Aditya K. Gupta, MD, PhD, FRCPC1,2 and Kelly A. Foley, PhD2
1Division of Dermatology, Department of Medicine, University of Toronto, Toronto, ON, Canada
2Mediprobe Research Inc., London, ON, Canada
Conflict of interest:
Minoxidil is a Health Canada and US FDA-approved medication for hair loss in men and women. While 5% minoxidil foam has been approved for men since 2006, Health Canada and the FDA only approved 5% minoxidil foam for female pattern hair loss (FPHL) in 2014. Recent Phase III clinical trials demonstrated the efficacy of once daily 5% minoxidil foam for treatment of FPHL, where a significant change from baseline in the target area hair count was observed compared to placebo. Similar changes in hair count for 5% foam and twice daily 2% minoxidil solution established noninferiority of the 5% foam formulation. Five percent minoxidil foam provides an additional option for women with FPHL and will soon be available in Canada.
androgenetic alopecia, AGA, female pattern hair loss, FPHL, 5% minoxidil foam, hair loss, treatment, clinical efficacy
Female pattern hair loss (FPHL), also known as androgenetic alopecia (AGA), is one of the most common forms of alopecia in women. Onset of hair loss can occur as early as one’s 20s and affect as many as 40% of Caucasian women over the age of 70 years.1,2 FPHL can be a source of social distress and greatly impair quality of life.3 There are a variety of treatments for FPHL including antiandrogen medications, topical treatments, laser/light devices, and hair transplantation,4 with choice of treatment depending on the extent of hair loss, patient health, cost, and preference. The goal of treatment is to slow hair loss and potentially increase hair growth; however, treatment is not always successful.
Until recently, the only US FDA-approved medication for women was 2% minoxidil solution, while both the 2% and 5% solutions are available for men. Minoxidil may stimulate hair growth by increasing the anagen phase of the hair cycle, but the exact mechanisms are currently unknown.5 In 2006, the FDA approved 5% minoxidil foam for the treatment of androgenetic alopecia in men after clinical testing showed that it increased hair growth after 48 weeks of twice daily use.6,7 Additionally, the incidence of pruritus in men was lower with the 5% foam than the 5% solution, likely due to propylene glycol in the solution formulation.6,7 Because of its efficacy in treating male hair loss, 5% minoxidil became a viable option for women suffering from FPHL. Clinical trial results in women suggest that 5% minoxidil foam is an effective treatment for FPHL, leading to its Health Canada and FDA approvals for this indication in 2014.8
Past Clinical Evidence
In Phase III clinical trials, both the 5% and 2% minoxidil formulations have demonstrated similar efficacy in promoting hair growth in women with hair thinning over the frontoparietal scalp. Lucky et al. conducted a 48-week randomized, doubleblind, placebo controlled trial that assessed target area hair count (TAHC) following twice daily application of 5% minoxidil solution, 2% minoxidil solution, or 5% solution vehicle in women with frontoparietal hair loss that could be accompanied with, or without, frontal hairline recession.9 Patient and investigator assessments of hair growth and scalp coverage were performed in addition to TAHC. Both the 5% and 2% minoxidil solutions showed significantly higher TAHCs compared to placebo (P < 0.001, Table 1). The investigator assessments followed the same pattern as the TAHC results; however, patient-reported assessment of hair growth was significantly greater in the 5% minoxidil solution group than the 2% minoxidil solution or vehicle groups.9
The efficacy of once daily application of 5% minoxidil foam against 2% minoxidil solution in the treatment of frontoparietal hair loss in women was investigated in a randomized, singleblind Phase III trial.10 Change in non-vellus hair count and width, blind evaluator and patient review of photographs, and patient assessment of product aesthetics and benefits were assessed after 24 weeks of use. Five percent minoxidil foam applied once daily was shown to be noninferior to twice daily 2% minoxidil solution, as measured by change in non-vellus hair count (Table 2) and hair width. Women in the 5% foam group agreed more strongly that treatment did not interfere with grooming routines than did women in the 2% solution group (P = 0.002).10 In separate studies, both the twice daily use of 5% minoxidil solution and once daily use of 5% minoxidil foam were shown to be noninferior compared to twice daily use of 2% minoxidil solution.
Recent Clinical Trials
Two randomized, double-blind, parallel, international multicenter Phase III trials of 5% minoxidil foam were recently completed. Both trials assessed the efficacy of once daily use of 5% minoxidil foam in female participants aged 18 years and older.11,12 In the first trial, participants were assigned to once a day treatment with 5% minoxidil foam or vehicle foam for 24 weeks (minoxidil: n=203, vehicle: n=201).11 Efficacy was assessed at weeks 12 and 24 and safety and adverse events were monitored every 6 weeks. At weeks 12 and 24, changes in TAHC from baseline were significantly higher in the minoxidil-treated group than the vehicle-treated group (P < 0.0001, Table 2). Also at 24 weeks, patient-reported assessment of scalp coverage was determined to be significantly higher with minoxidil treatment compared to vehicle (P < 0.0001).11
Participants in the second trial were assigned to once a day treatment with 5% minoxidil foam or 2% minoxidil solution twice daily for 52 weeks (n=161 in each group).12 TAHC was assessed at weeks 12, 24, and 52 and safety and adverse events were monitored regularly. The change in TAHC from baseline in the 5% minoxidil group was shown to be similar to that of the 2% topical minoxidil solution group at weeks 12 (P < 0.4158) and 24 (P = 0.9170, Table 2), as well as at week 52 (P = 0.5980).12
|Lucky et al.9||2x day/48 weeks||5% solution||101||24.5 ± 21.9*|
|2% solution||108||20.7 ± 17.6*|
|Placebo solution||51||9.4 ± 14.6|
|Blume-Peytavi et al.10,15||1x day/24 weeks||5% foam||56||31.9 ± 19.40|
|2x day/24 weeks||2% solution||57||28.4 ± 18.90|
|Table 1. Change from baseline in target area hair count of previous Phase III trials of 5% minoxidil
† TAHC = target area hair count (hairs per cm2). Values represent mean ± standard deviation (SD) change in TAHC from baseline.
* P < 0.001, each minoxidil solution different from vehicle
|Study||Regimen||Treatment||n||TAHC 12 weeks†||TAHC 24 weeks†|
|Phase III RCT11||1x day/24 weeks||5% Minoxidil foam||200||16.4 ± 21.5*||13.5 ± 22.3*|
|Vehicle foam||197||5.4 ± 15.3||4.0 ± 16.2|
|Phase III RCT12||1x day/52 weeks||5% Minoxidil foam||161||24.9 ± 26.0||23.7 ± 22.9|
|2x day/52 weeks||2% Minoxidil solution||161||22.5 ± 22.8||23.8 ± 24.7|
|Table 2. Efficacy outcomes of recent Phase III trials of 5% minoxidil foam
† TAHC = target area hair count (hairs per cm2). Values represent mean ± SD change in TAHC from baseline.
* P < 0.0001, 5% minoxidil different from vehicle RCT = randomized controlled trial
Five percent minoxidil foam was well tolerated in each of the recent clinical trials. The number of participants reporting adverse events after using 5% minoxidil foam was similar to that of participants who used 2% minoxidil solution or vehicle. The most common adverse events reported in at least 2% of participants included weight gain, headache, pruritus, and nasal and upper respiratory tract infections.11,12 These are similar to the adverse events reported previously by Lucky et al. and Blume- Peytavi et al., who also reported dermatitis, dandruff, erythema, and burning/stinging in both 5% and 2% minoxidil treatment groups.9,10 Additionally, 5% foam may encourage greater compliance, as Blume-Peytavi et al. reported that pruritus and dandruff occurred significantly less with application of 5% foam than with the 2% solution.10
Hypertrichosis is a well-known concern among women using hair growth products. While hypertrichosis has been reported with the use of 5% minoxidil,9,10,13 unwanted growth in sideburn areas was significantly less with 5% foam than with the 2% solution.10 Advice to women to further limit hypertrichosis includes application of the medication 2-4 hours prior to bedtime and hand washing immediately after application;8 however, the presence of hirsutism or hypersensitivity may increase susceptibility to unwanted hair growth that is beyond physician and patient control.13,14
Six participants in the 5% minoxidil group reported serious adverse events (SAEs) in the placebo controlled trial (1 incidence each of cardiac disorder, gastritis, dehydration, osteoarthritis, ovarian neoplasm, uterine leiomyoma, renal failure, and hypertensive crisis) in comparison to 4 participants in the vehicle group (1 incidence each of fatigue, ovarian cancer, memory impairment, mental status changes, and PTSD; 2 incidences each of cardiac disorder and asthenia).11 In the comparative trial, 2 participants treated with 5% minoxidil reported SAEs (wrist fracture and anxiety) in comparison to 8 participants in the 2% minoxidil group (1 incidence each of angina pectoris, abdominal pain, bile duct stone, anal abscess, influenza, metastatic neoplasm, menometrorrhagia, and asthma).12 The SAEs are not considered to be clinically relevant to the drug.
Recent clinical trials of 5% minoxidil foam for the treatment of FPHL have demonstrated it to be safe and effective, with hair growth outcomes similar to that of the traditional 2% minoxidil solution.11,12 Phase III clinical trials demonstrated that hair growth with once daily use of 5% minoxidil foam is noninferior to twice daily use of 2% minoxidil solution in women with frontoparietal hair loss.10,12 Patient-reported improvement in hair volume and coverage appears to be greater with 5% minoxidil foam and once daily application does not substantially interfere with grooming routines.10 Adverse events may occur with both 5% foam and 2% solution, but these rarely lead to discontinued use. Susceptibility to hypertrichosis may be individual-specific, and should be discussed with patients as a possible side-effect of minoxidil use.
It is suggested that 5% minoxidil be applied for 3-6 months before noticeable improvement can be observed.8 While the results of clinical trials demonstrate a statistically significant increase in the total hair count, sometimes these results may fall short of patient expectations; therefore, patients need to be informed that individual results may vary even after 6-12 months of therapy.4,16 Recent evidence demonstrates that a sulfotransferase enzyme test can successfully identify non-responders to minoxidil.17 To our knowledge, this test is not commercially available. In addition, some patients may experience an increase in hair shedding, or at least continued hair loss, for the first few months and should be counselled accordingly.4,16 When women experience improvement in hair growth, continued treatment is required or else improvement will likely be lost and hair loss will revert back to its natural course.4,18
Five percent minoxidil foam, applied only once daily, has the potential for milder side effects, improved compliance, and greater patient satisfaction with treatment. Indeed, the use of minoxidil as a treatment for FPHL has been shown to improve women’s quality of life.3 Additionally, 5% minoxidil foam provides an alternative option for women who do not wish to use, or who are unable to use, oral anti-androgen or hormonal contraceptive medications as hair loss treatments. The recent approval and availability of 5% minoxidil foam in Canada provides a safe and effective treatment for women with FPHL.
- Blumeyer A, Tosti A, Messenger A, et al. Evidence-based (S3) guideline for the treatment of androgenetic alopecia in women and in men. J Dtsch Dermatol Ges. 2011 Oct;9 Suppl 6:S1-57.
- Norwood OT. Incidence of female androgenetic alopecia (female pattern alopecia). Dermatol Surg. 2001 Jan;27(1):53-4.
- Zhuang XS, Zheng YY, Xu JJ, et al. Quality of life in women with female pattern hair loss and the impact of topical minoxidil treatment on quality of life in these patients. Exp Ther Med. 2013 Aug;6(2):542-6.
- Herskovitz I, Tosti A. Female pattern hair loss. Int J Endocrinol Metab. 2013 Oct;11(4):e9860.
- Messenger AG, Rundegren J. Minoxidil: mechanisms of action on hair growth. Br J Dermatol. 2004 Feb;150(2):186-94.
- Olsen EA, Dunlap FE, Funicella T, et al. A randomized clinical trial of 5% topical minoxidil versus 2% topical minoxidil and placebo in the treatment of androgenetic alopecia in men. J Am Acad Dermatol. 2002 Sep;47(3):377-85.
- Olsen EA, Whiting D, Bergfeld W, et al. A multicenter, randomized, placebocontrolled, double-blind clinical trial of a novel formulation of 5% minoxidil topical foam versus placebo in the treatment of androgenetic alopecia in men. J Am Acad Dermatol. 2007 Nov;57(5):767-74.
- Drugs@FDA: FDA Approved Drug Products. Women’s rogaine 5% minoxidil topical aerosol, approval history and label. Available at: http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.DrugDetails. Accessed September 1, 2014.
- Lucky AW, Piacquadio DJ, Ditre CM, et al. A randomized, placebo-controlled trial of 5% and 2% topical minoxidil solutions in the treatment of female pattern hair loss. J Am Acad Dermatol. 2004 Apr;50(4):541-53.
- Blume-Peytavi U, Hillmann K, Dietz E, et al. A randomized, single-blind trial of 5% minoxidil foam once daily versus 2% minoxidil solution twice daily in the treatment of androgenetic alopecia in women. J Am Acad Dermatol. 2011 Dec;65(6):1126-34 e2.
- Johnson & Johnson Consumer and Personal Products Worldwide. A phase 3 multi-center parallel design clinical trial to compare the efficacy and safety of 5% minoxidil foam vs. vehicle in females for the treatment of female pattern hair loss (androgenetic alopecia). In: ClinicalTrials.gov, Identifier: NCT01226459. Last updated June 3, 2014. Available at: http://clinicaltrials.gov/ct2/show/results/NCT01226459?term=minoxidil§=X4301256#othr. Accessed September 1, 2014.
- Johnson & Johnson Consumer and Personal Products Worldwide. A phase 3 multi-center parallel design clinical trial to compare the efficacy and safety of 5% minoxidil foam vs. 2% minoxidil solution in females for the treatment of female pattern hair loss – androgenetic alopecia. In: ClinicalTrials.gov, Identified: NCT01145625. Last updated May 19, 2014. Available at: http:// clinicaltrials.gov/ct2/show/study/NCT01145625?term=minoxidil§=X430126. Accessed September 1, 2014.
- Dawber RP, Rundegren J. Hypertrichosis in females applying minoxidil topical solution and in normal controls. J Eur Acad Dermatol Venereol. 2003 May;17(3):271-5.
- Peluso AM, Misciali C, Vincenzi C, et al. Diffuse hypertrichosis during treatment with 5% topical minoxidil. Br J Dermatol. 1997 Jan;136(1):118-20.
- Hillmann K, Geburtsort K. Results of an investigator-initiated, two-armed, randomized, controlled clinical trial to proof efficacy of a 5% minoxidil topical foam once daily versus a 2% minoxidil solution twice daily on hair volume in women with mild to moderate androgenetic alopecia. Free University of Berlin; 2013. Available at: http://www.diss.fu-berlin.de/diss/receive/FUDISS_thesis_000000095104. Accessed September 1, 2014.
- Levy LL, Emer JJ. Female pattern alopecia: current perspectives. Int J Womens Health. 2013;5:541-56.
- Goren A, Shapiro J, Roberts J, et al. Clinical utility and validity of minoxidil response testing in androgenetic alopecia. Dermatol Ther. 2014 Aug 12. [Epub ahead of print]
- Rogers NE. Medical therapy for female pattern hair loss (FPHL). Hair Transpl Forum Int. 2014;24(3):81,86-8.