Effectiveness and safety of the ablative fractional 2940-nm Er: YAG laser for the treatment of androgenetic alopecia.

Laser sources have established their potential effect in inducing hair regrowth. No large cohort study has evaluated the effect of ablative fractional 2940-nm erbium yttrium aluminum garnet (Er: YAG) laser in the treatment of androgenetic alopecia (AGA). To investigate the efficacy and safety of the ablative fractional 2940-nm Er: YAG laser in combination with medication therapy for the treatment of AGA. We performed a retrospective study between first July 2021 to 30th December 2021. All included patients received oral finasteride and topical minoxidil, or combined with six sessions of Er: YAG laser at 2-week intervals. Patients were divided into medication or combined therapy groups. The efficacy of the two therapies was evaluated by the investigator's Global Assessment (IGA) scores and the patient's Likert satisfaction scale at week 12 and week 24. Changes in total, terminal and villous hair count, total and terminal hair diameter, and AGA grade were also recorded. Adverse events were evaluated at each follow-up. A total of 192 male patients with AGA were included, including 67 receiving combination treatment, and 125 receiving medication treatment. At week 24, the combination treatment afforded superior outcomes in the IGA score, patient's global assessment, total and terminal hair counts, and diameters (all P<0.05). No severe adverse events were reported in both groups. The combined therapy of ablative fractional Er: YAG laser and medication was superior in treating male AGA than single medication therapy without serious adverse effects.

Incorporation of Finasteride-Loaded Microspheres into Personalized Microneedle for Sustained Transdermal Delivery.

Although finasteride (FNS) tablets are considered the most effective drug for the treatment of androgenetic alopecia (AGA), their clinical applications are limited due to the associated side effects including decreased libido, breast enlargement, and liver dysfunction. In this study, we have developed a personalized microneedle (PMN) with a double-layer structure that incorporates FNS-loaded microspheres (MPs) to accommodate irregular skin surfaces. This design enables the sustained release of FNS, thereby reducing potential side effects. The needle body was synthesized with high-strength hyaluronic acid (HA) as the base material substrate. The backing layer utilized methacrylate gelatin (GelMA) with specific toughness, enabling PMN to penetrate the skin while adapting to various skin environments. The length of PMN needles (10 × 10) was approximately 600 µm, with the bottom of the needles measuring about 330 µm × 330 µm. The distance between adjacent tips was around 600 µm, allowing the drug to penetrate the stratum corneum of the skin. The results of the drug release investigation indicated the sustained and regulated release of FNS from PMN, as compared to that of pure FNS and FNS-MPs. Further, the cytotoxicity assay demonstrates that PMS displays good cytocompatibility. Altogether, this mode of administration has immense potential for the development of delivery of other drugs, as well as in the medical field.

Anxiety-, and depression-like behavior following short-term finasteride administration is associated with impaired synaptic plasticity and cognitive behavior in male rats.

Finasteride, a 5α-Reductase inhibitor, is used to treat male pattern baldness and benign prostatic hyperplasia. Several clinical studies show that chronic finasteride treatment induces persistent depression, suicidal thoughts and cognitive impairment and these symptoms are persistent even after its withdrawal. Previous results from our lab showed that repeated administration of finasteride for six days induces depression-like behavior. However, whether short-term finasteride administration induces anxiety-like behavior and memory impairment and alters synaptic plasticity are not known, which formed the basis of this study. Finasteride was administered to 2-2.5 months old male Wistar rats for six days and subjected to behavioral evaluation, biochemical estimation and synaptic plasticity assessment. Anxiety-like behavior was evaluated in the elevated plus maze (EPM), open field test (OFT), light/dark test (LDT), and novelty suppressed feeding test (NSFT), and learning and memory using novel object recognition test (NORT) and novel object location test (NOLT) and depression-like behavior in the sucrose preference test (SPT). Synaptic plasticity in the hippocampal Schaffer collateral-CA1 was evaluated using slice field potential recordings. Plasma corticosterone levels were estimated using ELISA. Finasteride administration induced anxiety-like behavior in the EPM, OFT, LDT and NSFT, and depression-like behavior in the SPT. Further, finasteride induced hippocampal dependent spatial learning and memory impairment in the NOLT. In addition, finasteride decreased basal synaptic plasticity and long-term potentiation (LTP) in the hippocampus. A trend of increased plasma corticosterone levels was observed following repeated finasteride administration. These results indicate the potential role of corticosterone and synaptic plasticity in finasteride-induced effects and further studies will pave way for the development of novel neurosteroid-based therapeutics in neuropsychiatric diseases.

Approaches for estimating the clinical starting dose of new dosage forms: An example of a long-acting injectable formulation of finasteride.

In our previous study, a long-acting injectable (LAI) formulation of finasteride was prepared as a new dosage form of PROPECIA®, and in vivo pharmacokinetics (PKs)-pharmacodynamics (PDs) was evaluated in beagle dogs. The resulting PK-PD profiles of the formulation showed pharmacological effects and achievability for monthly delivery. In this study, a first-in-human (FIH) dose of the LAI formulation loaded with finasteride was predicted. The three approaches were used for estimating a FIH dose of the LAI formulation: (1) No observed adverse effect level (NOAEL)-based approach; (2) Pharmacokinetically-guided approach; (3) Pharmacokinetic/pharmacodynamic model-based approach. The advantage, assumptions, limitations, and estimated FIH dose from each approach was discussed and compared since there is no consensus on the best approach. For the prediction of clinical exposures and estimation of FIH doses, the clinical PK-PD parameters were allometrically scaled from the nonclinical data, extracted from reported clinical studies, or fixed from published literature. The starting dose range of the LAI formulation (as finasteride) was estimated to be 16.80-81.06 mg from the three approaches, and the PK/PD model-based approach suggests the most optimal starting dose (16.80 mg) of the LAI formulation. The approaches for estimating starting doses presented in the study could be used as a basis for an Investigational New Drug (IND) application of new dosage forms.

Preparation and optimization of aloe ferox gel loaded with Finasteride-Oregano oil nanocubosomes for treatment of alopecia.

Alopecia areata is a skin disorder characterized by scarless, localized hair loss that is usually managed by topical treatments that might further worsen the condition. Therefore, the current study aimed to develop nano-cubosomes loaded with finasteride (FI) and oregano oil (Or) to improve drug solubility and permeation through skin and then incorporate it into an aloe ferox gel base. An l-optimal coordinate exchange design was adopted to optimize nano-cubosomes. Phytantriol and Alkyl Acrylate were employed as the lipid material, and surfactant respectively for cubosomes manufacture. The produced formulations were assessed for their particle size, entrapment efficiency (EE%), FI steady-state flux (Jss) and minimum inhibitory concentration (MIC) against Pro-pionibacterium acnes. Optimal FI-Or-NCu had a particle size of 135 nm, EE% equals 70%, Jss of 1.85 µg/cm2.h, and MIC of 0.44 µg/ml. The optimum formulation loaded gel gained the highest drug release percent and ex vivo skin permeation compared to FI aqueous suspension, and pure FI loaded gel. Aloe ferox and oregano oil in the optimized gel formulation had a synergistic activity on the FI permeation across the skin and against the growth of p. acne bacteria which could favor their use in treating alopecia. Thus, this investigation affirms the ability of FI-Or-NCu loaded aloe ferox gel could be an effective strategy that would enhance FI release and permeation through skin and maximize its favorable effects in treating alopecia.

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.

Chemical profiles of the active fraction from Prinsepia utilis Royle leaves and its anti-benign prostatic hyperplasia evaluation in animal models.

BACKGROUND: The Prinsepia utilis Royle leaves (P. utilis) is a folk herb used for benign prostatic hyperplasia (BPH) control by ethnic minorities for centuries in China with rich in resources. Our previous studies have confirmed the anti-BPH effect of its water extract (QCJ) and the active fraction (Fr. B) separated from the QCJ by animal test. The Fr. B from P. utilis should be a potential candidate for BPH control. METHODS: In this study, the chemical ingredients of Fr. B were identified by UPLC-QTOF-MS, and quantified by HPLC. Murine animal models were divided into 8 groups, Sham rats, BPH rats, BPH rats administered with finasteride (1 mg/kg), BPH rats administered with Pule'an (460 mg/kg), BPH rats administered with low, high dosage of QCJ (860 mg/kg, 2580 mg/kg respectively), BPH rats administered with low, high dosage of Fr. B (160 mg/kg, 480 mg/kg respectively). The expression of vascular endothelial growth factor (VEGF) in the prostate tissue of rats was tested, and serum levels of dihydrotestosterone (DHT), testosterone (T), estradiol (E2), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and total superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), malondialdehyde (MDA) in prostate homogenate were measured. One-way ANOVA followed by LSD was used for statistical analysis. RESULTS: The BPH rats treated by Fr. B exhibited significant reductions of VEGF and MDA levels, as well as significant increases of SOD, GSH-Px and CAT in the prostate tissue after 28 day administration (P < 0.05). Moreover, Fr. B significantly reduced DHT, DHT/E2 ratio, TNF-α, while increased T levels in serum of BPH rats (P < 0.05). UPLC-QTOF-MS analysis revealed 10 flavonoids as the key constituents of this fraction, which accounted for 54.96% of all substance of Fr. B. The relative contents of compound 1, 2 are 11.1%, 13% in Fr. B respectively. CONCLUSIONS: These results indicated that the Fr. B obtained from P. utilis alleviated the symptoms of BPH rats through multiple mechanisms including reduction of DHT/E2 ratio, inhibition of growth factor, anti-inflammation and anti-oxidation, in which flavonoids might be the key constituents. It supported the hypothesis that the Fr. B should be further explored as a candidate for BPH patients.

5α-reductase inhibitors: Evaluation of their potential confounding effect on GC-C-IRMS doping analysis.

5α-reductase inhibitors (5-ARIs) are considered by the World Anti-doping Agency as potential confounding factors in evaluating the athlete steroid profile, since they may interfere with the urinary excretion of several diagnostic compounds. We herein investigated 5α-reductase inhibitors from a different perspective, by verifying their influence on the carbon isotopic composition of 5α- and 5ß-reduced testosterone and nandrolone metabolites. The GC-C-IRMS analysis was performed on a set of urine samples collected from three male Caucasian volunteers after the acute and chronic administration of finasteride in combination with the intake of 19-norandrostenedione, a nandrolone precursor. The excretion and the isotopic profile of androsterone (A), etiocholanolone (Etio) 5α-androstane-3α,17ß-diol (5αAdiol), and 5ß-androstane-3α,17ß-diol (5ßAdiol) were determined as well as those of 19-norandrosterone (19-NA) and 19-noretiocholanolone (19-NE). Pregnanediol (PD) and pregnanetriol (PT) were also measured as endogenous reference compounds to define the individual endogenous isotopic profile. Our results confirmed the impact of finasteride, especially if chronically administered, on the enzymatic pathway of testosterone and nandrolone, and pointed out the influence of 5-ARIs on δ13 C values of the selected target compounds determined in the IRMS confirmation analysis.

Peripheral androgen blockade in men with castrate-sensitive biochemical recurrent prostate cancer.

The aim of the study was to evaluate the feasibility of utilizing peripheral androgen blockade in men with biochemical recurrent castrate-sensitive prostate cancer. A registration study to track outcomes of men with biochemical recurrent castrate-sensitive prostate cancer treated with peripheral androgen blockade utilizing concomitant administration of finasteride and bicalutamide. Men were on intermittent peripheral blockade for a median 20.2 months, continuous peripheral blockade for a median 6.8 months, intermittent triple dose peripheral androgen blockade for a median 10.7 months, and continuous triple dose peripheral androgen blockade for 4.4 months before failing therapy. Six men (21%) had additional therapies during treatment that included metastasis-directed therapy (5/37, 14%), systemic Lu-177 (2/37, 5%), and salvage RT (1/37, 3%). The median time to progression, which includes time from initiation through all therapies to the initiation of ADT, was 37.6 months (IQR 20-74.7). From the start of PAB, median time to castrate resistance was 49.8 months (IQR 40.9-NR). After starting ADT, median time to castrate resistance was 8.8 months (IQR 4.6-17.7). Our data support the exploration of PAB as a treatment option in carefully selected patients who present with biochemical recurrence after failure of definitive local therapy for prostate cancer.

Risk of Depression Associated With Finasteride Treatment.

BACKGROUND: Finasteride is one of several inhibitors of the 5α-reductase that converts testosterone to dihydrotestosterone used to treat hair loss and benign prostatic enlargement. Emerging clinical observations indicate that such treatment may be associated with depression, anxiety, and possibly increased suicidal risks, in addition to sexual dysfunction, even after its discontinuation. METHODS: We carried out a systematic review of reports pertaining to association of finasteride treatment with clinical depression or other adverse psychiatric effects. We analyzed reported risks of depression by pooling of rates and by meta-analysis of comparisons of subjects treated with finasteride or not. FINDINGS: Crude pooled rates of depressive symptoms with versus without finasteride were 3.33% (confidence interval, 3.22%-3.44%) versus 2.54% (2.44%-2.64%); random-effects meta-analysis yielded an odds ratio of 2.14 (1.40-3.27) (both P < 0.0001). In addition, risk of suicidal ideation or behavior was greater with versus without finasteride (21.2% [21.0%-21.5%] vs 14.0% [13.8%-14.2%], P < 0.0001), and risk of sustained sexual dysfunction was high (60.1% [37.3%-82.9%]). CONCLUSIONS: The findings support a growing impression that finasteride is associated with adverse psychiatric effects that can persist in association with sexual dysfunction after discontinuing finasteride treatment.

Protective effect of black mulberry (Morus nigra L) fruit hydroalcoholic extract against testosterone-induced benign prostatic hyperplasia in rats / Efecto protector del extracto hidroalcohólico de las moras (Morus nigra L) en la hiperplasia prostática benigna no inducida por testosterona, en ratas

BACKGROUND: Finding new agents for prevention and/or treatment of benign prostatic hyperplasia (BPH) especially from natural sources is a demanding field. OBJECTIVES: This study aimed to evaluate the effect of black mulberry (BM) (Morus nigra) fruit hydroalcoholic extract on the establishment of BPH in rats. MATERIALS AND METHODS: Forty-nine adult male rats were randomly assigned into 7 equal groups: I: Sham control (SC), a sham surgery was performed. II: positive control (PC), rats were castrated and received testosterone propionate, at 10mg/kg/day S.C. for BPH induction. III: comparative control (CC), BPH was induced and the rats received finasteride at 5mg/kg/day P.O. IV-VII: (T1-T4): BPH was induced and the rats received BM extract at 25, 50, 100 and 200mg/kg/day P.O. for 4 consecutive weeks. RESULTS: Finasteride and/or BM extract especially at the two higher dosages, significantly affected prostate weight, prostatic index, percent of inhibition, serum and prostatic levels of dihydrotestosterone (DHT), serum prostate-specific antigen (PSA), antioxidant parameters of prostatic tissue as well as histopathological and histomorphometric parameters (epithelial thickness and acinar area) of prostate. CONCLUSIONS: BM extract has protective effects against experimentally-induced BPH in rats with regard to histopathological and biochemical parameters which may be related to its antioxidant as well as DHT reducing properties in prostatic tissue

ANTECEDENTES: El hallazgo de nuevos agentes para prevenir y/o tratar la hiperplasia prostática benigna (HBP), procedentes especialmente de fuentes naturales, es un campo exigente. OBJETIVOS: El objetivo de este estudio fue evaluar el efecto del extracto hidroalcohólico de las moras (Morus nigra) sobre el establecimiento de HBP en ratas. MATERIALES Y MÉTODOS: Se asignaron aleatoriamente 49 ratas adultas macho en 7 grupos iguales: I: grupo control (GC), en el que se practicó cirugía de control; II: control positivo (CP), en el que se castró a las ratas y se les administró propionato de testosterona, a una dosis de 10mg/kg/día sc para inducción de BPH. III: control comparativo (CC), en el que se indujo BPH y se administró a las ratas finasterida a una dosis de 5mg/kg/día po; IV-VII: (T1-T4), en el que se indujo BPH y se administró a las ratas extracto de moras a una dosis de 25, 50, 100 y 200mg/kg/día po durante 4 días consecutivos. RESULTADOS: La finasterida y/o el extracto de moras, especialmente en 2 dosis elevadas, afectaron significativamente al peso prostático, al índice prostático, al porcentaje de inhibición, a los niveles séricos y prostáticos de dihidrotestosterona (DHT), al antígeno prostático específico sérico (PSA), a los parámetros antioxidantes del tejido prostático, así como a los parámetros histopatológicos e histomorfométricos (espesor epitelial y área acinar) de la próstata. CONCLUSIONES: El extracto de mora tiene efectos protectores frente a HPB experimentalmente inducido en ratas, con respecto a sus parámetros histopatológicos y bioquímicos, y que pueden guardar relación con sus propiedades antioxidantes y reductoras de DHT en el tejido prostático

Physicochemical Characterization of Finasteride Nanosystem for Enhanced Topical Delivery.

INTRODUCTION: The current work aimed to formulate a novel chitosan-based finasteride nanosystem (FNS-NS) for skin delivery to optimize the drug availability in skin for a longer time and enhance ex vivo performance of finasteride against androgenic alopecia. METHODS: Both undecorated and chitosan decorated FNS-NSs were synthesized by a high energy emulsification technique. All the prepared nanosystems were further subjected to physicochemical characterizations like pH, viscosity, encapsulation efficiency, surface morphology and in vitro drug release behavior. The influence of the nanosystem on the drug permeation and retention in rat skin was examined using Franz diffusion cell apparatus. RESULTS: The droplet size of developed nanosystems ranged from 41 to 864 nm with a low polydispersity index. The zeta potential of the nanosystems was between -10 mV and +56 mV. This chitosan decorated nanosystem exhibited controlled drug release, ie about 78-97% in 24 h. Among all the nanosystems, our chitosan decorated formulation (F5) had low drug permeation (16.35 µg/cm2) and higher drug retention (10.81 µg/cm2). CONCLUSION: The abovementioned results demonstrate satisfactory in vitro drug release, skin retention profiles and ex vivo performance with chitosan decorated FNS-NS (F5). This optimized formulation could increase drug availability in skin and could become a promising carrier for topical delivery to treat androgenic alopecia.

Alterations of gut microbiota composition in post-finasteride patients: a pilot study.

PURPOSE: Post-finasteride syndrome (PFS) has been reported in a subset of patients treated with finasteride (an inhibitor of the enzyme 5alpha-reductase) for androgenetic alopecia. These patients showed, despite the suspension of the treatment, a variety of persistent symptoms, like sexual dysfunction and cognitive and psychological disorders, including depression. A growing body of literature highlights the relevance of the gut microbiota-brain axis in human health and disease. For instance, alterations in gut microbiota composition have been reported in patients with major depressive disorder. Therefore, we have here analyzed the gut microbiota composition in PFS patients in comparison with a healthy cohort. METHODS: Fecal microbiota of 23 PFS patients was analyzed by 16S rRNA gene sequencing and compared with that reported in ten healthy male subjects. RESULTS: Sexual dysfunction, psychological and cognitive complaints, muscular problems, and physical alterations symptoms were reported in more than half of the PFS patients at the moment of sample collection. The quality sequence check revealed a low library depth for two fecal samples. Therefore, the gut microbiota analyses were conducted on 21 patients. The α-diversity was significantly lower in PFS group, showing a reduction of richness and diversity of gut microbiota structure. Moreover, when visualizing ß-diversity, a clustering effect was found in the gut microbiota of a subset of PFS subjects, which was also characterized by a reduction in Faecalibacterium spp. and Ruminococcaceae UCG-005, while Alloprevotella and Odoribacter spp were increased compared to healthy control. CONCLUSION: Gut microbiota population is altered in PFS patients, suggesting that it might represent a diagnostic marker and a possible therapeutic target for this syndrome.

Periprostatic fat thickness measured on MRI correlates with lower urinary tract symptoms, erectile function, and benign prostatic hyperplasia progression.

This study investigated the correlation between periprostatic fat thickness (PPFT) measured on magnetic resonance imaging and lower urinary tract symptoms, erectile function, and benign prostatic hyperplasia (BPH) progression. A total of 286 treatment-naive men diagnosed with BPH in our department between March 2017 and February 2019 were included. Patients were divided into two groups according to the median value of PPFT: high (PPFT >4.35 mm) PPFT group and low (PPFT <4.35 mm) PPFT group. After the initial evaluation, all patients received a combination drug treatment of tamsulosin and finasteride for 12 months. Of the 286 enrolled patients, 244 completed the drug treatment course. Patients with high PPFT had larger prostate volume (PV; P = 0.013), higher International Prostate Symptom Score (IPSS; P = 0.008), and lower five-item version of the International Index of Erectile Function (IIEF-5) score (P = 0.002) than those with low PPFT. Both high and low PPFT groups showed significant improvements in PV, maximum flow rate, IPSS, and quality of life score and a decrease of IIEF-5 score after the combination drug treatment. The decrease of IIEF-5 score was more obvious in the high PPFT group than that in the low PPFT group. In addition, more patients in the high PPFT group underwent prostate surgery than those in the low PPFT group. Moreover, Pearson's correlation coefficient analysis indicated that PPFT was positively correlated with age, PV, and IPSS and negatively correlated with IIEF-5 score; however, body mass index was only negatively correlated with IIEF-5 score.

Transdermal Drug Delivery for Hair Regrowth.

Today, about 50% of men and 15-30% of women suffer from hair loss as well as the associated psychological impact. Drug therapy, especially through topical administration, is the main treatment strategy for stimulating hair regrowth. However, challenges exist due to the skin barrier that hinders drug penetration. To this end, many efforts have been made to enhance drug penetration efficiency. This review focuses on the advancement of the transdermal drug delivery strategies for hair loss therapy reported in the last five years, especially those via nanoformulations for topical administration and microneedles for transdermal delivery. In addition, physical or chemical penetration enhancers are also introduced, which are often applied with the drug delivery systems to achieve a synergy effect.

5α-reductase inhibitors impact prognosis of urothelial carcinoma.

BACKGROUND: 5α-reductase inhibitors (5-ARIs) inhibit the pathway of converting the testosterone to dihydrotestosterone and are widely used in benign prostatic hyperplasia patients. Since androgen receptor activation may play a role in urothelial tumorigenesis, we conducted this retrospective cohort study to determine whether 5α-reductase inhibitors (5-ARIs) administration is associated with bladder cancer mortality, bladder cancer recurrence and upper tract urothelial carcinoma mortality, using the Taiwan National Health Insurance database. METHODS: The data of this retrospective cohort study were sourced from the Longitudinal Health Insurance Database of Taiwan, compiled by the Taiwan National Health Insurance database from 1996 to 2010. It consists of 18,530 men with bladder cancer, of whom 474 were 5-ARIs recipients and 4384 men with upper tract urothelial carcinoma, of whom 109 were 5-ARIs recipients. Propensity Score Matching on the age and geographic data was done at the ratio of 1:10. We analyzed the odds ratios (OR) and 95% confidence interval (CI) of the risk of bladder cancer death, bladder cancer recurrence rate and upper tract urothelial carcinoma related death by the 5-ARIs administration. RESULTS: Those who received 5-ARIs showed a lower risk of bladder cancer related death compared to nonusers in multivariable adjusted analysis (OR 0.835, 95% CI 0.71-0.98). However, there was no significant difference in the bladder cancer recurrence rate (OR 0.956, 95% CI 0.82-1.11) and upper tract urothelial carcinoma related mortality in multivariable adjusted analysis (OR 0.814, 95% CI 0.6-1.1). CONCLUSIONS: Patients who receive 5-ARIs have lower bladder cancer related mortality compared to those who don't. 5-ARIs may prove to be a viable strategy to improve bladder cancer outcomes.

Finasteride Use Is Associated with Higher Odds of Obstructive Sleep Apnea: Results from the US Food and Drug Administration Adverse Events Reporting System.

Finasteride is a 5-α reductase inhibitor indicated for the treatment of androgenetic alopecia and benign prostatic hyperplasia (BPH). Finasteride has been associated with various adverse events, such as erectile dysfunction, fatigue, cognitive impairment, sleep disturbances, including insomnia, depression, and suicidal behavior. These symptoms are sometimes considered features of the "post-finasteride syndrome" (PFS) and are also encountered in obstructive sleep apnea (OSA). The overlapping clinical features of PFS and OSA suggest that OSA could possibly play a mediating role in some of the PFS-related symptoms. There are no reported studies of the association of finasteride use and OSA. The objective of this study was to determine whether finasteride use is associated with a potential safety signal of OSA compared to a baseline potential safety signal for all other drugs in the US Food and Drugs Administration Adverse Event Reporting System (FAERS) database. A case by non-case disproportionality approach was used, whereby a reporting odds ratio (ROR) with 95% confidence interval (CI) was calculated. Cases of finasteride-associated OSA were compared to a reference potential safety signal of OSA with all other drugs in the database. A similar calculation was carried out for finasteride-associated insomnia to confirm previous reports of a greater than expected reporting of insomnia with finasteride use. A significant disproportionality (ROR = 5.65 [95% CI 4.83-6.62, z = 21.56, P < 0.0001]) in reporting of OSA with the use of finasteride was observed. The potential safety signal for OSA with finasteride remained significantly higher when finasteride use for hair loss and BPH was examined separately. Finasteride use was associated with a greater than expected reporting of insomnia (ROR = 1.93 [95% CI 1.77-2.09, z = 15.958, P < 0.0001]). A limitation of this study is that selection bias is inherent in FAERS and adverse events could be underreported. Finasteride use may be associated with a potential safety signal for OSA. Patients complaining of PFS-related symptoms may benefit from a further sleep evaluation to rule out underlying OSA.

Water-stable and finasteride-loaded polyvinyl alcohol nanofibrous particles with sustained drug release for improved prostatic artery embolization - In vitro and in vivo evaluation.

Prostatic artery embolization (PAE) has been a well-established treatment for benign prostatic hyperplasia (BPH). To enhance the therapeutic efficacy, a strategy is to use embolic agent preloaded with 5α-reductase inhibitors for localized drug delivery. In this study, finasteride (FNS) was encapsulated into the polyvinyl alcohol (PVA) nanofibers via co-electrospinning technique, followed by heat treatment and cryogenic grinding to convert them into nanofibrous particles as a drug-loaded embolic agent. The FNS was found to be distributed uniformly in PVA nanofibers, and the processed FNS/PVA nanofibrous particles were 272 µm in mean particle size. Besides, the studies on the composition, thermal properties, swelling ratio, and water stability of the nanofibers and drug showed that the FNS remained its crystalline state in PVA nanofibers. The heat treatment increased the crystallinity of nanofibers and rendered them water stability. Both FNS and PVA possessed excellent thermal stability at high temperature (150 °C). In addition, in vitro drug release studies suggested the FNS followed a favorable sustained release up to 744 h. Furthermore, the cell viability and hemocompatibility assays indicated the nanofibers possessed excellent cytocompatibility and with no evidence of hemolysis. More importantly, the in vivo PAE procedures on beagles demonstrated the crosslinked FNS/PVA nanofibrous particles exhibited higher embolization efficacy with more obvious prostate volume (PV) reduction compared to crosslinked PVA nanofibrous particles after embolization for 1, 3, and 6 months (P < 0.05). Therefore, such drug-loaded PVA nanofibrous particles combined physical embolization and localized medical therapy together, which offer great potential to be used as an effective embolic agent for BPH therapy.

Early postnatal neuroactive steroid manipulation differentially affects recognition memory and passive avoidance performance in male rats.

Early postnatal neuroactive steroids (NAS) play a significant role in the neurodevelopment. Their alteration can modify adult behavior, such as anxiety or learning. For this reason, we set out to observe if neonatal NAS levels alteration affects two types of learning implying low or high levels of emotional content, such as recognition memory and aversive learning respectively. Thus, we tested allopregnanolone or finasteride administered from postnatal days 5-9. In adulthood, recognition memory was assessed using the object recognition test, as well as aversive learning throughout the passive avoidance test (PA). Because of the important emotional component of PA, which can be influencing learning, we evaluated anxiety-like behavior by means of the open field test (OF). The results indicated that those animals administered with finasteride showed higher recognition levels of a familiar object. On the other hand, they showed an impairment in a stressful learning, such as PA. However, no effects of finasteride were observed on anxiety-like behavior in OF, despite it has been reported that neonatal finasteride treatment can promote an anxiety-like profile in the elevated plus-maze test in adulthood. Regarding neonatal allopregnanolone, animals showed higher levels in OF exploration only when they were already familiar with the apparatus. Furthermore, neonatal allopregnanolone did not affect recognition memory or aversive learning. In conclusion, the neonatal NAS manipulation by means of finasteride differently affected two types of learning implying distinct stress levels. Altogether, the results show the importance of the emotional content to explain the effects of neonatal NAS manipulation on learning.

Enhanced Follicular Delivery of Finasteride to Human Scalp Skin Using Heat and Chemical Penetration Enhancers.

PURPOSE: The aim of this work was to evaluate whether improved topical delivery of finasteride, focussed to the hair follicles of human scalp skin could be achieved with application of short durations of heat and use of specific chemical penetration enhancers. METHODS: Franz cell experiments with human scalp skin were performed with a range of chemical penetration enhancers at 32°C and 45°C to simulate normal and heated conditions. Selected chemical penetration enhancers were taken forward for finite dose Franz cell studies which examined the effect of heat produced by a prototype external heating system that supplied either 20 or 30 min of additional heat over both a 24 h and a 1 h time period. RESULTS: Short durations of externally applied heat significantly increased finasteride penetration into human scalp skin after 24 h. Analysis of drug distribution in the skin after 1 h and 24 h indicated that both heat and chemical penetration enhancer selection influenced drug delivery to the hair follicles. CONCLUSION: The use of short durations of heat in combination with specific chemical penetration enhancers was able to increase the delivery of finasteride to human scalp skin and provide focussed drug delivery to the hair follicles.