madman
Super Moderator
Abstract
Purpose
Although anti-hypertensive medications, including thiazides and β-blockers (BBs) in particular, have been suggested to cause erectile dysfunction (ED) their real contribution is still conflicting. The aim of this paper is to summarize available evidence providing an evidence-based critical analysis of the topic.
Methods
An overall comprehensive narrative review was performed using Medline, Embase and Cochrane search. In addition, to better understand the impact of BBs on ED a specific systematic review was also performed.
Results
The negative role of centrally acting drugs, such as clonidine and α-methyldopa, is well documented although limited controlled trials are available. Angiotensin-converting enzyme inhibitors (ACEis), angiotensin receptor blockers (ARBs), and calcium-channel-blockers (CCBs) have neutral (CCBs) or even positive (ACEis and ARBs) effects on erectile function. Despite some preliminary negative reports, more recent evidence does not confirm the negative impact of thiazides. BBs should be still considered the class of medications more often associated with ED, although better outcomes can be drawn with nebivolol.
Conclusion
Sexual function should be assessed in all patients with arterial hypertension, either at diagnosis or after the prescription of specific medications. A close related patient-physician interaction and discussion can overcome possible negative outcomes allowing a successful management of possible side effects.
Introduction
Arterial hypertension (AH) represents a well-recognized public health issue estimated to affect over one billion individuals worldwide [1] as well as an established risk factor for the development of cardiovascular disease (CVD), chronic kidney disease (CKD), cognitive decline and premature mortality [2, 3]. The blood pressure (BP) lowering effect of antihypertensive medications offers considerable benefits in reducing the impact of such morbidities and related mortality [4]. However, evidence about their possible negative impact on male sexual function is still the object of an intense debate [5, 6]. The Treatment of Mild Hypertension Study (TOMHS) was one of the first large population trials describing an association between AH and sexual dysfunction in both male and female participants [7].Since then, a large body of evidence clarified how the presence of AH is associated to an increased risk of erectile dysfunction (ED) across different study populations [8–12].Accordingly, available data suggest that ED is two-times higher in subjects with AH when compared to those derived from the general population [13]. Several pathogenetic mechanisms have been suggested including either central (e.g. catecholamine depletion) or peripheral mechanisms (e.g. metabolic and hormonal profile impairment; see also below) [5, 6, 14]. Notably, antihypertensive medications such as thiazide and β-blockers (BBs) have been found, more frequently than others, to play a detrimental role on sexual function [2, 6, 13, 14]. Calcium-channel-blockers(CCBs) or α-blockers (ABs) have shown essentially neutral effects on ED [6, 14], although negative role of α-blockerson ejaculatory function have been reported [15]. Conversely, angiotensin receptor blockers (ARBs) have been suggested to exert the most favourable impact on erectile function [2, 6, 14]. However, it should be recognized that the available evidence is still poor and often derived from expert opinion, rather than evidence-based data. Similarly, the net impact of BBs on male sexual function in men suffering AH is still a matter of debate. While some older trials, based on self-reported erectile function, pointed towards a possible sexual impairment in both healthy and hypertensive men [16, 17], others, based on standardized erectile function assessment methods (International Index of Erectile Function or IIEF), could not confirm such an association [18]. Similarly, a large network meta-analysis including 25 studies accounting for more than 7700 patients showed a neutral effect on erectile function [5]. In addition,there is evidence suggesting that patient knowledge and prejudice about BB side effects could represent a major determinant of ED onset [19]. Moreover, the different pharmacodynamic profiles of BB action are likely responsible for the different impacts on sexual function observed when different molecules are compared; indeed working evidence showed how nebivolol, a third generation BB, is rather associated with slight improvement [20] or no impact on patient IIEF (see below [21]).
The aim of the present review is to provide a summary of the available data related to the possible association between ED and the use of AH medications with a particular focus on the impact of BBs.
*Antihypertensive drugs and ED in symptomatic patients
*Antihypertensive drugs and ED in the general population
*Central acting-drugs: clonidine and α-methyldopa
*Diuretics
*Calcium-channel blockers
*ACE-inhibitors and angiotensin-receptor blockers
*Beta-blockers
Several limitations should be recognized. The quality of the available studies assessing the impact of AH medications on ED is overall modest or poor and only a limited number of well-designed placebo-controlled RCTs are available. In addition, it should be recognized that erectile function data were often not considered the main outcome of the available studies. Finally, in the vast majority of cases, sexual function was derived from patient self reported questions rather than from validated questionnaires.
In conclusion, in line with what was previously reported [5, 13, 30, 38, 87], we showed that BBs represent the class of AH medications more often associated with ED, although better results can be obtained with the use of nebivolol. However, we need to clarify that in many cases, the observed negative effects on ED can be managed with adequate information, preventing negative prejudices and wrong beliefs that can result in worse long-term mortality and morbidity outcomes. In line with what was reported by the ESH [2] and our Society [6], sexual function should be assessed in all patients with AH at diagnosis and after the introduction of specific medications. Although conflicting results have been reported, the use of BBs should be recommended in the presence of specific indications, including angina, post-myocardial infarction, heart failure or when heart-rate control is required [2]. This approach can allow to overcome negative outcomes related to the use of AH drugs and to adequately and timely manage possible side effects.
Purpose
Although anti-hypertensive medications, including thiazides and β-blockers (BBs) in particular, have been suggested to cause erectile dysfunction (ED) their real contribution is still conflicting. The aim of this paper is to summarize available evidence providing an evidence-based critical analysis of the topic.
Methods
An overall comprehensive narrative review was performed using Medline, Embase and Cochrane search. In addition, to better understand the impact of BBs on ED a specific systematic review was also performed.
Results
The negative role of centrally acting drugs, such as clonidine and α-methyldopa, is well documented although limited controlled trials are available. Angiotensin-converting enzyme inhibitors (ACEis), angiotensin receptor blockers (ARBs), and calcium-channel-blockers (CCBs) have neutral (CCBs) or even positive (ACEis and ARBs) effects on erectile function. Despite some preliminary negative reports, more recent evidence does not confirm the negative impact of thiazides. BBs should be still considered the class of medications more often associated with ED, although better outcomes can be drawn with nebivolol.
Conclusion
Sexual function should be assessed in all patients with arterial hypertension, either at diagnosis or after the prescription of specific medications. A close related patient-physician interaction and discussion can overcome possible negative outcomes allowing a successful management of possible side effects.
Introduction
Arterial hypertension (AH) represents a well-recognized public health issue estimated to affect over one billion individuals worldwide [1] as well as an established risk factor for the development of cardiovascular disease (CVD), chronic kidney disease (CKD), cognitive decline and premature mortality [2, 3]. The blood pressure (BP) lowering effect of antihypertensive medications offers considerable benefits in reducing the impact of such morbidities and related mortality [4]. However, evidence about their possible negative impact on male sexual function is still the object of an intense debate [5, 6]. The Treatment of Mild Hypertension Study (TOMHS) was one of the first large population trials describing an association between AH and sexual dysfunction in both male and female participants [7].Since then, a large body of evidence clarified how the presence of AH is associated to an increased risk of erectile dysfunction (ED) across different study populations [8–12].Accordingly, available data suggest that ED is two-times higher in subjects with AH when compared to those derived from the general population [13]. Several pathogenetic mechanisms have been suggested including either central (e.g. catecholamine depletion) or peripheral mechanisms (e.g. metabolic and hormonal profile impairment; see also below) [5, 6, 14]. Notably, antihypertensive medications such as thiazide and β-blockers (BBs) have been found, more frequently than others, to play a detrimental role on sexual function [2, 6, 13, 14]. Calcium-channel-blockers(CCBs) or α-blockers (ABs) have shown essentially neutral effects on ED [6, 14], although negative role of α-blockerson ejaculatory function have been reported [15]. Conversely, angiotensin receptor blockers (ARBs) have been suggested to exert the most favourable impact on erectile function [2, 6, 14]. However, it should be recognized that the available evidence is still poor and often derived from expert opinion, rather than evidence-based data. Similarly, the net impact of BBs on male sexual function in men suffering AH is still a matter of debate. While some older trials, based on self-reported erectile function, pointed towards a possible sexual impairment in both healthy and hypertensive men [16, 17], others, based on standardized erectile function assessment methods (International Index of Erectile Function or IIEF), could not confirm such an association [18]. Similarly, a large network meta-analysis including 25 studies accounting for more than 7700 patients showed a neutral effect on erectile function [5]. In addition,there is evidence suggesting that patient knowledge and prejudice about BB side effects could represent a major determinant of ED onset [19]. Moreover, the different pharmacodynamic profiles of BB action are likely responsible for the different impacts on sexual function observed when different molecules are compared; indeed working evidence showed how nebivolol, a third generation BB, is rather associated with slight improvement [20] or no impact on patient IIEF (see below [21]).
The aim of the present review is to provide a summary of the available data related to the possible association between ED and the use of AH medications with a particular focus on the impact of BBs.
*Antihypertensive drugs and ED in symptomatic patients
*Antihypertensive drugs and ED in the general population
*Central acting-drugs: clonidine and α-methyldopa
*Diuretics
*Calcium-channel blockers
*ACE-inhibitors and angiotensin-receptor blockers
*Beta-blockers
Several limitations should be recognized. The quality of the available studies assessing the impact of AH medications on ED is overall modest or poor and only a limited number of well-designed placebo-controlled RCTs are available. In addition, it should be recognized that erectile function data were often not considered the main outcome of the available studies. Finally, in the vast majority of cases, sexual function was derived from patient self reported questions rather than from validated questionnaires.
In conclusion, in line with what was previously reported [5, 13, 30, 38, 87], we showed that BBs represent the class of AH medications more often associated with ED, although better results can be obtained with the use of nebivolol. However, we need to clarify that in many cases, the observed negative effects on ED can be managed with adequate information, preventing negative prejudices and wrong beliefs that can result in worse long-term mortality and morbidity outcomes. In line with what was reported by the ESH [2] and our Society [6], sexual function should be assessed in all patients with AH at diagnosis and after the introduction of specific medications. Although conflicting results have been reported, the use of BBs should be recommended in the presence of specific indications, including angina, post-myocardial infarction, heart failure or when heart-rate control is required [2]. This approach can allow to overcome negative outcomes related to the use of AH drugs and to adequately and timely manage possible side effects.
