madman
Super Moderator
Abstract
Purpose To determine the effect of major antihypertensive classes on erectile function (EF) in patients with or at high risk of cardiovascular disease.
Methods We performed a systematic review and frequentist network meta-analysis of randomized controlled trials assessing the effect of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, β-blockers, calcium channel blockers, and thiazide diuretics on EF compared to each other and to placebo (PROSPERO: CRD42020189529). Similarly, we performed a network meta-analysis to explore the effect of different β-blockers on erectile function (nebivolol, other vasodilating, and nonvasodilating β-blockers, placebo). Records were identified through a search of PubMed, Cochrane Library, and Scopus databases and sources of grey literature until September 2020.
Results We included 25 studies (7784 patients) in the qualitative and 16 studies in the quantitative synthesis. The risk of bias was concerning or high in the majority of studies, and inconsistency was also high. No significant differences in EF were demonstrated in the pairwise comparisons between major antihypertensive classes. Similarly, when placebo was set as the reference treatment group, no treatment strategy yielded significant effects on EF. In the β-blockers analysis, nebivolol contributed a beneficial effect on EF only when compared to non-vasodilatory β-blockers (OR 2.92, 95%CI 1.3–6.5) and not when compared to placebo (OR 2.87, 95%CI 0.75–11.04) or to other vasodilatory β-blockers (OR 2.15, 95%CI 0.6–7.77).
Conclusion All antihypertensive medication classes seem to exert neutral or insignificant effects on EF. Further high-quality studies are needed to better explore the effects of antihypertensive medication on EF.
Introduction
Erectile dysfunction (ED) is a disease, highly prevalent in the general population, and its prevalence increases with age [1, 2]. ED not only exerts a negative influence on the patients’ quality of life, but it is also considered a marker of increased incidence of cardiovascular events [3, 4]. Furthermore, ED clusters with other cardiovascular risk factors, a finding indicating that ED is a manifestation of a systemic vascular disorder [5]. In particular, ED is twice as prevalent and more severe in the hypertensive compared to the general population [6].
To complicate things further, accumulated evidence suggests that antihypertensive agents often exert unfavorable outcomes on erectile function, thus compromising medication adherence, a factor crucial for hypertension management [7, 8]. Hypertension societies have issued recommendations and consensus papers on ED and its association with antihypertensive medications [6, 9]. Based on existing data, such documents suggest that among major antihypertensive classes, thiazide diuretics and β-blockers possess the worst profile regarding erectile function, while angiotensin receptor blockers (ARBs) the most favorable [6, 7, 10]. Still, recommendations do not comprehensively address this matter as they are mostly based on scarce data or evidence from expert opinions [11]. The latter is also reflected in the insufficient knowledge of the effects of cardiovascular medication on sexual function among physicians [12]. Of importance, contrary to other antihypertensive classes, β-blockers display substantial within-class heterogeneity in terms of effectiveness and adverse cardiac and metabolic profile [13]. In particular, experimental and clinical studies suggest that, unlike other βblockers, nebivolol is beneficial in terms of erectile function preservation [13].
*Within this framework, we aimed to systematically synthesize the available evidence and generate a network meta-analysis, aiming to determine the comparative effects of major classes of antihypertensive medications on erectile function. Due to within-class heterogeneity among β-blockers, we also generated a network meta-analysis exploring the effects of different β-blockers on erectile function.
Discussion
This systematic review and network meta-analysis suggest that there is insufficient evidence to support that any of the main antihypertensive classes exert significant detrimental or beneficial effects on erectile function when compared to each other or to placebo. On the comparative leg of the analysis, on a low strength of evidence, all major antihypertensive classes seem to exert a neutral effect on erectile function. Focusing on β-blockers, nebivolol may provide some beneficial effects on erectile function compared to non-vasodilatory β-blockers, on a low strength of evidence. However, compared to placebo or to other vasodilatory β-blockers, nebivolol did not show any significant beneficial effect on erectile function.
Conclusion
Our systematic review and network meta-analysis suggests that all antihypertensive drugs seem to exert a neutral or insignificant effect on erectile function compared to each other or to placebo. Given that evidence is still weak on the matter, our analysis does not support the current ESC/ESH guidelines statement that ED may be induced or aggravated by thiazide diuretics and β-blockers, while ACE-i, ARBs, CCBs, and vasodilating β-blockers may present neutral or even beneficial effects on erectile function. Therefore, carefully designed, large RCTs with standardized interventions and outcome are needed to better explore the effects of antihypertensive medication on erectile function.
Purpose To determine the effect of major antihypertensive classes on erectile function (EF) in patients with or at high risk of cardiovascular disease.
Methods We performed a systematic review and frequentist network meta-analysis of randomized controlled trials assessing the effect of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, β-blockers, calcium channel blockers, and thiazide diuretics on EF compared to each other and to placebo (PROSPERO: CRD42020189529). Similarly, we performed a network meta-analysis to explore the effect of different β-blockers on erectile function (nebivolol, other vasodilating, and nonvasodilating β-blockers, placebo). Records were identified through a search of PubMed, Cochrane Library, and Scopus databases and sources of grey literature until September 2020.
Results We included 25 studies (7784 patients) in the qualitative and 16 studies in the quantitative synthesis. The risk of bias was concerning or high in the majority of studies, and inconsistency was also high. No significant differences in EF were demonstrated in the pairwise comparisons between major antihypertensive classes. Similarly, when placebo was set as the reference treatment group, no treatment strategy yielded significant effects on EF. In the β-blockers analysis, nebivolol contributed a beneficial effect on EF only when compared to non-vasodilatory β-blockers (OR 2.92, 95%CI 1.3–6.5) and not when compared to placebo (OR 2.87, 95%CI 0.75–11.04) or to other vasodilatory β-blockers (OR 2.15, 95%CI 0.6–7.77).
Conclusion All antihypertensive medication classes seem to exert neutral or insignificant effects on EF. Further high-quality studies are needed to better explore the effects of antihypertensive medication on EF.
Introduction
Erectile dysfunction (ED) is a disease, highly prevalent in the general population, and its prevalence increases with age [1, 2]. ED not only exerts a negative influence on the patients’ quality of life, but it is also considered a marker of increased incidence of cardiovascular events [3, 4]. Furthermore, ED clusters with other cardiovascular risk factors, a finding indicating that ED is a manifestation of a systemic vascular disorder [5]. In particular, ED is twice as prevalent and more severe in the hypertensive compared to the general population [6].
To complicate things further, accumulated evidence suggests that antihypertensive agents often exert unfavorable outcomes on erectile function, thus compromising medication adherence, a factor crucial for hypertension management [7, 8]. Hypertension societies have issued recommendations and consensus papers on ED and its association with antihypertensive medications [6, 9]. Based on existing data, such documents suggest that among major antihypertensive classes, thiazide diuretics and β-blockers possess the worst profile regarding erectile function, while angiotensin receptor blockers (ARBs) the most favorable [6, 7, 10]. Still, recommendations do not comprehensively address this matter as they are mostly based on scarce data or evidence from expert opinions [11]. The latter is also reflected in the insufficient knowledge of the effects of cardiovascular medication on sexual function among physicians [12]. Of importance, contrary to other antihypertensive classes, β-blockers display substantial within-class heterogeneity in terms of effectiveness and adverse cardiac and metabolic profile [13]. In particular, experimental and clinical studies suggest that, unlike other βblockers, nebivolol is beneficial in terms of erectile function preservation [13].
*Within this framework, we aimed to systematically synthesize the available evidence and generate a network meta-analysis, aiming to determine the comparative effects of major classes of antihypertensive medications on erectile function. Due to within-class heterogeneity among β-blockers, we also generated a network meta-analysis exploring the effects of different β-blockers on erectile function.
Discussion
This systematic review and network meta-analysis suggest that there is insufficient evidence to support that any of the main antihypertensive classes exert significant detrimental or beneficial effects on erectile function when compared to each other or to placebo. On the comparative leg of the analysis, on a low strength of evidence, all major antihypertensive classes seem to exert a neutral effect on erectile function. Focusing on β-blockers, nebivolol may provide some beneficial effects on erectile function compared to non-vasodilatory β-blockers, on a low strength of evidence. However, compared to placebo or to other vasodilatory β-blockers, nebivolol did not show any significant beneficial effect on erectile function.
Conclusion
Our systematic review and network meta-analysis suggests that all antihypertensive drugs seem to exert a neutral or insignificant effect on erectile function compared to each other or to placebo. Given that evidence is still weak on the matter, our analysis does not support the current ESC/ESH guidelines statement that ED may be induced or aggravated by thiazide diuretics and β-blockers, while ACE-i, ARBs, CCBs, and vasodilating β-blockers may present neutral or even beneficial effects on erectile function. Therefore, carefully designed, large RCTs with standardized interventions and outcome are needed to better explore the effects of antihypertensive medication on erectile function.
