most conservative (lowest) projection was employed. Prevalence estimates of ED were employed for data from MMAS 1987 ± 1989 for ages 40 ± 69 and MMAS 1995 ± 1997 for ages 70 ± 79 y.
Figure 4 From observation to experimentation: history of the development of scienti®c knowledge concerning erectile dysfunction (ED). Moving left to right, this diagram represents the chronologic improvement in the knowledge base about ED, from uncontrolled observations to experimental evidence from ®eld trials.
by sociodemographic status (education, income) and also health status.
Improving the epidemiological knowledge of ED: from observation to experimentation Figure 4 summarizes the recent development of scienti®c knowledge concerning ED. Moving from the left toward the right-hand side of Figure 4 (indicated with bold arrow) represents improvement in the knowledge base about ED. We have thus moved from uncontrolled observations to crosssectional surveys and prospective studies towards International Journal of Impotence Research
experimental evidence from ®eld trials. Prior to about 1980, and with the notable exceptions of Kinsey in 194810 and Masters and Johnson in 1966,11 little was known about ED and clinical opinion prevailed. Real progress was made after the 1992 NIH Consensus Conference on ED,12 during which a working de®nition was agreed upon. With this de®nition, `the persistent inability to attain and maintain a penile erection adequate for sexual performance' investigators could begin to measure ED. That landmark conference also called for `major research efforts to improve diagnostic classi®cation for epidemiologic purposes'. It was a milestone event because it underscored key features of ED: (a) that it is a subjectively identi®ed state for each man
Epidemiology of erectile dysfunction JB McKinlay
(the means for its `objective' measurement with technology still require improvement and validation); (b) that it focuses on behavior (penile erections) and not underlying aspects of libido (sexual drive or interest); and (c) it recognized that ED, like most medical conditions, is not an either=or condition. Degrees of ED are recognized in the MMAS, where important distinctions are made between Complete, Moderate, Minimal and No ED. The MMAS often combines `Complete ED' and `Moderate ED' into a single category. `Minimal ED' is often considered a transitional state (in¯uenced perhaps by mood or episodic depression) and usefully grouped together with `No ED'. Once reliable incidence rates were established, it was possible to relate the presence of various chronic disease conditions (eg, heart disease, diabetes, hypertension and depression) to the development of new cases of ED. Various risk factors and lifestyles have been linked to the development of chronic diseases. For example, elevated cholesterol, smoking, lack of physical activity and hypertension are thought to be precursors of chronic heart disease (CHD)13 and this same report also suggested a strong relationship between ED and cardiovascular disease. It was possible with the MMAS to determine whether these risk behaviors (which are related to major diseases) are also linked to the development of ED, independent of the chronic diseases for which they are precursors. This linkage marked a distinct step to the right in Figure 4. Elsewhere, we looked at the relationship of both active and passive smoking to the development of ED. The adjusted rate of incident ED was signi®cantly higher in cigarette smokers (24%) than in nonsmokers (14%), with an adjusted odds ratio (OR) 1.97 and 95% con®dence interval (CI) of 1.07 ± 3.63. Passive exposure to cigarette smoke (if present both at home and at work) doubled the odds of incident ED (adjusted OR 2.07, 95% CI 1.04 ± 4.13). Cigar smoking was also strongly predictive of incident ED, with adjusted OR 2.45, 95% CI 1.9 ± 5.50. Former smokers were no more likely than nonsmokers to incur ED. These results are therefore strongly suggestive that passive smoking has the same effect on ED as active smoking. Among smokers, each increase in passive exposure increased the likelihood of incident ED. Cigar smokers had an equivalent increase in incident of ED (OR 2.45). It is noteworthy that all three forms of smoking (cigarettes, cigars and passive exposure) had equivalent independent effects on ED. Weight is a strong independent behavioral predictor of ED. The adjusted rate of incident ED in men who were overweight (BMI > 30.0 kg=m2) at baseline was 22%, signi®cantly higher than those who were not overweight (12%), with adjusted OR 1.96,95% CI 1.17 ± 3.28. While these new results represent a desirable move from cross-sectional to prospective analyses of
cohort data, they still remain observational. The next step, representing a type of `quasi-experiment', was to see if changes in the risk factors that are known to be associated with ED also result in changes in incident ED. Using MMAS data, Derby and her colleagues14 recently examined the extent to which changes in smoking, heaving drinking, sedentary lifestyle and obesity are associated with incident ED. Only physical activity (an increase from the ®rst time point (T1) to the second time point (T2)) seemed to be bene®cial, ie, those becoming more active over time seemed to have less ED, compared with those who did not change their activity levels.
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Measuring ED in epidemiologic ®eld studies Several well-known questionnaires are available for the measurement of ED.15,16 These instruments were developed in clinical settings, mainly for self-selected atypical populations seeking treatment for ED: they have limited use in ®eld studies with population-based samples (not patients). Major limitations of these questionnaires are: (a) they are sometimes lengthy and increase respondent burden (with multiple detailed queries on sensitive topics); (b) if items are omitted or skipped (common in selfadministered questionnaires) it is often dif®cult to calculate an overall score (resulting in missing data); (c) wordy questionnaires present dif®culties for poorly educated respondents and increase translational misunderstandings when used in cross-cultural studies. There is a need for a simple appropriate method for validly measuring degrees ED in population-based epidemiologic studies. Asking one single question has been shown to provide useful information in many other areas of health care. We developed such a question for population studies of ED and have carefully assessed its metric properties against the two established indices previously developed and validated in clinical settings.17 It should be noted that the MMAS single question approach may be inappropriate for clinical studies, which require instruments that are sensitive enough to detect changes with medical and surgical treatments, or which must be speci®c enough to optimize case ®ndings where screening is followed by clinical evaluations. A single, direct question approach provides a practical means of assessing ED in population-based studies. With further development it should be possible to include a single question concerning ED in large national health studies (eg, NHANES) to provide estimates of ED for selected population groups and geographic regions. International Journal of Impotence Research
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Acknowledgements
Figure 5 Only a tiny proportion of US males seek treatment for ED: results from a national survey; n 1384 (men 639). Source: American Association of Retired Persons (AARP).18
Health services research and ED Very little health services research has focused speci®cally on ED. The willingness of older men to: (a) actually seek medical care; and (b) receive appropriate effective treatment once the health system has been accessed, are now important public health issues, especially with the availability of apparently effective, well-tolerated user-friendly oral preparations. We have recently considered some of the health services research and policy implications for many countries of the availability of new treatments for ED.6 While the MMAS could not include questions concerning health care utilization for ED, some new data are available for the United States from a national survey sample recently conducted for the American Association of Retired Persons (AARP, 1999).18 The results are summarized in Figure 5 and show that only about 10% of men report seeking or receiving treatment for `sexual problems', and only half of these (5% of all US males > 45 y of age) have ever tried or are using sildena®l (ViagraTM).
Summary Some results from the largest population-based longitudinal study of male health and aging (the ongoing MMAS) are presented. Thus far, the information gathered provides the following important information about ED in our society: (i) ED is a prevalent medical condition; (ii) it has behavioral precursors that are amenable to change; (iii) it has serious implications for quality of life; (iv) despite the availability of new pharmacologic interventions, the vast majority of aging men (even those reporting complete or moderate ED) do not seek medical care for the condition. International Journal of Impotence Research
The Massachusetts Male Aging Study (MMAS) is supported by grants from the National Institutes of Health, NIDDK (DK 44995) and NIA (AG 04673). All members of the MMAS Team made important contributions to this paper: Andre Araujo, Isik Aytack, Carol Derby, Henry Feldman Irwin Goldstein, Katherine Johannes, Kenneth Kleinman, Robert Krane, Christopher Longcope, and Elizabeth Mohr. Lisa Marceau and Agnes Migliaccio assisted with the development of the ®nal manuscript. For information on the MMAS contact Dr John B McKinlay (
[email protected]).
References 1 Krane RJ, Goldstein I, de Tejada IS. Impotence. New Engl J Med 1989; 321: 1648 ± 1659. 2 Feldman HA et al. Impotence and its medical and psychosocial correlates: results from the Massachusetts Male Aging Study. J Urol 1994; 151: 54 ± 61. 3 McKinlay JB. Medical and psychological in¯uences on erectile dysfunction Ð results from a community study. The 9th Scienti®c Congress of the Kuwait Medical Association. Sociol Epidemiol Biostat 1994; 353 ± 358. 4 McKinlay JB, Longcope C, Gray A. The questionable physiologic and epidemiologic basis for a male climacteric syndrome: preliminary results from the Massachusetts Male Aging Study. Maturitas 1989; 11: 103 ± 105. 5 Kleinman KP, Feldman HA, Johannes CB, McKinlay JB. A new surrogate variable for erectile dysfunction status in the Massachusetts Male Aging Study. J Clin Epidemiol 2000; 53: 78 ± 78. 6 McKinlay JB et al. International differences in the epidemiology of male erectile dysfunction (MED). (Abstract.) Int J Impot Res 1998; 10(Suppl 1): S42. 7 Aytac IA, McKinlay JB, Krane RJ. The likely worldwide increase in erectile dysfunction between 1995 and 2025 and some possible policy consequences. Br J Urol Int 1999; 84: 450 ± 456. 8 Wei M et al. Total cholesterol and high density lipoprotein cholesterol as important predictors of erectile dysfunction. Am J Epidemiol 1994; 140: 930 ± 937. 9 Johannes CB et al. Incidence of erectile dysfunction in men ages 40 ± 69: longitudinal results from the Massachusetts Male Aging Study. J Urol 2000; 163: 460 ± 463. 10 Kinsey AC, Pomeroy WB, Martin CE. Sexual Behavior in the Human Male. WB Saunders: Philadelphia, 1948. 11 Masters WH, Johnson VE. Human Sexual Response. Little Brown: Boston, MA, 1966. 12 NIH Consensus Development Panel on Impotence. JAMA 1993; 270: 83 ± 90. 13 Feldman HA et al. Erectile dysfunction and coronary risk: prospective results from the MMAS. Prev Med 2000; 30: 328 ± 338. 14 Derby CA et al. Modi®able risk factors and incidence of erectile dysfunction: implications for prevention. Urology (in press). 15 Rosen RC et al. The International Index of Erectile Function (IIEF): a multidimensional scale for assessment of erectile dysfunction. Urology 1997; 49: 822 ± 830. 16 O'Leary MP et al. A brief male sexual function inventory for urology. Urology 1995; 46: 694 ± 706. 17 Derby CA et al. Measurement of erectile dysfunction in population-based studies: the use of a single question selfassessment in the Massachusetts Males Aging Study. Int J Impot Res 2000 (in press).
Epidemiology of erectile dysfunction JB McKinlay 18 American Association of Retired Persons, Modern Maturity Magazine, Washington DC, 1999.
Appendix Open discussion following Dr McKinlay's presentation Dr Wilson: We convert your single question into, `how many times out of 10 are you successful at intercourse?'. If they answer `2 out of 10' or `8 out of 10' successes, those results can be correlated with penile Doppler ®ndings and we can also predict their responsiveness to Viagra. If they answer 4 or 5 out of 10, Viagra is questionable, and we have to use injections; if they are never successful, we use an implant because nothing else works. Dr Sharlip: When you present this material to epidemiological groups, do they have any criticisms or point out any limitations of your methodology? Dr McKinlay: Because this is a population study and not a convenient sample of patients, one problem is the response rate. Another problem is the diurnal variation of the hormone levels. Dr Sharlip: How reliable is the application of your data to populations in other parts of the world, such as Asia? Dr McKinlay: The Massachusetts study is a very small proportion of the general population and even a random sample in Massachusetts under-represents Hispanic and African American men. ED may be higher in those populations because there are racial and ethnic differences in diabetes, smoking, weight and hypertension. But when we extrapolate to worldwide estimates, we take the most conservative projections and I am con®dent that our projections of 300 million cases of ED by 2025 is a considerable underestimate. Dr Sharlip: There may be 300-plus million men in the world who have erectile dysfunction, but how many of them care?
Dr McKinlay: A lot of men think it's an aging condition. Clearly, frequency of intercourse and erections goes down with age but so do their expectations. But, we believe that ED, independent of every other risk factor, predicts subsequent heart disease. So they shouldn't dismiss it, because it may be the single most important biobehavioral marker of the largest killer of aging men.
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Dr Wagner: What about depression, does that also correlate with treated and untreated? Dr McKinlay: Probably Ð yes, but to do a good analysis on depression drugs was dif®cult because there were so many different drugs and the numbers were small for any single drug. Dr Montague: Does physical activity reverse or slow down the progression from a moderate=severe to a minimal or moderate situation? Dr McKinlay: ED.
It reduces the probability of getting
Dr Melman: How did you de®ne physical activity? It seemed from your data that men who exercised and then stopped were worse off than men who never exercised at all. Dr Broderick: I also raise a technical point about how you described to your interviewees what 200 kcal per day meant. Dr McKinlay: The instrument used was a validated one, the Pathenbagger Scale, which asks how much they walked and how often they sweated and all of these things. When you crunch the numbers you can actually calculate kilocalories of energy expended. Dr Broderick: It brings up a paradox though, because that's certainly asking more than one question. So the attempt to reduce the questions to enhance epidemiologic data is wonderful, but even within your own study, to ascertain the most protective thing takes a trained interviewer, or many questions.
International Journal of Impotence Research
