ABSTRACT
Background:
Androgenetic alopecia leads to progressive hair loss in susceptible individuals if left untreated. Topical minoxidil represents an evidence-based treatment for female androgenetic alopecia, though with variable success.
Aims and Objectives:
Treatment of minoxidil non-responders remains challenging, as does treatment of patients with propylene glycol sensitivity or irritable scalp syndrome.
Materials and Methods:
Single-center, retrospective cohort of 50 female patients with androgenetic alopecia failing to respond to a minimum of 6 months of standard 5% topical minoxidil solution either once daily or b.i.d. depending on the severity of the alopecia. Patients were switched to propylene glycol-free, North American Witch Hazel (Hamamelis virginiana)-based solution of 5% minoxidil sulfate (5% minoxidil sensitive solution). Efficacy and safety of treatment were evaluated, including stereotactic global photography and epiluminiscence microscopy with digital imaging taken at baseline, at 3, and at 6 months of treatment.
Results:
70% of patients showed observable clinical improvement with combined global photographic and epiluminiscence microscopic assessment with digital imaging, and 22% epiluminiscence microscopic-only improvement as evidence of treatment efficacy. The treatment was well tolerated, particularly in patients with propylene glycol sensitivity and patients with irritable scalp syndrome.
Conclusions:
These results suggest that propylene glycol-free, North American witch hazel (Hamamelis virginiana)-based solution of 5% minoxidil is effective and safe for treatment of female androgenetic alopecia, specifically in minoxidil non-responders and patients with propylene glycol sensitivity or irritable scalp syndrome.
Keywords: 5%, minoxidil-sensitive solution, female androgenetic alopecia, irritable scalp syndrome, minoxidil nonresponders, propylene glycol sensitivity
INTRODUCTION
Androgenetic alopecia leads to progressive hair loss in susceptible individuals if left untreated. Topical minoxidil represents an evidence-based treatment for female androgenetic alopecia (FAGA), though with variable success. Treatment of patients with propylene glycol sensitivity, the usual solvent in commercial preparations of topical minoxidil, or irritable scalp syndrome remains challenging, as does that of minoxidil nonresponders.
A sensitive scalp is a frequent problem in daily clinical practice and often represents a major challenge for dermatologists. In particular, patients with hair loss or alopecia frequently also complain of scalp problems that must be taken into account for successful treatment programs and treatment compliance. The main complaint of these patients relates to a sensitive scalp, for which various causes are taken into consideration: atopic disposition with tendency to sebostasis, irritation, and dermatitis; type IV hypersensitivity to particular shampoo ingredients, such as cocamidopropyl betaine or preservatives; age-related dryness of the skin; irritation from cosmetic hair treatments; and finally, some specific dermatological scalp conditions, such as seborrheic dermatitis, psoriasis, and their treatment sequels, especially those due to the prolonged use of topical corticosteroids. In some cases, symptoms of scalp sensitivity, itching, burning, and tension, are due to the drying out and irritating effect of alcohol-based topicals and the propylene glycol contained as a solvent in these preparations. In others, the condition evolves in the vertex area where the scalp is maximally exposed to ultraviolet radiation (UVR) and is considered a chronic UVR-related condition with analogies to rosacea.[1] At the same time, there is increasing evidence that UVR exposure also exerts a negative effect on hair growth and alopecia,[2] presumably by generating reactive oxygen species, while hair papilla fibroblasts of the balding scalp have been shown to have an increased sensitivity to oxidative stress.[3]
PATIENTS AND METHODS
Hamamelis.swiss HAIR TONIC (Apomedica, Sagl Switzerland) based on Virginian witch hazel has been specially developed for the care and treatment of the sensitive scalp. The main active principles of the principal ingredient Hamamelis virginiana are the flavonoids and tannins, as a natural source of antioxidants. Additional herbals contained in the tonic promote skin metabolism and blood flow (rosemary, field horsetail), act inhibitory of the proliferation of Cutibacterium spp. (rosemary), have anti-dandruff activity (rosemary), strengthen the connective tissue (field horsetail), and stimulate healthy hair growth (birch, stinging nettle). This observational study aims to report the effects of a propylene glycol-free, North American witch hazel (Hamamelis virginiana)-based solution of 5% minoxidil sulfate (5% minoxidil sensitive solution, 5MSS) with the ingredients: minoxidil sulfate, hamamelis.swiss HAIR TONIC (Apomedica, Sagl Switzerland), glycerin, and water.
A single-center, retrospective cohort of female patients with androgenetic alopecia failing to respond to a minimum of 6 months of conventional 5% topical minoxidil solution either once daily or b.i.d. depending on the severity of the alopecia, were switched to the 5MSS. Patient demographics, clinical effect, and safety were evaluated, including stereotactic global photography and epiluminescence microscopy with digital imaging taken at baseline and at 3 and 6 months of treatment [Table 1]. Patients who were allergic, intolerant, or noncompliant to minoxidil or had other causes of hair loss (alopecia areata, telogen effluvium, and scarring alopecia) were not subjected to treatment.
Table 1.
Case series of female androgenetic alopecia types I through III switched from 5% minoxidil base solution to propylene glycol-free, North American witch-hazel (Hamamelis virginiana)-based solution of 5% minoxidil sulfate (5% minoxidil-sensitive solution)
| Case number | Age | Ludwig type | Global photographic assessment (central part width) at 3 or 6 months of follow-up | Epiluminescence microscopy (diversity of hair shaft diameter) at 3 or 6 months of follow-up |
|---|---|---|---|---|
| 1 | 45 | II | Improved | Improved |
| 2 | 46 | I | Improved | Improved |
| 3 | 39 | I | Improved | Improved |
| 4 | 55 | II | Improved | Improved |
| 5 | 50 | III | Equal | Equal |
| 6 | 54 | I | Improved | Improved |
| 7 | 62 | I | Improved | Improved |
| 8 | 64 | II | Improved | Improved |
| 9 | 58 | I | Equal | Improved |
| 10 | 46 | I | Improved | Improved |
| 11 | 38 | II | Improved | Improved |
| 12 | 56 | I | Equal | Improved |
| 13 | 52 | I | Improved | Improved |
| 14 | 55 | I | Improved | Improved |
| 15 | 40 | III | Equal | Equal |
| 16 | 46 | I | Improved | Improved |
| 17 | 56 | II | Equal | Improved |
| 18 | 63 | II | Improved | Improved |
| 19 | 46 | I | Improved | Improved |
| 20 | 43 | II | Improved | Improved |
| 21 | 51 | I | Improved | Improved |
| 22 | 34 | II | Improved | Improved |
| 23 | 28 | I | Equal | Improved |
| 24 | 32 | I | Improved | Improved |
| 25 | 57 | III | Improved | Improved |
| 26 | 52 | II | Improved | Improved |
| 27 | 59 | II | Equal | Improved |
| 28 | 48 | I | Improved | Improved |
| 29 | 36 | I | Improved | Improved |
| 30 | 50 | II | Equal | Equal |
| 31 | 36 | II | Equal | Improved |
| 32 | 39 | I | Improved | Improved |
| 33 | 56 | I | Equal | Improved |
| 34 | 48 | II | Improved | Improved |
| 35 | 36 | I | Equal | Improved |
| 36 | 33 | I | Equal | Improved |
| 37 | 46 | I | Equal | Improved |
| 38 | 33 | II | Improved | Improved |
| 39 | 26 | I | Improved | Improved |
| 40 | 64 | I | Improved | Improved |
| 41 | 51 | II | Improved | Improved |
| 42 | 57 | II | Improved | Improved |
| 43 | 57 | I | Improved | Improved |
| 44 | 44 | II | Improved | Improved |
| 45 | 34 | III | Equal | Improved |
| 46 | 44 | II | Improved | Improved |
| 47 | 26 | II | Improved | Improved |
| 48 | 58 | II | Equal | Improved |
| 49 | 25 | I | Improved | Improved |
| 50 | 43 | I | Improved | Improved |
RESULTS
A total of 50 female patients were analyzed, aged 25–64 years (mean: 46 ± 10.5 standard deviation [SD]), with FAGA Ludwig types I through III. 70% of patients showed observable clinical improvement with combined global photographic and epiluminescence microscopic assessment with digital imaging [Figure 1a-d] and 22% with epiluminescence microscopic-only. Improvement was most obvious on global photographic assessment in Ludwig type II, followed by least in Ludwig type III because of the hair density as a limiting factor or Ludwig type I because the hair part width was less obviously enlarged. In these cases, epiluminescence microscopy showed improvement as evidence of treatment efficacy.
Figure 1.
(a-c) A 63-year-old female before and after switch from 5% minoxidil base solution b.i.d. to 5% propylene glycol-free, North American witch hazel (Hamamelis virginiana)-based solution of 5% minoxidil sulfate (5% minoxidil-sensitive solution): (a and b) global photographic assessment, (c and d) epiluminescence microscopy with digital imaging
The treatment was well tolerated, particularly in patients with propylene glycol sensitivity and patients with irritable scalp syndrome. No major adverse effects were noted.
DISCUSSION
We have originally presented a scientific poster on the occasion of the 2017 EADV Meeting in Geneva, Switzerland, demonstrating the efficacy of 10% topical minoxidil sulfate solution once daily in patients refractory to topical 5% minoxidil base b.i.d. In this preliminary study, a total of 44 patients were analyzed: 13 males (29.5%) and 31 females (70.5%), aged 18–72 years, with Hamilton-Norwood type androgenetic alopecia class III or above, or Ludwig type androgenetic alopecia I to III, respectively. Before switching, all patients had treated with 5% topical minoxidil base b.i.d. for a mean duration of 30.8 months (9–120 months, SD 23.22 months) as monotherapy (64.6%) or combination therapy (36.4%, with 1 mg oral finasteride, low-level laser therapy, or platelet-rich plasma). The mean duration of 10% topical minoxidil sulfate treatment was 4.09 months (range 3–10 months, SD 1.7). 97.7% of patients showed observable clinical improvement with global photographic improvement in 31.8%, combined dermoscopic and global photographic improvement in 65.9%, and dermoscopic-only improvement in 2.3%. Apparent hair density and scalp coverage improved in the central part, vertex, and frontotemporal areas.[4]
Minoxidil is converted by follicular sulfotransferase to minoxidil sulfate,[5] which acts as a potassium-channel opener,[6] mediated by sulfonylurea receptor 2B.[7] The sulfated metabolite accounts for the vasorelaxant activity in the treatment of arterial hypertension and hair growth-promoting property. There is a wide interindividual variation in the level of follicular sulfotransferase enzymatic activity, and the level can predict treatment response to topical minoxidil in androgenetic alopecia.[8,9,10,11] Because of the demonstration of feasibility of replacement of topical minoxidil b.i.d. by a higher concentration of minoxidil once daily without loss of efficacy,[12] we decided to replace 5% topical minoxidil base solution b.i.d. with 10% topical minoxidil sulfate once daily in a propylene glycol-free,[13] North American witch-hazel (H. virginiana)-based lotion (originally: Erol Energy® lotion, new product name: hamamelis. Swiss HAIR TONIC, Apomedica Sagl Switzerland) to enhance patient comfort, specifically in patients with propylene glycol sensitivity or an irritable scalp syndrome, as formerly reported.[14]
Furthermore, the herbal-based scalp solution of Hamamelis Swiss hair tonic exhibits additional antioxidant properties, promotes skin metabolism and blood flow, acts inhibitory of the proliferation of Cutibacterium spp., has antidandruff activity, strengthens the connective tissue, and stimulates healthy hair growth.
In fact, there is growing evidence from data involving collections and characterization of hair samples from various unhealthy scalp conditions to help establish a link between scalp condition, hair growth, and quality.[15] A number of observations have found that premature hair loss may be caused by poor scalp conditions associated with oxidative stress, such as psoriasis[16,17,18] and dandruff/seborrheic dermatitis.[18,19,21] The effect on the preemergent hair fiber may alter the anchoring force of the fiber with the follicle, as evidenced by an increased proportion both of catagen and telogen,[18] and of dysplastic anagen hairs (anagen hairs devoid of hair root sheaths) in the trichogram (hair pluck) of scalp pathologies, such as dandruff, seborrheic dermatitis, and psoriasis.[22,23]
Therefore, we decided to study the efficacy of a propylene glycol-free, North American witch-hazel (H. virginiana)-based herbal solution of 5% minoxidil sulfate for the treatment of FAGA refractory to 5% topical minoxidil base (5.0 g) in 96% alcohol, 85% glycerin (10.0 g), and water (20.0 g). 70% of patients showed observable clinical improvement with combined global photographic and epiluminescence microscopic assessment with digital imaging with the best results in patients with FAGA Ludwig type II and 22% with epiluminescence microscopic-only improvement as evidence of treatment efficacy, specifically in FAGA Ludwig types I and III. The treatment was well tolerated, particularly in patients with propylene glycol sensitivity and irritable scalp syndrome.
CONCLUSIONS
These results suggest that propylene glycol-free, North American witch-hazel (H. virginiana)-based solution of 5% minoxidil sulfate is effective and safe for the treatment of FAGA, specifically in minoxidil nonresponders and patients with propylene glycol sensitivity or irritable scalp syndrome. Stability and penetration issues have formerly been discussed with respect to topical minoxidil sulfate formulations.[24] Our results represent the first proof-of-concept that topical minoxidil sulfate nevertheless may fulfill the criteria for clinical efficacy, at least in the Hamamelis Swiss hair tonic (Apomedica Sagl Switzerland)-based formulation for the sensitive scalp.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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