Dissolving microneedles for alopecia treatment.

Alopecia is a treatable benign disease, however, approximately 15-30% of women and 50% of men suffer from alopecia, which greatly affects patient's self-esteem and quality of life. Currently, commercial products for alopecia treatment include topical minoxidil solution, oral finasteride tablets and oral baricitinib tablets. However, the barrier of stratum corneum, systemic adverse effects and poor cure rate limit the application of commercial products. Therefore, researchers investigated the mechanism of alopecia, and developed new drugs that could target lactate dehydrogenase-related pathways, remove excessive reactive oxygen in hair follicles, and reduce the escape of hair follicle stem cells, thus injecting new strength into the treatment of alopecia. Moreover, starting from improving drug stratum corneum penetration and reducing side effects, researchers have developed hair loss treatment strategies based on dissolved microneedles (MNs), such as drug powders/microparticles, nanoparticles, biomimetic cell membranes, phototherapy and magnetically responsive soluble microneedles, which show exciting alopecia treatment effects. However, there are still some challenges in the practical application of the current alopecia treatment strategy with soluble microneedles, and further studies are needed to accelerate its clinical translation.

Androgenetic alopecia in transgender and gender diverse populations: A review of therapeutics.

Androgenetic alopecia (AGA) management is a significant clinical and therapeutic challenge for transgender and gender-diverse (TGD) patients. Although gender-affirming hormone therapies affect hair growth, there is little research about AGA in TGD populations. After reviewing the literature on approved treatments, off-label medication usages, and procedures for treating AGA, we present treatment options for AGA in TGD patients. The first-line treatments for any TGD patient include topical minoxidil 5% applied to the scalp once or twice daily, finasteride 1 mg oral daily, and/or low-level laser light therapy. Spironolactone 200 mg daily is also first-line for transfeminine patients. Second-line options include daily oral minoxidil dosed at 1.25 or 2.5 mg for transfeminine and transmasculine patients, respectively. Topical finasteride 0.25% monotherapy or in combination with minoxidil 2% solution are second-line options for transmasculine and transfeminine patients, respectively. Other second-line treatments for any TGD patient include oral dutasteride 0.5 mg daily, platelet-rich plasma, or hair restoration procedures. After 6-12 months of treatment, AGA severity and treatment progress should be assessed via scales not based on sex; eg, the Basic and Specific Classification or the Bouhanna scales. Dermatologists should coordinate care with the patient's primary gender-affirming clinician(s) so that shared knowledge of all medications exists across the care team.

Inhibitory effects of Centella asiatica (L.) Urban on enlarged prostate through androgen receptor and PI3K/Akt signaling pathways.

Centella asiatica (L.) Urban (C. asiatica) is a traditional herbal medicine that has been used for wound healing and anti-inflammation since ancient times. Various biological effects of C. asiatica ethanolic extract (CAE) were previously reported. However, in our previous study, C. asiatica aqueous extract (CAA) exhibited higher inhibitory activity on benign prostatic hyperplasia (BPH) than CAE. Therefore, the aim of this study was to investigate the effect of CAA on BPH, and elucidate the inhibitory mechanism through in vitro and in vivo experiments as well as metabolite analysis of CAA. A BPH rat model was induced by daily subcutaneous injection of testosterone propionate (TP, 3 mg kg-1) dissolved in corn oil for 4 weeks after castration. The experimental group, the CAA treatment group, was orally administered CAA (100 mg kg-1) for 4 weeks while inducing prostatic hyperplasia. Saw palmetto extract (Saw, 100 mg kg-1) and Finasteride (Fi, 1 mg kg-1) were used as positive controls and were administered orally for 4 weeks. CAA significantly inhibited androgen receptor signaling related factors overexpressed by dihydrotestosterone (DHT) treatment in prostate cell lines. Afterwards, the testosterone-induced BPH model was used to verify the alleviation efficacy of CAA in prostatic hyperplasia. Prostate size and the thickness of the prostate tissue epithelium were significantly decreased in the group treated with CAA compared to those in the BPH group. The results of protein expression in the prostate tissue confirmed that CAA inhibited androgen receptor signaling in BPH and decreased the expression of growth factors. Moreover, CAA suppressed the expression of the PI3K/Akt pathway and cell proliferation-related factors compared to the BPH group. Taken together, these results indicate that CAA improves the inhibitory efficacy of BPH by inhibiting the androgen receptor and PI3K/Akt pathways, suggesting that CAA may be a promising candidate for biopharmaceutical formulations of BPH.

The extract of Celtis choseniana Nakai alleviates testosterone-induced benign prostatic hyperplasia through inhibiting 5α reductase type 2 and the Akt/NF-κB/AR pathway.

Benign prostatic hyperplasia (BPH) is a chronic male disease characterized by the enlarged prostate. Celtis chosenianaNakai (C. choseniana) is medicinally used to alleviate pain, gastric disease, and lung abscess. In this study, the effect of C. choseniana extract on BPH was investigated using testosterone-induced rats. Sprague Dawley rats were divided into five groups: control, BPH (testosterone 5 mg·kg-1), Fina (finasteride 2 mg·kg-1), and C. choseniana (50 and 100 mg·kg-1). After four weeks of TP treatment with finasteride or C. choseniana, prostate weights and DHT levels were measured. In addition, the prostates were histopathologically examined and measured for protein kinase B (Akt)/nuclear factor-κB (NF-κB)/AR signaling, proliferation, apoptosis, and autophagy. Prostate weight and epithelial thickness were reduced in the C. choseniana groups compared with that in the BPH group. The extract of C. choseniana acted as a 5α reductase inhibitor, reducing DHT levels in the prostate. Furthermore, the extract of C. choseniana blocked the activation of p-Akt, nuclear NF-κB activation and reduced the expression of AR and PSA compared with BPH. Moreover, the expression of Bax, PARP-1, and p53 increased, while the expression of bcl-2 decreased. The present study demonstrated that C. choseniana extract alleviated testosterone-induced BPH by suppressing 5α reductase and Akt/NF-κB activation, reducing AR signaling and inducing apoptosis and autophagy in the prostate. These results suggested that C. choseniana probably contain potential herbal agents to alleviate BPH.

The extract of Celtis choseniana Nakai alleviates testosterone-induced benign prostatic hyperplasia through inhibiting 5α reductase type 2 and the Akt/NF-κB/AR pathway / 中国天然药物

Benign prostatic hyperplasia (BPH) is a chronic male disease characterized by the enlarged prostate. Celtis chosenianaNakai (C. choseniana) is medicinally used to alleviate pain, gastric disease, and lung abscess. In this study, the effect of C. choseniana extract on BPH was investigated using testosterone-induced rats. Sprague Dawley rats were divided into five groups: control, BPH (testosterone 5 mg·kg-1), Fina (finasteride 2 mg·kg-1), and C. choseniana (50 and 100 mg·kg-1). After four weeks of TP treatment with finasteride or C. choseniana, prostate weights and DHT levels were measured. In addition, the prostates were histopathologically examined and measured for protein kinase B (Akt)/nuclear factor-κB (NF-κB)/AR signaling, proliferation, apoptosis, and autophagy. Prostate weight and epithelial thickness were reduced in the C. choseniana groups compared with that in the BPH group. The extract of C. choseniana acted as a 5α reductase inhibitor, reducing DHT levels in the prostate. Furthermore, the extract of C. choseniana blocked the activation of p-Akt, nuclear NF-κB activation and reduced the expression of AR and PSA compared with BPH. Moreover, the expression of Bax, PARP-1, and p53 increased, while the expression of bcl-2 decreased. The present study demonstrated that C. choseniana extract alleviated testosterone-induced BPH by suppressing 5α reductase and Akt/NF-κB activation, reducing AR signaling and inducing apoptosis and autophagy in the prostate. These results suggested that C. choseniana probably contain potential herbal agents to alleviate BPH.

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.

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.

[Chemoprevention of prostate cancer - a plea]. / Chemoprävention des Prostatakarzinoms - Ein Plädoyer.

The high disease prevalence, the presentation in older age, a frequently slowly progressing course of disease, and high costs make the diagnosis of and therapy for prostate cancer a special challenge for urologists. Effective prevention of the disease may help to improve some of the problems mentioned above. Two randomised, controlled studies have proved that effective chemoprevention of prostate cancer is viable using 5α-reductase inhibitors (finasteride, dutasteride). Furthermore, there is increasing evidence that other compounds, e. g., selective oestrogen receptor modulators (SERMs), NSAIDs and statins might also be effective. This review investigates potential risks and benefits of chemoprevention including a consideration of health economical aspects. The authors conclude that the options of chemoprevention should be investigated in an open and unbiased way.

Ganoderma lucidum is an inhibitor of testosterone-induced prostatic hyperplasia in rats.

The aim of the present study was to find out whether Ganoderma lucidum (GL) can be used as a clinically effective medicine for the management of prostatic hyperplasia. In vitro studies were conducted to assess the 5α-reductase inhibitory potential of GL. A biochemical marker viz. ß-sitosterol was identified and characterised in the extracts utilising high-performance thin-layer chromatography. Testosterone (3 mg kg(-1) s.c.) was administered to the rats along with the test extracts (10, 20 and 50 mg kg(-1) p.o.) and ß-sitosterol (10 and 20 mg kg(-1) p.o.) for a period of 28 days. Finasteride was used as a positive control (1 mg kg(-1) p.o.). GL extracts attenuated the increase in the prostate/body weight ratio induced by testosterone. Petroleum ether extract exhibiting the best activity. Ethanolic extract also exhibited significant activity. The urine output also improved significantly, which emphasise the clinical implications of the study. Testosterone levels measured weekly and prostate-specific antigen (PSA) levels measured at the end of the study also support our claims. The PSA levels decreased in the extract-treated groups, indicating their usefulness in the treatment of benign prostatic hyperplasia. Histological studies have shown a considerable improvement in the prostatic histoarchitecture in the extract-treated groups when compared to the testosterone-treated group.

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.

Evaluation of male sexual function in patients with Lower Urinary Tract Symptoms (LUTS) associated with Benign Prostatic Hyperplasia (BPH) treated with a phytotherapeutic agent (Permixon), Tamsulosin or Finasteride.

OBJECTIVES: Sexual function is one of the aspects in the treatment of lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) that has gained increasing attention. We compared the influence on men's sexuality of Permixon, a lipido-sterolic extract of Serenoa Repens, with Tamsulosin and Finasteride using a specific validated questionnaire exploring patient's sexual functions. METHODS: A database was created comprising patients from 3 main double-blind, randomized studies - Permixon vs. Finasteride, Permixon vs. Tamsulosin and Permixon 160 mg vs. 320 mg including a total of 2511 patients. Three hundred fifty four were on Tamsulosin, 545 on Finasteride and 1612 patients on Permixon. LUTS were assessed using the I-PSS questionnaire. Peak flow rates and prostate volume were recorded. The MSF-4 questionnaire, including 4 items that explore the patient's interest in sex, quality of erection, achievement of orgasm and ejaculation, was used across the studies. This questionnaire was demonstrated as highly reproducible and both psychometrically and clinically valid across different cultures. Correlation coefficients were given to assess the linear relationship between continuous variables. RESULTS: At 3 months, there were no statistically significant differences between the three treatment groups in terms of I-PSS or Qmax evolutions (all p values > 0.05). At 6 months, as compared to pretreatment data, there was a slight increase in sexual disorders in Tamsulosin (+0.3) and Finasteride (+0.8) treated patients while it slightly improved with Permixon therapy (-0.2). Ejaculation disorders were the most frequently reported side effects after Tamsulosin or Finasteride (both +0.2 on the specific MSF-4 question 4). There was no correlation between the evolution of the MSF-4 scores and the evolution in I-PSS neither in patients treated with Permixon, Finasteride or Tamsulosin. However, there was a slight correlation between the MSF-4 score at baseline and the I-PSS at baseline (r2 = 0.032). Although there was a correlation between the MSF-4 and age at baseline (r2 = 0.1452), there was no correlation between the evolution in MSF-4 during therapy and the age of the patients. CONCLUSION: The present study demonstrates that Permixon therapy has no negative impact on male sexual function. Both Finasteride and Tamsulosin had a slight impact on sexual function, especially on ejaculation, although these effects were rare and in line with previous reports about these two drugs.

[Prostate cancer. Introduction].

Basic, epidemiological and clinical issues to be solved on prostate cancer were discussed as a preface. Sharp increase of prostate cancer incidence in Asian countries, almost constant level of latent cancer are intriguing epidemiological and pathological issues. Treatment of locally advanced prostate cancer, hormone-refractory prostate cancer has been a long-standing clinical challenge. New radiotherapy is expected for further advancement. Heterogeneity, clonility, multiplicity of prostate cancer are interesting pathological challenges.

Impact of a novel neoadjuvant and adjuvant hormone-deprivation approach on quality of life, voiding function, and sexual function after prostate brachytherapy.

BACKGROUND: Data demonstrate a benefit from neoadjuvant and adjuvant hormone-deprivation therapy with luteinizing hormone-releasing hormone agonists in patients who are treated with radiotherapy for localized prostate carcinoma; however, this approach has detrimental effects on quality of life (QOL). A cross-sectional study was undertaken to evaluate the impact on QOL, voiding function, and sexual function of an alternative hormone-deprivation approach. METHODS: Three hundred fifty patients with clinical T1c-T2b prostate carcinoma were treated from March 1997 to August 2000 either with palladium 103 brachytherapy (BTM) without hormone therapy or with 8 months of adjuvant and neoadjuvant hormone-deprivation therapy with an antiandrogen and finasteride (BTM+H), were mailed the Functional Assessment of Cancer Therapy (FACT) global well being QOL instrument (FACT-G), the American Urological Association symptom score (AUASS), and specific items addressing urinary control and sexual function from validated instruments. Differences between treatment groups were assessed as a function of time since treatment. RESULTS: Seventy-two percent of patients responded to the questionnaire. No differences in overall FACT-G scores, AUASS scores, or AUASS subscale scores between the BTM group and the BTM+H group were found. The BTM+H group initially had lower personal well being FACT-G subscale scores, more urinary incontinence, and lower odds of attaining an erection sufficient for intercourse initially, although these differences disappeared with longer follow-up. CONCLUSIONS: The use of neoadjuvant and adjuvant antiandrogen and finasteride with brachytherapy is associated with QOL equal to that of brachytherapy alone for the treatment of patients with localized prostate carcinoma, allowing the advantages of hormone manipulation in terms of tumor control without its downside.

Transurethral prostate resection and bleeding: a randomized, placebo controlled trial of role of finasteride for decreasing operative blood loss.

PURPOSE: Bleeding associated with transurethral prostate resection can often be significant and lead to increased morbidity and occasionally mortality. It has been shown that finasteride decreases bleeding in patients with hematuria of prostatic origin. We hypothesized that bleeding in patients undergoing transurethral prostate resection could be decreased by giving finasteride for 2 weeks before surgery. MATERIALS AND METHODS: A total 70 patients scheduled to undergo elective transurethral prostate resection were randomized to receive 5 mg. finasteride daily or placebo for 2 weeks before surgery. Serum hemoglobin was measured before and after surgery, and the following day. The volume of irrigation fluid used and its hemoglobin concentration as well as resected prostate weight were recorded. RESULTS: Of the 68 patients who underwent transurethral prostate resection 2 were withdrawn before surgery, and so 32 received finasteride and 36 received placebo. There was significantly less mean blood loss in irrigation fluid in the finasteride group than in the control group (43.6 versus 69.3 gm. hemoglobin, p = 0.011). The mean difference was more significant when blood loss per gm. resected prostate was calculated (2.65 versus 4.65 gm. hemoglobin per gm. prostate, p < 0.01). CONCLUSIONS: This study shows that finasteride given for 2 weeks preoperatively decreases bleeding in patients undergoing transurethral prostate resection. Further study is required to determine the optimal timing and dose duration to minimize blood loss and identify how relevant such a decrease in bleeding is in clinical practice.

[With alpha blockers, finasteride and nettle root against benign prostatic hyperplasia. Which patients are helped by conservative therapy?]. / Mit Alphablockern, Finasterid und Brennesselwurzel gegen die BPH. Welchen Patienten hilft die konservative Therapie?

Symptomatic benign prostatic hyperplasia (BPH), which a man has a 50% chance of developing during the course of his lifetime, should receive stage-related treatment. While Vahlensieck stage I disease requires no therapy, stages II and III are indications for medication. Established medications for the treatment of BPH in current use are alpha-blockers, finasteride, and the phytotherapeutic agents pumpkin seed (cucurbitae semen), nettle root (urticae radix), the phytosterols contained in Hypoxis rooperi, rye pollen and the fruits of saw palmetto (sabalis serrulati fructus). If the patient responds, these medicaments can be given life-long, or intermittently. The hard criterion for the rational use of drug treatment of BPH is, over the long term, the reduction in the number of prostate operations. In stage IV disease surgical measures--after prior compensation of renal function--are to the fore.

Benign prostatic hyperplasia and erectile dysfunction--is there a link?

There is little evidence to support a link between benign prostatic hyperplasia (BPH) and erectile dysfunction (ED). Any apparent relationship may reflect the fact that both are common conditions with a similar gender and age distribution. However, the surgical treatment of BPH (e.g. TURP or open prostatectomy) may cause ED as a postoperative complication in some patients. Similarly, the medical treatment of BPH with finasteride may be associated with ED (< 5% in one study). However, alpha-blockade is not associated with this side-effect.