The Italian Society of Andrology and Sexual Medicine (SIAMS), along with ten other Italian Scientific Societies, guidelines on the diagnosis and management of erectile dysfunction (2023)
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The Italian Society of Andrology and Sexual Medicine (SIAMS), along with ten other Italian Scientific Societies, guidelines on the diagnosis and management of erectile dysfunction
Iatrogenic medical
Recommendation #17. All patients treated with anti-androgenic drugs must be informed about possible negative effects on erectile function (Good clinical Practice).
Recommendation #18. We recommend investigating erectile function in all men treated with most antidepressants or antipsychotic medications (1ØØØØ).
Recommendation #19. We suggest investigating sexual function in young patients with a history of previous treatment with drugs affecting the serotoninergic pathway or the conversion of testosterone to dihydrotestosterone (2ØOOO).
Recommendation #20. We suggest against using beta-blockers as a first-line therapy in patients with de-novo diagnosed arterial hypertension, if no specific cardiological indications are present (2ØOO).
Evidence
As reported above, T is the key regulator of male sexual response. Hence, the occurrence of ED in men treated with drugs with anti-androgenic effects is not surprising. Accordingly, a recent meta-analysis of the available studies documented that androgen deprivation therapy in patients with prostate cancer resulted in a 5- to sixfold increased risk of reduced libido and in a threefold increased risk of ED [113, 114]. Similar observations can be drawn when 5-alpha reductase inhibitors (5-ARIs) are considered, in fact they were associated with an up to 70% increased risk of ED [104].
Since the mechanism of action of several antipsychotic or antidepressant medications is based on the modulation of serotonergic (increasing) and dopaminergic (decreasing) transmission, the use of these drugs is frequently associated with the development of ED or with male sexual function impairment [115]. Among anti-psychotics, quetiapine, ziprasidone, perphenazine, aripiprazole and brexpiprazole (with the last two associated with the lowest impact on sexual life) have been related to lower rates of sexual dysfunction (16–27%), when compared to olanzapine, risperidone, haloperidol, and clozapine (40–60%), probably as a consequence of their lower effect on PRL increase [116]. Among antidepressants, bupropion, a norepinephrine and dopamine reuptake inhibitor, has shown limited or no influence on sexual dysfunction, both when depressed population and healthy volunteers were considered [115]. Similarly, antidepressants with a mixed (serotonergic and norepinephrine/ dopamine) mechanism of action were associated with lower sexual side effects when compared to pure serotonin-reuptake inhibitors (SSRI) [117]. Among pure SSRI, vortioxetine is a serotonin transporter blocker also interacting with several serotoninergic receptors (antagonist for the 5-HT3 and 5-HT7 receptors, partial agonist for 5-HT1B, and agonist for 5-HT1A). Due to these peculiar properties, vortioxetine has shown lower sexual side effects when compared to other SSRIs [115, 118].
Persistent sexual dysfunction after discontinuation of SSRIs, 5-ARIs, and isotretinoin has been reported and named post-SSRI sexual dysfunction (PSSD), post-finasteride syndrome (PFS), and post-retinoid sexual dysfunction (PRSD), with anhedonia, pathognomonic sexual anesthesia and ED as frequent but not unique symptoms referred by the patients. These syndromes, which appear more common in young males, despite a lack of specific treatment, deserve careful sexological, medical, and psychiatric attention [119].
Several anti-hypertensive medications have been often inappropriately associated with ED. Among them, β-blockers and thiazide diuretics were those with the highest incidence of ED [37]. However, it should be emphasized that the vast majority of the reports come from observational and uncontrolled trials limiting the evidence. Recently, it has been performed a network meta-analysis exploring the role of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, β-blockers, calcium channel blockers, and thiazide diuretics on erectile function when compared to each other and to placebo [37]. By including 25 studies and 7784 patients, it has been reported no significant differences in erectile function among the aforementioned anti-hypertensive classes in pairwise comparisons. Similar data were derived when placebo RCTs were considered. In addition, when different classes of β-blockers were analyzed, nebivolol resulted in less significant effects on erectile function when compared to non-vasodilatory β-blockers but not when placebo was considered [37]. In line with these data, almost 20 years ago, Silvestri et al., [120], in a well-designed RCT, documented that the negative effects related to the use of β-blockers on erectile function are strongly influenced by the knowledge and prejudice about their related side effects commonly called “nocebo effects”.
Remarks
As reported above, a recent meta-analysis of the available RCTs did not confirm the frequently reported increased risk of ED related to the use of β-blockers. However, it is important to recognize that the quality of the available evidence is limited, and the same authors recognized that the risk of bias was high or at least concerning in the majority of studies included in their analysis [37]. Hence, it is our opinion that β-blockers should not be used as a first-line therapy especially in young de novo subjects with arterial hypertension and low CV risk.
Full text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9876440/
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