Abstract
Coffee intake is suggested to have a positive impact on chronic diseases, yet its role in urological diseases such as erectile dysfunction (ED) remains unclear. We investigated the association of coffee intake with incidence of ED by conducting the Health Professionals Follow-Up Study, a prospective analysis of 21,403 men aged 40–75 years old. Total, regular, and decaffeinated coffee intakes were self-reported on food frequency questionnaires. ED was assessed by mean values of questionnaires in 2000, 2004 and 2008. Multivariable adjusted Cox proportional hazards models were used to compute hazard ratios for patients with incident ED (n = 7,298). No significant differences were identified for patients with incident ED after comparing highest (≥4 cups/day) with lowest (0 cups/day) categories of total (hazard ratio (HR) = 1.00, 95% confidence interval (CI): 0.90, 1.11) and regular coffee intakes (HR = 1.00, 95% CI: 0.89, 1.13). When comparing the highest category with lowest category of decaffeinated coffee intake, we found a 37% increased risk of ED (HR = 1.37, 95% CI: 1.08, 1.73), with a significant trend (P trend = 0.02). Stratified analyses also showed an association among current smokers (P trend = 0.005). Overall, long-term coffee intake was not associated with risk of ED in a prospective cohort study.
Keywords: coffee, decaffeinated coffee, erectile dysfunction
Coffee is a rich source of caffeine, antioxidants and anti-inflammatory compounds (1–4), and has been implicated to have a potentially beneficial role against chronic diseases. Yet, the role of coffee intake in urological diseases, specifically in erectile dysfunction (ED), remains undetermined (5–9). The prevalence of ED in American men aged 20 years or older is 18.4%, which suggests that more than 18 million people are affected (10, 11). Further, in a prospective study, 17.7% of men (aged 40–75 years) reported incident ED during a 14-year follow-up (12). Among older men, these numbers substantially increase, which affects overall quality of life (11, 13, 14).
An inverse association between coffee intake and improved erectile function is biologically plausible. In addition to being a major source of polyphenols, coffee has the potential to increase testosterone levels (15–17), initiate a series of pharmacologic reactions that lead to the relaxation of the cavernous smooth muscle, and improve blood supply through penile arteries (18). In a previous cross-sectional analysis using the National Health and Nutrition and Examination Survey from 2001–2004, a nationally representative sample of the US noninstitutionalized male population, the equivalent of 2–3 cups of coffee per day was associated with a lower likelihood of ED (19). A further investigation of this association was conducted among men with comorbidities such as obesity, hypertension and diabetes, which are strong risk factors for ED. The findings remained the same among obese and hypertensive men, but not among men with diabetes.
Given the inherent limitations of the cross-sectional study design and a relatively small total sample size (n = 3,724) in the National Health and Nutrition and Examination Survey analyses, we decided to investigate prospectively the association of caffeinated and decaffeinated beverages with risk of ED in the Health Professionals Follow-up Study (HPFS). In the HPFS, we used an analytic sample of 21,403 men, 7,298 patients with incident ED, and a follow-up period of 10 years. Additionally, we investigated these associations among men with lifestyle factors and comorbid conditions such as obesity, hypertension, diabetes, history of smoking, and marital status.
METHODS
The HPFS is an ongoing prospective cohort study that started in 1986 with 51,529 middle-aged US male health professionals which included dentists, pharmacists, optometrists, osteopaths physicians, podiatrists, and veterinarians. They are followed-up with mailed questionnaires every 2 years to update their information on lifestyle and health outcomes and every 4 years to assess usual diet (94% response rate) (20). The HPFS is approved by the Human Subjects Committee at the Harvard T.H. Chan School of Public Health.
Outcome assessment
On the 2000 questionnaire, HPFS participants were asked to rate their ability (without treatment) to have and maintain an erection sufficient for intercourse. Each question included a time grid with year/month increments (before 1986, 1986–1989, 1990–1994, 1995 or later, and in the past 3 months) to allow participants to report historically if and when erectile function changed. Participants were again asked to report their current function (without treatment) in 2004 and 2008. Response options on the 5-point scale included very poor, poor, fair, good, and very good. Only men who at baseline in 1998 were without prior diagnosis of ED; prostate, bladder, or testicular cancer; or CVD were included in our analyses. Date of diagnosis was defined as the date of return of the 2000 questionnaire, and we censored at first report of ED. Reports of poor or very poor erectile function in any of the periods from 2000 to 2008 were considered incident cases of ED (21, 22).
Coffee intake assessment
Dietary data, including coffee intake, was collected from HPFS participants using food frequency questionnaires (FFQ), which calculated the cumulative dose of coffee intake. FFQ were administered in 1998 and subsequently every 4 years through 2010. In the FFQ, participants reported how frequently they consumed a specified portion of a food item over the previous year, with 9 possible answers ranging from “never or less than once a month” to “6 or more times per day.” The FFQ included questions to assess the daily intake (number of cups) of regular and decaffeinated coffee. Previously, Feskanich et al. (23) conducted a validation study and found a high correlation (r = 0.93) between participant reports of coffee intake on the FFQ compared with 2 1-week diet records separated by 6 months.
Statistical analysis
Each participant contributed person-time from the date of return of the 1998 questionnaire to the date of first report of ED or the end of follow-up in 2010. Coffee intake data was categorized according to levels of regular, decaffeinated and total (regular and decaffeinated) coffee intake. Because cardiovascular diseases share many similar diet risk factors as ED, we stopped updating the coffee intake and diet intake information when any cardiovascular disease was diagnosed during follow-up. In order to avoid bias due to reverse causality, we conducted analyses using cumulative average intake with a lag of 4 years to avoid using data on coffee intake from completed FFQ immediately before ED diagnosis (24) or development of cardiovascular disease and prostate, bladder or testicular cancers during follow-up.
Cox proportional hazards regressions were conducted to adjust for potential confounding by ED risk factors that were previously identified in this cohort and in other studies. We used left-truncated Cox proportional hazards for time-varying covariates, with a counting process data structure using age in months as the time scale. We also stratified based on calendar year to estimate the hazard ratios for coffee intake in relation to the risk of ED by using the lowest intake of quintile as the referent group (25, 26). Covariates were updated every other year. Multivariable models were adjusted for smoking (never, past, or current 1–14, 15–24, ≥25 cigarettes/day), BMI (weight in kilograms divided by height in meters squared; <25.0, 25.0–29.9, or ≥30.0), alcohol consumption (gram/day; 0, 0.1–4.9, 5.0–14.9, 15.0–29.9, or ≥30.0), total physical activity (metabolic equivalent task/week; quintiles), history of diabetes (yes vs. no), history of hypertension (yes vs. no), history of hypercholesterolemia (yes vs. no), history of cardiovascular disease (yes vs. no), energy intake (kcal/day; quintiles), marital status (married, divorced, separated, widowed, or never married), race (white, African-American, Asian-American, or other), Alternative Healthy Eating Index score (quintiles), difficulty of falling into sleep (yes vs. no), waking up during the night (yes vs. no), not feeling rested upon waking (yes vs. no), medication for lowering cholesterol (yes vs. no), medication for lowering blood pressure (yes vs. no) and sleep medicine (yes vs. no). To test for a linear trend across categories of coffee intake, we modeled intake as a continuous variable using the median intake for each category.
We conducted further stratified analyses to determine whether comorbidities and lifestyle factors such as hypertension, BMI, smoking, alcohol consumption and marital status modify the association between coffee intake and ED. Multiplicative interaction terms were incorporated into the models and likelihood-ratio tests were used to test for interaction. All analyses were conducted with SAS software, version 9 (SAS Institute, Inc., Cary, North Carolina). All P values were 2-sided and P < 0.05 indicated statistical significance.
RESULTS
During 10 years of follow-up among the 21,403 participants (median age of 62 years), a total of 7,298 men (34%) reported incident ED. Baseline characteristics of the participants according to categories of coffee intake in 1998 are shown in Tables 1 and 2. Overall, in 1998, 65% of cohort participants reported drinking at least 1 cup of coffee (total coffee) per day, and 11% reported consuming 4 or more cups of coffee daily. Men with higher total coffee intake had higher physical activity level, were more likely to be current smokers, and consumed more alcohol (Table 1). Similar results were observed among men with higher intake of regular coffee; in addition, they were less likely to be hypertensive and had poorer diet quality as measured by Alternative Healthy Eating Index scores (Table 2). High decaffeinated coffee drinkers had higher BMI and higher cholesterol levels, consumed more alcohol, and were more likely to be current or former smokers and hypertensive, but had slightly higher diet quality scores (Table 3).
Table 1.
Baseline Age-Adjusted Characteristics by Total Coffee Consumption, Health Professionals Follow-up Study, 1998–2010
| Characteristic | Coffee Intake, cups/day | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| None (n = 2,753) |
0.01–0.50 (n = 2,506) |
0.50–0.99 (n = 2,208) |
1.00–3.99 (n = 11,576) |
≥4.00 (n = 2,360) | P for Trend | ||||||
| % | Mean (SD) | % | Mean (SD) | % | Mean (SD) | % | Mean (SD) | % | Mean (SD) | ||
| Age, years | 60.3 (8.1) | 61.3 (8.5) | 62.6 (8.7) | 62.5 (8.5) | 61.2 (7.6) | ||||||
| BMIa | 25.5 (3.7) | 25.3 (3.4) | 25.7 (3.3) | 26.1 (3.4) | 26.5 (3.5) | <0.0001 | |||||
| Physical activity, METs/week | 37.9 (41.1) | 37.9 (43.1) | 38.2 (40.1) | 36.4 (39.2) | 33.8 (36.5) | <0.0001 | |||||
| Currently married | 91 | 88 | 90 | 89 | 90 | 0.71 | |||||
| Smoking status | |||||||||||
| Never | 79 | 68 | 61 | 47 | 34 | <0.0001 | |||||
| Past | 19 | 30 | 37 | 49 | 55 | <0.0001 | |||||
| Current | 2 | 2 | 2 | 5 | 12 | <0.0001 | |||||
| Self-reported disease | |||||||||||
| Hypertension | 13 | 14 | 16 | 15 | 12 | 0.59 | |||||
| High cholesterol | 40 | 45 | 46 | 46 | 43 | <0.0001 | |||||
| Difficulty falling asleepb | 21 | 20 | 21 | 21 | 19 | 0.99 | |||||
| Waking during the nightb | 55 | 54 | 58 | 59 | 58 | <0.0001 | |||||
| Not feeling rested upon wakingb | 23 | 23 | 23 | 23 | 24 | 0.99 | |||||
| Medication | |||||||||||
| Low blood pressure | 19 | 23 | 25 | 24 | 20 | 0.005 | |||||
| Lower cholesterol | 11 | 11 | 14 | 13 | 12 | 0.0002 | |||||
| Sleep medicationb | 3 | 3 | 3 | 4 | 3 | 0.04 | |||||
| Alcohol consumption, g/day | 4.7 (9.7) | 8.4 (12.1) | 9.7 (12.4) | 13.0 (14.4) | 13.8 (15.7) | <0.0001 | |||||
| Calories, kcal/day | 1,972 (604) | 1,967 (394) | 1,944 (601) | 2.011 (602) | 2.092 (692) | <0.0001 | |||||
| AHEI score | 49.7 (11.7) | 52.7 (11.4) | 52.2 (11.2) | 51.3 (11) | 49.8 (10.7) | 0.72 | |||||
| Regular coffee | 0 (0) | 0.1 (0.1) | 0.4 (0.3) | 1.6 (1.0) | 3.6 (1.5) | <0.0001 | |||||
| Decaffeinated coffee | 0 (0) | 0.1 (0.1) | 0.3 (0.3) | 0.7 (0.8) | 1.3 (1.5) | <0.0001 | |||||
Abbreviations: AHEI, Alternative Healthy Eating Index; BMI, body mass index; MET, metabolic equivalent of task; SD, standard deviation.
a Weight (kg)/height (m)2.
b Variables were ascertained in 2004 questionnaire.
Table 2.
Baseline Age-Adjusted Characteristics by Regular Coffee Consumption, Health Professionals Follow-up Study, 1998–2010
| Characteristics | Coffee Intake, cups/day | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| None (n = 4,058) |
0.01–0.50 (n = 4,112) |
0.50–0.99 (n = 2,732) |
1.00–3.99 (n = 9,167) |
≥4.00 (n = 1,334) | P for Trend | ||||||
| % | Mean (SD) | % | Mean (SD) | % | Mean (SD) | % | Mean (SD) | % | Mean (SD) | ||
| Age, years | 61.7 (8.7) | 62.3 (8.5) | 62.5 (8.6) | 62.0 (8.3) | 60.3 (7.2) | ||||||
| BMIa | 25.6 (3.5) | 25.6 (3.3) | 26.0 (3.5) | 26.2 (3.4) | 26.4 (3.4) | <0.0001 | |||||
| Physical activity, METs/week | 38.3 (42.8) | 37.4 (39.3) | 36.6 (38.9) | 36.2 (39.3) | 32.2 (34.9) | <0.0001 | |||||
| Currently married | 91 | 90 | 89 | 89 | 88 | <0.0001 | |||||
| Smoking status | |||||||||||
| Never | 72 | 61 | 52 | 45 | 34 | <0.0001 | |||||
| Past | 26 | 36 | 45 | 49 | 52 | <0.0001 | |||||
| Current | 2 | 3 | 4 | 5 | 14 | <0.0001 | |||||
| Self-reported disease | |||||||||||
| Hypertension | 15 | 16 | 17 | 14 | 10 | 0.0002 | |||||
| High cholesterol | 43 | 47 | 47 | 45 | 42 | 0.47 | |||||
| Difficulty falling asleepb | 22 | 22 | 24 | 20 | 21 | 0.09 | |||||
| Waking during the nightb | 56 | 57 | 59 | 59 | 56 | 0.02 | |||||
| Not feeling rested upon wakingb | 23 | 24 | 23 | 23 | 22 | 0.29 | |||||
| Medication | |||||||||||
| Low blood pressure | 22 | 24 | 25 | 22 | 18 | 0.10 | |||||
| Lower cholesterol | 12 | 13 | 14 | 13 | 11 | 0.97 | |||||
| Sleep medicationb | 3 | 3 | 3 | 4 | 3 | 0.40 | |||||
| Alcohol consumption, g/day | 6.2 (11.1) | 10.0 (13.3) | 10.9 (12.6) | 13.5 (14.7) | 13.9 (15.7) | <0.0001 | |||||
| Calories, kcal/day | 1,944 (587) | 1,976 (605) | 1,980 (607) | 2,033 (606) | 2,100 (642) | <0.0001 | |||||
| AHEI score | 50.7 (11.7) | 52.3 (11.2) | 52.2 (10.9) | 50.9 (11) | 48.8 (10.6) | <0.0001 | |||||
| Total coffee | 0.3 (0.7) | 0.9 (1.0) | 1.5 (0.9) | 2.7 (1.0) | 5.0 (0.9) | <0.0001 | |||||
| Decaffeinated coffee | 0.3 (0.7) | 0.7 (1.0) | 0.8 (0.9) | 0.6 (0.8) | 0.3 (0.6) | <0.0001 | |||||
Abbreviations: AHEI, Alternative Healthy Eating Index; BMI, body mass index; MET; metabolic equivalent of task; SD, standard deviation.
a Weight (kg)/height (m)2.
b Variables were ascertained in the 2004 questionnaire.
Table 3.
Baseline Age-Adjusted Characteristics by Decaffeinated Coffee Consumption, Health Professionals Follow-up Study, 1998–2010
| Characteristic | Coffee Intake, cups/day | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| None (n = 6,787) |
0.01–0.50 (n = 7,280) |
0.50–0.99 (n = 3,041) |
1.00–3.99 (n = 4,088) |
≥4.00 (n = 207) |
P for Trend | ||||||
| % | Mean (SD) | % | Mean (SD) | % | Mean (SD) | % | Mean (SD) | % | Mean (SD) | ||
| Age, years | 61.2 (8.3) | 61.5 (8.3) | 62.6 (8.5) | 63.4 (8.3) | 63.3 (8.3) | ||||||
| BMIa | 25.9 (3.6) | 25.8 (3.3) | 26.0 (3.3) | 26.3 (3.4) | 26.8 (3.5) | <0.0001 | |||||
| Physical activity, METs/week | 36.1 (40) | 37.2 (40.8) | 36.4 (36.9) | 36.6 (39.1) | 34.6 (38.9) | 0.60 | |||||
| Currently married | 88 | 89 | 90 | 92 | 95 | <0.0001 | |||||
| Smoking status | |||||||||||
| Never | 59 | 56 | 51 | 41 | 31 | <0.0001 | |||||
| Past | 35 | 41 | 45 | 53 | 59 | <0.0001 | |||||
| Current | 6 | 3 | 4 | 5 | 11 | 0.90 | |||||
| Self-reported disease | |||||||||||
| Hypertension | 13 | 13 | 16 | 17 | 20 | <0.0001 | |||||
| High cholesterol | 41 | 45 | 47 | 49 | 51 | <0.0001 | |||||
| Difficulty falling asleepb | 19 | 22 | 22 | 21 | 23 | 0.03 | |||||
| Waking during the nightb | 53 | 58 | 62 | 62 | 62 | <0.0001 | |||||
| Not feeling rested upon wakingb | 21 | 23 | 25 | 24 | 17 | 0.008 | |||||
| Medication | |||||||||||
| Low blood pressure | 20 | 22 | 26 | 26 | 25 | <0.0001 | |||||
| Lower cholesterol | 11 | 12 | 14 | 15 | 12 | <0.0001 | |||||
| Sleep medicationb | 3 | 3 | 3 | 4 | 3 | 0.0007 | |||||
| Alcohol consumption, g/day | 9.8 (14.3) | 11.1 (13.1) | 11.8 (13.4) | 12.7 (14.7) | 14.6 (17.2) | <0.0001 | |||||
| Calories, kcal/day | 1,992 (614) | 2,014 (602) | 2,000 (611) | 1,999 (595) | 2,110 (604) | 0.40 | |||||
| AHEI score | 49.3 (11.5) | 52.2 (10.9) | 52.0 (11) | 51.8 (10.8) | 51.0 (10.4) | <0.0001 | |||||
| Regular coffee | 1.3 (1.6) | 1.4 (1.3) | 1.3 (1.2) | 1.2 (1.2) | 1.1 (1.2) | <0.0001 | |||||
| Decaffeinated coffee | 1.3 (1.6) | 1.6 (1.3) | 2.0 (1.2) | 3.0 (1.3) | 5.6 (1.3) | <0.0001 | |||||
Abbreviations: AHEI, Alternative Healthy Eating Index; BMI, body mass index; MET; metabolic equivalent of task; SD, standard deviation.
a Weight (kg)/height (m)2.
b Variables were ascertained in the 2004 questionnaire.
Age-adjusted associations tended to show positive trends, but after adjusting for potential confounders including history of cardiovascular disease and lifestyle risk factors, we did not find any statistically significant association between greater intakes of total coffee (P for trend = 0.37) or regular coffee (P for trend = 0.90) and ED (Table 4). No significant differences were identified after comparing the highest (≥4 cups/day) and lowest (0 cups/day) categories of total coffee (hazard ratio (HR) = 1.00, 95% confidence interval (CI): 0.90, 1.11) and regular coffee (HR = 1.00, 95% CI: 0.89, 1.13) intakes. However, in comparing highest (≥4 cups/day) with lowest (0 cups/day) categories of decaffeinated coffee, there was a 37% increased risk of ED (HR = 1.37, 95% CI: 1.08, 1.73), and the trend was significant (P for trend = 0.02).
Table 4.
Multivariable Associations of Cumulative Average Intakes of Total, Regular, and Decaffeinated Coffee With Erectile Dysfunction (n = 21,403), Health Professionals Follow-up Study, 1998–2010
| Coffee Type and Consumption | No. of Person-Years | No. of ED Cases | Model 1a | Model 2b | ||||
|---|---|---|---|---|---|---|---|---|
| HR | 95% CI | P for Trend | HR | 95% CI | P for Trend | |||
| Total coffee, cups/day | 0.004 | 0.37 | ||||||
| Nonec | 24,630 | 829 | 1.00 | Referent | 1.00 | Referent | ||
| 0.01–0.50 | 23,167 | 764 | 0.92 | 0.83, 1.01 | 0.93 | 0.84, 1.03 | ||
| 0.50–0.99 | 19,705 | 738 | 0.94 | 0.85, 1.03 | 0.92 | 0.83, 1.02 | ||
| 1.00–3.99 | 103,629 | 4,242 | 1.04 | 0.96, 1.12 | 0.99 | 0.92, 1.08 | ||
| ≥4.00 | 18,861 | 725 | 1.08 | 0.97, 1.19 | 1.00 | 0.90, 1.11 | ||
| Regular coffee, cups/day | 0.09 | 0.90 | ||||||
| Nonec | 34,791 | 1,243 | 1.00 | Referent | 1.00 | Referent | ||
| 0.01–0.50 | 36,999 | 1,424 | 1.04 | 0.97, 1.12 | 1.05 | 0.97, 1.13 | ||
| 0.50–0.99 | 23,978 | 963 | 1.05 | 0.96, 1.14 | 1.03 | 0.94, 1.12 | ||
| 1.00–3.99 | 83,857 | 3,279 | 1.06 | 0.99, 1.13 | 1.03 | 0.96, 1.10 | ||
| ≥4.00 | 10,365 | 359 | 1.07 | 0.95, 1.20 | 1.00 | 0.89, 1.13 | ||
| Decaffeinated coffee, cups/day | 0.0005 | 0.02 | ||||||
| Nonec | 58,716 | 2,069 | 1.00 | Referent | 1.00 | Referent | ||
| 0.01–0.50 | 69,458 | 2,515 | 0.99 | 0.93, 1.05 | 1.00 | 0.94, 1.06 | ||
| 0.50–0.99 | 26,540 | 1,074 | 1.03 | 0.96, 1.11 | 1.02 | 0.95, 1.10 | ||
| 1.00–3.99 | 34,000 | 1,566 | 1.09 | 1.02, 1.17 | 1.06 | 0.99, 1.13 | ||
| ≥4.00 | 1,278 | 74 | 1.54 | 1.22, 1.95 | 1.37 | 1.08, 1.73 | ||
Abbreviations: CI, confidence interval; ED, erectile dysfunction; HR, hazard ratio.
a Model 1 was adjusted for age in months and calendar time.
b Model 2 was adjusted for the variables in model 1 and smoking (never, past, or current, categorized as 1–14, 15–24, ≥25 cigarettes/day), body mass index (weight in kilometers divided by height in meters squared; <25.0, 25.0–29.9, or ≥30.0), alcohol consumption (grams/day; 0, 0.1–4.9, 5.0–14.9, 15.0–29.9, or ≥30.0), total physical activity (metabolic equivalent of tasks per week; quintiles), history of diabetes (yes vs. no), history of hypertension (yes vs. no), history of hypercholesterolemia (yes vs. no), history of cardiovascular disease (yes vs. no), energy intake (kcal/day; quintiles), Alternative Healthy Eating Index score (quintiles), marital status (married, divorced, separated, widowed, or never married), race (white, African-American, Asian-American, or other), difficulty of falling into sleep (yes vs. no), waking during the night (yes vs. no), not feeling rested upon waking (yes vs. no), and use of cholesterol-lowering, blood pressure–lowering, or sleep-enhancing medication (yes vs. no).
c Included men who drank no regular or decaffeinated coffee.
Further analyses were conducted to assess possible reverse causation, that is, if development of ED led to a change in coffee habits. Thus, we examined coffee intake with a 4-year lag period between total, regular, and decaffeinated coffee intakes and ED (Table 5). We did not find any statistically significant trend associated between intakes of total (P for trend = 0.63), regular (P for trend = 0.74) and decaffeinated (P for trend = 0.64) coffee and ED. Also, there were no significant differences between the highest and lowest categories of total (HR = 0.92, 95% CI: 0.81, 1.04) and regular (HR = 0.89, 95% CI: 0.77, 1.02) coffee intakes. After comparing the highest category of decaffeinated coffee intake with the lowest ((≥4 vs. 0 cups/day), we found a 43% increased risk of ED (HR = 1.43, 95% CI: 1.10, 1.87).
Table 5.
Four-Year Latent Period in the Multivariable Associationsa of Total, Regular, and Decaffeinated Coffee Intakes With Erectile Dysfunction, Health Professionals Follow-up Study, 2002–2010
| Type of Coffee | Coffee Intake, cups/day | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| No Coffeeb | 0.01–0.50 | 0.50–0.99 | 1.00–3.99 | ≥4.00 | P for Trend | ||||||
| HR | 95% CI | HR | 95% CI | HR | 95% CI | HR | 95% CI | HR | 95% CI | ||
| Total | 1.00 | Referent | 0.87 | 0.77, 0.98 | 0.86 | 0.76, 0.97 | 0.93 | 0.85, 1.02 | 0.92 | 0.81, 1.04 | 0.63 |
| Regular | 1.00 | Referent | 0.93 | 0.84, 1.02 | 0.98 | 0.88, 1.09 | 0.98 | 0.91, 1.07 | 0.89 | 0.77, 1.02 | 0.74 |
| Decaffeinated | 1.00 | Referent | 0.95 | 0.89, 1.03 | 0.95 | 0.87, 1.05 | 0.99 | 0.91, 1.08 | 1.43 | 1.10, 1.87 | 0.64 |
Abbreviations: CI, confidence interval; HR, hazard ratio.
a Models were adjusted for age in months, calendar time, smoking (never, past, or current, categorized as 1–14, 15–24, ≥25 cigarettes/day), body mass index (weight in kilometers divided by height in meters squared; <25.0, 25.0–29.9, or ≥30.0), alcohol consumption (grams/day; 0, 0.1–4.9, 5.0–14.9, 15.0–29.9, or ≥30.0), total physical activity (metabolic equivalent of tasks per week; quintiles), history of diabetes (yes vs. no), history of hypertension (yes vs. no), history of hypercholesterolemia (yes vs. no), history of cardiovascular disease (yes vs. no), energy intake (kcal/day; quintiles), Alternative Healthy Eating Index score (quintiles), marital status (married, divorced, separated, widowed, or never married), race (white, African-American, Asian-American, or other), difficulty of falling into sleep (yes vs. no), waking during the night (yes vs. no), not feeling rested upon waking (yes vs. no), and use of cholesterol-lowering, blood pressure–lowering, or sleep-enhancing medication (yes vs. no).
b Included men who drank no regular or decaffeinated coffee.
In stratified and multivariable analyses, we examined the association between coffee and ED across strata of smoking status (Table 6). We also stratified across strata of BMI categories, hypertension, marital status, and alcohol consumption (Web Tables 1–4, available at https://academic.oup.com/aje). No significant results were reported among strata of smoking status for total (P for interaction = 0.11) and regular (P for interaction = 0.80) coffee intakes, Table 4). However, among current smokers there was a positive trend associated between decaffeinated coffee intake and ED (P for trend = 0.005 and P for interaction = 0.06).
Table 6.
Associationsa of Cumulative Average Intakes of Total Coffee, Regular Coffee, and Decaffeinated Coffee With Erectile Dysfunction, Stratified by Smoking Status, Health Professionals Follow-up Study, 1998–2010
| Type of Coffee and Smoking Status | Coffee Intake, cups/day | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| No Coffeeb | 0.01–0.50 | 0.50–0.99 | 1.00–3.99 | ≥4.00 | P for Trend | P for Interaction | ||||||
| HR | 95% CI | HR | 95% CI | HR | 95% CI | HR | 95% CI | HR | 95% CI | |||
| Total coffee | 0.11 | |||||||||||
| Never smoker | 1.00 | Referent | 0.98 | 0.87, 1.10 | 0.91 | 0.80, 1.04 | 0.98 | 0.89, 1.08 | 0.99 | 0.84, 1.15 | 0.78 | |
| Past smoker | 1.00 | Referent | 0.90 | 0.74, 1.09 | 0.97 | 0.80, 1.17 | 1.01 | 0.86, 1.17 | 1.02 | 0.85, 1.22 | 0.23 | |
| Current smoker | 1.00 | Referent | 0.72 | 0.27, 1.93 | 0.72 | 0.26, 2.02 | 1.45 | 0.72, 2.95 | 1.23 | 0.59, 2.56 | 0.14 | |
| Regular coffee | 0.80 | |||||||||||
| Never smoker | 1.00 | Referent | 1.01 | 0.92, 1.12 | 0.98 | 0.87, 1.10 | 1.00 | 0.92, 1.10 | 1.06 | 0.87, 1.29 | 0.86 | |
| Past smoker | 1.00 | Referent | 1.11 | 0.97, 1.26 | 1.09 | 0.95, 1.25 | 1.07 | 0.95, 1.20 | 1.05 | 0.88, 1.25 | 0.76 | |
| Current smoker | 1.00 | Referent | 1.23 | 0.62, 2.44 | 1.85 | 0.93, 3.70 | 1.50 | 0.84, 2.67 | 1.20 | 0.63, 2.27 | 0.55 | |
| Decaffeinated coffee | 0.06 | |||||||||||
| Never smoker | 1.00 | Referent | 1.00 | 0.92, 1.09 | 0.97 | 0.87, 1.08 | 1.02 | 0.92, 1.13 | 1.30 | 0.82, 2.06 | 0.72 | |
| Past smoker | 1.00 | Referent | 0.94 | 0.86, 1.03 | 1.00 | 0.89, 1.11 | 1.00 | 0.91, 1.10 | 1.31 | 0.98, 1.74 | 0.34 | |
| Current smoker | 1.00 | Referent | 1.54 | 1.07, 2.21 | 1.54 | 0.98, 2.40 | 1.63 | 1.13, 2.35 | 2.64 | 0.88, 7.87 | 0.005 | |
Abbreviations: CI, confidence interval; HR, hazard ratio.
a Included men who drank no regular or decaffeinated coffee.
b Models were adjusted for age in months, calendar time, smoking (never, past, or current, categorized as 1–14, 15–24, ≥25 cigarettes/day), body mass index (weight in kilometers divided by height in meters squared; <25.0, 25.0–29.9, or ≥30.0), alcohol consumption (grams/day; 0, 0.1–4.9, 5.0–14.9, 15.0–29.9, or ≥30.0), total physical activity (metabolic equivalent of tasks per week; quintiles), history of diabetes (yes vs. no), history of hypertension (yes vs. no), history of hypercholesterolemia (yes vs. no), history of cardiovascular disease (yes vs. no), energy intake (kcal/day; quintiles), Alternative Healthy Eating Index score (quintiles), marital status (married, divorced, separated, widowed, or never married), race (white, African-American, Asian-American, or other), difficulty of falling into sleep (yes vs. no), waking during the night (yes vs. no), not feeling rested upon waking (yes vs. no), and use of cholesterol-lowering, blood pressure–lowering, or sleep-enhancing medication (yes vs. no).
Among categories of BMI (<25.0, 25.0–29.9, or ≥30.0), the associations of total, regular and decaffeinated coffee intake with ED did not reach statistical significance (P for interaction = 0.07, 0.16, and 0.88, respectively; Web Table 1). Similar findings were identified after stratifying for history of hypertension (P for interaction = 0.25, 0.25, and 0.72, respectively; Web Table 2), marital status (P for interaction = 0.32, 0.67, and 0.08, respectively, Web Table 3), and alcohol consumption (P for interaction = 0.70, 0.99, and 0.93, respectively; Web Table 4). Further stratified analyses were conducted by age (<70 or ≥70), history of diabetes (yes vs. no), medication for lowering blood pressure (yes vs. no), and difficulty of falling into sleep (yes vs. no), but no significant associations were found (data not shown).
DISCUSSION
In the present large observational study that investigated prospectively the association of coffee intake with ED, we observed no significant associations between intakes of total and regular coffee and ED. For decaffeinated coffee intake, there was a significant association after comparing the highest with the lowest intake and also a significant trend. In stratified analyses, none of the modifiable lifestyle factors influenced the association of coffee intake with ED, though the positive association between decaffeinated coffee and ED was observed most strongly in the stratum of current smokers, and possibly suggests residual confounding.
Coffee intake has potential health benefits for various health outcomes (27–30). Yet, the present prospective investigation, which included 21,403 men followed for 10 years with a 34% rate of patients with incident ED (n = 7,298), did not support this association. Unlike in other studies in which investigators found potential associations that could potentially be the result of residual confounding (31), we controlled for a large number of confounders (e.g., sleep problems).
Relatively few studies have investigated the independent association between coffee intake and ED in prospective population-based studies, including our previous study (19), in which we found an inverse association. However, in that previous study, we used cross-sectional data and a smaller sample size (n = 3,724). In a population-based prospective study of 202 patients with incident ED among Finnish men with 5 years of follow-up, Shiri et al. (9) found no association between coffee consumption and ED. No data were provided on decaffeinated coffee intake.
Some aspects of our prospective study merit discussion. Although we observed an increased risk for ED in men who consumed 4 cups/day or more of decaffeinated coffee compared with those who consumed 0 cups/day, we interpret these findings cautiously for the following reasons. First, only 0.9% of men consumed 4 of cups/day or more of decaffeinated coffee. Second, there is no strong biological plausibility between decaffeinated coffee intake and ED. During the process of decaffeination, some of the polyphenols and anti-inflammatory compounds may be removed (32–36), but we found no association between regular coffee consumption and ED. It is possible that deleterious chemical compounds may be added to the decaffeinated coffee in the process of decaffeination (34–39). Third, heavy drinkers of decaffeinated coffee had an unusual lifestyle, with comorbid characteristics such as higher BMI, more current and past smoking history, as well as more hypertension, high cholesterol and higher alcohol consumption, but they also had slightly better diets (Alternative Healthy Eating Index score). Interestingly, we observed an association between decaffeinated coffee intake and ED only among current smokers, suggesting that residual confounding may have accounted for the association.
Strengths of the present study include the large sample size, number of patients with incident ED, long follow-up data from participants, and detailed data on ED risk factors. These strengths increased our statistical power for the categorical comparison groups and generalizability for studies with similar study populations, and also reduced residual confounding because of our well-characterized risk factors. We used repeated measurements and assessed cumulative dietary intake to more accurately assess long-term coffee intake and reduce measurement error. Yet, the present study has some limitations as well. First, definition of ED was self-reported by participants, which will inevitably be imperfect. However, health professionals tend to report medical conditions with high accuracy, and we have previously reported on classic risk factors for ED such as BMI and physical activity (12) which have been confirmed in other populations with more detailed assessments of patients with incident ED. Although we adjusted for several potential confounders, there is still the possibility of confounding from additional unmeasured factors. However, due to our detailed and updated adjustment for confounders, it is unlikely that these would fully account for the observed findings. Second, although detailed assessment of coffee intake was conducted, this was done every 4 years, therefore, any shorter-term (<4 years) fluctuation of the intake could have been missed. However, coffee intake is consistent over time. Third, no data were available on the preparation methods of coffee, information which can provide insight on the alteration of the chemical composition of coffee. Fourth, it is possible that coffee consumption over a longer time period could have influenced risk. Yet, it is notable that coffee consumption is relatively consistent over time and drinking habits during the study period correlated with prior coffee drinking. Fifth, future studies should focus on investigating a nonlinear association between coffee intake and ED. Finally, reverse causation did not seem to play a role in our findings, but it is possible that subtle alterations in health could have influenced coffee consumption even after including a 4-year lag in our sensitivity analyses.
In summary, we did not find an association, either positive or negative, between total or regular coffee intake and ED. However, decaffeinated-coffee intake seemed to be associated with ED, possibly because of residual confounding. None of the modifiable lifestyles factors influenced the association of coffee intake with ED.
Supplementary Material
ACKNOWLEDGMENTS
Author affiliations: Division of Epidemiology, Human Genetics and Environmental Sciences, University of Texas School of Public Health, Houston, Texas (David S. Lopez, Marcia de Oliveira Otto); Division of Urology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, Texas (David S. Lopez, Run Wang, Steven Canfield); Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts (Lydia Liu, Eric B. Rimm, Edward Giovannucci); Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts (Lydia Liu, Eric B. Rimm, Edward Giovannucci); Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts (Eric B. Rimm, Edward Giovannucci); Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece (Konstantinos K. Tsilidis); and Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom (Konstantinos K. Tsilidis).
This work was supported by the National Institutes of Health and by the UTHealth McGovern Medical School-Division of Urology and Dr. Osama I. Mikhail (UTHealth) (grants UM1 CA167552 and R01 HL35464).
Conflict of interest: none declared.
Abbreviations
- BMI
body mass index
- CI
confidence interval
- ED
erectile dysfunction
- FFQ
food frequency questionnaire
- HPFS
Health Professionals Follow-up Study
- HR
hazard ratio
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