S
calp hair grows in cycles, with each hair follicle undergoing 10-30 cycles in its lifetime.1 Diffuse hair shedding is the result of a disruption of one phase of the hair cycle,2,3 i.e., anagen (active hair growth), catagen (involution) or telogen (resting). The anagen phase can last 2-8 years.4 The catagen phase lasts 4-6 weeks, and the telogen phase lasts 2-3 months. The exogen phase (the release of dead hair) coincides with the end of the telogen phase. Most people have about 100,000 scalp hairs; normally 10-15% of these are in the telogen phase.5 Shedding of 100-150 telogen hairs per day is normal.4 Anagen hair loss is never normal. The most common cause of diffuse hair loss is androgenetic alopecia (male-pattern alopecia). In men, androgenetic alopecia causes typical temporal recession (thinning of the hair around the temples) and thinning at the vertex (Hamilton patterns). In women, *Consultant DermatologistBNR Skin Clinic, Near Garuda Mall, Bangalore **Research Associate, R&D Center The Himalaya Drug Company, Makali, Bangalore Address for correspondence
Dr Suprabha Hegde
Research Associate, R&D Center
The Himalaya Drug Company, Makali, Bangalore - 562 123 E-mail: dr.suprabha@himalayahealthcare.com
Polyherbal Formulation (Hairzone Solution) in the
Management of Diffuse Hair Loss: Post Marketing
Safety and Efficacy Study
J PrAsAd*, suPrABhA hegde**
ABSTRACT
Hair loss is a common and distressing problem, affecting men and women of all the ages and ranging from a small bare patch to a more diffuse and obvious pattern. The purpose of this study is to evaluate the safety and efficacy of Hairzone solution in diffuse hair loss. Twenty-eight cases were included in the study according to the subject selection criteria. All the patients
were advised to gently massage the solution into the scalp part by part, covering the whole area of the scalp and to rinse it in the morning. The response to therapy was evaluated at monthly intervals for a period of six months. The changes in various parameters from baseline values and the values at each visit for six months were evaluated statistically using Graph Pad Prism
Version 4.03 for windows, Graph Pad Software, San Diego, California, United States. The criteria for evaluation were signs
and symptoms such as reduction in hairfall by 1-minute combing test, reduction in associated symptoms like itching and
overall impression. The study clearly demonstrated the beneficial effects of Hairzone solution in diffuse hair loss as evident by
reduced hair fall by 1-minute combing test, in addition to decrease in itching. Hair loss was reduced in 21 of 28 patients. Further safety of the product was also substantiated by clinical parameters. Therefore, it can be concluded that Hairzone solution is
safe and effective in the management of diffuse hair loss.
keywords: Hairzone solution, diffuse hair loss
a more diffuse alopecia is generally seen (Ludwig pattern). Other causes of diffuse hair loss include telogen effluvium, severe iron deficiency and protein deficiencies. These conditions cause thinning of hair over the whole scalp, in contrast to the frontovertical loss seen in androgenetic alopecia. They can also exacerbate the hair thinning of androgenetic alopecia. Both hypothyroidism and hyperthyroidism can cause diffuse telogen hair loss that is usually reversible once the euthyroid state is restored.5,6 Chronic systemic
disorders can cause telogen hair shedding. Telogen hair loss has also been reported in autoimmune diseases and in chronic infections.7,8 Poor protein intake, essential fatty acid deficiency and malabsorption are few other factors that cause diffuse hair loss.
When assessing diffuse hair loss, it is important to examine the scalp closely to exclude an inflammatory scalp disease or scarring alopecia. Assessment should also include: Detailed medical history, complete blood count, comprehensive metabolic panel, thyroid function tests, iron and ferritin levels, and zinc level to identify any underlying systemic disease, thyroid disease and nutritional deficiency. The hair shafts should be examined for length, diameter and breakage. Broken
hairs can suggest trichotillomania, traction alopecia, tinea capitis or a trichodystrophy. Signs of hyperandrogenism such as acne, seborrhea and hirsutism should also be identified. Skin and nail examinations are important parts of the clinical examination. Hair pull tests can be also useful.9 The
hair pull test will be positive where the hair is thinning, but negative away from the thinning areas. Certain species of fungi fluoresce green under a Wood’s lamp, and Malassezia (Pityrosporum) species, which cause seborrheic dermatitis, fluoresce orange.10 Bacterial and fungal cultures should be obtained if pustules or scales, respectively, are present on the scalp. Light microscopy of clipped hair can reveal hair-shaft abnormalities. A 4 mm scalp biopsy is helpful in most hair-loss conditions.9
If signs of androgen excess are present, an androgen screen is needed to exclude an androgen-secreting tumor or other endocrinopathy.11
Anagen hair loss is usually managed with observation and support. In men, medical treatment of androgenetic alopecia includes topical minoxidil (2% or 5%) and oral finasteride. Treatment with finasteride can cause decreased libido, impotence and ejaculation disorders.12 Finasteride may also induce depression.13 Women can also use topical minoxidil; A hyperandrogenic state may limit the success of treatment with minoxidil.14 In these women, spironolactone 100-200 mg daily may slow the rate of hair loss.15,16 Antiandrogens cause feminization
of the male fetus; hence, all women of childbearing age should be on a reliable form of contraception.11
Women with evidence of a hyperandrogenic state requesting combined oral contraceptives would benefit from using antiandrogenic progesterones, such as drospirenone.17 Finasteride is ineffective in postmenopausal women with female pattern hair loss.18 Over-the-counter topical preparations, hair extensions, and hairpieces are available for women with poor response to treatment.
Hairzone solution, a polyherbal formulation is available in the market and is known to be beneficial in patients suffering from hair loss.
AIM OF THE STUDY
To evaluate the safety and efficacy of Hairzone solution in diffuse hair loss.
MATERIAL AND METHODS
This study was an open post marketing clinical trial conducted at BNR Skin Clinic, Bangalore, between June 2010 and March 2011. The study protocol, case report
forms, regulatory documents, product information and informed consent forms were approved by Independent Ethics Committee. A total of 28 patients of both sexes, in the age group of 18-40 years, who were suffering from diffuse hair loss, and who were willing to give informed written consent were enrolled in the study. Patients on immunosuppressive drugs, patients applying other topical therapy for diffuse hair loss, in the last two weeks prior to the initiation of the study, patients with evidence of skin infection and pregnant and lactating women were excluded from the study. Patients who were not willing to give informed written consent were excluded from the study.
Study Procedure
Each patient’s demographic medical history (especially local fungal infection, dandruff, pediculosis, trichotillomania, stress, diet, past illness and drugs), and treatment details were recorded. All the enrolled patients underwent a thorough clinical examination including scalp skin examination, which included the assessment of number of hairs lost in 1-minute combing test and the presence of alopecic patches. All the patients were advised to gently massage the solution into the scalp part by part, covering the whole area of the scalp and to rinse it in the morning. The response to therapy was evaluated at once a month for the period of six months. The criteria for evaluation were signs and symptoms like reduction in associated symptoms like itching, 1-minute comb test and overall impression.
Response for 1-minute comb test was evaluated as number of hair fall. Itching was evaluated on an Analog scale of 0-3 (0-Nil, 1-Moderate, 2-Good, 3-Excellent). The overall response was in turn correlated with response to the treatment as follows:
Grade 0: No improvement
Grade 1: Poor response <25% reduction Grade 2: Moderate response 25-49% reduction Grade 3: Good response 50-74% reduction Grade 4: Excellent response >75% reduction
All the adverse events, either reported or observed by the patients, were recorded with information about severity, date of onset, duration and action taken regarding the study drug. Relation of adverse events to study medication was predefined as ‘Unrelated’ (a reaction that does not follow a reasonable temporal sequence from the administration of the drug), ‘Possible’ (follows a known response pattern to the suspected
drug, but could have been produced by the patient’s clinical state or other modes of therapy administered to the patient), and ‘Probable’ (follows a known response pattern to the suspected drug that could not be reasonably explained by the known characteristics of the patient’s clinical state).
Patients were allowed to voluntarily withdraw from the study, if they had experienced serious discomfort during the study or sustained serious clinical events requiring specific treatment. For patients withdrawing from the study, efforts were made to ascertain the reason for dropout. Noncompliance (defined as failure to take <80% of the medication) was not regarded as treatment failure, and reasons for noncompliance were noted.
Primary and Secondary Endpoints
The predefined primary efficacy endpoint was a decrease in the symptom score for diffuse hair loss.
The predefined secondary safety endpoints were acute and chronic safety, as assessed by the incidence of adverse events and patient compliance to therapy.
Statistical Analysis
Statistical analysis was done according to intention-to-treat principles. The changes in various parameters from baseline values and follow-up visits at once a month for six months were evaluated for hair loss in 1-minute comb test by repeated measures of ANOVA followed by Tukey’s multiple comparison test. Itching was analyzed by repeated measures of ANOVA using Friedman test followed by Dunnett’s multiple comparison test. Statistical analysis was performed using GraphPad Prism Version 4.03 for windows, GraphPad Software, San Diego, California, United States.
RESULTS
The demographic details of subjects included in the study are listed in Table 1. There were eight males and 20 females in the study. Duration of illness was 2.60 ± 1.99 years.
The number of hair loss in 1-minute comb test at the end of first month was 31.79 ± 10.02 (Table 2). It reduced with treatment to 26.79 ± 10.99 (p < 0.05) at the end of two months, to 20.36 ± 8.38 (p < 0.05) at the end of three months, which further reduced to 16.61 ± 9.34 (p < 0.001) at the end of four months, to 12.86 ± 10.04
(p < 0.001) at the end of five months and which further reduced to 9.82 ± 9.08 (p < 0.001) at six months; the significance values are as compared to the values in the first month.
Itching at the end of first month was 1.53 ± 0.70. It reduced with treatment to 1.21 ± 0.54 at the end of two months, which again reduced to 0.95 ± 0.62 at the end of three months, to 0.58 ± 0.61 (p < 0.01) at the end of four months, to 0.47 ± 0.51 (p < 0.01) at the end of five months and further reduced to 0.47 ± 0.51 (p < 0.01) at six months; all the significance values are as compared to the first month values (Table 3). Assessment of overall response is listed in Table 4. At the end of the study, 4 (10.71%) cases reported marked improvement, 9 (35.71%) cases reported moderate improvement, 10 (35.71%) cases reported slight improvement and 5 cases reported no change (Table 4). Hair loss reduced in 21/28 patients (75%); 25% patients reported no change. The safety evaluation of the investigational product was also evaluated. It was found that there were no adverse effects on application of the product for the period of the study.
Table 1. Demographic Data of Patients on Entry Number of patients 28
Male: Female Male: 8; Female: 20
Diet Vegetarian: 60 Mixed: 40
Mean age (years) 34.07 ± 9.60
Weight in kg (mean ± SD) 62.40 ± 14.30
H/o smoking (n) 8
H/o alcohol consumption (n) 2
Duration of hair loss (years) 2.60 ± 1.99
H/o: History of.
Table 2. Number of Hair Loss in 1-minute
Treatment period Hair loss Significance
1st month 31.79 ± 10.02 -2nd month 26.79 ± 10.99 ap< 0.05 3rd month 20.36 ± 8.38 ap < 0.001, bp < 0.01 4th month 16.61 ± 9.34 a,bp < 0.001 5th month 12.86 ± 10.04 a,b,cp < 0.001 6th month 9.82 ± 9.08 a,b,c,dp < 0.001 aAs compared to first month, bas compared to second month, cas
compared to third month, das compared to fourth month.
Statistical analysis: Repeated measures of ANOVA following Tukey’s multiple comparison test.
DISCUSSION
Various factors contribute to hair fall/loss. Genetic predisposition and hormonal factors predominantly contribute to the above. Disease states such as typhoid, malaria, jaundice, etc. and use of chemotherapeutic agents also cause hair fall. Hormone therapy, use of α-reductase inhibitors and vasodilators like minoxidil are widely used to reduce the hair fall/loss. The synthetic drug, minoxidil is a potent vasodilator appears safe for long-term treatment. Treatments available for the various forms of alopecia have limited success with unwanted adverse effects. New technologies in cosmetic transplant surgery and hair replacement systems are available that can be completely undetectable.
The present study shows that Hairzone solution is beneficial in the management of diffuse hair loss. Hairzone solution consists of potent herbs, namely
Butea monosperma and Butea parviflora.
B. monosperma inhibits degeneration of hair follicles, extends the anagen phase of hair growth cycle and enhances proliferation and maturation of precursor epithelial cells of the final hair strand. It prevents the massive apoptosis in the proximal hair bulb and stimulates the multiplication of hair fiber cells with the stimulation of anagenic phase, and reduce the catagenic and telogenic phase.19
B. monosperma displays antifungal activity against
Cladosporium cladosporioides;20 it also has a significant bactericidal effect21 and potential antiviral activities.22
B. monosperma has astringent action,23,24 which shrinks or constricts body tissues, usually locally after topical medicinal application. Externally, applied astringents cause mild coagulation of skin proteins, dry, harden and protect the skin. Mildly astringent solutions are used to alleviate minor skin irritations resulting from superficial cuts, allergies, insect bites or fungal infections. B. monosperma has potent free radical scavenging activity, and has proven effective in promoting the therapeutic activity of Hairzone solution.25
B. parviflora inhibits hair follicle degeneration and extends the anagen phase of hair growth cycle. It enhances proliferation and maturation of precursor epithelial cells of the final hair strand; it also prevents the massive apoptosis in the proximal hair bulb.
B. parviflora stimulates the multiplication of hair fiber cells with the stimulation of anagenic phase, and reduces the catagenic and telogenic phase. It has antimicrobial action.26
The efficacy of Hairzone solution can be attributed to the synergistic effects of both these herbs, B. monosperma
and B. parviflora. CONCLUSION
This post marketing study clearly demonstrates the beneficial effects of Hairzone solution in diffuse hair loss. There was significant reduction in hair fall after two months of treatment, which further continued to show reduction until the end of the study. Similarly, itching also reduced with treatment and there was significant relief from four months until the end of the study. Hair loss reduced in 21 out of 28 cases treated with Hairzone solution. Further safety of the product was also substantiated by clinical parameters. Therefore, it can be concluded that Hairzone solution is safe and effective in diffuse hair loss.
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Table 3. Effect of Hairzone Solution on Itching
Treatment period Itching score Significance
1st month 1.53 ± 0.70 -2nd month 1.21 ± 0.54 NS 3rd month 0.95 ± 0.62 NS 4th month 0.58 ± 0.61 ap < 0.01 5th month 0.47 ± 0.51 ap < 0.01, bp < 0.05 6th month 0.47 ± 0.51 ap < 0.01, bp < 0.05 aAs compared to first month, bas compared to second month.
Statistical analysis: repeated Measures of ANOVA using Freidman fest followed by Dunnett’s multiple comparison test.
Table 4. Overall Impression
Overall impression response
Symptoms become worse 0
No change 5 (17.87%)
Slight improvement 10 (35.71%)
Moderate improvement 9 (35.71%)
Marked improvement 4 (10.71%)
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