Finasteride

The number of articles evaluating platelet-rich plasma (PRP) efficacy in androgenic alopecia (AGA) have exponentially increased during the last decade. A systematic review on this field was performed by assessing in the selected studies the local injections of PRP compared to any control for AGA. The protocol was developed in accordance with the Preferred Reporting for Items for Systematic Reviews and Meta-Analyses-Protocols (PRISMA-P) guidelines. A multistep search of the PubMed, MEDLINE, Embase, PreMEDLINE, Ebase, CINAHL, PsycINFO, Clinicaltrials.gov, Scopus database, and Cochrane databases was performed to identify studies on hair loss treatment with platelet-rich plasma. Of the 163 articles initially identified, 123 articles focusing on AGA were selected and, consequently, only 12 clinical trials were analyzed. The studies included had to match predetermined criteria according to the PICOS (patients, intervention, comparator, outcomes, and study design) approach. In total, 84% of the studies reported a positive effect of PRP for AGA treatment. Among them, 50% of the studies demonstrated a statistically significant improvement using objective measures and 34% of the studies showed hair density and hair thickness improvement, although no p values or statistical analysis was described. In total, 17% of the studies reported greater improvement in lower-grade AGA, while 8% noted increased improvement in higher-grade AGA. Only 17% of the studies reported that PRP was not effective in treating AGA. The information analyzed highlights the positive effects of PRP on AGA, without major side effects and thus it be may considered as a safe and effective alternative procedure to treat hair loss compared with Minoxidil® and Finasteride®.

Human steroid 5α-reductase 2 (SRD5A2) is an integral membrane enzyme in steroid metabolism and catalyzes the reduction of testosterone to dihydrotestosterone. Mutations in the SRD5A2 gene have been linked to 5α-reductase deficiency and prostate cancer. Finasteride and dutasteride, as SRD5A2 inhibitors, are widely used antiandrogen drugs for benign prostate hyperplasia. The molecular mechanisms underlying enzyme catalysis and inhibition for SRD5A2 and other eukaryotic integral membrane steroid reductases remain elusive due to a lack of structural information. Here, we report a crystal structure of human SRD5A2 at 2.8 Å, revealing a unique 7-TM structural topology and an intermediate adduct of finasteride and NADPH as NADP-dihydrofinasteride in a largely enclosed binding cavity inside the transmembrane domain. Structural analysis together with computational and mutagenesis studies reveal the molecular mechanisms of the catalyzed reaction and of finasteride inhibition involving residues E57 and Y91. Molecular dynamics simulation results indicate high conformational dynamics of the cytosolic region that regulate NADPH/NADP+ exchange. Mapping disease-causing mutations of SRD5A2 to our structure suggests molecular mechanisms for their pathological effects. Our results offer critical structural insights into the function of integral membrane steroid reductases and may facilitate drug development.

Context5α-Reductase (5αR) types 1 and 2 catalyze the A-ring reduction of steroids, including androgens and glucocorticoids. 5α-R inhibitors lower dihydrotestosterone in benign prostatic hyperplasia; finasteride inhibits 5αR2, and dutasteride inhibits both 5αR2 and 5αR1. In rodents, loss of 5αR1 promotes fatty liver.ObjectiveOur objective was to test the hypothesis that inhibition of 5αR1 causes metabolic dysfunction in humans.Design, setting, and participantsThis double-blind randomized controlled parallel group study at a clinical research facility included 46 men (20-85 years) studied before and after intervention.InterventionOral dutasteride (0.5 mg daily; n = 16), finasteride (5 mg daily; n = 16), or control (tamsulosin; 0.4 mg daily; n = 14) was administered for 3 months.Main outcome measureGlucose disposal was measured during a stepwise hyperinsulinemic-euglycemic clamp. Data are mean (SEM).ResultsDutasteride and finasteride had similar effects on steroid profiles, with reduced urinary androgen and glucocorticoid metabolites and reduced circulating DHT but no change in plasma or salivary cortisol. Dutasteride, but not finasteride, reduced stimulation of glucose disposal by high-dose insulin (dutasteride by -5.7 [3.2] μmol/kg fat-free mass/min, versus finasteride +7.2 [3.0], and tamsulosin +7.0 [2.0]). Dutasteride also reduced suppression of nonesterified fatty acids by insulin and increased body fat (by 1.6% [0.6%]). Glucose production and glycerol turnover were unchanged. Consistent with metabolic effects of dutasteride being mediated in peripheral tissues, mRNA for 5αR1 but not 5αR2 was detected in human adipose tissue.ConclusionDual inhibition of 5αRs, but not inhibition of 5αR2 alone, modulates insulin sensitivity in human peripheral tissues rather than liver. This may have important implications for patients prescribed dutasteride for prostatic disease.

Traditional blending electrospinning has a series of issues during implementation, and the corresponding monolithic nanofibers can always be updated through the intentional design of core-sheath nanostructures. In this study, a modified coaxial electrospinning approach was employed to refine the electrospinning process by eliminating abnormal phenomena, while simultaneously imparting core-sheath nanostructures and improved transdermal finasteride (FIN) delivery performance. Using an electrospinnable ethylcellulose (EC) solution containing FIN as the core fluid and an unspinnable polyvinylpyrrolidone (PVP)/sodium dodecyl sulfate (SDS) solution as the sheath fluid, medicated core-sheath nanofibers (E3) were fabricated continuously and robustly. The monolithic nanofibers (E2) from a conventional blending electrospinning were prepared as a comparison. FIN existed in an amorphous state within both E2 and E3 nanofibers, attributed to its excellent compatibility with EC. The sustained release profiles of nanofibers E2 and E3 are similar, but the penetration rates of FIN molecules from the nanofibers E2 and E3 always have significant differences from the initial tests at 0.5 h (10.32 ± 4.31% and 12.85 ± 5.14% for nanofibers E2 and E3, respectively) to the final tests at 4.0 h (38.16 ± 5.47% and 51.31 ± 5.19% for nanofibers E2 and E3, respectively). The mechanism underlying the robust preparation enabled by the unspinnable sheath fluid is proposed: it prevents multiple abnormal phenomena inherent to single-fluid blending processes. This protocol offers a versatile strategy to upgrade traditional single-fluid blending electrospinning products, endowing them with an improved functional performance.