Results from this prospective study provide support for a positive association between LUTS and incident ED. The increasing risk of ED with increasing AUA symptom score was observed with both standard categories and quintiles of the score. The positive association was stronger when men without any of the six symptoms were the referent. We also found that the association between LUTS and ED may be stronger in younger men.
Because most studies to date have been cross-sectional, we also performed a cross-sectional analysis (versus 0–7, 8–14: RR=1.28, 15–19: RR=1.36, 20–35: RR=1.44) and these findings were comparable to our prospective results. The inferences from our cross-sectional results and those previously published are the same. Cross-sectional studies have reported ORs for the LUTS-ED association ranging from 1.39 to 9.9. 2,5,8,9,12,13,15
Only one study 18
reported no association between LUTS and ED, but it had methodologic limitations.
Our results are similar to those from the one published prospective study (comparing LUTS ≥12 to 0 OR=3.1, 95%CI 1.5–6.4). 16
However, our substantially larger study allowed us to categorize LUTS into finer categories and conduct stratified analyses, as well as multiple sensitivity analyses.
Although our results are consistent with the existing literature, it is difficult to compare the magnitude of our results with those from previous studies. First, LUTS was not consistently categorized among studies. In the other prospective study, men with a score ≥ 12 were compared with men with a score of 0 16
; other studies selected different cutpoints. Second, the previous studies reported odds ratios as estimates of the risk ratio, whereas we report risk ratios. Because LUTS and ED are common among older men, for positive associations, the odds ratio will overestimate the risk ratio. Therefore, our directly calculated risk ratios are somewhat smaller than previous estimates for this association.
Several possible noncausal and causal explanations for the apparent association between LUTS and ED exist.
- ED and LUTS are both strongly positively associated with age, which could lead to their spurious association if age is not fully taken into account 19; most of the prior studies took into account age to some extent,2,6–9,11–14,16 although one did not. 10
- LUTS and ED share many similar risk factors, which could cause an apparent statistical association even if a biological association does not exist. Although some of the prior studies conducted multivariable adjustment 2,5,6,9,13,16, many did not. 7,8,10–12,14,15
- Treatment for LUTS may influence ED. 19 5α-Reductase inhibitors have been shown to decrease sexual function, whereas some evidence suggests that α1-adrenergic receptor blockers may improve sexual function. 19 In the past, transurethral resection of the prostate (TURP) was a common surgical treatment for LUTS and studies have reported differing information as to how surgery influences sexual function. 19
- Several pathophysiologic pathways may underlie both conditions. Increased α1-adrenergic activity and changes in α1-adrenergic receptor subtypes expressed increase smooth muscle tone; these changes may be common causes of both LUTS and ED. 19 Decreases in nitric oxide bioavailability in older men may cause endothelial dysfunction, which may lead to both LUTS and ED. 19
- BPH nodules, which may compress the urethra and produce LUTS, may be an independent risk factor for ED. This hypothesis is supported by studies suggesting that removal of BPH nodules during TURP improves erectile function. 20
- Decreased quality of life associated with LUTS may have a negative psychological influence that may manifest as decreased sexual function. 19
Our results suggest that the association between LUTS and ED is not due to residual confounding by age or solely the effect of treatment: we controlled for age as a continuous variable and created separate categories of exposure for men who had received treatment for LUTS and still observed in untreated men an association between LUTS and ED. We observed an increased risk of ED among men who had undergone surgery or were taking medication for BPH compared with men with no or low LUTS, although their ED risk was lower than for men with severe LUTS. It is not clear whether this finding is due to BPH treatment or reflects that men who received treatment had worse LUTS. Alternatively, these findings may suggest that treatment for severe LUTS moderates ED risk in men with severe LUTS.
Residual confounding by risk factors for LUTS and ED, particularly co-morbidities, is unlikely because the associations were unchanged when restricted analyses were conducted. Nevertheless, it is possible that our results could be partly explained by confounding by unrecognized, shared risk factors for LUTS and ED. Our results cannot distinguish among the other proposed explanations for the association between LUTS and ED.
The association between LUTS and ED was more pronounced among younger than older men, although the absolute increase in risk was comparable (~15% increase comparing severe to no/low symptoms). In younger men, a greater proportion of ED may be caused by the same pathophysiologic mechanisms that cause LUTS in older men, but in older men a greater proportion of ED may be caused by other factors, such as co-morbidities. Alternatively, the difference by age may reflect a difference in the accuracy of reporting ED by age because of differential expectations by age about the quality of erectile function.
The prospective design and large sample size are strengths of our study. We assessed both LUTS and ED by mailed questionnaires, which may have minimized embarrassment and increased the accuracy of report. Further, because LUTS status was collected prior to occurrence and assessment of ED, the extent of any inaccuracy in the report of LUTS is unlikely to be different by ED status, and any such bias would tend to attenuate the association. We asked the men in 2000 when in the past they first experienced ED, and thus, there is the potential for inaccurate recollection of ED. However, the association between LUTS and incident ED was comparable for both remotely recollected ED (back to 1995) and for very recently recollected ED (in the past 3 months), suggesting that inaccurate remote recall is not greatly influencing the observed association.