Impact of 5-Alpha-Reductase Inhibitors Use at the Time of Prostatic Artery Embolization for Treatment of Benign Prostatic Obstruction.

PURPOSE: To compare the 12-month post-prostatic artery embolization (PAE) clinical outcomes of patients who were and were not taking 5-alpha-reductase inhibitors (5ARIs) at the time of PAE. MATERIALS AND METHODS: A retrospective review was conducted of patients who underwent PAE from 2010 to 2017 due to lower urinary tract symptoms, secondary to benign prostatic hyperplasia (BPH). One hundred fifty-five patients were included and divided in 2 groups; these groups did not present statistically significant differences in their baseline characteristics-those taking 5ARIs (Y-5ARIs, n = 40) and those not taking 5ARIs (N-5ARIs, n = 115). International Prostate Symptom Score (IPSS), the sub-item Quality of Life (QoL), and the incidence of clinical failure were used as primary endpoints. Secondary endpoints included mean prostate volume reduction and mean peak flow rate (Qmax) improvement. Clinical failure or recurrence was defined as absence of symptomatic improvement (IPSS ≥ 8 or QoL ≥ 3) or the need for invasive BPH treatment (PAE or transurethral resection of the prostate) during the 12-month follow-up period. RESULTS: After 12-month follow-up, IPSS, QoL, and prostatic volume were significantly lower compared to baseline in both groups, and Qmax showed a significant increase. No statistically significant differences were observed in outcomes between N-5ARIs and Y-5ARIs, and the clinical failure rate for both groups was approximately 20%. CONCLUSIONS: The use of 5ARIs did not show a detrimental effect on clinical outcomes of PAE, in either subjective (IPSS, QoL, and clinical failure) or objective (prostatic volume and Qmax) parameters.

Urologists' attitudes to sexual complications of LUTS/BPH treatments.

INTRODUCTION: Many LUTS/BPH treatments currently available may affect sexual function (SD). We wished to assess urologists' attitude and practice in this area. METHODS: Attendees of an international meeting were randomly selected, interviewed and stratified by professional status and LUTS/BPH cases seen per month. There were four questions: treatment options offered, frequency of discussing erectile dysfunction (ED) with each treatment, frequency of discussing ejaculatory dysfunction (EjD) with each treatment, and offering alternative treatment based on the risks of sexual dysfunction. RESULTS: 199 of the 245 interviewed (81%) were urologists. The most common treatments offered were α-blockers (99.5%), 5-ARI (95.0%) and TURP (92.5%). About 70% of the specialists discuss ED before α-blockers (not known to cause ED). Regarding EjD, 70% discuss this prior to prescribing α-blockers, 60% before 5-ARI therapy, while 80% before TURP. A significant minority fails to discuss this complication in all areas. Many respondents do not routinely discuss alternative therapies on the risk of SD. The higher the caseload, the less likely was a urologist to offer alternative therapies, with 37% of urologists seeing over 30 LUTS/BPH patients per month stating they would "Not at all often" offer alternative therapies for this reason. CONCLUSIONS: There is a significant discrepancy in attitudes to counselling patients on SD related to LUTS/BPH treatments. This may, in some cases, affect the validity of consent to the treatment. Most urologists do not discuss alternative treatments with patients based on the risks of different outcomes and complications, and this seems more marked in those with the busier practices. This may sit ill with the concept of personalised healthcare.

Early Surgical Intervention is Beneficial in Avoiding Complications in Patients with Male Lower Urinary Tract Symptoms.

In 2018, owing to the variety of true minimally invasive and effective treatment modalities available, early surgery in patients suffering from lower urinary tract symptoms due to benign prostatic enlargement is a valid, safe, and effective option compared to long-term less effective medical treatment.

Rationale and design of the CANARI study: a case-control study investigating the association between prostate cancer and 5-alpha-reductase inhibitors for symptomatic benign prostate hypertrophy by linking SNIIRAM and pathology laboratories in a specific region in France.

Benign prostate hypertrophy (BPH) could be associated with low urinary symptoms requiring medical treatment: 5-alpha-reductase inhibitors (5-ARI) or ɑ-blockers. Two clinical trials investigating 5-ARI use in prostate cancer (PCa) primary prevention highlighted a potential safety signal with an increased risk of high-grade PCa. Later observational studies failed to show similar results but have some limits. This paper focuses on describing the protocol of the CANARI study and its feasibility, as regards the matching process of two pseudo-anonymous databases. The study concerned patients living in the Brittany region (France) between 2010 and 2013. We designed a case-control study nested within a cohort of men treated by medical drugs licensed for symptomatic BPH between 2010 and 2011. Cases were patients with incident PCa diagnosed between 2012 and 2013 identified through French Health database (SNIIRAM). Gleason score was searched through Brittany pathology laboratories. Controls were patients without PCa diagnosis. Local pathology laboratories database was constituted in Brittany, gathering Gleason scores. No unique identification number is available in France; linkage of SNIIRAM and Brittany pathology laboratories database was made by deterministic matching. We matched 859 cases to Gleason grading (119 had Gleason score ≥8 and 740 had Gleason <8); around 22% of cases received 5-ARI and 78% α-blockers or phytotherapy. The CANARI study investigated in a population of men treated for BPH the risk of PCa with 5-ARI, according to Gleason grade thanks to SNIIRAM database enriched by local pathological results.

[Pharmacological treatment of benign prostatic hyperplasia]. / Medikamentöse Therapie des benignen Prostatasyndroms.

The pharmacological treatment of benign prostatic hyperplasia (BPH) is indicated when men suffer from lower urinary tract symptoms (LUTS) but there are no absolute indications for prostate surgery or severe bladder outlet obstruction. Phytotherapy can be used in men with mild to moderate LUTS and alpha-blockers can quickly and effectively decrease the LUTS and symptomatic disease progression. Phosphodiesterase type 5 inhibitors (PDE5-I) are an alternative to alpha-blockers when men experience bothersome side effects from alpha-blockers or erectile dysfunction. If patients predominantly have bladder storage symptoms and a small prostate, muscarinic receptor antagonists are a viable treatment option. The combination of alpha-blocker plus muscarinic receptor antagonist is more efficacious in reducing LUTS than the single drugs alone. The 5 alpha-reductase inhibitors (5ARI) can significantly decrease LUTS and disease progression (e.g. acute urinary retention and need for prostate surgery) in men with larger prostates (> 30-40 ml). The combination of 5ARI plus alpha-blocker can reduce LUTS and disease progression more effectively than drug monotherapy. Combination therapy with PDE5-I (tadalafil) plus 5ARI (finasteride) reduces LUTS more substantially than 5ARI alone and, additionally, PDE5-Is reduce the sexual side effects during 5ARI treatment.

5-Alpha Reductase Inhibitors and the Risk of Prostate Cancer Mortality in Men Treated for Benign Prostatic Hyperplasia.

OBJECTIVE: To compare the risk of prostate cancer mortality among men treated with 5- alpha reductase inhibitors (5-ARIs) with those treated with alpha-adrenergic blockers (ABs) in community practice settings. PATIENTS AND METHODS: A retrospective matched cohort (N=174,895) and nested case-control study (N=18,311) were conducted in 4 regions of an integrated health care system. Men 50 years and older who initiated pharmaceutical treatment for benign prostatic hyperplasia between January 1, 1992, and December 31, 2007, and had at least 3 consecutive prescriptions were followed through December 31, 2010. Adjusted subdistribution hazard ratios, accounting for competing risks of death, and matched odds ratios were used to estimate prostate cancer mortality associated with 5-ARI use (with or without concomitant ABs) as compared with AB use. RESULTS: In the cohort study, 1,053 men died of prostate cancer (mean follow-up, 3 years), 15% among 5-ARI users (N= 25,388) and 85% among AB users (N=149,507) (unadjusted mortality rate ratio, 0.80). After accounting for competing risks, it was found that 5-ARI use was not associated with prostate cancer mortality when compared with AB use (adjusted subdistribution hazard ratio, 0.85; 95% CI, 0.72-1.01). Similar results were observed in the case-control study (adjusted matched odds ratio, 0.95; 95% CI, 0.78-1.17). CONCLUSION: Among men being pharmaceutically treated for benign prostatic hyperplasia, 5-ARI use was not associated with an increased risk of prostate cancer-specific mortality when compared with AB use. The increased prevalence of high-grade lesions at the time of diagnosis noted in our study and the chemoprevention trials may not result in increased prostate cancer mortality.

5α-Reductase inhibitors increase acute coronary syndrome risk in patients with benign prostate hyperplasia.

BACKGROUND: This study explored the possible association between the use of two typical 5ARIs (finasteride and dutasteride) and the risk of acute coronary syndrome (ACS) in patients with benign prostate hyperplasia (BPH). METHODS: From the claims data of the Taiwan National Health Insurance (NHI) Taiwan, we identified 1843 ACS cases among BPH patients and randomly selected 7330 controls without ACS, with a similar mean age of 73 years. Multivariate logistic regression analysis estimated the odds ratio (OR) and 95 % confidence interval (CI) for the relationship between the 5ARIs medications and ACS risk. RESULTS: We found that BPH patients who had received treatment with both finasteride and dutasteride were at a higher risk of ACS with an OR of 3.47 (95 % CI 1.05-11.5), compared to patients without 5ARIs treatment. Furthermore, the dosage analysis showed that there were no significant associations between ACS risk and uses of a single drug medication regardless the dosages. The ORs for those who took only dutasteride were 1.07 (95 % CI 0.39-2.99) with low dose and 0.73 (95 % CI 0.38-1.44) with high dose. The ORs for those who took only finasteride were 1.30 (95 % CI 0.89-1.92) with low dose and 0.98 (95 % CI 0.19-5.13) with high dose. CONCLUSION: This population-based nested case-control study suggests that 5ARI use may increase ACS risk among patients with BPH when patients were exposed to both finasteride and dutasteride.

5α-Reductase inhibitors in androgenetic alopecia.

PURPOSE OF REVIEW: The authors will review the current literature on efficacy and safety of 5-alpha reductase inhibitors (5αRIs) for androgenetic alopecia (AGA). RECENT FINDINGS: The 5αRI finasteride and dutasteride are effective in treating AGA and promoting hair regrowth. 5αRI can be given orally, topically and more recently through mesotherapy. However, there has been an increasing concern about permanent sexual adverse events such as impotence and infertility. Most of these reports are published as case reports, and two studies reporting persistent sexual side-effects after discontinuation of finasteride had serious method limitations, as patients were recruited from a website. To our knowledge, permanent sexual adverse events have yet to be published in higher quality studies, such as randomized controlled trials. Although patients treated with 5αRIs have an increased incidence of sexual adverse events, these events decrease if discontinued or over time with continued therapy. SUMMARY: Sexual side-effects are uncommon and resolve spontaneously in most patients even without discontinuing therapy. Significant effort is underway to find delivery systems that optimize delivery and reduce systemic absorption of topical 5αRs including hydroxypropyl chitosan and liposomal and nanoparticulate systems.

Phase III prostate cancer chemoprevention trials.

Chemoprevention refers to the use of pharmacologic interventions to delay, prevent, or reverse carcinogenesis with the ultimate goal of reducing cancer incidence. Two large, population-based, phase 3 prostate cancer prevention trials reported that 5-alpha reductase inhibitors significantly reduce prostate cancer risk. However, this class of agents were also associated with increased detection of high-grade prostate cancer. Another large, phase 3 prostate cancer prevention clinical trial showed no benefit for long-term supplementation with the trace element Se, given in the form of selenomethionine, or vitamin E, either individually or in combination. Paradoxically, a significant increase in prostate cancer was observed among men randomized to receive vitamin E alone. A great deal of progress had been made in the field of prostate cancer prevention over the past decade. Future studies will focus on prevention of disease progression in men on Active Surveillance, immunotherapy, mechanistically based drug combinations, and novel biomarkers of risk and benefit.

Management of lower urinary tract symptoms related to benign prostatic hyperplasia in real-life practice in france: a comprehensive population study.

BACKGROUND: Male lower urinary tract symptoms (LUTS) are one of the most treated diseases, but little is known about patient trajectories in current clinical practice. OBJECTIVE: To describe the dynamic treatment patterns of LUTS presumably due to benign prostatic obstruction (BPO). DESIGN, SETTINGS, AND PARTICIPANTS: All prescriptions of α1-adrenergic receptor blocking agents (α1-blockers), 5α-reductase inhibitors (5-ARIs), and phytotherapy, and all surgeries related to BPO performed in France from 2004 to 2008 were identified using two distinct administrative claim databases maintained by the National Health Insurance system that covers the entire population. After linking the two data sets, all consecutive treatment events were analyzed for each patient. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Drug prescription details were assessed for each year, region, and prescriber qualification. Medical treatment initiation, interruption, evolution, and events after surgical management (hospital stay, reoperation, complication rates, and subsequent medical prescriptions) were also investigated. RESULTS AND LIMITATIONS: Overall, 2 620 269 patients were treated within 5 yr, with important geographic variations. Medical treatment was interrupted for approximately 16% of patients. The α1-blockers were prescribed most frequently, but phytotherapy surprisingly accounted for 27% of all monotherapies and 54% of all combination therapies. General practitioners and urologists (92% and 3.7% of overall prescribers, respectively) exhibited a similar prescription profile. Treatment initiation was medical in 95.4% of cases, consisting primarily of monotherapy using α1-blockers (60.3%), phytotherapy (31.8%), or 5-ARIs (7.9%). Treatment was modified at extremely high rates within 12 mo of initiation (8.7%, 14.6%, and 12.9%, respectively). The median hospital stay for surgical management was far higher than in clinical trials. Long-term surgical complications and reoperation rates favored open prostatectomy. Incidence of pharmacologic treatment after surgery was as high as 13.8% at 12 mo. CONCLUSIONS: This unique dynamic evaluation of clinical practice revealed unexpected results that contrast with previously published evidence from clinical trials. This approach may merit monitored and targeted measures to improve the level of care in the field.

A randomized double blind, vehicle controlled bilateral comparison study of the efficacy and safety of finasteride 0.5% solution in combination with intense pulsed light in the treatment of facial hirsutism.

OBJECTIVE: We sought to determine whether topical finasteride can enhance the efficacy of intense pulsed light hair removal. MATERIALS AND METHODS: An intense pulsed light (IPL) treatment with radiofrequency (RF) was performed every four weeks, resulting in up to three sessions, and again at the end of the study - 6 months after the start of the experiment. Each patient also applied either finasteride or placebo solution twice daily to each side of the chin in a double-blinded manner. RESULTS: A total of 77 patients were included in the study. Mean hair density before treatment in finasteride side of the patient's chin was 19.7 ± 11.7 and in placebo side was 19.1 ± 11.3. After three sessions of IPL + RF treatment, combined with twice daily application of finasteride and placebo solutions, at the end of 6-month period mean hair density of 8 ± 6.3 and 9 ± 5.6 was achieved in finasteride and placebo side respectively. Statistically significant difference was found between finasteride and placebo solution. CONCLUSIONS: We have demonstrated that the addition of finasteride solution to IPL + RF hair removal may result in a more reduction of unwanted facial hair in women when the combination is used for up to 6 months.

Real-world use of Permixon® in benign prostatic hyperplasia--determining appropriate monotherapy and combination treatment.

INTRODUCTION: Benign prostatic hyperplasia (BPH) is a major health concern for aging men. The resulting lower urinary tract symptoms may have a profound effect on a patient's quality of life and it is recognized that patient acceptability of treatment is key to decreasing the human and economic burden of the condition. Alphaadrenergic antagonists (alpha-blockers), 5-alphareductase inhibitors (5-ARIs), and phytotherapy as monotherapy or in combination, form the mainstay of medical treatment. METHODS: The Adelphi Permixon Study, a cross-sectional study of representative consulting patients with BPH in two European countries, was undertaken to examine the reasons for choice of medication. Physicians completed patient record forms, and data were analyzed for clinical outcomes and their relationship with the choice of appropriate therapy. RESULTS: Patients receiving combination therapies for BPH are likely to be older and are more likely to be retired than those on monotherapy. Combination therapy is adopted in the real-world setting as first-line therapy on a not-infrequent basis. The analyses demonstrated an association between choice of Permixon® (Pierre Fabre Medicament, Castres, France) as appropriate monotherapy or in combination with alpha-blockers, and the following: BPH severity; treatment of general urinary symptoms, including storage and voiding symptoms; improvement of urinary flow rate; lack of a risk of sexual problems; and reduction of inflammation. Permixon combination with an alpha-blocker is associated with benefits in terms of speed of onset of action, reduction of inflammation, and a positive benefit regarding sexual problems when compared with use of alpha-blocker monotherapy. CONCLUSION: In the real clinical world, Permixon is considered an appropriate treatment for BPH as both monotherapy and in combination with alpha-blockers. Prescribing Permixon in combination with alpha-blockers can be demonstrated to provide benefits beyond use of either therapy alone.

Adverse side effects of 5α-reductase inhibitors therapy: persistent diminished libido and erectile dysfunction and depression in a subset of patients.

INTRODUCTION: 5α-reductase inhibitors (5α-RIs), finasteride and dutasteride, have been approved for treatment of lower urinary tract symptoms, due to benign prostatic hyperplasia, with marked clinical efficacy. Finasteride is also approved for treatment of hair loss (androgenetic alopecia). Although the adverse side effects of these agents are thought to be minimal, the magnitude of adverse effects on sexual function, gynecomastia, depression, and quality of life remains ill-defined. AIM: The goal of this review is to discuss 5α-RIs therapy, the potential persistent side effects, and the possible mechanisms responsible for these undesirable effects. METHODS: We examined data reported in various clinical studies from the available literature concerning the side effects of finasteride and dutasteride. MAIN OUTCOME MEASURES: Data reported in the literature were reviewed and discussed. Results. Prolonged adverse effects on sexual function such as erectile dysfunction and diminished libido are reported by a subset of men, raising the possibility of a causal relationship. CONCLUSIONS: We suggest discussion with patients on the potential sexual side effects of 5α-RIs before commencing therapy. Alternative therapies may be considered in the discussion, especially when treating androgenetic alopecia.