Tadalafil versus tamsulosin as combination therapy with 5-alpha reductase inhibitors in benign prostatic hyperplasia, urinary and sexual outcomes.

PURPOSE: To compare the urological and sexual outcomes of using either tamsulosin/finateride or tadalafil/finasteride as combination therapies in patients with large prostate. PATIENTS AND METHODS: Selection criteria included prostate volume > 40 ml and IPSS > 7. Patients with severe erectile dysfunction (IIEF-erectile functions ≤ 10) were excluded. Patients were randomized into group I (tamsulosin/finasteride) and group II (tadalafil/finasteride). The primary endpoint was to define urinary and sexual function changes (IPSS, IPSS-quality of life, urinary flow rates and IIEF domains) within each group. The secondary endpoint was to compare the treatment induced changes between both groups. RESULTS: At 4th and 12th weeks, 131 and 127 patients were available in both groups, respectively. Both groups showed significant LUTS improvement (IPSS changes: - 4.9 ± 2.7 and - 4.3 ± 2.9 at 4th week and - 6.1 ± 3 and - 5.4 ± 2.8 points by the 12th week in both groups, respectively). Group I had better average flow rates at both follow-up visits. Meanwhile, maximum flow rates were comparable in both groups at 12th week (13.5 ± 3.9vs. 12.6 ± 3.7, p > 0.05). In group I, all IIEF domains were significantly lowered at both visits (p < 0.05). Group II showed significant increase in IIEF-erectile function scores (1.3 ± 1.1 and 1.8 ± 1.2 at the 4th and 12th weeks) with a transient significant reduction of IIEF-orgasm and sexual desire noted only by the 4th week (- 0.8 ± 0.4 and - 0.6 ± 0.4, respectively). CONCLUSION: Within three months, both combinations are comparably effective in improving BPH related LUTS. Tamsulosin/finasteride provided significantly better Qmax only at 4th week. Tadalafil/finasteride had the advantage of improving sexual performance over the other combination.

How Would You Manage This Patient With Benign Prostatic Hyperplasia? : Grand Rounds Discussion From Beth Israel Deaconess Medical Center.

Lower urinary tract symptoms due to benign prostatic hyperplasia (BPH) are common in older patients assigned male sex at birth, regardless of gender identity, and treatment of these symptoms is therefore common in primary care practice. In 2021, the American Urological Association published guidelines for management of BPH. They recommend using a standardized scoring system such as the International Prostate Symptom Score to help establish a diagnosis and to monitor the efficacy of interventions, α-blockers as the first-choice pharmacotherapy option, and 5α-reductase inhibitors for patients with prostate size estimated to be at least 30 cc. Tadalafil is another option regardless of erectile dysfunction. Combination therapies with α-blockers and 5α-reductase inhibitors, anticholinergic agents, or ß3-agonists are effective options. A surgical referral is warranted if the BPH results in chronic kidney disease, refractory urinary retention, or recurrent urinary tract infections; if there is concern for bladder or prostate cancer; or if symptoms do not respond to medical therapy. In this article, a general internal medicine physician and a urologist discuss the treatment options and how they would apply their recommendations to a patient who wishes to learn more about his options.

The impact of 5-alpha-reductase inhibitors on mortality in a prostate cancer chemoprevention setting: a meta-analysis.

PURPOSE: This study aims to evaluate the impact of 5-alpha-reductase inhibitors (5ARI) for prostate cancer (PCa) primary prevention on specific and overall mortality (primary outcomes), the incidence of PCa diagnosis and disease aggressiveness (secondary outcomes). METHODS: We searched MEDLINE, EMBASE, Cochrane, ClinicalTrials and BVS through April 2018 according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement to identify randomized clinical trials (RCT) and cohort studies (CS). We included articles with data on mortality or PCa incidence for men using 5ARI previously to PCa diagnosis. RESULTS: Regarding the included studies, nine had data on mortality, 16 on PCa incidence and 12 on Gleason scores (GS). We found that the use of 5ARI had no impact on overall mortality (RR 0.93 95% CI 0.78-1.11) and PCa-related mortality (RR 1.35 95% CI 0.50-3.94), nor on high-grade PCa diagnosis (RR 1.06 95% CI 0.72-1.56). We identified a relative risk reduction of 24% in moderate-grade PCa diagnosis (RR 0.76 95% CI 0.59-0.98) and low-grade PCa diagnosis (RR 0.76 95% CI 0.59-0.97) Also, a reduction of 26% in overall PCa diagnosis was observed in the RCT subgroup analysis (RR 0.74 95% CI 0.65-0.84). CONCLUSION: 5ARI significantly reduced the risk of being diagnosed with PCa, not increasing high-grade disease, overall or cancer-specific mortality. Due to the relatively short mean follow-up of most studies, the mortality analysis is limited.

[Comparative analysis of the effectiveness of early and delayed initiation of combined DRUG therapy for bph].

INTRODUCTION: Currently, -blockers (-AB) and 5-alpha-reductase inhibitors (I-5-AR) are recommended as the drugs of choice for the treatment of patients with benign prostatic hyperplasia (BPH). However, despite the clear advantages of combination therapy, at the initial stages of treatment, I-5-AR is either not prescribed at all, or added to therapy after a few months. The aim of our study is to study the effectiveness of early and various options for delayed combined drug therapy of patients with BPH using -AB and I-5-AR. MATERIALS AND METHODS: The study included 90 patients with BPH, who were divided into three groups of 30 people. In group 1, monotherapy with drugs from the -AB group was performed for 6 months, after which they were transferred to treatment with a combined drug. In group 2, monotherapy was performed for three months, after which they were also transferred to treatment with a combined drug. And in group 3, patients were prescribed combination therapy from day 1. RESULTS: Early combination therapy with dutasteride was more effective than delayed Therapy for 6 months. There were no significant differences in the main parameters studied between patients who simultaneously started combination therapy and switched to it after 3 months, by the end of the 12th month of treatment. However, early therapy is a combined drug made it possible to achieve a more rapid effect in relation to LUTS. CONCLUSION: Thus, the data obtained confirm the clinical recommendations regarding the expediency of early initiation of combined therapy with an -adrenoblocker and a 5-reductase inhibitor in patients with moderate and severe LUTS caused by BPH and the risk of disease progression. Postponing the transition to combination therapy for 6 months or more may lead to a decrease in the effectiveness of treatment of patients in this category.

Medication Discontinuation Following Transurethral Prostatectomy: an Unrecognized Effectiveness Measure?

PURPOSE OF REVIEW: Freedom from medication is a common goal for patients undergoing surgical treatment of benign prostatic hyperplasia (BPH)/lower urinary tract symptoms (LUTS). Knowing medication discontinuation rates following various forms of transurethral prostatectomy may aid patient counseling and assessing the comparative effectiveness of different approaches. This review examined discontinuation rates of BPH/LUTS medications following transurethral prostatectomy. RECENT FINDINGS: Rates of BPH/LUTS medication use after transurethral resection of the prostate varied from 15% to 55%, and discontinuation rates were 54-95% across medications and follow-up periods. For laser prostatectomy, approximately 18% of patients continued medications postoperatively and discontinuation rates ranged from 53% to 75%. Minimal data on holmium laser enucleation existed. For reference, medication discontinuation rates after transurethral needle ablation or microwave therapy were only 15-28%. No recommendations or best practices inform the use of medical therapy following BPH surgery. Rates of BPH/LUTS medication use following transurethral prostatectomy are considerable.

Post-finasteride syndrome - does it really exist?

Inhibitors of 5α-steroid reductase are drugs used to treat androgen-dependent conditions including prostate diseases and androgenic alopecia. Finasteride was the first on the market and is currently the most widely used inhibitor. Dutasteride was the second inhibitor to be approved and has a similar safety profile. Common adverse events of treatment consist of sexual disorders and a negative affect balance. It was described that the prolonged use of 5α-steroid reductase inhibitors in patients with alopecia can cause persistent side effects called a post-finasteride syndrome (PFS), that is not just a simple coexistence of events, but rather a definite syndrome with an iatrogenic background. PFS occurs in susceptible individuals even after small doses of the drug and can last for a long time after the discontinuation of treatment. A deterioration in the quality of life in affected individuals does not justify use of the drug. Wider recognition of PFS symptoms, its incidence, course, prevention, and treatment possibilities will allow the indications for drug use to be reconsidered and treatment to be more personalized. Knowledge about PFS will also help to provide the best treatment for affected individuals and to properly educate patients before obtaining an informed consent for therapy with 5α-steroid reductase inhibitors.

Controversies in the treatment of androgenetic alopecia: The history of finasteride.

Male androgenetic alopecia (AGA) affects up to 60% of men by the age of 50. Currently, there are only two approved drugs for the treatment of male AGA: topical minoxidil and oral finasteride. Topical minoxidil is readily available over the counter and has a well-established safety record. However, following 24 weeks of treatment, less than 40% of men respond to the drug. Additionally, due to the topical route of administration, compliance with minoxidil remains low. In contrast, oral finasteride, a 5-alpha reductase inhibitor, demonstrated efficacy in arresting hair loss in more than 80% of patients following 12 months of treatment. However, controversy surrounding potential adverse sexual side effects has negatively affected public perception of the drug and may significantly reduce the number of patients that can benefit from the drug.

[Medical treatment of patients with benign prostatic hyperplasia with 5-reductase inhibitors].

The results of studies comparing the therapy of benign prostatic hyperplasia with 5-reductase inhibitors and 1-blockers are presented in the article. Benign prostatic hyperplasia is a common disease in older men. Pathogenetic treatment allows to block a progression of prostatic hyperplasia and is of greatest interest in the treatment of this disease. The obtained data reliably demonstrate the advantage and safety of long-term pathogenetic therapy with dutasteride compared with symptomatic tamsulosin monotherapy with regard to quality of life and subjective symptoms. In addition, pathogenetic therapy provides better results in preventing the progression of benign prostatic hyperplasia.

[Combination drug therapy in patients with BPH].

Introuction. One of the risk factors for LUTS is an infravesical obstruction, which is most often caused by benign prostatic hyperplasia (BPH). BPH symptoms are formed due to three components: static (mechanical), dynamic, and impaired functional capacity of the bladder. Medical treatment with 1-blockers decreases the outflow obstruction. 5-alpha reductase inhibitors are used to inhibit the static component of BPH. AIM: To investigate the effectiveness of various modifications of medical therapy of BPH using -blockers and 5-reductase inhibitors and combinations thereof. MATERIALS AND METHODS: The study comprised 90 BPH patients who were divided into three groups, with each group containing 30 people. Patients of group I, II and III received monotherapy with -blockers, a combination of 5-reductase and -blockers, and fixed-dose combination drug Duodart, respectively. Evaluation of the treatment effectiveness included filling out voiding diaries, completing the I-PSS and QL questionnaires, uroflowmetry, transrectal ultrasonography of the prostate and estimation of the incidence of adverse effects. Also, compliance with the treatment was evaluated, and the number of patients who had episodes of acute urinary retention and required surgical treatment during the 12 month treatment course was registered. RESULTS: Compared to monotherapy, combination therapy with -blockers and 5-reductase inhibitors more effectively reduces the LUTS, increases Qmax and prevents the disease progression, which manifests in a lower incidence of AUR and fewer surgical interventions in groups II and III. However, the combination therapy can be associated with some side effects. Patients who received fixed-dose combination drug Duodart had a greater compliance rate than patients on the combination of drugs, which, in our opinion, is associated with fewer cases of AUR and surgical interventions. CONCLUSION: The use of Duodart in patients with BPH effectively alleviates LUTS and reduces the risk of the disease progression, which manifests itself in a reduced number of complications and thereby contributes to improving the quality of life of patients.

Effects of Steroidal Antiandrogen or 5-alpha-reductase Inhibitor on Prostate Tissue Hormone Content.

BACKGROUND: The effects of a steroidal antiandrogen (AA) and 5-alpha-reductase inhibitor (5ARI) on prostate tissue hormone content and metabolism are not fully elucidated. The objective of this study is to investigate the hormone content and metabolism of the prostate tissues of patients treated with AA or 5ARI using the ultra-sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. METHODS: Thirty-nine patients with benign prostatic hyperplasia (BPH) undergoing transurethral surgery were included. Serum and prostate tissue hormone and prostate tissue hormone metabolism analyses were performed using LC-MS/MS after 1 month of treatment with chlormadinone acetate (CMA; steroidal AA, 50 mg/day) or dutasteride (DUTA; dual 5ARI, 0.5 mg/day). RESULTS: Serum testosterone (T), dihydrotestosterone (DHT), and adrenal androgen levels were lower in the CMA group than the control group. Prostate tissue T and DHT levels were also lower in the CMA group than the control group. In the DUTA group, only serum and prostate DHT concentrations were reduced compared to the control group; in contrast, those of other hormones, especially T and 4-androstene-3,17-dione in the prostate tissue, showed marked elevations up to 70.4- and 11.4-fold normal levels, respectively. Moreover, the hormone metabolism assay confirmed that the conversion of T to DHT was significantly suppressed while that of T to 4-androstene-3,17-dione was significantly accelerated in the prostate tissue of DUTA-treated patients. CONCLUSIONS: Although treatment with AA and 5ARI show similar clinical outcomes, their effect on tissue hormone content and metabolism varied greatly. Prostate 77: 672-680, 2017. © 2017 Wiley Periodicals, Inc.

Is There a Role for Preoperative 5 Alpha Reductase Inhibitors in Reducing Prostate Vascularity and Blood Loss?

Benign prostatic hyperplasia (BPH) and the related medical problems are a major burden as health care costs and as a cause of patient morbidity. The introduction of medical therapy largely offered an alternative to surgical therapy, and these medications have been linked with multiple positive BPH-related outcomes. With ubiquitous use, however, a variety of adverse side effects and unsupported claims to these medications have been reported both in scientific literature and popular press. The use of 5 alpha reductase inhibitors (5ARIs) to reduce recurrent bleeding due to BPH is a reasonable option for men with recurrent trips to the physician or hospital. After a largely anecdotal report of their use in the preoperative period to reduce bleeding during BPH surgery, there was interest in the use of 5ARIs for this indication considering the effusive bleeding that can occur during BPH-related surgery, a dreaded and not uncommon complication. While the pathophysiology for the use of 5ARI to reduce BPH-related bleeding is sound, the actual clinical outcomes still require scrutiny to determine if the efficacy is both scientifically valid and clinically significant. This report will review the current literature on this topic and make attempts to determine if the use of a 5ARI before BPH-related surgery should be encouraged.

Hidradenitis Suppurativa in Children Treated with Finasteride-A Case Series.

BACKGROUND: Hidradenitis suppurativa (HS) is rare in childhood, with only 2% of cases in patients younger than 11 years. It is a chronic, recurrent, debilitating condition for which no universally effective treatment has been developed. We present five cases of children with HS diagnosed between the ages of 6 and 11 years. METHODS: Patients were treated with oral finasteride 1 to 5 mg/day. All had entered puberty at the time of treatment initiation. All had normal laboratory results before starting treatment. The maximum duration of treatment was 24 months. RESULTS: Four patients were female. Two were overweight. Three had been previously treated with oral antibiotics, and two of these with oral isotretinoin, with partial or no improvement. Overall improvement of the disease was observed in all patients, with a reduction of the frequency and intensity of the flares. No adverse effects were observed or reported during treatment. CONCLUSION: Treatment of HS can be challenging. The options available include antimicrobials, immunosuppressants, hormonal therapies, lasers, and surgery. The authors report the largest series of children with HS treated with finasteride. The results support the use of finasteride as monotherapy for the treatment of this disease in children. Further studies are necessary to fully understand the role of this drug in the management of this disease.

Efficacy and safety of combination therapy with tamsulosin, dutasteride and imidafenacin for the management of overactive bladder symptoms associated with benign prostatic hyperplasia: A multicenter, randomized, open-label, controlled trial (DIrecT Study).

OBJECTIVES: To evaluate the efficacy and safety of a combination therapy with dutasteride and imidafenacin in patients with benign prostatic hyperplasia and persistent overactive bladder symptoms. METHODS: A total of 163 patients presenting an enlarged prostate (volume >30 mL) and persistent overactive bladder symptoms despite at least 8 weeks of tamsulosin were randomized to receive tamsulosin and dutasteride, or tamsulosin, dutasteride and imidafenacin at a 1:1 ratio. The primary end-point was the mean change from baseline to week 24 in total overactive bladder symptom score. RESULTS: The mean change in total overactive bladder symptom score from baseline at week 24 was -1.99 (95% confidence interval -2.57 to -1.41) in the tamsulosin and dutasteride group, and -3.12 (95% confidence interval -3.72 to -2.52) in the tamsulosin, dutasteride and imidafenacin group. The tamsulosin, dutasteride and imidafenacin group significantly improved total overactive bladder symptom score at week 24 as compared with the tamsulosin and dutasteride group; the mean difference was -1.18 (-2.02 to -0.34). The between-group difference was statistically significant as early as week 4. The total International Prostate Symptom Score, storage subscore, quality of life index, and benign prostatic hyperplasia impact index also significantly improved in the tamsulosin, dutasteride and imidafenacin group. CONCLUSIONS: Tamsulosin, dutasteride and imidafenacin combination therapy improves overactive bladder symptoms and quality of life without causing serious adverse drug reactions in patients with enlarged prostate not responding to tamsulosin. This combination therapy seems to represent a promising therapeutic option in these patients.

Chemoprevention of prostate cancer.

Large prospective randomized trials, such as the Prostate Cancer Prevention Trial (PCPT), Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial, and Selenium and Vitamin E Cancer Prevention Trial (SELECT), have provided practitioners with considerable data regarding methods of treatment and prevention of prostate cancer. The best-studied medications for prevention are 5 alpha-reductase inhibitors. Their efficacy and side effects are well characterized. Other medications, dietary nutrients, and supplements have not been as well studied and generally do not demonstrate efficacy for disease prevention with an acceptable level of evidence.

BPH update: medical versus interventional management.

Benign prostatic hyperplasia (BPH) is a common condition that afflicts a large proportion of aging men. The primary care physician has an important role with the identification and early treatment of bothersome urinary symptoms caused by BPH. This includes a detailed history and physical exam, as well as initiation of a number of medications such as alpha-blockers, 5-alpha reductase inhibitors and phosphodiesterase-5 inhibitors. It is also very important for the primary care giver to determine when additional evaluation and referral to a urologist needs to occur, specifically when surgical intervention is needed. This review will summarize the management of this common disorder and is designed to aid the generalist with the pertinent information needed to provide excellent care.

Effects of dutasteride on serum free-testosterone and clinical significance of testosterone changes.

Sixty-two patients with benign prostate hyperplasia (BPH) who were being treated with dutasteride participated in this study. Prostate volume, uroflowmetry, blood tests, the International Prostate Symptom Score (IPSS) and International Index of Erectile Function (IIEF-5) were determined before and 1, 3 and 12 months after the treatment with dutasteride. Patients were divided into two groups based on changes in serum testosterone after 1 month: Group A (>20% increase; n = 33) or Group B (<20% increase; n = 29). Serum free-testosterone levels were 20.4% higher after 1 month and remained constant thereafter. When Groups A and B were compared, baseline free-testosterone levels were significantly lower in Group A, IPSS QOL was significantly better in Group A at 3 and 12 months, and no significant differences were observed in uroflowmetry, prostate volume, IPSS or IIEF-5. A univariate analysis identified serum free-testosterone levels and the IPSS storage symptom subscore as significant factors influencing IPSS QOL at 12 months, and only the IPSS storage symptom subscore appeared to be independently related to IPSS QOL. These results indicate that dutasteride increases serum free-testosterone levels in BPH patients, particularly with low baseline free-testosterone levels, and the increase in free-testosterone may have further add-on impacts on their urinary tract symptoms.

[Finasteride adverse effects: An update]. / Efectos adversos de finasteride: mitos y realidades. Una revisión actualizada.

Finasteride is a 5-α reductase inhibitor that is widely used in the management of benign prostate hyperplasia and male pattern hair loss. It is well known that these agents improve the quality of life in men suffering from these conditions. However, they are associated with some transient and even permanent adverse effects. The aim of this article is to clarify the controversies about the safety of finasteride by analyzing the evidence available in the literature.

Adverse effects of 5α-reductase inhibitors: What do we know, don't know, and need to know?

Steroids are important physiological orchestrators of endocrine as well as peripheral and central nervous system functions. One of the key processes for regulation of these molecules lies in their enzymatic processing by a family of 5α-reductase (5α-Rs) isozymes. By catalyzing a key rate-limiting step in steroidogenesis, this family of enzymes exerts a crucial role not only in the physiological control but also in pathological events. Indeed, both 5α-R inhibition and supplementation of 5α-reduced metabolites are currently used or have been proposed as therapeutic strategies for a wide array of pathological conditions. In particular, the potent 5α-R inhibitors finasteride and dutasteride are used in the treatments of benign prostatic hyperplasia (BPH), as well as in male pattern hair loss (MPHL) known as androgenetic alopecia (AGA). Recent preclinical and clinical findings indicate that 5α-R inhibitors evoke not only beneficial, but also adverse effects. Future studies should investigate the biochemical and physiological mechanisms that underlie the persistence of the adverse sexual side effects to determine why a subset of patients is afflicted with such persistence or irreversible adverse effects. Also a better focus of clinical research is urgently needed to better define those subjects who are likely to be adversely affected by such agents. Furthermore, research on the non-sexual adverse effects such as diabetes, psychosis, depression, and cognitive function are needed to better understand the broad spectrum of the effects these drugs may elicit during their use in treatment of AGA or BPH. In this review, we will summarize the state of art on this topic, overview the key unresolved questions that have emerged on the pharmacological targeting of these enzymes and their products, and highlight the need for further studies to ascertain the severity and duration of the adverse effects of 5α-R inhibitors, as well as their biological underpinnings.

Short-term pretreatment with a dual 5α-reductase inhibitor before bipolar transurethral resection of the prostate (B-TURP): evaluation of prostate vascularity and decreased surgical blood loss in large prostates.

OBJECTIVE: To investigate if short-term treatment with dutasteride (8 weeks) before bipolar transurethral resection of the prostate (B-TURP) can reduce intraoperative bleeding, as dutasteride a dual 5α-reductase inhibitor (5-ARI) blocks the conversion of testosterone into its active form dihydrotestosterone (DHT), and reduces prostate volume and prostate-specific antigen (PSA) levels, while increasing urinary flow rate. PATIENTS AND METHODS: In all, 259 patients were enrolled and randomised to two groups: Group A, receiving placebo and Group B, receiving dutasteride (0.5 mg daily for 8 weeks). Blood samples were taken before and after B-TURP for serum chemistry evaluation. In particular we evaluated blood parameters associated with blood loss [haemoglobin (Hb) and haematocrit (Ht)] and prostate vascularity [vascular endothelial growth factor (VEGF) immunoreactivity and microvessel density (MVD) using cluster of differentiation 34 (CD34) immunoreactivity]. RESULTS: Total testosterone, DHT, PSA level and prostate volume were evaluated and with the exception of DHT and PSA level there was no statistically significant differences between the groups. When comparing changes in Hb and Ht between Group A and Group B before and after B-TURP, there was a statistically significant difference only in patients with large prostates of ≥50 mL (ΔHb 3.86 vs 2.05 g/dL and ΔHt 4.98 vs 2.64%, in Groups A and B, respectively). There was no significant difference in MVD and VEGF index in prostates of <50 mL, conversely in large prostates the difference become statistically significant. CONCLUSIONS: Dutasteride was able to reduce operative and perioperative bleeding only in patients with large prostates (≥50 mL) that underwent B-TURP. Our findings are confirmed by Hb and Ht values reported before and after the B-TURP and reductions in the molecular markers for VEGF and CD34 in the dutasteride-treated specimens.