The currently approved treatment for female pattern hair loss (FPHL) includes topical minoxidil administration; however, this treatment fails to achieve hair regrowth in some patients. Finasteride, a ...selective 5α-reductase inhibitor (5-ARI), may be considered as an alternative treatment. However, because of its potential teratogenic effects, clinical studies and use of finasteride for FPHL are limited. In this review, we aim to summarize the literature regarding the pharmacology, clinical efficacy, and adverse effects of oral finasteride for the treatment of FPHL and to provide novel therapeutic options including topical finasteride and dutasteride, a new generation 5-ARI, for the treatment of FPHL.
•Finasteride does not show acute effects either immediately or 24h after administration in both the FST and splash test.•Three doses of finasteride increased the latency to groom and decreased the ...total grooming duration in the splash test.•Six doses of finasteride also induced a depression-like phenotype in the FST and splash test.
The enzyme 5α-Reductase (5α-R) catalyzes the formation of dihydrotestosterone, which is involved in male pattern hair loss and benign prostatic hyperplasia. Finasteride inhibits 5α-R and is used to treat both these conditions. Several clinical studies show that chronic finasteride treatment induces persistent depression, suicidal thoughts, and cognitive impairment. The neural mechanisms underlying these effects of finasteride are not known and it is imperative that an animal model that mimics the clinical neuropsychiatric effects of finasteride is developed. Accordingly, we evaluated the behavioral effects of acute and repeated finasteride administration. Two months old male Wistar rats were administered with either vehicle (hydroxypropyl-β-cyclodextrin) or different doses of finasteride, subcutaneously, either acutely (30 min or 2 h) or for 1, 3, and 6 days (one dose per day). Behavioral despair and motivational behavior were evaluated in the forced swim test (FST) and splash test, respectively. FST and splash test were video-recorded and analyzed offline. Finasteride did not show any effects in the acute, one day or three days studies in the FST. However, repeated finasteride administration for 6 days significantly increased the immobility time. In the splash test, finasteride (100 mg/kg) administration increased the latency to groom and decreased the grooming duration implying lack of motivation in the three-day study. In the six-day study, latency to groom was significantly increased by the 100 mg/Kg dose. Further, a significant dose dependent decrease in the grooming duration was observed. In summary, our results indicate that repeated finasteride administration induces depression-like behavior in rats. This study provides the evidence that an animal model of finasteride-induced depression is feasible to investigate the cellular and molecular mechanisms, and the pharmacology underlying the neuropsychiatric effects of finasteride. Further, these results provide insights into the potential involvement of neurosteroids in depression and will lead to the development of novel therapeutics for its treatment.
In this study, optimized freeze-dried finasteride nanoparticles (NPs) were prepared from drug nanosuspension formulation that was developed using the bottom-up technique. The effects of four ...formulation and processing variables that affect the particle size and solubility enhancement of the NPs were explored using the response surface optimization design. The optimized formulation was morphologically characterized using transmission electron microscopy (TEM). Physicochemical interaction among the studied components was investigated. Crystalline change was investigated using X-ray powder diffraction (XRPD). Crystal growth of the freeze-dried NPs was compared to the corresponding aqueous drug nanosuspension. Freeze-dried NPs formulation was subsequently loaded into hard gelatin capsules that were examined for in vitro dissolution and pharmacokinetic behavior. Results revealed that in most of the studied variables, some of the quadratic and interaction effects had a significant effect on the studied responses. TEM image illustrated homogeneity and shape of the prepared NPs. No interaction among components was noticed. XRPD confirmed crystalline state change in the optimized NPs. An enhancement in the dissolution rate of more than 2.5 times from capsules filled with optimum drug NPs, when compared to capsules filled with pure drug, was obtained. Crystal growth, due to Ostwald ripening phenomenon and positive Gibbs free energy, was reduced following lyophilization of the nanosuspension formulation. Pharmacokinetic parameters from drug NPs were superior to that of pure drug and drug microparticles. In conclusion, freeze-dried NPs based on drug nanosuspension formulation is a successful technique in enhancing stability, solubility, and in vitro dissolution of poorly water-soluble drugs with possible impact on the drug bioavailability.
Background Androgenetic alopecia, or male pattern hair loss, is a hair loss disorder mediated by dihydrotestosterone, the potent form of testosterone. Currently, minoxidil and finasteride are Food ...and Drug Administration (FDA)–approved, and HairMax LaserComb, which is FDA-cleared, are the only treatments recognized by the FDA as treatments of androgenetic alopecia. Objective This systematic review and meta-analysis assesses the efficacy of nonsurgical treatments of androgenetic alopecia in comparison to placebo for improving hair density, thickness, growth (defined by an increased anagen:telogen ratio), or subjective global assessments done by patients and investigators. Methods A systematic review of randomized controlled trials was conducted. PubMed, Embase, and Cochrane were searched up to December 2016, with no lower limit on the year. We included only randomized controlled trials of good or fair quality based on the US Preventive Services Task Force quality assessment process. Results A meta-analysis was conducted separately for 5 groups of studies that tested the following hair loss treatments: low-level laser light therapy in men, 5% minoxidil in men, 2% minoxidil in men, 1 mg finasteride in men, and 2% minoxidil in women. All treatments were superior to placebo ( P < .00001) in the 5 meta-analyses. Other treatments were not included because the appropriate data were lacking. Limitations High heterogeneity in most studies. Conclusions This meta-analysis strongly suggests that minoxidil, finasteride, and low-level laser light therapy are effective for promoting hair growth in men with androgenetic alopecia and that minoxidil is effective in women with androgenetic alopecia.
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.
Background
Androgenetic alopecia (AGA) is one of the most common chronic problems seen by dermatologists worldwide. It is characterized by progressive hair loss, especially of scalp hair, and has ...distinctive patterns of loss in women versus men, but in both genders the central scalp is most severely affected. It often begins around puberty and is known to effect self-esteem and the individual’s quality of life. In contrast to the high prevalence of AGA, approved therapeutic options are limited. In addition to the scarce pharmacologic treatments, there are numerous nonprescription products claimed to be effective in restoring hair in androgenetic alopecia.
Objectives
The purpose of this paper is to review published medical and non-medical treatments for male and female AGA using the American College of Physicians evidence assessment methods. MEDLINE, EMBASE and Cochrane Library were searched for systematic reviews, randomized controlled trials, open studies, case reports and relevant studies of the treatment of male and female AGA. The relevant articles were classified according to grade and level of evidence.
Results
The medical treatments with the best level of evidence classification for efficacy and safety for male AGA are oral finasteride and topical minoxidil solution. For female AGA, topical minoxidil solution appears to be the most effective and safe treatment. The medical treatments corresponding to the next level of evidence quality are some commonly used therapeutic non-FDA-approved options including oral and topical anti-hormonal treatments. Surgical treatment of follicular unit hair transplantation is an option in cases that have failed medical treatment although there is high variation in outcomes.
Limitations
Some articles, especially those concerning traditional herbs claimed to promote hair regrowth, were published in non-English, local journals.
Conclusions
An assessment of the evidence quality of current publications indicates that oral finasteride (for men only) and topical minoxidil (for men and women) are the best treatments of AGA.
The aim of this study was to investigate what the consequences of induced drug metabolism, caused by St. John's wort (SJW,
Hypericum perforatum) treatment, would have on the plasma, biliary and ...urinary pharmacokinetics of finasteride and its two previously identified phase I metabolites (hydroxy-finasteride and carboxy-finasteride). Twelve healthy men were administered 5
mg finasteride directly to the intestine via a catheter with a multi-channel tubing system, Loc-I-Gut, before and after 14 days SJW (300
mg b.i.d, hyperforin 4%) treatment. Bile samples were withdrawn via the Loc-I-Gut device from the proximal jejunum. LC–ESI-MS/MS was used to analyze finasteride and its metabolites in plasma, bile and urine. HPLC-UV was used to analyze hyperforin in plasma. The herbal treatment significantly reduced the peak plasma concentration (
C
max), the area under the plasma concentration–time curve (AUC
0–24h) and the elimination half-life (
t
1/2) of finasteride. The geometric mean ratios (90% CI) were 0.42 (0.36–0.49), 0.66 (0.56–0.79) and 0.54 (0.48–0.61), respectively. Finasteride was excreted unchanged to a minor extent into bile and urine. Hydroxy-finasteride was not detected in plasma, bile or urine. Carboxy-finasteride was quantified in all three compartments and its plasma pharmacokinetics was significantly affected by SJW treatment. Hyperforin concentration in plasma was 21
±
7
ng/ml approximately 12
h after the last dose of the 14 days SJW treatment. In conclusion, SJW treatment for 2 weeks induced the metabolism of finasteride and caused a reduced plasma exposure of the drug. New knowledge was gained about the biliary and urinary excretion or the drug and its metabolites.
Androgenetic alopecia (AGA) is a benign condition with variable psychosocial impact, with some individuals adapting well while others needing therapeutic support. Although 5α-reductase inhibitors ...like finasteride and dutasteride have proven effective in ameliorating AGA, their use/selection is currently a subject of debate.
Treatment of AGA with 5α-reductase inhibitors lead to variable adverse effects and relatively unstable results (therapeutic efficacy ending with treatment cessation), so the choice of optimal therapy is not straightforward. This paper presents a general perspective regarding AGA based on studies listed in PubMed, to better understand/appreciate the opportunity for long term use of medication for a biological condition having non-life threatening implications. Studies focussed on adverse effects suggest that finasteride should be used with caution in AGA, due to considerable and persistent side effects induced in some men. In contrast, efficacy data indicate that dutasteride (a stronger inhibitor) presents superior therapeutic results compared to finasteride.
This paper argues that finasteride should be preferred to dutasteride in the treatment of AGA. Thus, finasteride preserves important physiological roles of dihydrotestosterone (unrelated to AGA) and, in addition, its adverse effects seem to be (at least in part) predictable.
Summary
Concern regarding adverse effects of finasteride is increasing. We aimed to determine the type and frequency of symptoms in men having long‐term sexual and non‐sexual side effects after ...finasteride treatment (a condition recently called post‐finasteride syndrome, PFS) against androgenetic alopecia (AGA). Subjects were recruited at the Urology Unit of the Trieste University‐Hospital, and from a dedicated website. Out of 79 participants, 34% were white Italians, mean age was 33.4 ± 7.60 years, mean duration of finasteride use was 27.3 ± 33.21 months; mean time from finasteride discontinuation was 44.1 ± 34.20 months. Symptoms were investigated by an ad hoc 100 questions' questionnaire, and by validated Arizona Sexual Experience Scale (ASEX) and Aging Male Symptom Scale (AMS) questionnaires. By ASEX questionnaire, 40.5% of participants declared getting and keeping erection very difficult, and 3.8% never achieved; reaching orgasm was declared very difficult by 16.5%, and never achieved by 2.5%. By the ad hoc questionnaire, the most frequent sexual symptoms referred were loss of penis sensitivity (87.3%), decreased ejaculatory force (82.3%), and low penile temperature (78.5%). The most frequent non‐sexual symptoms were reduced feeling of life pleasure or emotions (anhedonia) (75.9%); lack of mental concentration (72.2%), and loss of muscle tone/mass (51.9%). We contributed to inform about symptoms of PFS patients; unexpectedly loss of penis sensitivity was more frequent than severe erectile dysfunction and loss of muscle tone/mass was affecting half of the subjects. Further studies are necessary to investigate the pathophysiological and biochemical pathways leading to the post‐finasteride syndrome.
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