Medical therapy for lower urinary tract symptoms (LUTS) is imperfect. While both alpha blockers (ABs) and 5-alpha reductase inhibitors (5ARIs) were effective when compared to placebo in reducing patient symptoms in large randomized clinical trials (RCTs), the effect was not as large as most patients and clinicians would like [1], [2], and [3]. For example, men in the Medical Therapy of Prostatic Symptoms study [1] randomized to combination AB and 5ARI therapy had a median reduction of 7.4 points in American Urological Association (AUA) symptom score at 4 yr. This, however, is much less impressive when considering that men in the placebo arm had a median reduction in symptom score of 4.9 points at the same time point. In fact, numerous RCTs have reported a strong placebo effect in the control arm [3] and [4] When this is considered in combination with the relatively high rate of side effects associated with the various interventions in these trials [1] and [2], it is not surprising that many patients with LUTS ultimately decide to discontinue their medications. In some cases, these patients may elect for surgical interventions, but many choose to just live with their symptoms.
In this issue of European Urology, Cindolo and colleagues [5] present data that confirm what others have also shown [6] : long-term adherence rates for AB and 5ARI medications are very low. Using a population-based administrative database of pharmacy claims from Italy, they identified 213 936 men older than 40 yr who received at least one prescription for AB or 5ARI therapy (alone or in combination). Of these, 97 407 (46%) completed 6 mo of therapy and constituted the analytic cohort. The 1-yr adherence across all LUTS medication types was only 29% among these patients. Combination therapy with ABs and 5ARIs had the lowest 1-yr adherence rates, with only 9% of patients continuing combination therapy, compared to 18% on 5ARIs alone and 35% on ABs alone. Patients who discontinued medical therapy, regardless of type, were 2.8 times more likely to be hospitalized for benign prostatic hyperplasia (BPH)-related surgery. Furthermore, patients on 5ARI or combination therapy were significantly less likely to be hospitalized for BPH surgery. Given these findings, the authors conclude that because adherence was low and may affect clinical outcomes, “there is a need for new strategies to increase patient adherence to prescribed treatment and more appropriate prescribing by physicians.” This conclusion is based on an implicit assumption that discontinuation of the LUTS medication caused patients to require additional treatment, and that had patients simply stayed on the medication, no additional treatment would have been needed. In my opinion, this assumption may not be true.
It is a basic epidemiologic tenet that association in prospective observational cohort studies does not necessarily equate to causation [7] . In the current example, it is possible that discontinuation of the medication directly resulted in disease progression, but it is more likely that the medication either did not adequately reduce patient symptoms or was associated with side effects that resulted in patients electing to stop the treatment. Should we therefore design interventions to increase adherence to these problematic and minimally effective drugs? Obviously not; we might as well attempt to increase adherence to placebo agents. After all, 40% of patients in the placebo arm of the American phase 3 registration trial for tamsulosin experienced more than a 25% improvement in AUA symptom score compared to baseline [4] . I believe that discontinuation rates for these agents are primarily a reflection of their effectiveness (or lack thereof) and their side-effect profiles. Our focus needs to be on developing agents and interventions that are more effective and make patients feel better, as opposed to trying to get patients to be more compliant with the current drug regimens.
Medical therapy for lower urinary tract symptoms (LUTS) is imperfect. While both alpha blockers (ABs) and 5-alpha reductase inhibitors (5ARIs) were effective when compared to placebo in reducing patient symptoms in large randomized clinical trials (RCTs), the effect was not as large as most patients and clinicians would like [1], [2], and [3]. For example, men in the Medical Therapy of Prostatic Symptoms study [1] randomized to combination AB and 5ARI therapy had a median reduction of 7.4 points in American Urological Association (AUA) symptom score at 4 yr. This, however, is much less impressive when considering that men in the placebo arm had a median reduction in symptom score of 4.9 points at the same time point. In fact, numerous RCTs have reported a strong placebo effect in the control arm [3] and [4] When this is considered in combination with the relatively high rate of side effects associated with the various interventions in these trials [1] and [2], it is not surprising that many patients with LUTS ultimately decide to discontinue their medications. In some cases, these patients may elect for surgical interventions, but many choose to just live with their symptoms.
In this issue of European Urology, Cindolo and colleagues [5] present data that confirm what others have also shown [6] : long-term adherence rates for AB and 5ARI medications are very low. Using a population-based administrative database of pharmacy claims from Italy, they identified 213 936 men older than 40 yr who received at least one prescription for AB or 5ARI therapy (alone or in combination). Of these, 97 407 (46%) completed 6 mo of therapy and constituted the analytic cohort. The 1-yr adherence across all LUTS medication types was only 29% among these patients. Combination therapy with ABs and 5ARIs had the lowest 1-yr adherence rates, with only 9% of patients continuing combination therapy, compared to 18% on 5ARIs alone and 35% on ABs alone. Patients who discontinued medical therapy, regardless of type, were 2.8 times more likely to be hospitalized for benign prostatic hyperplasia (BPH)-related surgery. Furthermore, patients on 5ARI or combination therapy were significantly less likely to be hospitalized for BPH surgery. Given these findings, the authors conclude that because adherence was low and may affect clinical outcomes, “there is a need for new strategies to increase patient adherence to prescribed treatment and more appropriate prescribing by physicians.” This conclusion is based on an implicit assumption that discontinuation of the LUTS medication caused patients to require additional treatment, and that had patients simply stayed on the medication, no additional treatment would have been needed. In my opinion, this assumption may not be true.
It is a basic epidemiologic tenet that association in prospective observational cohort studies does not necessarily equate to causation [7] . In the current example, it is possible that discontinuation of the medication directly resulted in disease progression, but it is more likely that the medication either did not adequately reduce patient symptoms or was associated with side effects that resulted in patients electing to stop the treatment. Should we therefore design interventions to increase adherence to these problematic and minimally effective drugs? Obviously not; we might as well attempt to increase adherence to placebo agents. After all, 40% of patients in the placebo arm of the American phase 3 registration trial for tamsulosin experienced more than a 25% improvement in AUA symptom score compared to baseline [4] . I believe that discontinuation rates for these agents are primarily a reflection of their effectiveness (or lack thereof) and their side-effect profiles. Our focus needs to be on developing agents and interventions that are more effective and make patients feel better, as opposed to trying to get patients to be more compliant with the current drug regimens.
Medical therapy for lower urinary tract symptoms (LUTS) is imperfect. While both alpha blockers (ABs) and 5-alpha reductase inhibitors (5ARIs) were effective when compared to placebo in reducing patient symptoms in large randomized clinical trials (RCTs), the effect was not as large as most patients and clinicians would like [1], [2], and [3]. For example, men in the Medical Therapy of Prostatic Symptoms study [1] randomized to combination AB and 5ARI therapy had a median reduction of 7.4 points in American Urological Association (AUA) symptom score at 4 yr. This, however, is much less impressive when considering that men in the placebo arm had a median reduction in symptom score of 4.9 points at the same time point. In fact, numerous RCTs have reported a strong placebo effect in the control arm [3] and [4] When this is considered in combination with the relatively high rate of side effects associated with the various interventions in these trials [1] and [2], it is not surprising that many patients with LUTS ultimately decide to discontinue their medications. In some cases, these patients may elect for surgical interventions, but many choose to just live with their symptoms.
In this issue of European Urology, Cindolo and colleagues [5] present data that confirm what others have also shown [6] : long-term adherence rates for AB and 5ARI medications are very low. Using a population-based administrative database of pharmacy claims from Italy, they identified 213 936 men older than 40 yr who received at least one prescription for AB or 5ARI therapy (alone or in combination). Of these, 97 407 (46%) completed 6 mo of therapy and constituted the analytic cohort. The 1-yr adherence across all LUTS medication types was only 29% among these patients. Combination therapy with ABs and 5ARIs had the lowest 1-yr adherence rates, with only 9% of patients continuing combination therapy, compared to 18% on 5ARIs alone and 35% on ABs alone. Patients who discontinued medical therapy, regardless of type, were 2.8 times more likely to be hospitalized for benign prostatic hyperplasia (BPH)-related surgery. Furthermore, patients on 5ARI or combination therapy were significantly less likely to be hospitalized for BPH surgery. Given these findings, the authors conclude that because adherence was low and may affect clinical outcomes, “there is a need for new strategies to increase patient adherence to prescribed treatment and more appropriate prescribing by physicians.” This conclusion is based on an implicit assumption that discontinuation of the LUTS medication caused patients to require additional treatment, and that had patients simply stayed on the medication, no additional treatment would have been needed. In my opinion, this assumption may not be true.
It is a basic epidemiologic tenet that association in prospective observational cohort studies does not necessarily equate to causation [7] . In the current example, it is possible that discontinuation of the medication directly resulted in disease progression, but it is more likely that the medication either did not adequately reduce patient symptoms or was associated with side effects that resulted in patients electing to stop the treatment. Should we therefore design interventions to increase adherence to these problematic and minimally effective drugs? Obviously not; we might as well attempt to increase adherence to placebo agents. After all, 40% of patients in the placebo arm of the American phase 3 registration trial for tamsulosin experienced more than a 25% improvement in AUA symptom score compared to baseline [4] . I believe that discontinuation rates for these agents are primarily a reflection of their effectiveness (or lack thereof) and their side-effect profiles. Our focus needs to be on developing agents and interventions that are more effective and make patients feel better, as opposed to trying to get patients to be more compliant with the current drug regimens.
Medical therapy for lower urinary tract symptoms (LUTS) is imperfect. While both alpha blockers (ABs) and 5-alpha reductase inhibitors (5ARIs) were effective when compared to placebo in reducing patient symptoms in large randomized clinical trials (RCTs), the effect was not as large as most patients and clinicians would like [1], [2], and [3]. For example, men in the Medical Therapy of Prostatic Symptoms study [1] randomized to combination AB and 5ARI therapy had a median reduction of 7.4 points in American Urological Association (AUA) symptom score at 4 yr. This, however, is much less impressive when considering that men in the placebo arm had a median reduction in symptom score of 4.9 points at the same time point. In fact, numerous RCTs have reported a strong placebo effect in the control arm [3] and [4] When this is considered in combination with the relatively high rate of side effects associated with the various interventions in these trials [1] and [2], it is not surprising that many patients with LUTS ultimately decide to discontinue their medications. In some cases, these patients may elect for surgical interventions, but many choose to just live with their symptoms.
In this issue of European Urology, Cindolo and colleagues [5] present data that confirm what others have also shown [6] : long-term adherence rates for AB and 5ARI medications are very low. Using a population-based administrative database of pharmacy claims from Italy, they identified 213 936 men older than 40 yr who received at least one prescription for AB or 5ARI therapy (alone or in combination). Of these, 97 407 (46%) completed 6 mo of therapy and constituted the analytic cohort. The 1-yr adherence across all LUTS medication types was only 29% among these patients. Combination therapy with ABs and 5ARIs had the lowest 1-yr adherence rates, with only 9% of patients continuing combination therapy, compared to 18% on 5ARIs alone and 35% on ABs alone. Patients who discontinued medical therapy, regardless of type, were 2.8 times more likely to be hospitalized for benign prostatic hyperplasia (BPH)-related surgery. Furthermore, patients on 5ARI or combination therapy were significantly less likely to be hospitalized for BPH surgery. Given these findings, the authors conclude that because adherence was low and may affect clinical outcomes, “there is a need for new strategies to increase patient adherence to prescribed treatment and more appropriate prescribing by physicians.” This conclusion is based on an implicit assumption that discontinuation of the LUTS medication caused patients to require additional treatment, and that had patients simply stayed on the medication, no additional treatment would have been needed. In my opinion, this assumption may not be true.
It is a basic epidemiologic tenet that association in prospective observational cohort studies does not necessarily equate to causation [7] . In the current example, it is possible that discontinuation of the medication directly resulted in disease progression, but it is more likely that the medication either did not adequately reduce patient symptoms or was associated with side effects that resulted in patients electing to stop the treatment. Should we therefore design interventions to increase adherence to these problematic and minimally effective drugs? Obviously not; we might as well attempt to increase adherence to placebo agents. After all, 40% of patients in the placebo arm of the American phase 3 registration trial for tamsulosin experienced more than a 25% improvement in AUA symptom score compared to baseline [4] . I believe that discontinuation rates for these agents are primarily a reflection of their effectiveness (or lack thereof) and their side-effect profiles. Our focus needs to be on developing agents and interventions that are more effective and make patients feel better, as opposed to trying to get patients to be more compliant with the current drug regimens.
Medical therapy for lower urinary tract symptoms (LUTS) is imperfect. While both alpha blockers (ABs) and 5-alpha reductase inhibitors (5ARIs) were effective when compared to placebo in reducing patient symptoms in large randomized clinical trials (RCTs), the effect was not as large as most patients and clinicians would like [1], [2], and [3]. For example, men in the Medical Therapy of Prostatic Symptoms study [1] randomized to combination AB and 5ARI therapy had a median reduction of 7.4 points in American Urological Association (AUA) symptom score at 4 yr. This, however, is much less impressive when considering that men in the placebo arm had a median reduction in symptom score of 4.9 points at the same time point. In fact, numerous RCTs have reported a strong placebo effect in the control arm [3] and [4] When this is considered in combination with the relatively high rate of side effects associated with the various interventions in these trials [1] and [2], it is not surprising that many patients with LUTS ultimately decide to discontinue their medications. In some cases, these patients may elect for surgical interventions, but many choose to just live with their symptoms.
In this issue of European Urology, Cindolo and colleagues [5] present data that confirm what others have also shown [6] : long-term adherence rates for AB and 5ARI medications are very low. Using a population-based administrative database of pharmacy claims from Italy, they identified 213 936 men older than 40 yr who received at least one prescription for AB or 5ARI therapy (alone or in combination). Of these, 97 407 (46%) completed 6 mo of therapy and constituted the analytic cohort. The 1-yr adherence across all LUTS medication types was only 29% among these patients. Combination therapy with ABs and 5ARIs had the lowest 1-yr adherence rates, with only 9% of patients continuing combination therapy, compared to 18% on 5ARIs alone and 35% on ABs alone. Patients who discontinued medical therapy, regardless of type, were 2.8 times more likely to be hospitalized for benign prostatic hyperplasia (BPH)-related surgery. Furthermore, patients on 5ARI or combination therapy were significantly less likely to be hospitalized for BPH surgery. Given these findings, the authors conclude that because adherence was low and may affect clinical outcomes, “there is a need for new strategies to increase patient adherence to prescribed treatment and more appropriate prescribing by physicians.” This conclusion is based on an implicit assumption that discontinuation of the LUTS medication caused patients to require additional treatment, and that had patients simply stayed on the medication, no additional treatment would have been needed. In my opinion, this assumption may not be true.
It is a basic epidemiologic tenet that association in prospective observational cohort studies does not necessarily equate to causation [7] . In the current example, it is possible that discontinuation of the medication directly resulted in disease progression, but it is more likely that the medication either did not adequately reduce patient symptoms or was associated with side effects that resulted in patients electing to stop the treatment. Should we therefore design interventions to increase adherence to these problematic and minimally effective drugs? Obviously not; we might as well attempt to increase adherence to placebo agents. After all, 40% of patients in the placebo arm of the American phase 3 registration trial for tamsulosin experienced more than a 25% improvement in AUA symptom score compared to baseline [4] . I believe that discontinuation rates for these agents are primarily a reflection of their effectiveness (or lack thereof) and their side-effect profiles. Our focus needs to be on developing agents and interventions that are more effective and make patients feel better, as opposed to trying to get patients to be more compliant with the current drug regimens.
Medical therapy for lower urinary tract symptoms (LUTS) is imperfect. While both alpha blockers (ABs) and 5-alpha reductase inhibitors (5ARIs) were effective when compared to placebo in reducing patient symptoms in large randomized clinical trials (RCTs), the effect was not as large as most patients and clinicians would like [1], [2], and [3]. For example, men in the Medical Therapy of Prostatic Symptoms study [1] randomized to combination AB and 5ARI therapy had a median reduction of 7.4 points in American Urological Association (AUA) symptom score at 4 yr. This, however, is much less impressive when considering that men in the placebo arm had a median reduction in symptom score of 4.9 points at the same time point. In fact, numerous RCTs have reported a strong placebo effect in the control arm [3] and [4] When this is considered in combination with the relatively high rate of side effects associated with the various interventions in these trials [1] and [2], it is not surprising that many patients with LUTS ultimately decide to discontinue their medications. In some cases, these patients may elect for surgical interventions, but many choose to just live with their symptoms.
In this issue of European Urology, Cindolo and colleagues [5] present data that confirm what others have also shown [6] : long-term adherence rates for AB and 5ARI medications are very low. Using a population-based administrative database of pharmacy claims from Italy, they identified 213 936 men older than 40 yr who received at least one prescription for AB or 5ARI therapy (alone or in combination). Of these, 97 407 (46%) completed 6 mo of therapy and constituted the analytic cohort. The 1-yr adherence across all LUTS medication types was only 29% among these patients. Combination therapy with ABs and 5ARIs had the lowest 1-yr adherence rates, with only 9% of patients continuing combination therapy, compared to 18% on 5ARIs alone and 35% on ABs alone. Patients who discontinued medical therapy, regardless of type, were 2.8 times more likely to be hospitalized for benign prostatic hyperplasia (BPH)-related surgery. Furthermore, patients on 5ARI or combination therapy were significantly less likely to be hospitalized for BPH surgery. Given these findings, the authors conclude that because adherence was low and may affect clinical outcomes, “there is a need for new strategies to increase patient adherence to prescribed treatment and more appropriate prescribing by physicians.” This conclusion is based on an implicit assumption that discontinuation of the LUTS medication caused patients to require additional treatment, and that had patients simply stayed on the medication, no additional treatment would have been needed. In my opinion, this assumption may not be true.
It is a basic epidemiologic tenet that association in prospective observational cohort studies does not necessarily equate to causation [7] . In the current example, it is possible that discontinuation of the medication directly resulted in disease progression, but it is more likely that the medication either did not adequately reduce patient symptoms or was associated with side effects that resulted in patients electing to stop the treatment. Should we therefore design interventions to increase adherence to these problematic and minimally effective drugs? Obviously not; we might as well attempt to increase adherence to placebo agents. After all, 40% of patients in the placebo arm of the American phase 3 registration trial for tamsulosin experienced more than a 25% improvement in AUA symptom score compared to baseline [4] . I believe that discontinuation rates for these agents are primarily a reflection of their effectiveness (or lack thereof) and their side-effect profiles. Our focus needs to be on developing agents and interventions that are more effective and make patients feel better, as opposed to trying to get patients to be more compliant with the current drug regimens.
Medical therapy for lower urinary tract symptoms (LUTS) is imperfect. While both alpha blockers (ABs) and 5-alpha reductase inhibitors (5ARIs) were effective when compared to placebo in reducing patient symptoms in large randomized clinical trials (RCTs), the effect was not as large as most patients and clinicians would like [1], [2], and [3]. For example, men in the Medical Therapy of Prostatic Symptoms study [1] randomized to combination AB and 5ARI therapy had a median reduction of 7.4 points in American Urological Association (AUA) symptom score at 4 yr. This, however, is much less impressive when considering that men in the placebo arm had a median reduction in symptom score of 4.9 points at the same time point. In fact, numerous RCTs have reported a strong placebo effect in the control arm [3] and [4] When this is considered in combination with the relatively high rate of side effects associated with the various interventions in these trials [1] and [2], it is not surprising that many patients with LUTS ultimately decide to discontinue their medications. In some cases, these patients may elect for surgical interventions, but many choose to just live with their symptoms.
In this issue of European Urology, Cindolo and colleagues [5] present data that confirm what others have also shown [6] : long-term adherence rates for AB and 5ARI medications are very low. Using a population-based administrative database of pharmacy claims from Italy, they identified 213 936 men older than 40 yr who received at least one prescription for AB or 5ARI therapy (alone or in combination). Of these, 97 407 (46%) completed 6 mo of therapy and constituted the analytic cohort. The 1-yr adherence across all LUTS medication types was only 29% among these patients. Combination therapy with ABs and 5ARIs had the lowest 1-yr adherence rates, with only 9% of patients continuing combination therapy, compared to 18% on 5ARIs alone and 35% on ABs alone. Patients who discontinued medical therapy, regardless of type, were 2.8 times more likely to be hospitalized for benign prostatic hyperplasia (BPH)-related surgery. Furthermore, patients on 5ARI or combination therapy were significantly less likely to be hospitalized for BPH surgery. Given these findings, the authors conclude that because adherence was low and may affect clinical outcomes, “there is a need for new strategies to increase patient adherence to prescribed treatment and more appropriate prescribing by physicians.” This conclusion is based on an implicit assumption that discontinuation of the LUTS medication caused patients to require additional treatment, and that had patients simply stayed on the medication, no additional treatment would have been needed. In my opinion, this assumption may not be true.
It is a basic epidemiologic tenet that association in prospective observational cohort studies does not necessarily equate to causation [7] . In the current example, it is possible that discontinuation of the medication directly resulted in disease progression, but it is more likely that the medication either did not adequately reduce patient symptoms or was associated with side effects that resulted in patients electing to stop the treatment. Should we therefore design interventions to increase adherence to these problematic and minimally effective drugs? Obviously not; we might as well attempt to increase adherence to placebo agents. After all, 40% of patients in the placebo arm of the American phase 3 registration trial for tamsulosin experienced more than a 25% improvement in AUA symptom score compared to baseline [4] . I believe that discontinuation rates for these agents are primarily a reflection of their effectiveness (or lack thereof) and their side-effect profiles. Our focus needs to be on developing agents and interventions that are more effective and make patients feel better, as opposed to trying to get patients to be more compliant with the current drug regimens.
Medical therapy for lower urinary tract symptoms (LUTS) is imperfect. While both alpha blockers (ABs) and 5-alpha reductase inhibitors (5ARIs) were effective when compared to placebo in reducing patient symptoms in large randomized clinical trials (RCTs), the effect was not as large as most patients and clinicians would like [1], [2], and [3]. For example, men in the Medical Therapy of Prostatic Symptoms study [1] randomized to combination AB and 5ARI therapy had a median reduction of 7.4 points in American Urological Association (AUA) symptom score at 4 yr. This, however, is much less impressive when considering that men in the placebo arm had a median reduction in symptom score of 4.9 points at the same time point. In fact, numerous RCTs have reported a strong placebo effect in the control arm [3] and [4] When this is considered in combination with the relatively high rate of side effects associated with the various interventions in these trials [1] and [2], it is not surprising that many patients with LUTS ultimately decide to discontinue their medications. In some cases, these patients may elect for surgical interventions, but many choose to just live with their symptoms.
In this issue of European Urology, Cindolo and colleagues [5] present data that confirm what others have also shown [6] : long-term adherence rates for AB and 5ARI medications are very low. Using a population-based administrative database of pharmacy claims from Italy, they identified 213 936 men older than 40 yr who received at least one prescription for AB or 5ARI therapy (alone or in combination). Of these, 97 407 (46%) completed 6 mo of therapy and constituted the analytic cohort. The 1-yr adherence across all LUTS medication types was only 29% among these patients. Combination therapy with ABs and 5ARIs had the lowest 1-yr adherence rates, with only 9% of patients continuing combination therapy, compared to 18% on 5ARIs alone and 35% on ABs alone. Patients who discontinued medical therapy, regardless of type, were 2.8 times more likely to be hospitalized for benign prostatic hyperplasia (BPH)-related surgery. Furthermore, patients on 5ARI or combination therapy were significantly less likely to be hospitalized for BPH surgery. Given these findings, the authors conclude that because adherence was low and may affect clinical outcomes, “there is a need for new strategies to increase patient adherence to prescribed treatment and more appropriate prescribing by physicians.” This conclusion is based on an implicit assumption that discontinuation of the LUTS medication caused patients to require additional treatment, and that had patients simply stayed on the medication, no additional treatment would have been needed. In my opinion, this assumption may not be true.
It is a basic epidemiologic tenet that association in prospective observational cohort studies does not necessarily equate to causation [7] . In the current example, it is possible that discontinuation of the medication directly resulted in disease progression, but it is more likely that the medication either did not adequately reduce patient symptoms or was associated with side effects that resulted in patients electing to stop the treatment. Should we therefore design interventions to increase adherence to these problematic and minimally effective drugs? Obviously not; we might as well attempt to increase adherence to placebo agents. After all, 40% of patients in the placebo arm of the American phase 3 registration trial for tamsulosin experienced more than a 25% improvement in AUA symptom score compared to baseline [4] . I believe that discontinuation rates for these agents are primarily a reflection of their effectiveness (or lack thereof) and their side-effect profiles. Our focus needs to be on developing agents and interventions that are more effective and make patients feel better, as opposed to trying to get patients to be more compliant with the current drug regimens.
Medical therapy for lower urinary tract symptoms (LUTS) is imperfect. While both alpha blockers (ABs) and 5-alpha reductase inhibitors (5ARIs) were effective when compared to placebo in reducing patient symptoms in large randomized clinical trials (RCTs), the effect was not as large as most patients and clinicians would like [1], [2], and [3]. For example, men in the Medical Therapy of Prostatic Symptoms study [1] randomized to combination AB and 5ARI therapy had a median reduction of 7.4 points in American Urological Association (AUA) symptom score at 4 yr. This, however, is much less impressive when considering that men in the placebo arm had a median reduction in symptom score of 4.9 points at the same time point. In fact, numerous RCTs have reported a strong placebo effect in the control arm [3] and [4] When this is considered in combination with the relatively high rate of side effects associated with the various interventions in these trials [1] and [2], it is not surprising that many patients with LUTS ultimately decide to discontinue their medications. In some cases, these patients may elect for surgical interventions, but many choose to just live with their symptoms.
In this issue of European Urology, Cindolo and colleagues [5] present data that confirm what others have also shown [6] : long-term adherence rates for AB and 5ARI medications are very low. Using a population-based administrative database of pharmacy claims from Italy, they identified 213 936 men older than 40 yr who received at least one prescription for AB or 5ARI therapy (alone or in combination). Of these, 97 407 (46%) completed 6 mo of therapy and constituted the analytic cohort. The 1-yr adherence across all LUTS medication types was only 29% among these patients. Combination therapy with ABs and 5ARIs had the lowest 1-yr adherence rates, with only 9% of patients continuing combination therapy, compared to 18% on 5ARIs alone and 35% on ABs alone. Patients who discontinued medical therapy, regardless of type, were 2.8 times more likely to be hospitalized for benign prostatic hyperplasia (BPH)-related surgery. Furthermore, patients on 5ARI or combination therapy were significantly less likely to be hospitalized for BPH surgery. Given these findings, the authors conclude that because adherence was low and may affect clinical outcomes, “there is a need for new strategies to increase patient adherence to prescribed treatment and more appropriate prescribing by physicians.” This conclusion is based on an implicit assumption that discontinuation of the LUTS medication caused patients to require additional treatment, and that had patients simply stayed on the medication, no additional treatment would have been needed. In my opinion, this assumption may not be true.
It is a basic epidemiologic tenet that association in prospective observational cohort studies does not necessarily equate to causation [7] . In the current example, it is possible that discontinuation of the medication directly resulted in disease progression, but it is more likely that the medication either did not adequately reduce patient symptoms or was associated with side effects that resulted in patients electing to stop the treatment. Should we therefore design interventions to increase adherence to these problematic and minimally effective drugs? Obviously not; we might as well attempt to increase adherence to placebo agents. After all, 40% of patients in the placebo arm of the American phase 3 registration trial for tamsulosin experienced more than a 25% improvement in AUA symptom score compared to baseline [4] . I believe that discontinuation rates for these agents are primarily a reflection of their effectiveness (or lack thereof) and their side-effect profiles. Our focus needs to be on developing agents and interventions that are more effective and make patients feel better, as opposed to trying to get patients to be more compliant with the current drug regimens.
Medical therapy for lower urinary tract symptoms (LUTS) is imperfect. While both alpha blockers (ABs) and 5-alpha reductase inhibitors (5ARIs) were effective when compared to placebo in reducing patient symptoms in large randomized clinical trials (RCTs), the effect was not as large as most patients and clinicians would like [1], [2], and [3]. For example, men in the Medical Therapy of Prostatic Symptoms study [1] randomized to combination AB and 5ARI therapy had a median reduction of 7.4 points in American Urological Association (AUA) symptom score at 4 yr. This, however, is much less impressive when considering that men in the placebo arm had a median reduction in symptom score of 4.9 points at the same time point. In fact, numerous RCTs have reported a strong placebo effect in the control arm [3] and [4] When this is considered in combination with the relatively high rate of side effects associated with the various interventions in these trials [1] and [2], it is not surprising that many patients with LUTS ultimately decide to discontinue their medications. In some cases, these patients may elect for surgical interventions, but many choose to just live with their symptoms.
In this issue of European Urology, Cindolo and colleagues [5] present data that confirm what others have also shown [6] : long-term adherence rates for AB and 5ARI medications are very low. Using a population-based administrative database of pharmacy claims from Italy, they identified 213 936 men older than 40 yr who received at least one prescription for AB or 5ARI therapy (alone or in combination). Of these, 97 407 (46%) completed 6 mo of therapy and constituted the analytic cohort. The 1-yr adherence across all LUTS medication types was only 29% among these patients. Combination therapy with ABs and 5ARIs had the lowest 1-yr adherence rates, with only 9% of patients continuing combination therapy, compared to 18% on 5ARIs alone and 35% on ABs alone. Patients who discontinued medical therapy, regardless of type, were 2.8 times more likely to be hospitalized for benign prostatic hyperplasia (BPH)-related surgery. Furthermore, patients on 5ARI or combination therapy were significantly less likely to be hospitalized for BPH surgery. Given these findings, the authors conclude that because adherence was low and may affect clinical outcomes, “there is a need for new strategies to increase patient adherence to prescribed treatment and more appropriate prescribing by physicians.” This conclusion is based on an implicit assumption that discontinuation of the LUTS medication caused patients to require additional treatment, and that had patients simply stayed on the medication, no additional treatment would have been needed. In my opinion, this assumption may not be true.
It is a basic epidemiologic tenet that association in prospective observational cohort studies does not necessarily equate to causation [7] . In the current example, it is possible that discontinuation of the medication directly resulted in disease progression, but it is more likely that the medication either did not adequately reduce patient symptoms or was associated with side effects that resulted in patients electing to stop the treatment. Should we therefore design interventions to increase adherence to these problematic and minimally effective drugs? Obviously not; we might as well attempt to increase adherence to placebo agents. After all, 40% of patients in the placebo arm of the American phase 3 registration trial for tamsulosin experienced more than a 25% improvement in AUA symptom score compared to baseline [4] . I believe that discontinuation rates for these agents are primarily a reflection of their effectiveness (or lack thereof) and their side-effect profiles. Our focus needs to be on developing agents and interventions that are more effective and make patients feel better, as opposed to trying to get patients to be more compliant with the current drug regimens.
Medical therapy for lower urinary tract symptoms (LUTS) is imperfect. While both alpha blockers (ABs) and 5-alpha reductase inhibitors (5ARIs) were effective when compared to placebo in reducing patient symptoms in large randomized clinical trials (RCTs), the effect was not as large as most patients and clinicians would like [1], [2], and [3]. For example, men in the Medical Therapy of Prostatic Symptoms study [1] randomized to combination AB and 5ARI therapy had a median reduction of 7.4 points in American Urological Association (AUA) symptom score at 4 yr. This, however, is much less impressive when considering that men in the placebo arm had a median reduction in symptom score of 4.9 points at the same time point. In fact, numerous RCTs have reported a strong placebo effect in the control arm [3] and [4] When this is considered in combination with the relatively high rate of side effects associated with the various interventions in these trials [1] and [2], it is not surprising that many patients with LUTS ultimately decide to discontinue their medications. In some cases, these patients may elect for surgical interventions, but many choose to just live with their symptoms.
In this issue of European Urology, Cindolo and colleagues [5] present data that confirm what others have also shown [6] : long-term adherence rates for AB and 5ARI medications are very low. Using a population-based administrative database of pharmacy claims from Italy, they identified 213 936 men older than 40 yr who received at least one prescription for AB or 5ARI therapy (alone or in combination). Of these, 97 407 (46%) completed 6 mo of therapy and constituted the analytic cohort. The 1-yr adherence across all LUTS medication types was only 29% among these patients. Combination therapy with ABs and 5ARIs had the lowest 1-yr adherence rates, with only 9% of patients continuing combination therapy, compared to 18% on 5ARIs alone and 35% on ABs alone. Patients who discontinued medical therapy, regardless of type, were 2.8 times more likely to be hospitalized for benign prostatic hyperplasia (BPH)-related surgery. Furthermore, patients on 5ARI or combination therapy were significantly less likely to be hospitalized for BPH surgery. Given these findings, the authors conclude that because adherence was low and may affect clinical outcomes, “there is a need for new strategies to increase patient adherence to prescribed treatment and more appropriate prescribing by physicians.” This conclusion is based on an implicit assumption that discontinuation of the LUTS medication caused patients to require additional treatment, and that had patients simply stayed on the medication, no additional treatment would have been needed. In my opinion, this assumption may not be true.
It is a basic epidemiologic tenet that association in prospective observational cohort studies does not necessarily equate to causation [7] . In the current example, it is possible that discontinuation of the medication directly resulted in disease progression, but it is more likely that the medication either did not adequately reduce patient symptoms or was associated with side effects that resulted in patients electing to stop the treatment. Should we therefore design interventions to increase adherence to these problematic and minimally effective drugs? Obviously not; we might as well attempt to increase adherence to placebo agents. After all, 40% of patients in the placebo arm of the American phase 3 registration trial for tamsulosin experienced more than a 25% improvement in AUA symptom score compared to baseline [4] . I believe that discontinuation rates for these agents are primarily a reflection of their effectiveness (or lack thereof) and their side-effect profiles. Our focus needs to be on developing agents and interventions that are more effective and make patients feel better, as opposed to trying to get patients to be more compliant with the current drug regimens.
Medical therapy for lower urinary tract symptoms (LUTS) is imperfect. While both alpha blockers (ABs) and 5-alpha reductase inhibitors (5ARIs) were effective when compared to placebo in reducing patient symptoms in large randomized clinical trials (RCTs), the effect was not as large as most patients and clinicians would like [1], [2], and [3]. For example, men in the Medical Therapy of Prostatic Symptoms study [1] randomized to combination AB and 5ARI therapy had a median reduction of 7.4 points in American Urological Association (AUA) symptom score at 4 yr. This, however, is much less impressive when considering that men in the placebo arm had a median reduction in symptom score of 4.9 points at the same time point. In fact, numerous RCTs have reported a strong placebo effect in the control arm [3] and [4] When this is considered in combination with the relatively high rate of side effects associated with the various interventions in these trials [1] and [2], it is not surprising that many patients with LUTS ultimately decide to discontinue their medications. In some cases, these patients may elect for surgical interventions, but many choose to just live with their symptoms.
In this issue of European Urology, Cindolo and colleagues [5] present data that confirm what others have also shown [6] : long-term adherence rates for AB and 5ARI medications are very low. Using a population-based administrative database of pharmacy claims from Italy, they identified 213 936 men older than 40 yr who received at least one prescription for AB or 5ARI therapy (alone or in combination). Of these, 97 407 (46%) completed 6 mo of therapy and constituted the analytic cohort. The 1-yr adherence across all LUTS medication types was only 29% among these patients. Combination therapy with ABs and 5ARIs had the lowest 1-yr adherence rates, with only 9% of patients continuing combination therapy, compared to 18% on 5ARIs alone and 35% on ABs alone. Patients who discontinued medical therapy, regardless of type, were 2.8 times more likely to be hospitalized for benign prostatic hyperplasia (BPH)-related surgery. Furthermore, patients on 5ARI or combination therapy were significantly less likely to be hospitalized for BPH surgery. Given these findings, the authors conclude that because adherence was low and may affect clinical outcomes, “there is a need for new strategies to increase patient adherence to prescribed treatment and more appropriate prescribing by physicians.” This conclusion is based on an implicit assumption that discontinuation of the LUTS medication caused patients to require additional treatment, and that had patients simply stayed on the medication, no additional treatment would have been needed. In my opinion, this assumption may not be true.
It is a basic epidemiologic tenet that association in prospective observational cohort studies does not necessarily equate to causation [7] . In the current example, it is possible that discontinuation of the medication directly resulted in disease progression, but it is more likely that the medication either did not adequately reduce patient symptoms or was associated with side effects that resulted in patients electing to stop the treatment. Should we therefore design interventions to increase adherence to these problematic and minimally effective drugs? Obviously not; we might as well attempt to increase adherence to placebo agents. After all, 40% of patients in the placebo arm of the American phase 3 registration trial for tamsulosin experienced more than a 25% improvement in AUA symptom score compared to baseline [4] . I believe that discontinuation rates for these agents are primarily a reflection of their effectiveness (or lack thereof) and their side-effect profiles. Our focus needs to be on developing agents and interventions that are more effective and make patients feel better, as opposed to trying to get patients to be more compliant with the current drug regimens.
Medical therapy for lower urinary tract symptoms (LUTS) is imperfect. While both alpha blockers (ABs) and 5-alpha reductase inhibitors (5ARIs) were effective when compared to placebo in reducing patient symptoms in large randomized clinical trials (RCTs), the effect was not as large as most patients and clinicians would like [1], [2], and [3]. For example, men in the Medical Therapy of Prostatic Symptoms study [1] randomized to combination AB and 5ARI therapy had a median reduction of 7.4 points in American Urological Association (AUA) symptom score at 4 yr. This, however, is much less impressive when considering that men in the placebo arm had a median reduction in symptom score of 4.9 points at the same time point. In fact, numerous RCTs have reported a strong placebo effect in the control arm [3] and [4] When this is considered in combination with the relatively high rate of side effects associated with the various interventions in these trials [1] and [2], it is not surprising that many patients with LUTS ultimately decide to discontinue their medications. In some cases, these patients may elect for surgical interventions, but many choose to just live with their symptoms.
In this issue of European Urology, Cindolo and colleagues [5] present data that confirm what others have also shown [6] : long-term adherence rates for AB and 5ARI medications are very low. Using a population-based administrative database of pharmacy claims from Italy, they identified 213 936 men older than 40 yr who received at least one prescription for AB or 5ARI therapy (alone or in combination). Of these, 97 407 (46%) completed 6 mo of therapy and constituted the analytic cohort. The 1-yr adherence across all LUTS medication types was only 29% among these patients. Combination therapy with ABs and 5ARIs had the lowest 1-yr adherence rates, with only 9% of patients continuing combination therapy, compared to 18% on 5ARIs alone and 35% on ABs alone. Patients who discontinued medical therapy, regardless of type, were 2.8 times more likely to be hospitalized for benign prostatic hyperplasia (BPH)-related surgery. Furthermore, patients on 5ARI or combination therapy were significantly less likely to be hospitalized for BPH surgery. Given these findings, the authors conclude that because adherence was low and may affect clinical outcomes, “there is a need for new strategies to increase patient adherence to prescribed treatment and more appropriate prescribing by physicians.” This conclusion is based on an implicit assumption that discontinuation of the LUTS medication caused patients to require additional treatment, and that had patients simply stayed on the medication, no additional treatment would have been needed. In my opinion, this assumption may not be true.
It is a basic epidemiologic tenet that association in prospective observational cohort studies does not necessarily equate to causation [7] . In the current example, it is possible that discontinuation of the medication directly resulted in disease progression, but it is more likely that the medication either did not adequately reduce patient symptoms or was associated with side effects that resulted in patients electing to stop the treatment. Should we therefore design interventions to increase adherence to these problematic and minimally effective drugs? Obviously not; we might as well attempt to increase adherence to placebo agents. After all, 40% of patients in the placebo arm of the American phase 3 registration trial for tamsulosin experienced more than a 25% improvement in AUA symptom score compared to baseline [4] . I believe that discontinuation rates for these agents are primarily a reflection of their effectiveness (or lack thereof) and their side-effect profiles. Our focus needs to be on developing agents and interventions that are more effective and make patients feel better, as opposed to trying to get patients to be more compliant with the current drug regimens.
Medical therapy for lower urinary tract symptoms (LUTS) is imperfect. While both alpha blockers (ABs) and 5-alpha reductase inhibitors (5ARIs) were effective when compared to placebo in reducing patient symptoms in large randomized clinical trials (RCTs), the effect was not as large as most patients and clinicians would like [1], [2], and [3]. For example, men in the Medical Therapy of Prostatic Symptoms study [1] randomized to combination AB and 5ARI therapy had a median reduction of 7.4 points in American Urological Association (AUA) symptom score at 4 yr. This, however, is much less impressive when considering that men in the placebo arm had a median reduction in symptom score of 4.9 points at the same time point. In fact, numerous RCTs have reported a strong placebo effect in the control arm [3] and [4] When this is considered in combination with the relatively high rate of side effects associated with the various interventions in these trials [1] and [2], it is not surprising that many patients with LUTS ultimately decide to discontinue their medications. In some cases, these patients may elect for surgical interventions, but many choose to just live with their symptoms.
In this issue of European Urology, Cindolo and colleagues [5] present data that confirm what others have also shown [6] : long-term adherence rates for AB and 5ARI medications are very low. Using a population-based administrative database of pharmacy claims from Italy, they identified 213 936 men older than 40 yr who received at least one prescription for AB or 5ARI therapy (alone or in combination). Of these, 97 407 (46%) completed 6 mo of therapy and constituted the analytic cohort. The 1-yr adherence across all LUTS medication types was only 29% among these patients. Combination therapy with ABs and 5ARIs had the lowest 1-yr adherence rates, with only 9% of patients continuing combination therapy, compared to 18% on 5ARIs alone and 35% on ABs alone. Patients who discontinued medical therapy, regardless of type, were 2.8 times more likely to be hospitalized for benign prostatic hyperplasia (BPH)-related surgery. Furthermore, patients on 5ARI or combination therapy were significantly less likely to be hospitalized for BPH surgery. Given these findings, the authors conclude that because adherence was low and may affect clinical outcomes, “there is a need for new strategies to increase patient adherence to prescribed treatment and more appropriate prescribing by physicians.” This conclusion is based on an implicit assumption that discontinuation of the LUTS medication caused patients to require additional treatment, and that had patients simply stayed on the medication, no additional treatment would have been needed. In my opinion, this assumption may not be true.
It is a basic epidemiologic tenet that association in prospective observational cohort studies does not necessarily equate to causation [7] . In the current example, it is possible that discontinuation of the medication directly resulted in disease progression, but it is more likely that the medication either did not adequately reduce patient symptoms or was associated with side effects that resulted in patients electing to stop the treatment. Should we therefore design interventions to increase adherence to these problematic and minimally effective drugs? Obviously not; we might as well attempt to increase adherence to placebo agents. After all, 40% of patients in the placebo arm of the American phase 3 registration trial for tamsulosin experienced more than a 25% improvement in AUA symptom score compared to baseline [4] . I believe that discontinuation rates for these agents are primarily a reflection of their effectiveness (or lack thereof) and their side-effect profiles. Our focus needs to be on developing agents and interventions that are more effective and make patients feel better, as opposed to trying to get patients to be more compliant with the current drug regimens.
Medical therapy for lower urinary tract symptoms (LUTS) is imperfect. While both alpha blockers (ABs) and 5-alpha reductase inhibitors (5ARIs) were effective when compared to placebo in reducing patient symptoms in large randomized clinical trials (RCTs), the effect was not as large as most patients and clinicians would like [1], [2], and [3]. For example, men in the Medical Therapy of Prostatic Symptoms study [1] randomized to combination AB and 5ARI therapy had a median reduction of 7.4 points in American Urological Association (AUA) symptom score at 4 yr. This, however, is much less impressive when considering that men in the placebo arm had a median reduction in symptom score of 4.9 points at the same time point. In fact, numerous RCTs have reported a strong placebo effect in the control arm [3] and [4] When this is considered in combination with the relatively high rate of side effects associated with the various interventions in these trials [1] and [2], it is not surprising that many patients with LUTS ultimately decide to discontinue their medications. In some cases, these patients may elect for surgical interventions, but many choose to just live with their symptoms.
In this issue of European Urology, Cindolo and colleagues [5] present data that confirm what others have also shown [6] : long-term adherence rates for AB and 5ARI medications are very low. Using a population-based administrative database of pharmacy claims from Italy, they identified 213 936 men older than 40 yr who received at least one prescription for AB or 5ARI therapy (alone or in combination). Of these, 97 407 (46%) completed 6 mo of therapy and constituted the analytic cohort. The 1-yr adherence across all LUTS medication types was only 29% among these patients. Combination therapy with ABs and 5ARIs had the lowest 1-yr adherence rates, with only 9% of patients continuing combination therapy, compared to 18% on 5ARIs alone and 35% on ABs alone. Patients who discontinued medical therapy, regardless of type, were 2.8 times more likely to be hospitalized for benign prostatic hyperplasia (BPH)-related surgery. Furthermore, patients on 5ARI or combination therapy were significantly less likely to be hospitalized for BPH surgery. Given these findings, the authors conclude that because adherence was low and may affect clinical outcomes, “there is a need for new strategies to increase patient adherence to prescribed treatment and more appropriate prescribing by physicians.” This conclusion is based on an implicit assumption that discontinuation of the LUTS medication caused patients to require additional treatment, and that had patients simply stayed on the medication, no additional treatment would have been needed. In my opinion, this assumption may not be true.
It is a basic epidemiologic tenet that association in prospective observational cohort studies does not necessarily equate to causation [7] . In the current example, it is possible that discontinuation of the medication directly resulted in disease progression, but it is more likely that the medication either did not adequately reduce patient symptoms or was associated with side effects that resulted in patients electing to stop the treatment. Should we therefore design interventions to increase adherence to these problematic and minimally effective drugs? Obviously not; we might as well attempt to increase adherence to placebo agents. After all, 40% of patients in the placebo arm of the American phase 3 registration trial for tamsulosin experienced more than a 25% improvement in AUA symptom score compared to baseline [4] . I believe that discontinuation rates for these agents are primarily a reflection of their effectiveness (or lack thereof) and their side-effect profiles. Our focus needs to be on developing agents and interventions that are more effective and make patients feel better, as opposed to trying to get patients to be more compliant with the current drug regimens.
