Frontal Fibrosing Alopecia: An Update on Pathogenesis, Diagnosis, and Treatment.

Frontal fibrosing alopecia (FFA), first described by Kossard in the early 1990s, is a form of primary lymphocytic cicatricial alopecia characterized by selective involvement of the frontotemporal hairline and eyebrows. Since the original description, an increasing number of cases have been reported worldwide and the clinical aspects of the disease have been better characterized. However, the pathogenesis is still unknown and several hypotheses have been made about possible triggering factors, including hormones, neurogenic inflammation, smoking, UV filters, and ingredients in leave-on facial products. A genetic basis has also been hypothesized as the disease can occur in siblings and members of the same family. Besides its pathogenesis, research is also focused on treatment; FFA is a chronic condition and at present there is no validated or approved treatment for this disorder. Commonly prescribed topical treatments include corticosteroids, minoxidil, and calcineurin inhibitors. Systemic treatments include 5α-reductase inhibitors, hydroxychloroquine, and retinoids. Intralesional triamcinolone acetonide is also utilized, especially for the eyebrows. Other possible treatments include pioglitazone, naltrexone, tofacitinib, and lasers.

Serenoa repens extracts: In vitro study of the 5α-reductase activity in a co-culture model for Benign Prostatic Hyperplasia.

OBJECTIVES: Benign Prostatic Hyperplasia (BPH) is a form of benign tumor that occurs in humans mainly with ageing. It affects more than 50% of over 50 years old males and it is characterized by an increased synthesis of dihydrotestosterone (DHT), due to the 5α-reductase activity. The BPH therapeutic approach mainly uses 5α-reductase inhibitors, such as the active compounds present in the extracts deriving from species Serenoa repens. Many lipidosterolic extracts are available on the market, which are obtained with different solvents, among them ethanol is recognized as non-toxic and has less handling risks than hexane. The purpose of the present experimental study was to investigate in-vitro the potency of an ethanol extract of S. repens comparing it with an n-hexane one. MATERIALS AND METHODS: Two different lipido-sterolic extracts of S. repens have been tested: ethanol extract and n-hexane extract, two batches for each one. The inhibitory action of the extract was evaluated estimating in-vitro the activity of enzyme 5α-reductase type I (5α-RI), which was mainly active under the experimental condition of pH 7.5. DHT amount, synthesized from testosterone (1 µM), was evaluated in a co-culture model of epithelial cells and fibroblasts resulting from prostatic biopsy of a patient with BPH. RESULTS: The analysis of the resulting dose-response curves showed that the entire S. repens extracts inhibited the 5α-RI showing no difference between the two kinds of extract or between the batches. The resulting IC50 values were the following: 8.809 (95% CI = 5.133-15.56) and 9.464 (95% CI = 5.094- 18.27) for ethanol extracts; 11.08 (95% CI = 6.389-19.98) and 12.72 (95% CI = 7.758-21.53) for n-hexane extracts. CONCLUSIONS: The potency of ethanol extracts of S. repens was comparable with the one of n-hexane extracts.

Emerging, newly-approved treatments for lower urinary tract symptoms secondary to benign prostatic hypertrophy.

INTRODUCTION: Oral therapy with alpha-blockers or 5-alpha reductase inhibitors remains the most common treatment in men with lower urinary tract symptoms (LUTS) secondary to benign prostatic hypertrophy (BPH). For patients who progress or fail medical therapy, the standard of care surgical treatment continues to be transurethral resection of the prostate (TURP), which has long-studied and durable outcomes. Emerging, minimally invasive options for LUTS secondary to the BPH, however, have been developed over the last decade with promising results and minimal side effects typically associated with TURP, such as retrograde ejaculation and erectile dysfunction. MATERIALS AND METHODS: We performed a literature review on PubMed over the last 10 years using keywords such as 'lower urinary tract symptoms,' 'benign prostatic hypertrophy,' 'minimally invasive,' and 'outpatient.' All relevant studies that reported on important urinary endpoints were included for each newly-approved treatment option. Available literature across varying prostate volumes was presented. RESULTS: Newly-approved therapies for BPH include new thermal energy sources (Rezum, aquablation), mechanical stenting (UroLift), prostate artery embolization, and injectable agents. These emerging techniques could be considered in patients where preservation of sexual function is a priority since they have demonstrated comparable urinary outcomes to medical therapy while causing no significant sexual dysfunction. Only prostate artery embolization has been extensively analyzed and proven efficacious in patients with > 80 g prostates who cannot undergo surgery. CONCLUSION: We have summarized the newly-approved treatment options for men with LUTS secondary to BPH as an alternative to traditional medical or surgical therapy. As more minimally invasive, office-based technologies emerge, physician and patients will have the ability to choose a treatment that is more catered to patient expectations.

Fractional non-ablative laser-assisted drug delivery leads to improvement in male and female pattern hair loss.

Androgenetic alopecia, also known as male and female pattern hair loss, is a very prevalent condition; however, approved therapeutic options are limited. Fractionated laser has been proposed to assist in penetration of topical medications to the cutaneous tissue. We present four cases of androgenetic alopecia that underwent treatment with a non-ablative erbium glass fractional laser followed by the application of topical finasteride 0,05% and growth factors including basic fibroblast growth factor, insulin-like growth factor, vascular endothelial growth factor, and copper peptide 1%. During all laser treatment sessions, eight passes were performed, at 7 mJ, 3-9% of coverage and density of 120 mzt/cm2. A positive response was observed in all of the four patients. Photographs taken 2 weeks after the last session showed improvement in hair regrowth and density. No significant side effects were observed.

B-lymphocytic infiltration of the prostate to a patient with chronic lymphocytic leukemia. A case report.

Involvement of the prostate gland, as an early extra-nodal manifestation of a hematologic disease, or as a secondary infiltration is rare. Even rarer is the acute urinary retention due to infiltration by lymphocytes and simultaneously enlarged prostate. We present a case of a 61 years old male patient with a history of chronic lymphocytic leukemia, who was under oncological follow-up with no active treatment and had typical lower urinary tract symptoms due to benign prostatic hyperplasia and was receiving 5-alpha reductase inhibitor. After an acute urinary retention episode which was managed with a suprapubic catheter due to urethral catheter insertion failure, the patient was submitted to a transurethral prostatectomy. Histological examination revealed lymphocytic infiltration of the prostatic parenchyma by mostly small B cells. B-lymphocytic infiltration of the prostate gland, causes symptoms similar to benign prostatic hyperplasia. Acute urinary retention due to B-lymphocytic infiltration of the prostate is rare and the diagnosis is always histological and an oncological re-evaluation is necessary. The prognosis of these patients is related to the generalized disease rather than to the prostatic involvement.

The Effect of the Aqueous Extract of Bidens Pilosa L. on Androgen Deficiency Dry Eye in Rats.

BACKGROUND/AIMS: Bidens pilosa L. (Bp) is widely distributed in China and has been widely used as a traditional Chinese medicine. The aim of this study was to examine the effect of the extract of Bp on androgen deficiency dry eye and determine its possible mechanisms. METHODS: Twenty-four rats were randomly divided into four groups: Group Con (control), Group Sal (physiological saline), Group Fin (oral finasteride), and Group Bp (oral finasteride and Bp). The dry eye model was established in group Fin and group Bp. Aqueous tear quantity was measured with phenol red-impregnated cotton threads with anesthesia. Tear film breakup time (BUT) and corneal epithelial damage were evaluated by fluorescein staining. Animals were sacrificed at 28 days, and ocular tissues (lacrimal gland and cornea) were evaluated with light microscopy; gene microarray analysis for inflammatory cytokines and Western blot were also performed. RESULTS: Finasteride administration effectively induced dry eye in rats by 14 days after administration. Group Fin rats had significantly higher fluorescein staining scores and lower aqueous tear quantity and BUT than the group Con rats, and notable inflammatory cell infiltrates were observed in the lacrimal gland of group Fin rats. The fluorescein staining score, aqueous tear quantity and BUT significantly improved with Bp treatment in the group Bp rats, and the structures of the lacrimal gland were well maintained without significant lymphocyte infiltration. Cytokine antibody array data identified the cytokines B7-2/Cd86, IL-1ß, IL-4, IL-6, IL-10, MMP-8, FasL, TNF-α and TIMP-1 as candidates for validation by Western blot. Expression levels of pro-inflammatory cytokines, including IL-1ß, IL-6, and TNF-α, in group Fin were upregulated compared with group Con. Levels of anti-inflammatory cytokines, such as IL-4 and IL-10, in group Fin were also upregulated compared with those in group Con. Compared with group Fin, IL-1ß, FasL, and TNF-α were significantly decreased in group Bp. CONCLUSION: The extract of Bp appears to be effective for the treatment of androgen deficiency dry eye in rats by improving aqueous tear quantity, maintaining tear film stability, and inhibiting the inflammation of the lacrimal gland.

Blockade of Androgen Markers Using a Novel Betasitosterol, Thioctic Acid and Carnitine-containing Compound in Prostate and Hair Follicle Cell-based Assays.

Androgenetic alopecia (AGA) affects approximately 70% of men and 40% of women in an age-dependent manner and is partially mediated by androgen hormones. Benign prostatic hyperplasia (BPH) similarly affects 50% of the male population, rising by 10% each decade. Finasteride inhibits 5-alpha reductase (5AR) and is used to treat both disorders, despite offering limited clinical benefits accompanied by significant adverse side effects. Building on our previous work demonstrating the efficacy of naturally derived 5AR inhibitors (such as stigmasterol and beta sitosterol), we hypothesize that targeting 5AR as well as inflammatory pathways may yield improved efficacy in AGA and BPH. Here we address these dual pathomechanisms by examining the potency of a novel composition using in vitro assays of representative cell lines for AGA (hair follicle dermal papilla cells) and BPH (LNCaP prostate cells), respectively. Exposure of cells to the novel test composition down-regulated mRNA expression profiles characteristic of both disease processes, which outperformed finasteride. Changes in mRNA expression were corroborated at the protein level as assessed by western blotting. These studies provide proof of concept that novel, naturally derived compositions simultaneously targeting 5AR and inflammatory mediators may represent a rational approach to treating AGA and BPH. Copyright © 2016 John Wiley & Sons, Ltd.

Effect of Preoperative Finasteride on the Volume or Length Density of Prostate Vessels, Intraoperative, Postoperative Blood Loss during and after Monopolar Transurethral Resection of Prostate: A Dose Escalation Randomized Clinical Trial Using Stereolog Methods.

PURPOSE: To evaluate the effects of two preoperative treatment courses with Finasteride on intraoperative and postoperative bleeding complications and prostate blood vessel characteristics in men who underwent transurethral resection of prostate (TURP) using monopolar energy. MATERIALS AND METHODS: Men scheduled for TURP were randomized into group 1 (control n = 25, no medication), group 2 and 3 (n = 20 in each, 5 mg Finasteride daily for 2 and 4 weeks before TURP; respectively). Hematocrit level in the irrigation fluid, weight of the resected prostate chips, decreases in blood hemoglobin (Hb) level 6 and 24 hours after the operation together with volume and length density of prostate vessels using stereological methods were compared. RESULTS: The three groups were matched regarding preoperative demographic data, resection time and weight of the resected tissue. Men who received preoperative Finasteride (groups 2 and 3) had significantly lower hematocrit levels in irrigation fluid than control group (control, 0.59 ± 0.85, group 2, 0.25 ± 0.4, group 3, 0.175 ± 0.16; P = .028; Power = .80). However, no statistically significant difference was found in hematocrit level in irrigation fluid between groups 2 and 3 (0.25 ± 0.4 vs. 0.175 ± 0.16, 95% confidence interval (CI) = -0.28-0.42; P = .68). These values were independent of the weight of the resected tissue and resection time. There were no significant differences between the three groups in the decrease in Hb 6 hours (P = .58) and 24 hours after TURP (P = .65). The stereological and histological characteristics of blood vessels in suburethral prostate tissue were similar in all three groups. CONCLUSION: A 2-week preoperative course of daily Finasteride seems sufficient to significantly reduce intraoperative blood loss; this effect was independent of the weight of the resected tissue and resection time. Neither the 2-week nor the 4-week presurgical Finasteride regimen could significantly decrease postoperative blood loss, and neither regimen induced significant changes in characteristics of prostate tissue blood vessels.

Impact of preoperative 5α-reductase inhibitors on perioperative blood loss in patients with benign prostatic hyperplasia: a meta-analysis of randomized controlled trials.

BACKGROUND: The ability of 5α-reductase inhibitors (5ARIs) to decrease blood loss during transurethral resection of the prostate (TURP) for benign prostatic hyperplasia (BPH) remains controversial. We aimed to conduct a meta-analysis of all randomized controlled trials (RCTs) to establish the role of 5ARI use prior to TURP. METHODS: We searched studies from the electronic databases PubMed, Embase, Scopus, and Cochrane Library from inception to March 25, 2014. Meta-analysis was performed using the statistical software Review Manager version 5.1. RESULTS: Seventeen RCTs including 1489 patients were examined. We observed that preoperative treatment with finasteride can decrease total blood loss, blood loss per gram of resected prostate tissue, hemoglobin level alteration, microvessel density (MVD), and vascular endothelial growth factor level. Neither finasteride nor dutasteride reduced operative time, prostate volume, or the weight of gland resected. In contrast, pretreatment with dutasteride before TURP did not decrease the total blood loss or MVD. CONCLUSIONS: Pretreatment with finasteride does seem to reduce perioperative blood loss related to TURP for BPH patients. However, the effect of preoperative dutasteride was inconclusive. Further studies are required to strengthen future recommendations regarding the use of 5ARI as a standard pre-TURP treatment and its optimal regimen.

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.

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.

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.

Pharmacotherapy and herbal treatment of benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is the most common tumor in aging men, and is associated with lower urinary tract symptoms (LUTS). Treatment options include watchful waiting, life-style modification, pharmacologic treatment, and surgery. Alpha-adrenergic receptor blockers (α-blockers) decrease LUTS and increase urinary flow rates in men with symptomatic BPH. 5-Alpha-reductase inhibitors (5-ARIs) decrease the production of dihydrotestosterone within the prostate, which results in decreased prostate volume. For patients with moderate to severe symptoms and a large prostate, combination therapy with α-blockers and 5-ARIs can further improve clinical efficacy of treatment. Numerous plant-based products (phytomedicines) are increasingly used as an alternative or complement the conventional medication. For some patients, phosphodiesterase-5 inhibitors (PDE5-Is) or antimuscarinic agents may be added. Here, we discuss the current pharmacotherapy of BPH.

Design and in vitro evaluation of finasteride-loaded liquid crystalline nanoparticles for topical delivery.

In this study, liquid crystalline nanoparticles (LCN) have been proposed as new carrier for topical delivery of finasteride (FNS) in the treatment of androgenetic alopecia. To evaluate the potential of this nanocarrier, FNS-loaded LCN was prepared by ultrasonication method and characterized for size, shape, in vitro release, and skin permeation-retention properties. The particle size ranged from 153.8 to 170.2 nm with a cubical shape and exhibited controlled release profile with less than 20% of the drug released in the first 24 h. The release profile was significantly altered with addition of different additives. Formulation with lower monoolein exhibited higher skin permeation with a flux rate of 0.061±0.005 µg cm(-2) h(-1) in 24 h. The permeation however, significantly increased with glycerol, propylene glycol, and polyethylene glycol 400, while it declined for the addition of oleic acid. A similar trend was observed with skin retention study. In conclusion, FNS-loaded LCN could be advocated as a viable alternative for oral administration of the drug.

Transurethral resection of prostate and the role of pharmacological treatment with dutasteride in decreasing surgical blood loss.

PURPOSE: Transurethral resection of prostate (TURP) still represents the gold standard in the surgical treatment of symptomatic benign prostatic hyperplasia (BPH). The most frequent complication is represented by intra- and perioperative bleeding. Preoperative use of 5-alpha-reductase inhibitors (finasteride or dutasteride) to reduce surgical bleeding is still a topic of debate in literature. Previous studies provided favorable data on blood loss reduction by preoperative administration of finasteride or dutasteride. The aim of this study was to evaluate whether pretreatment with dutasteride for six weeks before surgery can reduce surgical blood loss. METHODS: A total of 142 patients with BPH-who were to undergo TURP-were enrolled and randomized into two groups. The dutasteride group comprising of 71 patients, was treated with dutasteride (0.5 mg/day) for 6 weeks before surgery and the control group, comprising of other 71 patients, did not receive dutasteride. Blood loss was evaluated in terms of a reduction in the serum hemoglobin level (ΔHb and ΔHCT), and was estimated by measuring the Hb and hematocrit levels before and 24 hours after surgery. RESULTS: None of the patients treated with dutasteride reported any side effects. A significantly lower mean blood loss was observed in the dutasteride group compared to the control group (ΔHb=-1.29 ± 0.81 v -1.83 ± 1.25, respectively, p<0.0027; ΔHCT=-5.67 ± 2.58 v -6.50 ± 2.40, respectively, p<0.0491). CONCLUSIONS: Our results showed that pretreatment with dutasteride for 6 weeks before TURP reduces the surgical bleeding considerably. This treatment schedule can be used routinely to decrease TURP surgical bleeding.

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.

[Impact of preoperative therapy with 5-α-reductase inhibitors in the treatment of benign prostatic hyperplasia]. / Impatto della terapia preoperatoria con inibitori dell'enzima 5-α reduttasi nel trattamento dell'iperplasia prostatica benigna.

Benign prostatic hyperplasia is considered a progressive disease intimately linked with aging. The long-term use of combination therapy with a 5-alpha-reductase inhibitor, together with an alpha blocker in men with moderate-severe symptoms, reduces the risk of clinical progression and BPH-related surgery. It is unclear what the impact is of preoperative therapy with 5-ARI in patients that undergo surgery. The aim of our study was to evaluate the impact of preoperative therapy with 5-alpha-reductase inhibitors on: a) indication on the type of surgery; b) surgical and functional outcomes; c) surgical complications. This is a prospective observational study. It will include all patients undergoing surgery by TURP or Open Prostatectomy in a period of 24 months. We expect results that demonstrate significant and favorable influence of pretreatment with 5-alpha-reductase inhibitors on certain outcomes. Therefore, therapy with 5-ARI could be considered as neoadjuvant to surgery, whatever this is.

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.

Inhibitory activities of Puerariae Flos against testosterone 5α-reductase and its hair growth promotion activities.

Crude drugs expected to have an estrogenic effect were screened for their inhibitory activity on testosterone 5α-reductase. Testosterone 5α-reductase is an enzyme catalyzing the conversion of testosterone to dihydrotestosterone, which possesses high affinity for the androgen receptor. Among the crude drugs tested, we focused on Puerariae Flos (the flowers of Pueraria thomsonii) due to its potent inhibitory activity and suitability for commercial use. The 50% ethanolic extract of Puerariae Flos (PF-ext) showed inhibitory activity of 60.2% at 500 µg/ml against testosterone 5α-reductase. Interestingly, it was more potent than that of Puerariae Radix (roots of Pueraria lobata). PF-ext also showed in vivo anti-androgenic activity using a hair growth assay in testosterone-sensitive male C57Black/6NCrSlc strain mice. We demonstrated saponins, including soyasaponin I and kaikasaponin III, to be active components in PF-ext. In addition, hair growth promotion activity in C3H/He mice at 2 mg/mouse/day of the topical administration of PF-ext was demonstrated. Thus, Puerariae Flos is a promising crude drug for treating androgenic alopecia.

Usefulness of prostate-specific antigen (PSA) rise as a marker of prostate cancer in men treated with dutasteride: lessons from the REDUCE study.

OBJECTIVES: To determine if dutasteride-treated men can be monitored safely and adequately for prostate cancer based on data from the Reduction by Dutasteride in Prostate Cancer Events (REDUCE) study. To analyse whether the use of treatment-specific criteria for repeat biopsy maintains the usefulness of prostate-specific antigen (PSA) level for detecting high grade cancers. PATIENTS AND METHODS: The REDUCE study was a randomized, double-blind, placebo-controlled investigation of whether dutasteride (0.5 mg/day) reduced the risk of biopsy-detectable prostate cancer in men with a previous negative biopsy. The usefulness of PSA was evaluated using biopsy thresholds defined by National Comprehensive Cancer Network guidelines in the placebo group and any rise in PSA from nadir (the lowest PSA level achieved while in the study) in the dutasteride group. The number of cancers detected on biopsy in the absence of increased/suspicious PSA level as well as sensitivity, specificity, positive predictive value and negative predictive value for high grade prostate cancer detection were analysed by treatment group. Prostate cancer pathological characteristics were compared between men who did and did not meet biopsy thresholds. RESULTS: Of 8231 men randomized, 3305 (dutasteride) and 3424 (placebo) underwent at least one prostate biopsy during the study and were included in the analysis. If only men meeting biopsy thresholds underwent biopsy, 25% (47/191) of Gleason 7 and 24% (7/29) of Gleason 8-10 cancers would have been missed in the dutasteride group, and 37% (78/209) of Gleason 7 and 22% (4/18) Gleason 8-10 cancers would have been missed in the placebo group. In both groups, the incidence of Gleason 7 and Gleason 8-10 cancers generally increased with greater rises in PSA. Sensitivity of PSA kinetics was higher and specificity was lower for the detection of Gleason 7-10 cancers in men treated with dutasteride vs placebo. Men with Gleason 7 and Gleason 8-10 cancer meeting biopsy thresholds had greater numbers of positive cores, percent core involvement, and biopsy cancer volume vs men not meeting thresholds. CONCLUSION: Using treatment-specific biopsy thresholds, the present study shows that the ability of PSA kinetics to detect high grade prostate cancer is maintained with dutasteride compared with placebo in men with a previous negative biopsy. The sensitivity of PSA kinetics with dutasteride was similar to (Gleason 8-10) or higher than (Gleason 7-10) the placebo group; however, biopsy decisions based on a single increased PSA measurement from nadir in the dutasteride group resulted in a lower specificity compared with using a comparable biopsy threshold in the placebo group, indicating the importance of confirmation of PSA measurements.