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Effect of alpha-adrenoceptor antagonists on sexual function. A systematic review and meta-analysis (2022)
Rawa Bapir, Kamran Hassan Bhatti, Ahmed Eliwa, Herney Andrés García-Perdomo, Nazim Gherabi, Derek Hennessey, Vittorio Magri, Panagiotis Mourmouris,Adama Ouattara, Gianpaolo Perletti, Joseph Philipraj, Alberto Trinchieri, Noor Buchholz
Background: Alpha-adrenoreceptor antagonists or alpha-blockers are used in the treatment of hypertension, in the therapy of benign prostatic hyperplasia, and in medical expulsive treatment of ureteral stones. These agents may affect sexual function, with differences between drugs within the same class, depending on their selectivity for receptor subtypes. The aim of this review was to analyze the effects of alpha-blockers on sexual function.
Materials and methods: We conducted a systematic review and meta-analysis by searching PubMed, EMBASE, and other databases for randomized controlled trials (RCTs) reporting sexual adverse effects in patients treated with alpha-blockers. Odds ratios for sexual dysfunction were calculated using random-effects Mantel-Haenszel statistics.
Results: Out of 608 records retrieved, 75 eligible RCTs were included in the meta-analysis. Compared with placebo, alpha-blockers were associated with increased odds of ejaculatory disorders both in patients with lower urinary tract symptoms (LUTS) associated to benign prostatic hyperplasia (BPH) (OR: 7.53, 95% CI: 3.77-15.02, Z = 5.73, p < 0.00001, I2 = 55%) and in patients with ureteral stones (OR: 2.88, 95% CI: 1.50-5.44, Z = 3.19, p < 0.001, I2 = 31%). Uroselective alpha-blockers showed higher odds of ejaculatory disorders. Conversely, nonselective alpha-blockers were not associated with higher odds of ejaculatory dysfunction. Silodosin was associated with increased odds of ejaculatory dysfunction compared with tamsulosin (OR: 3.52, 95% CI: 2.18-5.68, 15 series, 1512 participants, Z = 5.15, p < 0.00001, I2 = 0%). Naftopidil and alfuzosin showed lower odds of ejaculatory dysfunction compared to uroselective alpha-blockers.
No statistically significant differences in the odds of erectile dysfunction were observed when alpha-blockers were compared to placebo.
INTRODUCTION
Alpha adrenergic receptor (or adrenoreceptor) antagonists, also known as alpha-blockers, are a class of pharmacological agents acting as antagonists on various alpha-adrenergic receptors. Depending on receptor specificity, they bind and inhibit alpha1-receptors, alpha2-receptors, or both (1).
Alpha-1 adrenergic antagonists bind to type-1 alpha-adrenergic receptors, thus inhibiting smooth muscle contraction. Several subtypes of postsynaptic alpha1 receptors are present in vascular and nonvascular smooth muscle. Alpha 1A receptors are predominantly located in the smooth muscle of the genitourinary tract, where they regulate the tone of the bladder neck and of the smooth muscle fibers within the prostate. Alpha 1B receptors are more represented in the vascular smooth muscle and are involved in the regulation of the vascular tone. Receptors belonging to the alpha1D subtype regulate the contraction of the urinary bladder (2). The effects of alpha-adrenergic blocking agents depend on their selectivity (or non-selectivity) for specific receptor subtypes.
Nonselective alpha-1-adrenergic antagonists have been used for decades against hypertension. Blockade of alpha1B receptors can decrease vascular resistance in peripheral arterioles and increase venous capacitance, ultimately lowering blood pressure (3). At present, alpha1 adrenergic antagonists are no longer recommended as monotherapy, but only as adjunctive treatment of hypertension (4). Alpha-1-blockers are used for the treatment of symptoms of urinary obstruction due to benign prostatic hyperplasia because they can relax the smooth muscle fiber in the bladder neck and in prostate acting on alpha1A receptors. Initially, nonselective alpha-1 adrenergic antagonists such as doxazosin, terazosin, and alfuzosin were used for the management of bladder neck obstruction (5). Selective alpha1A blockers with high affinity for the alpha1A adrenergic receptor, such as tamsulosin and silodosin, have been subsequently developed to be specifically used in benign prostatic hyperplasia. Selectivity of these agents was aimed at decreasing their effect on blood pressure and at reducing the risk of unwanted effects, such as postural hypotension
Alpha1D-adrenoceptor antagonists have also been shown to be effective in alleviating both voiding and storage LUTS associated with BPH. Naftopidil is an alpha-1 adrenoceptor antagonist with a distinct selectivity for the alpha1D receptor showing a threefold selectivity for the alpha1D-adrenoceptor compared to the alpha1A-adrenoceptor (6). It is used for BPH management in Japan because of its fewer side effects, but there is limited evidence of its effectiveness in other populations (7). Alpha-1-adrenergic antagonists are also used to facilitate the spontaneous passage of stones in the distal ureter. When alpha-1-adrenergic antagonists are administered for benign prostatic hyperplasia and for medical expulsive therapy, their effect at various sites of the urogenital tract may affect sexual function, with differences between drugs within the same class.
The aim of this study is to review the existing evidence on the effect of alpha-1-adrenergic antagonists on sexual function.
DISCUSSION
Alpha-1 adrenoceptor blockers have been shown to be very effective in counteracting lower urinary tract symptoms associated with benign prostatic hyperplasia (85, 86), as well as in facilitating the spontaneous passage of stones from the distal ureter (87, 88). However, this class of drugs can lead to cardiovascular side effects and sexual dysfunction, thus potentially worsening the quality of life of patients and possibly causing a reduction in compliance to long-term treatment. Since alpha-adrenergic receptors are highly expressed in male genital organs, the adrenergic blockade can potentially affect erection, ejaculation, and sexual desire.
*Ejaculation
*Erection
CONCLUSIONS
In conclusion, because of the different effects of alpha1- adrenergic antagonists on sexuality, the sexual function of each patient should be assessed and discussed when alpha-blocker therapy is planned, and patients should be informed about the potential side effects of such treatment. When prescribing a specific alpha-blocker, the specialist should consider the needs and expectations of the patient, to ensure the best possible quality of life.
Rawa Bapir, Kamran Hassan Bhatti, Ahmed Eliwa, Herney Andrés García-Perdomo, Nazim Gherabi, Derek Hennessey, Vittorio Magri, Panagiotis Mourmouris,Adama Ouattara, Gianpaolo Perletti, Joseph Philipraj, Alberto Trinchieri, Noor Buchholz
Background: Alpha-adrenoreceptor antagonists or alpha-blockers are used in the treatment of hypertension, in the therapy of benign prostatic hyperplasia, and in medical expulsive treatment of ureteral stones. These agents may affect sexual function, with differences between drugs within the same class, depending on their selectivity for receptor subtypes. The aim of this review was to analyze the effects of alpha-blockers on sexual function.
Materials and methods: We conducted a systematic review and meta-analysis by searching PubMed, EMBASE, and other databases for randomized controlled trials (RCTs) reporting sexual adverse effects in patients treated with alpha-blockers. Odds ratios for sexual dysfunction were calculated using random-effects Mantel-Haenszel statistics.
Results: Out of 608 records retrieved, 75 eligible RCTs were included in the meta-analysis. Compared with placebo, alpha-blockers were associated with increased odds of ejaculatory disorders both in patients with lower urinary tract symptoms (LUTS) associated to benign prostatic hyperplasia (BPH) (OR: 7.53, 95% CI: 3.77-15.02, Z = 5.73, p < 0.00001, I2 = 55%) and in patients with ureteral stones (OR: 2.88, 95% CI: 1.50-5.44, Z = 3.19, p < 0.001, I2 = 31%). Uroselective alpha-blockers showed higher odds of ejaculatory disorders. Conversely, nonselective alpha-blockers were not associated with higher odds of ejaculatory dysfunction. Silodosin was associated with increased odds of ejaculatory dysfunction compared with tamsulosin (OR: 3.52, 95% CI: 2.18-5.68, 15 series, 1512 participants, Z = 5.15, p < 0.00001, I2 = 0%). Naftopidil and alfuzosin showed lower odds of ejaculatory dysfunction compared to uroselective alpha-blockers.
No statistically significant differences in the odds of erectile dysfunction were observed when alpha-blockers were compared to placebo.
INTRODUCTION
Alpha adrenergic receptor (or adrenoreceptor) antagonists, also known as alpha-blockers, are a class of pharmacological agents acting as antagonists on various alpha-adrenergic receptors. Depending on receptor specificity, they bind and inhibit alpha1-receptors, alpha2-receptors, or both (1).
Alpha-1 adrenergic antagonists bind to type-1 alpha-adrenergic receptors, thus inhibiting smooth muscle contraction. Several subtypes of postsynaptic alpha1 receptors are present in vascular and nonvascular smooth muscle. Alpha 1A receptors are predominantly located in the smooth muscle of the genitourinary tract, where they regulate the tone of the bladder neck and of the smooth muscle fibers within the prostate. Alpha 1B receptors are more represented in the vascular smooth muscle and are involved in the regulation of the vascular tone. Receptors belonging to the alpha1D subtype regulate the contraction of the urinary bladder (2). The effects of alpha-adrenergic blocking agents depend on their selectivity (or non-selectivity) for specific receptor subtypes.
Nonselective alpha-1-adrenergic antagonists have been used for decades against hypertension. Blockade of alpha1B receptors can decrease vascular resistance in peripheral arterioles and increase venous capacitance, ultimately lowering blood pressure (3). At present, alpha1 adrenergic antagonists are no longer recommended as monotherapy, but only as adjunctive treatment of hypertension (4). Alpha-1-blockers are used for the treatment of symptoms of urinary obstruction due to benign prostatic hyperplasia because they can relax the smooth muscle fiber in the bladder neck and in prostate acting on alpha1A receptors. Initially, nonselective alpha-1 adrenergic antagonists such as doxazosin, terazosin, and alfuzosin were used for the management of bladder neck obstruction (5). Selective alpha1A blockers with high affinity for the alpha1A adrenergic receptor, such as tamsulosin and silodosin, have been subsequently developed to be specifically used in benign prostatic hyperplasia. Selectivity of these agents was aimed at decreasing their effect on blood pressure and at reducing the risk of unwanted effects, such as postural hypotension
Alpha1D-adrenoceptor antagonists have also been shown to be effective in alleviating both voiding and storage LUTS associated with BPH. Naftopidil is an alpha-1 adrenoceptor antagonist with a distinct selectivity for the alpha1D receptor showing a threefold selectivity for the alpha1D-adrenoceptor compared to the alpha1A-adrenoceptor (6). It is used for BPH management in Japan because of its fewer side effects, but there is limited evidence of its effectiveness in other populations (7). Alpha-1-adrenergic antagonists are also used to facilitate the spontaneous passage of stones in the distal ureter. When alpha-1-adrenergic antagonists are administered for benign prostatic hyperplasia and for medical expulsive therapy, their effect at various sites of the urogenital tract may affect sexual function, with differences between drugs within the same class.
The aim of this study is to review the existing evidence on the effect of alpha-1-adrenergic antagonists on sexual function.
DISCUSSION
Alpha-1 adrenoceptor blockers have been shown to be very effective in counteracting lower urinary tract symptoms associated with benign prostatic hyperplasia (85, 86), as well as in facilitating the spontaneous passage of stones from the distal ureter (87, 88). However, this class of drugs can lead to cardiovascular side effects and sexual dysfunction, thus potentially worsening the quality of life of patients and possibly causing a reduction in compliance to long-term treatment. Since alpha-adrenergic receptors are highly expressed in male genital organs, the adrenergic blockade can potentially affect erection, ejaculation, and sexual desire.
*Ejaculation
*Erection
CONCLUSIONS
In conclusion, because of the different effects of alpha1- adrenergic antagonists on sexuality, the sexual function of each patient should be assessed and discussed when alpha-blocker therapy is planned, and patients should be informed about the potential side effects of such treatment. When prescribing a specific alpha-blocker, the specialist should consider the needs and expectations of the patient, to ensure the best possible quality of life.
