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Testosterone Replacement, Low T, HCG, & Beyond
When Testosterone Is Not Enough
Age related ED: How to Prevent it and Manage it
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<blockquote data-quote="madman" data-source="post: 211564" data-attributes="member: 13851"><p><strong>EAU Guidelines on Management of Non-Neurogenic Male Lower Urinary Tract Symptoms (LUTS), incl. Benign Prostatic Obstruction (BPO) 2021</strong></p><p><strong></strong></p><p><strong></strong></p><p><strong><u>5.2 Pharmacological treatment Male Lower Urinary Tract Symptoms</u></strong></p><p><strong></strong></p><p><strong>5.2.1 α1-Adrenoceptor antagonists (α1-blockers)</strong></p><p><strong></strong></p><p><strong><u>Mechanism of action</u>:</strong> <em><strong>α1-blockers aim to inhibit the effect of endogenously released noradrenaline on smooth muscle cells in the prostate and thereby reduce prostate tone and BOO [139]. </strong>However, α1-blockers have little effect on urodynamically determined bladder outlet resistance [140], and treatment-associated improvement of LUTS correlates poorly with obstruction [141]. Thus, other mechanisms of action may also be relevant. </em></p><p><em></em></p><p><em>Alpha 1-adrenoceptors located outside the prostate (e.g. urinary bladder and/or spinal cord) and α1-adrenoceptor subtypes (α1B- or α1D-adrenoceptors) may play a role as mediators of effects. Alpha 1-adrenoceptors in blood vessels, other non-prostatic smooth muscle cells, and the central nervous system may mediate adverse events.</em></p><p></p><p><strong><u>Currently available α1-blockers are</u> </strong><em>alfuzosin hydrochloride (alfuzosin); doxazosin mesylate (doxazosin); silodosin; tamsulosin hydrochloride (tamsulosin); terazosin hydrochloride (terazosin); and naftopidil. Alpha 1-blockers exist in different formulations. Although different formulations result in different pharmacokinetic and tolerability profiles, the overall difference in clinical efficacy between the different formulations seems modest.</em></p><p></p><p></p><p><strong><u>Tolerability and safety</u>:</strong> <em>Tissue distribution, subtype selectivity, and pharmacokinetic profiles of certain formulations may contribute to the tolerability profile of specific drugs. The most frequent adverse events of α1-blockers are asthenia, dizziness, and (orthostatic) hypotension. <strong>Vasodilating effects are most pronounced with <u>doxazosin and terazosin</u> and are less common with alfuzosin and tamsulosin [150].</strong> Patients with cardiovascular comorbidity and/or vaso-active co-medication may be susceptible to α1-blocker-induced vasodilatation [151]. In contrast, the frequency of hypotension with the α1A-selective blocker silodosin is comparable with placebo [152]. In a large retrospective cohort analysis of men aged > 66 years treated with α1-blockers the risks of falling (odds ratio [OR] 1.14) and of sustaining a fracture (OR 1.16) was increased, most likely as a result of induced hypotension [153].</em></p><p></p><p></p><p><strong><em>An SR concluded that α1-blockers do not adversely affect libido, have a <u>small beneficial effect on erectile function</u>, but can cause abnormal ejaculation [156]. </em></strong>Originally, abnormal ejaculation was thought to be retrograde, but more recent data demonstrate that it is due to a decrease or absence of seminal fluid during ejaculation, with young age being an apparent risk factor. <strong><em>In a recent meta-analysis, ejaculatory dysfunction (EjD) was significantly more common with α1-blockers than with placebo (OR 5.88). In particular, EjD was significantly more commonly related with tamsulosin or silodosin (OR 8.57 and 32.5) than placebo, <u>while both doxazosin and terazosin (OR 0.80 and 1.78) were associated with a low risk of EjD </u>[157].</em></strong> In the metaregression, the occurrence of EjD was independently associated with the improvement of urinary symptoms and flow rate, suggesting that the more effective the α1-blocker is the greater the incidence of EjD.</p></blockquote><p></p>
[QUOTE="madman, post: 211564, member: 13851"] [B]EAU Guidelines on Management of Non-Neurogenic Male Lower Urinary Tract Symptoms (LUTS), incl. Benign Prostatic Obstruction (BPO) 2021 [U]5.2 Pharmacological treatment Male Lower Urinary Tract Symptoms[/U] 5.2.1 α1-Adrenoceptor antagonists (α1-blockers) [U]Mechanism of action[/U]:[/B] [I][B]α1-blockers aim to inhibit the effect of endogenously released noradrenaline on smooth muscle cells in the prostate and thereby reduce prostate tone and BOO [139]. [/B]However, α1-blockers have little effect on urodynamically determined bladder outlet resistance [140], and treatment-associated improvement of LUTS correlates poorly with obstruction [141]. Thus, other mechanisms of action may also be relevant. Alpha 1-adrenoceptors located outside the prostate (e.g. urinary bladder and/or spinal cord) and α1-adrenoceptor subtypes (α1B- or α1D-adrenoceptors) may play a role as mediators of effects. Alpha 1-adrenoceptors in blood vessels, other non-prostatic smooth muscle cells, and the central nervous system may mediate adverse events.[/I] [B][U]Currently available α1-blockers are[/U] [/B][I]alfuzosin hydrochloride (alfuzosin); doxazosin mesylate (doxazosin); silodosin; tamsulosin hydrochloride (tamsulosin); terazosin hydrochloride (terazosin); and naftopidil. Alpha 1-blockers exist in different formulations. Although different formulations result in different pharmacokinetic and tolerability profiles, the overall difference in clinical efficacy between the different formulations seems modest.[/I] [B][U]Tolerability and safety[/U]:[/B] [I]Tissue distribution, subtype selectivity, and pharmacokinetic profiles of certain formulations may contribute to the tolerability profile of specific drugs. The most frequent adverse events of α1-blockers are asthenia, dizziness, and (orthostatic) hypotension. [B]Vasodilating effects are most pronounced with [U]doxazosin and terazosin[/U] and are less common with alfuzosin and tamsulosin [150].[/B] Patients with cardiovascular comorbidity and/or vaso-active co-medication may be susceptible to α1-blocker-induced vasodilatation [151]. In contrast, the frequency of hypotension with the α1A-selective blocker silodosin is comparable with placebo [152]. In a large retrospective cohort analysis of men aged > 66 years treated with α1-blockers the risks of falling (odds ratio [OR] 1.14) and of sustaining a fracture (OR 1.16) was increased, most likely as a result of induced hypotension [153].[/I] [B][I]An SR concluded that α1-blockers do not adversely affect libido, have a [U]small beneficial effect on erectile function[/U], but can cause abnormal ejaculation [156]. [/I][/B]Originally, abnormal ejaculation was thought to be retrograde, but more recent data demonstrate that it is due to a decrease or absence of seminal fluid during ejaculation, with young age being an apparent risk factor. [B][I]In a recent meta-analysis, ejaculatory dysfunction (EjD) was significantly more common with α1-blockers than with placebo (OR 5.88). In particular, EjD was significantly more commonly related with tamsulosin or silodosin (OR 8.57 and 32.5) than placebo, [U]while both doxazosin and terazosin (OR 0.80 and 1.78) were associated with a low risk of EjD [/U][157].[/I][/B] In the metaregression, the occurrence of EjD was independently associated with the improvement of urinary symptoms and flow rate, suggesting that the more effective the α1-blocker is the greater the incidence of EjD. [/QUOTE]
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Testosterone Replacement, Low T, HCG, & Beyond
When Testosterone Is Not Enough
Age related ED: How to Prevent it and Manage it
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