that both therapies significantly suppress plasma DHT levels. Caserini et al randomized 24 male patients in a single-center, open-label, parallel-group, exploratory study with subjects either applying topical solution to their shaved scalp twice daily, or taking a tablet once daily for seven days. Although there is decreased absorption of topical FNS compared to oral, the authors note a decrease in plasma DHT levels after one week of treatment with either topical or oral formulations. This study provides the first evidence that topical FNS slows AGA-associated hair loss by modulating DHT levels, while also reducing systemic exposure to the medication.12A follow-up study also by Caserini et al further examined the dose-dependent effects of topical FNS using a randomized, parallel-group design. The first part of this study examined 18 male patients applying 1 mL of topical FNS 0.25% solution to the scalp once or twice daily, versus administration of oral FNS 1 mg tablet once daily for seven days. There were an increase in alanine aminotransferase, pollakiuria, and testicular pain reported in two participants. In the second part, a group of 32 men received either placebo, or 100 μL (0.2275mg), 200 μL (0.455 mg), 300 μL (0.6285 mg) or 400 μL (0.91 mg) topical FNS 0.25% solution to apply to the scalp once daily for seven days. Interestingly, the results suggest that once daily application of topical FNS is more efficacious at decreasing scalp and plasma DHT levels than twice daily application, and is non-inferior to oral FNS administration. There were no significant differences between the varying concentrations of topical FNS, however the 300 and 400 μL doses are associated with higher plasma concentrations of FNS, and therefore at greater risk for systemic side effects. Presyncope, conjunctivitis, headache, and oropharyngeal pain were rarely reported. The authors concluded that the 100 and 200 μL doses of topical FNS applied daily may be the most effective treatment regimen for AGA.13Combining Topical Finasteride With Other AgentsResearch has also been completed to demonstrate the efficacy of topical FNS for AGA in comparison to topical combination therapies. A novel combination topical treatment by the name NuH Hair [topical FNS, dutasteride and minoxidil (MNX)], was formulated by Rafi and Katz. 15 male patients were asked to apply the solution daily for nine months and were given the option of adding three further components to their treatment protocol: 1) oral FNS 1 mg daily 2) topical MNX 5% foam applied at least once per day, and/or 3) topical ketoconazole 2% shampoo applied 2-3 times per week. Eight subjects chose aggressive treatment with all four treatment modalities simultaneously. While all 15 patients demonstrated significant growth of hair by the end of the treatment period, the eight patients who utilized all four treatment options experienced significant growth in as little as 30 days; for the patients using topical FNS/dutasteride/MNX alone, significant hair growth was experienced after three months. The topical FNS/dutasteride/MNX was formulated as a hypoallergenic lotion and found to be safe even in subjects with atopy.14A randomized, double-blind, comparative study assessed the efficacy and safety of twice daily topical MNX 3% versus topical combined MNX 3%/FNS 0.1% in 40 men with AGA for 24 weeks. Both groups demonstrated increased hair counts from baseline with the MNX 3%/FNS 0.1% group showed statically superior improvement compared to the MNX group.15 Further studies with retrospective assessment and prospective cohort tested a higher concentration of topical MNX 5%/FNS 0.1% for one year in 50 men with AGA who were previously treated with oral FNS 1 mg daily and topical MNX 5% twice a day for two years. Approximately 80% of patients either maintained or improved their baseline hair density using topical combination therapy.16
DISCUSSION
Topical application of FNS in the treatment of AGA is an area of research in its infancy and limited to a small number of randomized-controlled trials, prospective studies, and retrospective medical record review. Overall data from the studies on investigating the efficacy and safety of topical FNS in AGA show promising results and non-inferiority compared to systemic delivery.Although preliminary results on the use of topical FNS are limited, the studies reviewed demonstrate that topical FNS may be safe for use in patients wishing to avoid systemic side effects. This may be especially important for the female AGA population, in which systemic FNS is not approved due to hormonal suppression and is considered a category X drug during pregnancy.3 It is possible that topical FNS will follow the same path as topical retinoid derivatives (category C)17 and their parent systemic drug isotretinoin (category X),18 with the topical formulation of FNS considered relatively safe for use in pregnant females if the benefits outweigh the risk.With consistent inhibitory effects on scalp DHT levels while minimizing the systemic effects on serum DHT, doses of 100 μL (0.2275mg) and 200 μL (0.455 mg) topical FNS 0.25% solution applied daily appears to be the most efficacious concentration and frequency at this time.13 The use of topical FNS has not resulted in the report of serious side effects; however, there are reports of scalp irritation manifesting as erythema and contact dermatitis, as well as cases of increased liver enzymes, bed-wetting, testicular pain, headaches, presyncope, and oropharyngeal pain (Table 1).11,13,15 Although current evidence suggests that patients are satisfied and that the drug is well-tolerated, we believe large cohort studies examining the potential adverse effect profile of the drug are warranted.Several challenges arise from the available studies on topical FNS including the vehicle, concentration, as well as application
