madman
Super Moderator
Topical finasteride for male and female pattern hair loss: Is it a safe and effective alternative? (2021)
Aditya K. Gupta MD, PhD | Mesbah Talukder PhD
Abstract
Background: Oral finasteride is an FDA-approved treatment for androgenetic alopecia (AGA). Topical finasteride, while not FDA-approved, lacks the systemic adverse effects associated with oral finasteride. The efficacy of topical finasteride has been evaluated.
Aim: To review whether topical finasteride is a safe and effective treatment for male and female pattern hair loss.
Method: A structured search in PubMed and Google Scholar identified 864 records, with 32 articles meeting the inclusion criteria for review.
Results and discussion: In a phase III, randomized, controlled trial, the efficacies of topical 0.25% w/w finasteride spray (1–4 sprays; 50–200 μl/day) and once-daily finasteride 1 mg oral tablet were similar when administered for 24 weeks (mean change from baseline, 20.2 vs. 21.1 hairs/cm2 ). Additionally, a double-blind, randomized trial compared the efficacies of twice-daily finasteride 1% topical gel and once-daily finasteride 1 mg oral tablet for 6 months and found similar results in both groups. Moreover, a combination of topical minoxidil and topical finasteride may enhance efficacy. Topical finasteride reduces both scalp and plasma DHT levels. In an open-label pharmacodynamic study, a 7-day treatment of twice-daily finasteride 0.25% topical solution and once-daily finasteride 1 mg oral tablet provided similar inhibition of plasma DHT. Topical finasteride reduces the potential for systemic side effects, including the risk of sexual dysfunction. The side effects are localized to the application site, for example, scalp pruritus, burning sensation, irritation, contact dermatitis, and erythema.
Conclusion: Topical finasteride may be an alternative for those concerned about the oral formulation's systemic side effects.
1 | INTRODUCTION
Hairstyle frames our look and is often regarded as the expression of someone's personality.1 Approximately 50% of men experience male pattern hair loss (AGA) during their lifetime.1 Due to this slow and involuntary hair loss, millions of men suffer from emotional stress.1,2 Many deceitful internet sites claim “miracle cures” for male and female pattern hair loss, but the truth is most of them do not work.1 Oral finasteride is specifically recommended for male AGA, although some clinicians use it off-label for female pattern hair loss in postmenopausal women.3 Topical minoxidil is FDA-approved for male AGA and female pattern hair loss.3,4
The effectiveness of oral finasteride in the treatment of androgenetic alopecia (AGA) is well-established.5 Several clinical studies have shown that finasteride 1 mg oral tablet reduces hair loss and/ or enhances hair growth in male AGA patients compared with baseline or placebo, as early as 3 months after starting therapy, and extending to 5–10 years.5–10 Although oral finasteride is well-tolerated, some patients experience sexual dysfunction, possibly due to 5αreductase inhibition.5,11–13 Additionally, oral finasteride has been associated with an increased risk of depression, prompting regulators to include warnings in the product labeling in some countries.5,14,15 Conversely, topical finasteride may reduce the potential side effects of oral formulation due to its local action and an absence of systemic side effects.5,16
*This article reviews whether topical finasteride could be an effective alternative to oral finasteride for male and female pattern hair loss, and includes its pharmacokinetics, mechanism of action, and safety. It also discusses the finasteride/minoxidil topical combination and whether it can enhance efficacy.
3 | PHARMACOKINETICS
The maximum plasma drug (finasteride) concentration (Cmax) and the area under the plasma drug concentration-time curve (AUC) values for topical and oral finasteride are presented in Table 1.17 The bioavailability of topical finasteride was much lower compared with oral finasteride.17 The time to reach Cmax (tmax) was approximately 10 times higher for topical finasteride than for the oral formulation (Table 1).17 Pharmacokinetic studies could not find clear absorption and elimination phases for topical finasteride.17 Therefore, the calculations of extrapolated pharmacokinetic parameters such as elimination half-life (t1/2) and area under the plasma concentration-time curve from time zero to infinite time (AUC0–∞) were not possible.17
4 | PHARMACODYNAMICS
4.1 | Mechanism of action
Finasteride irreversibly binds 5α-reductase (5-AR) and prevents NADPH-mediated conversion of testosterone to dihydrotestosterone (DHT)4 (Figure 2). DHT is believed to convert terminal hair into vellus-like miniaturized hair, resulting in gradual hair loss.
Therefore, suppressing DHT levels may promote hair growth, perhaps via the Wnt/β-catenin signaling pathway (Figure 2).18 5-AR has three isoenzymes, type I, type II, and type III, among which type I and type II are expressed in the dermal papilla.4 Finasteride binds to type II isoenzyme 100-times more selectively than type I.19 When the drug binds with 5-AR at the dermal papilla level, scalp DHT level is reduced significantly, but not entirely, perhaps because of residual conversion of testosterone via 5-AR type I.4,19,20
Preliminary studies suggest that 5 mg/day of oral finasteride for 4 weeks significantly reduced the scalp DHT level compared with placebo.21 Additionally, a scalp DHT dose-ranging study showed that oral finasteride at ≥0.5 mg/day suppressed scalp DHT levels approximately by 65% after 6 weeks of treatment.4,21,22 Within 2 weeks of treatment discontinuation, the DHT levels returned to normal.4,16
4.2 | Effects of topical finasteride on plasma DHT level
In a single-center, open-label, parallel-group, pharmacodynamic, pharmacokinetic, exploratory study, 24 males with AGA were randomized into finasteride 0.25% topical solution and finasteride 1 mg oral tablet treatment groups.17 On Day 1, a single dose of finasteride 1 mg oral tablet reduced plasma DHT levels by 56 to 64% approximately (Table 2).17 In contrast, a single application of finasteride 0.25% topical solution reduced only approximately 18 to 19% (Table 2).17 The two treatments were significantly different in reducing plasma DHT levels (p < 0.0001).17 However, plasma DHT reduction levels were similar after multiple-dose treatments of topical and oral finasteride. The multiple-dose treatments of topical and oral finasteride corresponded to the application of 1 ml of finasteride 0.25% topical solution to the shaved scalp in the morning of Day 1 followed by twice-daily application from Day 2 to the morning of Day 8, and administration of finasteride 1 mg oral tablet once daily for 7 days.17 For topical finasteride, the DHT reduction level was 67.95 to 75.19%, and for oral, it was 61.87–71.97% (Table 2).17 Seven days of treatment with finasteride 0.25% topical solution twice daily (bid) and the 1 mg oral tablet once daily (od) provided similar inhibition of plasma DHT.17 The difference was statistically insignificant (p ≥ 0.1092).17
However, in a phase III, randomized, controlled trial, topical 0.25% w/w finasteride spray (1–4 sprays; 50–200 μl/day) for 24 weeks reduced the serum DHT concentration by 34.6% compared with the baseline (p < 0.05 vs. placebo) (Table 2).5 For oral finasteride (1 mg/ day for 24 weeks), the reduction was relatively higher (55.6%) than the topical form when compared with baseline (p < 0.05 vs. placebo).5 Notably, topical finasteride did not increase the plasma testosterone level as a result of reduced DHT concentration.5 In contrast, oral finasteride resulted in a positive shift in testosterone level in 6.7% of patients.5
5 | EFFICACY
5.1 | Topical vs. oral finasteride
Recently, a phase III, randomized clinical trial investigated the efficacy of finasteride topical spray in male patients aged 18–40 years with mild-to-moderate vertex male pattern hair loss (modified Norwood/Hamilton classification scale; III vertex, IV, or V).5 A total of 458 patients, of which 323 completed the study, were randomized at 2: 2: 1 into three treatment groups: topical finasteride group (topical finasteride and oral placebo), oral finasteride group (topical placebo and oral finasteride), and placebo group (topical placebo and oral placebo).5 Topical and oral finasteride corresponded to finasteride 0.25% w/w topical spray (2.275 mg/ml) and finasteride 1 mg oral tablet.5 Patients of each treatment group were instructed to apply 1–4 sprays (50–200 μl) of topical preparation depending on the hair loss severity and intake of a tablet once daily for 24 weeks.5 Twentyfour weeks after treatment, topical finasteride showed significant improvement in target area hair count (TAHC) compared with placebo (mean change from baseline, 20.2 vs. 6.7 hairs/cm2 ; p < 0.001) (Table 3).5 Additionally, TAHC improvements were numerically similar between topical and oral finasteride (mean change from baseline, 20.2 vs. 21.1 hairs/cm2 ) (Table 3).5 However, topical finasteride did not demonstrate a significant difference in hair diameter (Table 3).5
A double-blind, randomized clinical trial compared the efficacy of finasteride 1% topical gel and finasteride 1 mg oral tablet.23 The investigators randomized 45 male AGA patients into two groups, but seven patients discontinued the study.23 The age range of the patients was 22.8 ± 3.3 years, with a hair loss history of 23.10 ± 18.8 months.23 The first group (topical group) received finasteride 1% topical gel and placebo tablets, while the second group (oral group) received finasteride 1 mg tablets and gel base (no drug).23 Both groups were instructed to apply the gel twice daily to the scalp and intake the tablet once daily for 6 months.23 Upon treatment completion (6 months after the therapy), total hair count and terminal hair count significantly increased in both topical and oral finasteride groups compared with the baseline (Table 4).23 However, no significant difference was evident between these two groups—total hair count ( p = 0.642; topical vs. oral), terminal hair count ( p = 0.661; topical vs. oral), and size of alopecia ( p = 0.453; topical vs. oral).23 Overall, finasteride topical gel and oral tablet showed similar efficacies in the trial.23
5.2 | Topical finasteride plus topical minoxidil
A prospective, double-blind, randomized study compared the efficacies between 3% minoxidil solution alone and in combination with 0.25% finasteride solution in 30 postmenopausal women with female pattern hair loss.24 The participants of both treatment groups applied 1 ml of study solution to the balding area of the scalp twice daily for 24 weeks. At Week 24, hair density increased in both treatment groups. In the minoxidil/finasteride group, hair density increased by 24.7 hairs/cm 2, and in the minoxidil group, it was 21.9 hairs/cm 2 . 24 However, no statistical difference was evident between these two groups ( p = 0.88). In contrast, hair diameter significantly increased in the minoxidil/finasteride group compared with the minoxidil group ( p = 0.039).24 The minoxidil/ finasteride group and minoxidil group showed 11.9 μm and 7 μm mean an increase in hair diameter, respectively.24 Overall, the trial suggested that adding topical finasteride with minoxidil might enhance the efficacy.24
A separate randomized, double-blind controlled study in 40 patients with male androgenetic alopecia aged 18–60 years also supported this finding; 3% minoxidil plus 0.25% finasteride solution (MFX) is more efficacious than 3% minoxidil solution (MX) alone.25 The patients, randomized into two groups, applied 1 ml of MFX or MX solution twice daily for 24 weeks.25 At Week 24, while the mean change from baseline in total hair density in MFX group was 61.84 ± 15.65 hairs/cm 2, the MX group observed a 34.88 ± 10.24 hairs/cm 2 change in total hair density.25 The mean change from baseline in hair diameter was also greater in MFX group—17 ± 5.24 μm for MFX group, and 13 ± 4.15 μm for MX group.25 Changes in hair density and hair diameter between FMX and MX groups were statistically significant (p = 0.003 and p = 0.04, respectively). 25
Tanglertsampan also compared the efficacies of minoxidil and finasteride combination (3% minoxidil/ 0.1% finasteride lotion and minoxidil (3% lotion) alone.26 In this double-blind, comparative study, 40 male patients with AGA were randomized into minoxidil/ finasteride (MFX) and minoxidil (MX) groups and instructed to apply the lotion twice daily for 24 weeks.26 During the study period, seven patients discontinued due to a flood disaster in Bangkok— a reason which was unrelated to the treatment.26 The result was somewhat indecisive because, at Week 24, both MFX and MX groups experienced increased hair counts compared with baseline, but the increase was statistically significant for the MFX group (p = 0.044) and not for the MX group (p = 0.114).26 Additionally, after 24 weeks, the mean change in hair counts in the MFX and MX treatment groups was statistically indifferent (p = 0.503). However, the global photographic assessment, a 7-point scale, starting from greatly decreased (−3) to greatly increased (+3), showed significant improvement (p = 0.003) in the MFX group (1.84 ± 0.79) compared with the MX group (1.02 ± 0.69).26
6 | SAFETY
In males, the most commonly reported adverse events due to 1 mg/day oral finasteride tablet intake include decreased libido, erectile dysfunction, ejaculation disorder, and impotence.4 For females, the reported adverse effects are sexual dysfunction, menstrual irregularity, headache, and hypertrichosis.4 Most adverse events are potentially linked with DHT reduction in serum and other sexual organs' tissues.27 In such cases, the topical formulation may be an alternative to oral finasteride to minimize systemic adverse events.
6.1 | Side effects of topical finasteride
Topical finasteride formulations usually exhibit mild-to-moderate local side effects.27 Various clinical studies have reported scalp pruritus, burning sensation, irritation, contact dermatitis, and erythema.23,24,26,28,29 Some users may also experience mild and dry, flaky scalp, and heaviness on the topical site.24,27
6.2 | Phase III clinical trial
A recent phase III, randomized clinical trial that compared the efficacy and safety of topical and oral finasteride found the majority (96.9%) of treatment-emergent adverse events (TEAEs) to be mild or moderate.5 Additionally, treatment-emergent serious adverse events reported by 10 patients were considered unrelated to the study drug finasteride.5 Figure 3 presents the most common TEAEs—loss/reduction in libido, pruritus, and erythema in the placebo, oral, or topical finasteride group reported by ≥3 patients.5 Overall, the incidence of treatment-related TEAEs was 9.9%, 6.6%, and 11.9% in the topical, placebo, and oral finasteride arms, and the discontinuation rates due to the treatment-related TEAEs were 2.8%, 2.2%, and 7.1% in the respective treatment groups.5
7 | IN PRACTICE
7.1 | Prescribing trend
Dermatologists may prefer oral finasteride over topical finasteride to treat male pattern AGA since the oral formulation is FDA-approved.30,31 However, as more high-quality trials become available reporting on the efficacy and safety of topical finasteride, the trend in prescribing may tilt in favor of the topical over the oral formulation.
7.2 | Dosage regimen
The dose of topical finasteride is not well-established. In the phase III clinical trial, patients applied 1–4 sprays (50–200 μl) of finasteride 0.25% w/w topical spray to the scalp daily and left it in place for 6–8 h, then cleaned the scalp with shampoo.5 After 24 weeks of treatment, patients observed satisfactory outcomes.5 A separate source recommended twice daily application of 1 ml finasteride/ minoxidil solution (0.05%/5%) directly to the balding area of the scalp.32 Patients may need to wait 2–4 months to observe results.32
8 | CONCLUSION
The available clinical studies, including the phase III clinical trial5, suggest that topical finasteride may promote hair growth and reduce systemic adverse effects of oral therapy.4,5,16,23 The finasteride/minoxidil combined topical formulation may also enhance the efficacy, although the current studies showed statistically inconclusive results in some parameters.24,26 Topical finasteride monotherapy, and its combination with topical minoxidil, may be promising hair loss treatments in the near future. Further studies are required to investigate the consequences of long-term topical finasteride use and determine its proper formulation and dosage form—topical solution, gel, or spray, and potentially other formulations as well.
Aditya K. Gupta MD, PhD | Mesbah Talukder PhD
Abstract
Background: Oral finasteride is an FDA-approved treatment for androgenetic alopecia (AGA). Topical finasteride, while not FDA-approved, lacks the systemic adverse effects associated with oral finasteride. The efficacy of topical finasteride has been evaluated.
Aim: To review whether topical finasteride is a safe and effective treatment for male and female pattern hair loss.
Method: A structured search in PubMed and Google Scholar identified 864 records, with 32 articles meeting the inclusion criteria for review.
Results and discussion: In a phase III, randomized, controlled trial, the efficacies of topical 0.25% w/w finasteride spray (1–4 sprays; 50–200 μl/day) and once-daily finasteride 1 mg oral tablet were similar when administered for 24 weeks (mean change from baseline, 20.2 vs. 21.1 hairs/cm2 ). Additionally, a double-blind, randomized trial compared the efficacies of twice-daily finasteride 1% topical gel and once-daily finasteride 1 mg oral tablet for 6 months and found similar results in both groups. Moreover, a combination of topical minoxidil and topical finasteride may enhance efficacy. Topical finasteride reduces both scalp and plasma DHT levels. In an open-label pharmacodynamic study, a 7-day treatment of twice-daily finasteride 0.25% topical solution and once-daily finasteride 1 mg oral tablet provided similar inhibition of plasma DHT. Topical finasteride reduces the potential for systemic side effects, including the risk of sexual dysfunction. The side effects are localized to the application site, for example, scalp pruritus, burning sensation, irritation, contact dermatitis, and erythema.
Conclusion: Topical finasteride may be an alternative for those concerned about the oral formulation's systemic side effects.
1 | INTRODUCTION
Hairstyle frames our look and is often regarded as the expression of someone's personality.1 Approximately 50% of men experience male pattern hair loss (AGA) during their lifetime.1 Due to this slow and involuntary hair loss, millions of men suffer from emotional stress.1,2 Many deceitful internet sites claim “miracle cures” for male and female pattern hair loss, but the truth is most of them do not work.1 Oral finasteride is specifically recommended for male AGA, although some clinicians use it off-label for female pattern hair loss in postmenopausal women.3 Topical minoxidil is FDA-approved for male AGA and female pattern hair loss.3,4
The effectiveness of oral finasteride in the treatment of androgenetic alopecia (AGA) is well-established.5 Several clinical studies have shown that finasteride 1 mg oral tablet reduces hair loss and/ or enhances hair growth in male AGA patients compared with baseline or placebo, as early as 3 months after starting therapy, and extending to 5–10 years.5–10 Although oral finasteride is well-tolerated, some patients experience sexual dysfunction, possibly due to 5αreductase inhibition.5,11–13 Additionally, oral finasteride has been associated with an increased risk of depression, prompting regulators to include warnings in the product labeling in some countries.5,14,15 Conversely, topical finasteride may reduce the potential side effects of oral formulation due to its local action and an absence of systemic side effects.5,16
*This article reviews whether topical finasteride could be an effective alternative to oral finasteride for male and female pattern hair loss, and includes its pharmacokinetics, mechanism of action, and safety. It also discusses the finasteride/minoxidil topical combination and whether it can enhance efficacy.
3 | PHARMACOKINETICS
The maximum plasma drug (finasteride) concentration (Cmax) and the area under the plasma drug concentration-time curve (AUC) values for topical and oral finasteride are presented in Table 1.17 The bioavailability of topical finasteride was much lower compared with oral finasteride.17 The time to reach Cmax (tmax) was approximately 10 times higher for topical finasteride than for the oral formulation (Table 1).17 Pharmacokinetic studies could not find clear absorption and elimination phases for topical finasteride.17 Therefore, the calculations of extrapolated pharmacokinetic parameters such as elimination half-life (t1/2) and area under the plasma concentration-time curve from time zero to infinite time (AUC0–∞) were not possible.17
4 | PHARMACODYNAMICS
4.1 | Mechanism of action
Finasteride irreversibly binds 5α-reductase (5-AR) and prevents NADPH-mediated conversion of testosterone to dihydrotestosterone (DHT)4 (Figure 2). DHT is believed to convert terminal hair into vellus-like miniaturized hair, resulting in gradual hair loss.
Therefore, suppressing DHT levels may promote hair growth, perhaps via the Wnt/β-catenin signaling pathway (Figure 2).18 5-AR has three isoenzymes, type I, type II, and type III, among which type I and type II are expressed in the dermal papilla.4 Finasteride binds to type II isoenzyme 100-times more selectively than type I.19 When the drug binds with 5-AR at the dermal papilla level, scalp DHT level is reduced significantly, but not entirely, perhaps because of residual conversion of testosterone via 5-AR type I.4,19,20
Preliminary studies suggest that 5 mg/day of oral finasteride for 4 weeks significantly reduced the scalp DHT level compared with placebo.21 Additionally, a scalp DHT dose-ranging study showed that oral finasteride at ≥0.5 mg/day suppressed scalp DHT levels approximately by 65% after 6 weeks of treatment.4,21,22 Within 2 weeks of treatment discontinuation, the DHT levels returned to normal.4,16
4.2 | Effects of topical finasteride on plasma DHT level
In a single-center, open-label, parallel-group, pharmacodynamic, pharmacokinetic, exploratory study, 24 males with AGA were randomized into finasteride 0.25% topical solution and finasteride 1 mg oral tablet treatment groups.17 On Day 1, a single dose of finasteride 1 mg oral tablet reduced plasma DHT levels by 56 to 64% approximately (Table 2).17 In contrast, a single application of finasteride 0.25% topical solution reduced only approximately 18 to 19% (Table 2).17 The two treatments were significantly different in reducing plasma DHT levels (p < 0.0001).17 However, plasma DHT reduction levels were similar after multiple-dose treatments of topical and oral finasteride. The multiple-dose treatments of topical and oral finasteride corresponded to the application of 1 ml of finasteride 0.25% topical solution to the shaved scalp in the morning of Day 1 followed by twice-daily application from Day 2 to the morning of Day 8, and administration of finasteride 1 mg oral tablet once daily for 7 days.17 For topical finasteride, the DHT reduction level was 67.95 to 75.19%, and for oral, it was 61.87–71.97% (Table 2).17 Seven days of treatment with finasteride 0.25% topical solution twice daily (bid) and the 1 mg oral tablet once daily (od) provided similar inhibition of plasma DHT.17 The difference was statistically insignificant (p ≥ 0.1092).17
However, in a phase III, randomized, controlled trial, topical 0.25% w/w finasteride spray (1–4 sprays; 50–200 μl/day) for 24 weeks reduced the serum DHT concentration by 34.6% compared with the baseline (p < 0.05 vs. placebo) (Table 2).5 For oral finasteride (1 mg/ day for 24 weeks), the reduction was relatively higher (55.6%) than the topical form when compared with baseline (p < 0.05 vs. placebo).5 Notably, topical finasteride did not increase the plasma testosterone level as a result of reduced DHT concentration.5 In contrast, oral finasteride resulted in a positive shift in testosterone level in 6.7% of patients.5
5 | EFFICACY
5.1 | Topical vs. oral finasteride
Recently, a phase III, randomized clinical trial investigated the efficacy of finasteride topical spray in male patients aged 18–40 years with mild-to-moderate vertex male pattern hair loss (modified Norwood/Hamilton classification scale; III vertex, IV, or V).5 A total of 458 patients, of which 323 completed the study, were randomized at 2: 2: 1 into three treatment groups: topical finasteride group (topical finasteride and oral placebo), oral finasteride group (topical placebo and oral finasteride), and placebo group (topical placebo and oral placebo).5 Topical and oral finasteride corresponded to finasteride 0.25% w/w topical spray (2.275 mg/ml) and finasteride 1 mg oral tablet.5 Patients of each treatment group were instructed to apply 1–4 sprays (50–200 μl) of topical preparation depending on the hair loss severity and intake of a tablet once daily for 24 weeks.5 Twentyfour weeks after treatment, topical finasteride showed significant improvement in target area hair count (TAHC) compared with placebo (mean change from baseline, 20.2 vs. 6.7 hairs/cm2 ; p < 0.001) (Table 3).5 Additionally, TAHC improvements were numerically similar between topical and oral finasteride (mean change from baseline, 20.2 vs. 21.1 hairs/cm2 ) (Table 3).5 However, topical finasteride did not demonstrate a significant difference in hair diameter (Table 3).5
A double-blind, randomized clinical trial compared the efficacy of finasteride 1% topical gel and finasteride 1 mg oral tablet.23 The investigators randomized 45 male AGA patients into two groups, but seven patients discontinued the study.23 The age range of the patients was 22.8 ± 3.3 years, with a hair loss history of 23.10 ± 18.8 months.23 The first group (topical group) received finasteride 1% topical gel and placebo tablets, while the second group (oral group) received finasteride 1 mg tablets and gel base (no drug).23 Both groups were instructed to apply the gel twice daily to the scalp and intake the tablet once daily for 6 months.23 Upon treatment completion (6 months after the therapy), total hair count and terminal hair count significantly increased in both topical and oral finasteride groups compared with the baseline (Table 4).23 However, no significant difference was evident between these two groups—total hair count ( p = 0.642; topical vs. oral), terminal hair count ( p = 0.661; topical vs. oral), and size of alopecia ( p = 0.453; topical vs. oral).23 Overall, finasteride topical gel and oral tablet showed similar efficacies in the trial.23
5.2 | Topical finasteride plus topical minoxidil
A prospective, double-blind, randomized study compared the efficacies between 3% minoxidil solution alone and in combination with 0.25% finasteride solution in 30 postmenopausal women with female pattern hair loss.24 The participants of both treatment groups applied 1 ml of study solution to the balding area of the scalp twice daily for 24 weeks. At Week 24, hair density increased in both treatment groups. In the minoxidil/finasteride group, hair density increased by 24.7 hairs/cm 2, and in the minoxidil group, it was 21.9 hairs/cm 2 . 24 However, no statistical difference was evident between these two groups ( p = 0.88). In contrast, hair diameter significantly increased in the minoxidil/finasteride group compared with the minoxidil group ( p = 0.039).24 The minoxidil/ finasteride group and minoxidil group showed 11.9 μm and 7 μm mean an increase in hair diameter, respectively.24 Overall, the trial suggested that adding topical finasteride with minoxidil might enhance the efficacy.24
A separate randomized, double-blind controlled study in 40 patients with male androgenetic alopecia aged 18–60 years also supported this finding; 3% minoxidil plus 0.25% finasteride solution (MFX) is more efficacious than 3% minoxidil solution (MX) alone.25 The patients, randomized into two groups, applied 1 ml of MFX or MX solution twice daily for 24 weeks.25 At Week 24, while the mean change from baseline in total hair density in MFX group was 61.84 ± 15.65 hairs/cm 2, the MX group observed a 34.88 ± 10.24 hairs/cm 2 change in total hair density.25 The mean change from baseline in hair diameter was also greater in MFX group—17 ± 5.24 μm for MFX group, and 13 ± 4.15 μm for MX group.25 Changes in hair density and hair diameter between FMX and MX groups were statistically significant (p = 0.003 and p = 0.04, respectively). 25
Tanglertsampan also compared the efficacies of minoxidil and finasteride combination (3% minoxidil/ 0.1% finasteride lotion and minoxidil (3% lotion) alone.26 In this double-blind, comparative study, 40 male patients with AGA were randomized into minoxidil/ finasteride (MFX) and minoxidil (MX) groups and instructed to apply the lotion twice daily for 24 weeks.26 During the study period, seven patients discontinued due to a flood disaster in Bangkok— a reason which was unrelated to the treatment.26 The result was somewhat indecisive because, at Week 24, both MFX and MX groups experienced increased hair counts compared with baseline, but the increase was statistically significant for the MFX group (p = 0.044) and not for the MX group (p = 0.114).26 Additionally, after 24 weeks, the mean change in hair counts in the MFX and MX treatment groups was statistically indifferent (p = 0.503). However, the global photographic assessment, a 7-point scale, starting from greatly decreased (−3) to greatly increased (+3), showed significant improvement (p = 0.003) in the MFX group (1.84 ± 0.79) compared with the MX group (1.02 ± 0.69).26
6 | SAFETY
In males, the most commonly reported adverse events due to 1 mg/day oral finasteride tablet intake include decreased libido, erectile dysfunction, ejaculation disorder, and impotence.4 For females, the reported adverse effects are sexual dysfunction, menstrual irregularity, headache, and hypertrichosis.4 Most adverse events are potentially linked with DHT reduction in serum and other sexual organs' tissues.27 In such cases, the topical formulation may be an alternative to oral finasteride to minimize systemic adverse events.
6.1 | Side effects of topical finasteride
Topical finasteride formulations usually exhibit mild-to-moderate local side effects.27 Various clinical studies have reported scalp pruritus, burning sensation, irritation, contact dermatitis, and erythema.23,24,26,28,29 Some users may also experience mild and dry, flaky scalp, and heaviness on the topical site.24,27
6.2 | Phase III clinical trial
A recent phase III, randomized clinical trial that compared the efficacy and safety of topical and oral finasteride found the majority (96.9%) of treatment-emergent adverse events (TEAEs) to be mild or moderate.5 Additionally, treatment-emergent serious adverse events reported by 10 patients were considered unrelated to the study drug finasteride.5 Figure 3 presents the most common TEAEs—loss/reduction in libido, pruritus, and erythema in the placebo, oral, or topical finasteride group reported by ≥3 patients.5 Overall, the incidence of treatment-related TEAEs was 9.9%, 6.6%, and 11.9% in the topical, placebo, and oral finasteride arms, and the discontinuation rates due to the treatment-related TEAEs were 2.8%, 2.2%, and 7.1% in the respective treatment groups.5
7 | IN PRACTICE
7.1 | Prescribing trend
Dermatologists may prefer oral finasteride over topical finasteride to treat male pattern AGA since the oral formulation is FDA-approved.30,31 However, as more high-quality trials become available reporting on the efficacy and safety of topical finasteride, the trend in prescribing may tilt in favor of the topical over the oral formulation.
7.2 | Dosage regimen
The dose of topical finasteride is not well-established. In the phase III clinical trial, patients applied 1–4 sprays (50–200 μl) of finasteride 0.25% w/w topical spray to the scalp daily and left it in place for 6–8 h, then cleaned the scalp with shampoo.5 After 24 weeks of treatment, patients observed satisfactory outcomes.5 A separate source recommended twice daily application of 1 ml finasteride/ minoxidil solution (0.05%/5%) directly to the balding area of the scalp.32 Patients may need to wait 2–4 months to observe results.32
8 | CONCLUSION
The available clinical studies, including the phase III clinical trial5, suggest that topical finasteride may promote hair growth and reduce systemic adverse effects of oral therapy.4,5,16,23 The finasteride/minoxidil combined topical formulation may also enhance the efficacy, although the current studies showed statistically inconclusive results in some parameters.24,26 Topical finasteride monotherapy, and its combination with topical minoxidil, may be promising hair loss treatments in the near future. Further studies are required to investigate the consequences of long-term topical finasteride use and determine its proper formulation and dosage form—topical solution, gel, or spray, and potentially other formulations as well.
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