The combination of doxazosin and metyrosine as a preoperative treatment for pheochromocytomas and paragangliomas.

PURPOSE: Preoperative medical management is critical to prevent intraoperative cardiovascular complications in patients with pheochromocytomas and paragangliomas (PPGLs). Initial treatment involves α-adrenergic receptor blockers. However, while the routine use of metyrosine alongside these blockers is not strongly recommended due to a lack of evidence supporting its efficacy and associated safety concerns, there are previous studies on combination therapy with phenoxybenzamine and metyrosine. There are few reports on combination therapy with the selective α1-adrenergic receptor blocker doxazosin. Therefore, we investigated this combination treatment, which theoretically can affect perioperative outcomes in patients with PPGLs. To our knowledge, this is the first such study. METHODS: This retrospective single-center observational study involved 51 patients who underwent surgical resection of PPGLs at Kobe University Hospital between 2014 and 2022. All patients received doxazosin at maximum doses. Fourteen patients received concomitant metyrosine, while 37 received doxazosin alone. Their perioperative outcomes were compared. RESULTS: No severe event, such as acute coronary syndrome, was observed in either group. Intraoperatively, the doxazosin + metyrosine group exhibited a lower median minimum systolic blood pressure (56 [54-60] vs. 68 [59-74] mmHg, P = 0.03) and required lower median remifentanil (P = 0.04) and diltiazem (P = 0.02) doses than the doxazosin-alone group. CONCLUSION: The combination of metyrosine and doxazosin as a preoperative treatment for PPGLs affects intraoperative circulatory hemodynamics, such as a reduced occurrence of blood pressure elevation during surgery. Further research is necessary to identify patients who will benefit most from this combination treatment.

Assessment of Frailty and Association With Progression of Benign Prostatic Hyperplasia Symptoms and Serious Adverse Events Among Men Using Drug Therapy.

Importance: Benign prostatic hyperplasia (BPH) in older men can cause lower urinary tract symptoms (LUTS), which are increasingly managed with medications. Frailty may contribute to both symptom progression and serious adverse events (SAEs), shifting the balance of benefits and harms of drug therapy. Objective: To assess the association between a deficit accumulation frailty index and clinical BPH progression or SAE. Design, Setting, and Participants: This cohort study used data from the Medical Therapy of Prostatic Symptoms trial, which compared placebo, doxazosin, finasteride, and combination therapy in men with moderate-to-severe LUTS, reduced urinary flow rate, and no prior BPH interventions, hypotension, or elevated prostate-specific antigen. Enrollment was from 1995 to 1998, and follow-up was through 2001. Data were assessed in February 2021. Exposures: A frailty index (score range, 0-1) using 68 potential deficits collected at baseline was used to categorized men as robust (score ≤0.1), prefrail (score 0.1 to <0.25), or frail (score ≥0.25). Main Outcomes and Measures: Primary outcomes were time to clinical BPH progression and time to SAE, as defined in the parent trial. Adjusted hazard ratios (AHRs) were estimated using Cox proportional hazards regressions adjusted for demographic variables, treatment group, measures of obstruction, and comorbidities. Results: Among 3047 men (mean [SD] age, 62.6 [7.3] years; range, 50-89 years) in this analysis, 745 (24%) were robust, 1824 (60%) were prefrail, and 478 (16%) were frail at baseline. Compared with robust men, frail men were older (age ≥75 years, 12 men [2%] vs 62 men [13%]), less likely to be White (646 men [87%] vs 344 men [72%]), less likely to be married (599 men [80%] vs 342 men [72%]), and less likely to have 16 years or more of education (471 men [63%] vs 150 men [31%]). During mean (SD) follow-up of 4.0 (1.5) years, the incidence rate of clinical BPH progression was 2.2 events per 100 person-years among robust men, 2.9 events per 100 person-years among prefrail men (AHR, 1.36; 95% CI, 1.02-1.83), and 4.0 events per 100 person-years among frail men (AHR, 1.82; 95% CI, 1.24-2.67; linear P = .005). Larger point estimates were seen among men who received doxazosin or combination therapy, although the test for interaction between frailty index and treatment group did not reach statistical significance (P for interaction = .06). Risk of SAE was higher among prefrail and frail men (prefrail vs robust AHR, 1.81; 95% CI, 1.48-2.23; frail vs robust AHR, 2.86; 95% CI, 2.21-3.69; linear P < .001); this association was similar across treatment groups (P for interaction = .76). Conclusions and Relevance: These findings suggest that frailty is independently associated with greater risk of both clinical BPH progression and SAEs. Older frail men with BPH considering initiation of drug therapy should be counseled regarding their higher risk of progression despite combination therapy and their likelihood of experiencing SAEs regardless of treatment choice.

Doxazosin Attenuates Liver Fibrosis by Inhibiting Autophagy in Hepatic Stellate Cells via Activation of the PI3K/Akt/mTOR Signaling Pathway.

PURPOSE: To investigate the effect of doxazosin on autophagy and the activation of hepatic stellate cells (HSCs) in vivo and in vitro and determine the underlying mechanism. METHODS: In vivo, a mouse liver fibrosis model was induced by the intraperitoneal injection of carbon tetrachloride (CCl4). Doxazosin was administered at doses of 2.5, 5 and 10 mg/(kg*day) by gavage. After 20 weeks, blood and liver tissues were collected for serological and histological analysis, respectively. Blood analysis, hematoxylin and eosin (HE) staining, Masson's trichrome staining, immunohistochemistry and immunofluorescence staining were used to measure the extent of liver fibrosis in model and control mice. In vitro, the human HSC cell line LX-2 was cultured and treated with different doses of doxazosin for the indicated times. The effects of doxazosin on LX-2 cell proliferation and migration were examined by Cell Counting Kit-8 (CCK-8) and Transwell assays, respectively. The number of autophagosomes in LX-2 cells was observed by transmission electron microscopy (TEM). Infection with green fluorescent protein (GFP)-LC3B adenovirus, GFP-red fluorescent protein (RFP)-LC3B adenovirus and mCherry-EGFP-LC3 adeno-associated virus was performed to examine changes in autophagic flux in vitro and in vivo. Cell apoptosis was measured by flow cytometry in vitro and by TUNEL assays both in vitro and in vivo. Immunoblotting was performed to evaluate the expression levels of proteins related to fibrosis, autophagy, apoptosis, and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR). RESULTS: Doxazosin inhibited HSC proliferation and migration. HSC activation was attenuated by doxazosin in a concentration-dependent manner in vivo and in vitro. Doxazosin also blocked autophagic flux and induced apoptosis in HSCs. In addition, the PI3K/Akt/mTOR pathway was activated by doxazosin and regulated fibrosis, autophagy and apoptosis in HSCs. CONCLUSION: The study confirmed that doxazosin could inhibit autophagy by activating the PI3K/Akt/mTOR signaling pathway and attenuate liver fibrosis.

Doxazosin and erlotinib have anticancer effects in the endometrial cancer cell and important roles in ERα and Wnt/ß-catenin signaling pathways.

ERα and Wnt/ß-catenin pathways are critical for the progression of most endometrial cancers. We aimed to investigate the cytotoxic and apoptotic effects of tamoxifen and quinazoline derivative drugs of doxazosin and erlotinib, and their roles in ERα and Wnt/ß-catenin signaling pathways in human endometrial cancer RL 95-2 cell. 3-(4,5-Dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide assay and xCELLigence systems were performed to evaluate cytotoxicity. Furthermore, apoptotic induction was tested by Annexin V analysis. Caspase-3 and -9 activity and changes in the mitochondrial membrane potential were evaluated. The level of reactive oxygen species was measured by incubating with dichlorofluorescein diacetate. Protein ratios of p-ERα/ERα, GSK3ß/p-GSK3ß, and p-ß-catenin/ß-catenin and expression levels of ESR1, EGFR, c-Myc genes were evaluated to elucidate mechanisms in signaling pathways. We found that the tested drugs showed cytotoxic and apoptotic effects in the cells. Doxazosin significantly reduced ESR1 expression, slightly reduced the p-ß-catenin/ß-catenin ratio and c-Myc expression. Erlotinib significantly increased c-Myc expression while significantly decreasing the p-ß-catenin/ß-catenin and p-ERα/ERα ratio, and ESR1 expression. However, we observed that the cells develop resistance to erlotinib over a certain concentration, suggesting that ERα, ESR1, EGFR, and c-Myc may be a new target for overcoming drug resistance in the treatment of endometrial cancer. We also observed that erlotinib and doxazosin play an important role in the ERα signaling pathway and can act as potent inhibitors of PKA and/or tyrosine kinase in the Wnt/ß-catenin signaling pathway in RL 95-2 cell. In conclusion, doxazosin and erlotinib may have a possible therapeutic potential in human endometrial cancer.

The use of doxazosin before adrenalectomy for pheochromocytoma: is the duration related to intraoperative hemodynamics and postoperative complications?

PURPOSE: No conclusion exists for the optimum duration of preoperative administration of doxazosin (DOX) before adrenalectomy for pheochromocytoma. The purpose of this study is to investigate whether perioperative hemodynamics and postoperative outcomes are related to the duration of DOX administration. METHODS: In total, 132 patients managed preoperatively with single α-receptor blocker DOX were enrolled. All patients underwent adrenalectomy for pheochromocytoma in the Department of Urology, Peking University First Hospital, between January 2001 and July 2019. Patients were divided into three groups based on the duration of preoperative administration of DOX: group A (≤14 days), group B (15-30 days), and group C (>30 days). Patient and tumor characteristics, intraoperative hemodynamics, and postoperative outcomes were recorded and compared. RESULTS: These patients included 57 men and 75 women, with an average age of 48 years. Clinical characteristics, preoperative hemodynamics, medicine management and surgical approaches were comparable between the three groups. Among the three groups, we found that group C (>30 days) had the lowest intraoperative minimum heart rate [group A vs. group B vs. group C = 60 (52-67) vs. 59 (50-61) vs. 51.5 (50-58.75), p = 0.024] and highest risk of postoperative hypotension requiring vasopressor support [group A vs. group B vs. group C = 14 (20.3%) vs. 12 (27.9%) vs. 10 (50.0%), p = 0.032]. CONCLUSION: The current study indicated that preoperative management of pheochromocytoma with single α-receptor blocker DOX for more than 30 days after final dose adjustment might lead to intraoperative bradycardia and more postoperative hypotension requiring vasopressor support. Thus, our study does not support long-term (over 30 days) preoperative administration of pheochromocytoma with single α-receptor blocker DOX in the final dose.

Efficacy of α-Blockers on Hemodynamic Control during Pheochromocytoma Resection: A Randomized Controlled Trial.

CONTEXT: Pretreatment with α-adrenergic receptor blockers is recommended to prevent hemodynamic instability during resection of a pheochromocytoma or sympathetic paraganglioma (PPGL). OBJECTIVE: To determine which type of α-adrenergic receptor blocker provides the best efficacy. DESIGN: Randomized controlled open-label trial (PRESCRIPT; ClinicalTrials.gov NCT01379898). SETTING: Multicenter study including 9 centers in The Netherlands. PATIENTS: 134 patients with nonmetastatic PPGL. INTERVENTION: Phenoxybenzamine or doxazosin starting 2 to 3 weeks before surgery using a blood pressure targeted titration schedule. Intraoperative hemodynamic management was standardized. MAIN OUTCOME MEASURES: Primary efficacy endpoint was the cumulative intraoperative time outside the blood pressure target range (ie, SBP >160 mmHg or MAP <60 mmHg) expressed as a percentage of total surgical procedure time. Secondary efficacy endpoint was the value on a hemodynamic instability score. RESULTS: Median cumulative time outside blood pressure targets was 11.1% (interquartile range [IQR]: 4.3-20.6] in the phenoxybenzamine group compared to 12.2% (5.3-20.2)] in the doxazosin group (P = .75, r = 0.03). The hemodynamic instability score was 38.0 (28.8-58.0) and 50.0 (35.3-63.8) in the phenoxybenzamine and doxazosin group, respectively (P = .02, r = 0.20). The 30-day cardiovascular complication rate was 8.8% and 6.9% in the phenoxybenzamine and doxazosin group, respectively (P = .68). There was no mortality after 30 days. CONCLUSIONS: The duration of blood pressure outside the target range during resection of a PPGL was not different after preoperative treatment with either phenoxybenzamine or doxazosin. Phenoxybenzamine was more effective in preventing intraoperative hemodynamic instability, but it could not be established whether this was associated with a better clinical outcome.

Management of Insomnia and Anxiety in Myasthenia Gravis.

Myasthenia gravis is a neuroimmunological disorder leading to skeletal muscle weakness. Common symptoms of the disease, such as anxiety, depression, and insomnia, can cause significant distress in patients. Unfortunately, selecting an appropriate medication for treatment of psychiatric comorbidities can prove to be challenging for providers given the unique pharmacologic constraints that myasthenia gravis presents. The authors present the following clinical vignette and accompanying discussion in an attempt to highlight the special considerations that must be taken into account when treating anxiety and insomnia in patients with myasthenia gravis, as well as to provide an overview of available medication options through the lens of existing constraints.

A preliminary investigation into the effects of doxazosin on cognitive functioning in tobacco-deprived and -satiated smokers.

OBJECTIVE: To test the effects of doxazosin, an α1 antagonist, on cognitive functioning during tobacco withdrawal in smokers. METHODS: Participants (n = 35) were randomly assigned to receive placebo, 4-mg/day, or 8-mg/day doxazosin. They completed a continuous performance task and self-reported their withdrawal symptoms at baseline and twice following a medication titration period: once in a tobacco-deprived state and again in a nondeprived state. Ability to resist smoking was assessed using a laboratory smoking-lapse paradigm. RESULTS: Participants showed poorer cognitive performance on most measures taken from the continuous performance task when tobacco deprived. Eight-mg/day doxazosin improved inhibitory control during the nondeprivation session but did not affect sustained attention or reaction time. Participants receiving doxazosin reported fewer withdrawal symptoms during deprivation than those on placebo. Those showing the greatest improvement of inhibitory control under doxazosin were better able to resist smoking (i.e., latency to smoke) during a smoking lapse task. Self-reported withdrawal symptoms also were negatively associated with time to smoking. CONCLUSIONS: Doxazosin reduced symptoms of tobacco withdrawal according to self-report and cognitive assessment and improved inhibitory control above predrug levels. This research identifies potential mechanisms by which doxazosin might improve smoking outcomes.

Effect of doxazosin on stress reactivity and the ability to resist smoking.

Preclinical findings support a role for α1-adrenergic antagonists in reducing nicotine-motivated behaviors, but these findings have yet to be translated to humans. The current study evaluated whether doxazosin would attenuate stress-precipitated smoking in the human laboratory. Using a well-validated laboratory analogue of smoking-lapse behavior, this pilot study evaluated whether doxazosin (4 and 8 mg/day) versus placebo attenuated the effect of stress (vs neutral imagery) on tobacco craving, the ability to resist smoking and subsequent ad-libitum smoking in nicotine-deprived smokers ( n=35). Cortisol, adrenocorticotropin, norepinephrine, epinephrine, and physiologic reactivity were assessed. Doxazosin (4 and 8 mg/day vs placebo) decreased cigarettes per day during the 21-day titration period. Following titration, doxazosin (4 and 8 mg/day vs placebo) decreased tobacco craving. During the laboratory session, doxazosin (8 mg/day vs placebo) further decreased tobacco craving following stress versus neutral imagery. Doxazosin increased the latency to start smoking following stress, and reduced the number of cigarettes smoked. Dosage of 8 mg/day doxazosin increased or normalized cortisol levels following stress imagery and decreased cortisol levels following neutral imagery. These preliminary findings support a role for the noradrenergic system in stress-precipitated smoking behavior, and support further development of doxazosin as a novel pharmacotherapeutic treatment strategy for smoking cessation.

Antiangiogenic Effects of Doxazosin on Experimental Choroidal Neovascularization in Mice.

PURPOSE: The present study was designed to evaluate the effects of doxazosin on experimental choroidal neovascularization (CNV) in mice. METHODS: Six- to 8-week-old male C57BL/6 mice were divided into a control group and a doxazosin-treated group (5 mg/kg, i.p., daily). Experimental CNV was induced by laser photocoagulation. Seven and 14 days after laser induction, fluorescein angiography, choroidal flat mounts, and histological studies were performed to evaluate the fluorescence leakage, area, and thickness of CNV lesions, respectively. In addition, western blot analysis was carried out to assess the inhibitory effects of doxazosin on the PI3K/Akt/mTOR signaling pathway and the expression levels of hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF), which are involved in CNV model. RESULTS: Compared with the control group, the doxazosin-treated group demonstrated significantly less fluorescence leakage on day 7 and 14 after laser induction. Both the area and the thickness of CNV lesions in the doxazosin-treated group were significantly decreased. Mechanistically, PI3K/Akt/mTOR signaling pathway activation was significantly suppressed in the doxazosin-treated group. The expression of HIF-1α and VEGF was also notably reduced by systemic doxazosin treatment. CONCLUSIONS: Doxazosin exerts antiangiogenic actions in an experimental mouse model of CNV and may be a potential adjunctive therapy for neovascular age-related macular degeneration in humans.

Doxazosin oral intake therapy to relieve stent - related urinary symptoms and pain: a prospective, randomized, controlled study.

OBJECTIVE: To assess the impact of Doxazosin Oral Intake Therapy on urinary symptoms and pain in patients with indwelling ureteral stents Patients and Methods: A total of 239 patients with ureteral stone-related hydronephrosis who underwent a double-J stent insertion after ureteroscopic lithotripsy were enrolled. Patients were randomized to receive doxazosin cotrolled release 4 mg once daily for 4 weeks or matching placebo. Patients completed the brief-form Chinese version Ureteric Stent Symptom Questionnaire (USSQ) and quality of life (QoL) score 2 weeks and 4 weeks after stent placement and 4 weeks after stent withdrawal. The analgesic use was also recorded during the stenting period. RESULTS: Patients in Doxazosin Oral Intake Therapy group, in the first 2 weeks and second 2 weeks with the stent in situ, expressed significant lower daytime frequency (p=0.028 and p=0.038), nocturia (p=0.021 and p=0.008) and urgency (p=0.012 and p=0.014), respectively. Similarly, flank pain score, QoL score and analgesic use were also significant less in the stenting period. There was no significant difference in scores of urinary symptoms, pain and QoL during the post-stent period between two cohorts. CONCLUSIONS: Doxazosin Oral Intake Therapy reduced stent-related urinary symptoms, pain and the negative impact on QoL.

Doxazosin oral intake therapy to relieve stent - related urinary symptoms and pain: a prospective, randomized, controlled study

ABSTRACT Objective: To assess the impact of Doxazosin Oral Intake Therapy on urinary symptoms and pain in patients with indwelling ureteral stents Patients and Methods: A total of 239 patients with ureteral stone-related hydronephrosis who underwent a double-J stent insertion after ureteroscopic lithotripsy were enrolled. Patients were randomized to receive doxazosin cotrolled release 4 mg once daily for 4 weeks or matching placebo. Patients completed the brief-form Chinese version Ureteric Stent Symptom Questionnaire (USSQ) and quality of life (QoL) score 2 weeks and 4 weeks after stent placement and 4 weeks after stent withdrawal. The analgesic use was also recorded during the stenting period. Results: Patients in Doxazosin Oral Intake Therapy group, in the first 2 weeks and second 2 weeks with the stent in situ, expressed significant lower daytime frequency (p=0.028 and p=0.038), nocturia (p=0.021 and p=0.008) and urgency (p=0.012 and p=0.014), respectively. Similarly, flank pain score, QoL score and analgesic use were also significant less in the stenting period. There was no significant difference in scores of urinary symptoms, pain and QoL during the post-stent period between two cohorts. Conclusions: Doxazosin Oral Intake Therapy reduced stent-related urinary symptoms, pain and the negative impact on QoL.

The new insight of prostate-specific antigen reduction during finasteride therapy in aging men.

OBJECTIVE: To evaluate the effect of finasteride on prostate-specific antigen (PSA) in Chinese population. MATERIALS AND METHODS: From Feb 2011 to Jan 2012, 83 benign prostatic hyperplasia (BPH) patients with prostate volume (PV) >30 mL were enrolled in our study. All the patients were older than 50 years and all of them received combined therapy (finasteride + doxazosin). All the patients were required for 1-year follow-up. PSA level and PV was measured at the start, 6 and 12 months, respectively. RESULTS: 79 patients completed the follow up. PSA level reduced by approximately 40 % during finasteride therapy. We defined baseline PSA as PSA1, PSA at 6 months as PSA2, PSA at 12 months as PSA3. PSA1 was significantly correlated with PSA2/PSA1 and PSA3/PSA1. However, prostate volume was not correlated with PSA1. We divided the patients into three groups according to PSA level. Groups 1, 2, 3 represented the patients with PSA less than 2 ng/mL, between 2 and 4 ng/mL and greater than 4 ng/mL, respectively. Both the PSA2/PSA1 and the PSA3/PSA1 had significant difference among three groups. Furthermore, group 1 and group 2 both showed the fairly large data variance. CONCLUSIONS: When baseline PSA level was greater than 4 ng/mL, the doubling rule could be used for screening. When baseline PSA level was less than 4 ng/Ml, the doubling rule might not be an accurate predictor. We can use the PSA rise from nadir or proPSA to predict prostate cancer.

Determination of the efficiency of 8 mg doxazosin XL treatment in patients with an inadequate response to 4 mg doxazosin XL treatment for benign prostatic hyperplasia.

OBJECTIVE: To compare the efficacy of 4 mg and 8 mg doxazosin XL treatments in patients with benign prostatic hyperplasia-related lower urinary tract symptoms and determine the efficiency of 8 mg in those patients with inadequate response to 4 mg. METHODS: A total of 162 patients were included in this study. Of the patients, 108 were randomized to receive 4 mg doxazosin XL (group 1), and 54 were randomized to receive 8 mg (group 2) treatments. After 1 month of treatment, 31 patients in group 1 whose quality of life (QoL) score was unchanged or had deteriorated were switched to 8 mg doxazosin XL treatment (group 1b). RESULTS: The mean age was 59.8 years. After 1 month of treatment, the mean alteration in the International Prostate Symptom Score was 3.9 and 5.2 (P = .028), for the maximum urinary flow rate (Q(max)), it was 3.0 and 3.6 mL/s (P = .206), and for the QoL score it was 1.3 and 1.7 (P = .038) in groups 1 and 2, respectively. For group 1b, during the period in which the patients were receiving 4 and 8 mg doxazosin XL treatments; the International Prostate Symptom Score changes were 1.3 and 3.6 (P <.001), the Q(max) changes were 1.6 and 3.2 mL/s (P <.019), and the QoL changes were 0.4 and 1.8 (P <.001) in groups 1 and 2, respectively. CONCLUSION: With no changes in side effects, 8 mg doxazosin XL treatment is an efficient choice for patients who did not have an adequate response to 4 mg doxazosin XL treatment.

5α-Reductase inhibitor is less effective in men with small prostate volume and low serum prostatic specific antigen level.

BACKGROUND/PURPOSE: Large total prostate volumes (TPVs) or high serum prostate-specific antigen (PSA) levels indicate high-risk clinical progression of benign prostatic hyperplasia. This prospective study investigated the treatment outcome of combined 5α-reductase inhibitor and α-blocker in patients with and without large TPVs or high PSA levels. METHODS: Men aged ≥ 45 years with International Prostate Symptom scores (IPSS) ≥ 8, TPV ≥ 20 mL, and maximum flow rate ≤ 15 mL/s received a combination therapy (dutasteride plus doxaben) for 2 years. Patients with baseline PSA ≥ 4 ng/mL underwent prostatic biopsy for excluding malignancy. The changes in the parameters from baseline to 24 months after combination therapy were compared in those with and without TPV ≥ 40 mL or PSA levels ≥ 1.5 ng/mL. RESULTS: A total of 285 patients (mean age 72 ± 9 years) completed the study. Combination therapy resulted in significant continuous improvement in IPSS, quality of life index, maximum flow rate, and postvoid residual (all p < 0.0001) regardless of baseline TPV or PSA levels. However, only patients with baseline TPV ≥ 40 mL had significant improvements in IPSS-storage subscore, voided volume, reduction in TPV, transitional zone index, and PSA levels. In addition, patients with baseline TPV < 40 mL and PSA < 1.5 ng/mL had neither a reduction in TPV nor a decrease in serum PSA level. CONCLUSION: A high TPV indicates more outlet resistance, whereas elevated serum PSA level reflects glandular proliferation. Thus, patients with TPV<40 mL and low PSA levels has less benefit from 5α-reductase inhibitor therapy. The therapeutic effect of combined treatment may arise mainly from the α-blocker in these patients.

Comparison of the efficacy of isosorbide mononitrate and doxazosin in the treatment of lower urinary tract symptoms and benign prostatic hyperplasia: a randomized clinical trial.

OBJECTIVE: We aimed to compare the efficacy of isosorbide mononitrate and doxazosin in the treatment of lower urinary tract symptoms (LUTS). PATIENTS AND METHODS: 80 patients with LUTS were included in this randomized clinical study. All patients were evaluated with uroflowmetry, post-void residual (PVR) urine, prostate volume, International Prostate Symptom Score (IPSS), serum PSA, urinalysis and culture. 40 patients were prescribed doxazosin for 4 weeks, another 40 were prescribed isosorbide mononitrate for 4 weeks. Urologic re-evaluation was done at the end of the study. RESULTS: 74 patients completed the study. The mean age of patients was 59.6 ± 0.7 years, the mean PSA value was 1.7 ± 0.1 ng/ml and the mean prostate volume was 41.9 ± 1.7 ml. Doxazosin markedly improved IPSS (from 16.2 ± 0.7 to 9.5 ± 0.5), maximum urinary flow rate (from 10.9 ± 0.7 to 12.8 ± 0.6 ml/s) and PVR urine (from 68.1 ± 9.4 to 39.0 ± 4.4 ml) (p < 0.0001, p < 0.0001, p = 0.0004, respectively). Isosorbide only improved IPSS (from 16.5 ± 0.9 to 14.6 ± 0.8) (p = 0.032). CONCLUSIONS: Daily administration of isosorbide does not seem to be an alternative to α-blocker therapy. Controlled, randomized novel studies are required to establish that whether nitric oxide donors are an effective alternative in LUTS treatment.

Change in sexual function in men with lower urinary tract symptoms/benign prostatic hyperplasia associated with long-term treatment with doxazosin, finasteride and combined therapy.

PURPOSE: We examined the effects of doxazosin, finasteride and combined therapy in men with lower urinary tract symptoms associated with benign prostatic hyperplasia on sexual function, as assessed by the Brief Male Sexual Function Inventory during 4 years. MATERIALS AND METHODS: The MTOPS (Medical Therapy of Prostatic Symptoms) study was a multicenter, randomized, double-blind, placebo controlled clinical trial with a primary outcome of time to benign prostatic hyperplasia progression. Change in sexual function was a secondary outcome. We analyzed the records of 2,783 men enrolled in the study who completed the inventory at baseline and at least once during followup. RESULTS: In men enrolled in MTOPS sexual function decreased with time. Men assigned to finasteride and combined therapy experienced overall statistically significant but slight worsening of ejaculatory function compared with men on placebo. Men assigned to combined therapy also experienced significant worsening in erectile function and sexual problem assessment. There was no significant difference in changes in any inventory domain in men assigned to doxazosin alone compared to placebo. CONCLUSIONS: This study significantly extends understanding of the effects of long-term treatment with these drugs on sexual function in men with lower urinary tract symptoms associated with benign prostatic hyperplasia. Treatment with finasteride or combined therapy was associated with worsening sexual function while treatment with doxazosin alone was associated with minimal negative impact, if any. Physicians should discuss with their patients the possible long-term effects of these drugs for lower urinary tract symptoms associated with benign prostatic hyperplasia on sexual function.

Progression of lower urinary tract symptoms after discontinuation of 1 medication from 2-year combined alpha-blocker and 5-alpha-reductase inhibitor therapy for benign prostatic hyperplasia in men--a randomized multicenter study.

OBJECTIVE: To investigate the treatment outcome of discontinuing 1 medication from 2-year combination therapy for male benign prostatic hyperplasia/lower urinary tract symptoms. MATERIALS AND METHODS: Patients with International Prostate Symptom Score ≥ 8, total prostatic volume (TPV) >30 mL, and maximum flow rate (Qmax) <15 mL/s were randomly assigned to the 5α-reductase inhibitor (5ARI) discontinue (DC-5ARI) or α-blocker discontinue (DC-α-blocker) group. All patients received combination therapy with dutasteride (0.5 mg QD) and doxazosin (4 mg QD) for 2 years and then discontinued either one drug for 12 months. The primary endpoint was the occurrence of resuming medication. The secondary endpoints were the net parameters changed or the need of transurethral resection of the prostate (TURP). RESULTS: A total of 117 patients in DC-5ARI and 113 in DC-α-blocker group completed the study. The baseline TPV and Qmax were similar between groups before combination therapy. Resumption of combination therapy was significantly more in DC-5ARI than DC-α-blocker group (51.3% vs 31.0%; P = .005). The mean duration from discontinuing to resuming medication was 5.0 ± 4.4 months in DC-α-blocker and 7.8 ± 3.8 months in DC-5ARI group (P <.05). The TPV progression (29.1% vs 8.0%; P <.001) and the need for TURP (14.5% vs 7.1%; P = .043) were significantly higher in DC-5ARI than DC-α-blocker group. Patients with larger TPV (45.8 ± 18.1 mL) had significantly greater need for resuming 5ARI than smaller TPV (36.3 ± 16.9 mL; P = .007), and a lower Qmax might predict resuming α-blocker. CONCLUSION: After a 2-year combination therapy, discontinuation of either one drug induced benign prostatic hyperplasia progression in either group. Greater risk of resuming medication and needing TURP were noted in patients who discontinued 5ARI.