J ClinEpidemiolVol. 44, No. 4/5,pp. 439447, Printed in Great Britain. All rights resewed
1991
0895-4356/91 %3.00+ 0.00
Copyright 0 1991Pergamon Press plc
THE EFFECTIVENESS OF THE HAIR-RESTORER “DABAO”@ IN MALES WITH ALOPECIA ANDROGENETICA. A CLINICAL EXPERIMENT A. G. H. KESSELS,‘* R. L. L. M. CARDYNAALS,* R. L. L. BORGER,’ M. J. T. H. Go,’ J. C. C. A. LAMBERS,~ J. A. KNOTTNERUS~ and P. G. KNIPSCHILD’ ‘Department of Epidemiology/Health Care Research, University of Limburg, Maastricht, ‘Vialle Minerals, Venlo, 3Department of Dermatology, De Wever Hospital, Heerlen, and 4Department of
General Practice, University of Limburg, Maastricht, The Netherlands (Received 31 May 1990; received for publication 30 October 1990)
Abstract-In
a randomized, double-blind trial the effectiveness of 6 months’ use of a Chinese herb extract (Dabaoa) as a hair-restorer was studied on 396 males with alopecia androgenetica. The effect was evaluated by nonvellus hair counts, participants’ opinions and a panel’s judgement of a photo-report. Twenty-three participants withdrew prematurely from the study. In both the Dabao and placebo groups an increase in the amount of hair was observed; 133 and 109 hairs on a 5 cm* marked area, a difference of 24 hairs (p = 0.03, one-sided). Participants as well as the panel reached a similar conclusion. Regarding cosmetic effect, 42% of the participants in the Dabao group and 37% in the placebo group reported positive results. The average panel score for the cosmetic result on a scale of - 10 to + 10 was 0.46 in the Dabao and 0.21 in the placebo group, a difference of 0.24 (p = 0.04, one-sided). It appears from our study that, although the cosmetic effect over 6 months is modest, Dabao does have a certain effect on the growth of nonvellus hair. Alopecia androgenetica iment Male Age Photo-report Esthetics
Hair-restorer Administration topical Clinical experHamilton type Duration of baldness Hair count Dabao
INTRODUCTION
herb extracts. Several uncontrolled studies by means of photo-reporting suggest a positive action. Furthermore a randomized double-blind trial [8] was conducted in Japan in 1987. In this study, involving 109 persons, Dabao was compared with another hair-restorer on its subjective effect. Eighty-three percent of the Dabao users and 50% of the users of the alternative preparation demonstrated favourable results. For 2 years Dabao has been distributed free to a number of inhabitants of the city of Venlo, in The Netherlands. Here too a before/after comparison by means of photo-reporting revealed positive results. In order to assess the effect of Dabao, from September 1988 until April 1989 a clinical
Medicine has long viewed hair-restorers with a good deal of scepticism [l, 21. Tests concerning the effectiveness of minoxidil [3-71 have revived hopes for a solution to the age-old problem of baldness. For 7 years now, in a number of hospitals in China, such as the Peking Friendship Hospital, patients suffering from alopecia androgenetica and alopecia areata have been treated with Dabao@, a hair tonic with a base of Chinese *All corresnondence should be addressed to: A. G. H. Kessels,-Department of Epidemiology/Health Care Research, University of Limburg, P.O. Box 616, 6200 MD Maastricht,
The Netherlands. 439
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experiment was conducted on men suffering from alopecia androgenetica. In the literature about studies on the effect of hair-restorers, hair count is used as the most objective measure to determine a possible increase of hair growth. According to Koperski [9], however, an increase of the amount of hair does not necessarily give information about its cosmetic results. The future user will probably be especially interested in this qualitative aspect of hair growth. Therefore the most important outcome measurements of this study were counts of the number of nonvellus hair and the judgement of the cosmetic effect. In addition, the influence of the type of baldness (according to Hamilton’s classification [lo]), the duration of the baldness, and age on the effect of Dabao were investigated. Except for the prevailing scepticism about the effects of hair-restorers, the study methods as used in most trials have also been disputed [l l-131. Issues especially criticized were the method of effect measurements, the unexplained high effect of the placebo treatment, and the high number and insufficient documentation of the drop-outs. For this reason special attention will be paid to a precise description of the method of the effect measurement and factors that could possibly distort the results.
MATERIALS AND METHODS
The study was conducted as a randomized, placebo-controlled, double-blind experiment. Three hundred and ninety-six participants in the study were divided at random into two groups. The participants in one group used Dabao for 6 months, while those in the other used a placebo over the same length of time. Participants
Participants were recruited via advertisements in two local newspapers and their selection was based on several considerations. Preference was given to participants offering a high prospect of Dabao acting effectively. To reduce the influence of factors of disturbance, the test population was kept as homogeneous as possible. Furthermore, factors affecting compliance and the reliability of the outcome measurement were taken into account during selection. All this resulted in the following criteria for participation: -male -age 18-50 years
et al.
-type of baldness: alopecia androgenetica -maximum duration of baldness: 20 years -no previous therapy against baldness (hairrestorer, laser or transplant) -for a minimum period of 6 months, no other therapy that could affect the growth of the hair, such as cytostatic drugs, sex hormones, thyroid hormones, adrenocorticoids and growth hormones, heparin and high doses of salicylic acids -no skin diseases, in particular alopecia areata and psoriasis dark hair -good health (no serious or chronic diseases) -willingness to comply with the research procedure -no signs of a markedly irregular way of life -residence within 100 km of the study centre. Of the 8000 persons who showed interest in participating, 3000 completed application forms, and of these, 900 prospective participants were invited for an interview and a preliminary examination. Eventually 396 persons were selected. All participants confirmed in writing that they had been sufficiently informed about the procedures of the study. After selection and informed consent, randomization into two groups was performed in blocks of 10 consecutive participants, by means of a computer programme. The inflow was completed in 1 month. Treatment and compliance
Regardless ~of the degree of baldness, the participants received one 100 ml bottle of the preparation, sufficient for 1 month’s use. The Dabao preparation contained ethanol, water and herbal extracts and the placebo contained ethanol, water, artificial odours and colouring agents (Table 1). These agents were only added to achieve the closest possible resemblance, as to scent, colour and viscosity, between the placebo preparation and the Dabao preparation. A measuring cup and a syringe were supplied to measure the dose of 1.7 ml. This quantity had to be massaged into the dry scalp twice a day, for 4-5 minutes, after warming the scalp with a warm towel or with warm water. Regular application of the lotion was stimulated by making regular entries in a specially supplied therapy calendar. This calendar was also used to answer questions concerning compliance as accurately as possible. In order to monitor the degree of compliance indicated, the
The Effectiveness of a Hair-restorer on Alopecia Androgenetica
441
Table 1. The components of Dabao and of the placebo preparation Dabao 50% Ethanol 42% Water 8% Chinese herbal extracts consisting of (as far as known): -Saffron flowers (F/OS carrhami) -Mulberry leaves (Folium mori) --Stemona root (Radix stemonae) -Fruits of the pepper plant (Frucfus cap&i) -Sesame leaves (Folium sesami) -The skin of the fruit of Sechuan pepper
Placebo 50% Ethanol 48% Water 2% Odour and colouring agents* consisting of: --Cherry laurel water (Aqua laurocerusi art) Xinnamon water (Aquacinnamoni) -Licorice syrup (Sir Liquiritiae) -Sugar syrup (Sir simplex) -An aqueous solution of burned sugar (Solutio fusca FNA)
(Sichuan pericarpium zanthoxyli) qinger root (Rhizoma zingiberis recens) Chinese angelica root (Radix angelicae sinesis) -Bark of the Pseudolarix (Corfex pseudohzricis) -Fruits of the hawthorn (Fructus crafaegi)
*As far as is known, the placebo does not contain active substances with an allergic or pharmacological action.
participants were questioned about the quantity of lotion left. Side effects The Dabao preparation meets the requirements of the Cosmetics provisions 1979 under Dutch Commodities legislation. On the basis of toxicological studies [ 14, 151, and earlier experiences in China, Japan and The Netherlands, no side effects were known. At each consultation, participants were asked about any special experiences with the product and their scalp was examined by a doctor. In case side effects were suspected, a dermatologist was consulted. Blinding The participants as well as the persons performing the outcome measurement were blinded. The preparation was handed out in a closed non-transparent packaging. The participants were told not to bring the (partly empty) bottles to the follow-up consultations. Furthermore, in order to prevent possible recognition by the persons performing the effect measurements, participants had to wash their hair before each consultation. After 2 and 6 months the blinding was checked by asking each participant which preparation he thought he was using. The persons carrying out the outcome measurement also recorded their opinion of which preparation was being used. Effects During the first consultation the participant was asked about the spot where hair loss occurred most recently. On this spot, if possible at the intersection of hair and baldness, a mark was drawn. In view of its labour-intensive
nature, the hair count on this marked spot was carried out once every 2 months (see Fig. 1). In order to avoid inaccurate counting results, due to interobserver variability, each participant was always counted by the same doctor. Only nonvellus hair, i.e. hair longer than 2 cm and pigmented, was counted. To prevent the data obtained during previous contacts being a source of potential influence, such data were not disclosed to the people involved with the effect measurements. The cosmetic result was judged by a blinded independent panel, by means of a standardized slide report, displaying one general and one detailed picture, taken before and after treatment. The panel was composed of three women and three men. Half of the panel consisted of professionals involved in problems concerning baldness, viz. a dermatologist, a representative of the hairdresser’s association, and a beautician. The other half of the panel consisted of individuals uninvolved professionally and presumably capable of an objective and unbiased judgement, viz. an epidemiologist, a journalist and a health educator. The panel was requested to score a possible change in the cosmetic aspect and the certainty of hair decrease or increase, on a visual analogue scale. The average, computed from the scores of all panel members, was taken as the final outcome measurement. A third important outcome measurement was the participant’s opinion about the increase or decrease of the amount of hair and about the cosmetic aspect, both scored on a Spoint scale. Confounding variables and efect -mod@ers Factors which interfere with the outcome measured can distort the result if unevenly
A.G. H.
KESSELS et al.
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Fig. 1. Description of the hair count. Every 2 months the number of nonvellus hairs is determined in the same marked area. Nonvellus hairs are pigmented and longer than 2cm. During the first contact, the participant points out the area where according to him he lost hair most recently and here, at the intersection of hair and baldness, a mark is drawn with a fine-liner. By means of the apparatus shown in (A) and (B) the coordinates of this point are determined. This apparatus makes it possible to reproduce this point for each count accurate to less than 2 mm. When the participant is sitting on a chair, the head rest is adjusted. Next, the head (B) is secured by means of two elastic ear tubes (B, 3), provided with earplugs. The head can now only rotate in the sagittal plane. This movement is prevented by securing the nose by means of a nose plate (B, 4). The head rest and marker (B, 1) can be adjusted for height, cross position and angle; the ear tubes and the nose support are only adjustable for height. After marking the scalp, a circle is drawn round the point (B, 2) with the help of a disc (C) having a surface of 5 cm*. The illumination is standardized by fixing the strength and the angle of the light source. The hairs are counted according to the Dallwitz method. This means that the comb is inserted about 1cm from the outline circle. Hereafter the comb is moved against the hair implantation, towards the circle. If the comb has crossed the edge of the circle, it is kept stationary. With a small hook the hairs are then removed from under the comb and counted. As soon as a row of hairs has been counted, the comb is shifted slightly and the next row is counted. This process is repeated until all hairs within the circle have been counted.
distributed among the study groups. If one of the two doctors counts with a more positive disposition, he will obtain a larger increase in the number of hairs in both the Dabao group and the placebo group. However, if, among the participants counted by this particular doctor, there is by chance a higher proportion of Dabao users, the result will be distorted in favour of Dabao. Other factors which can influence the hair count as well as the opinion of the panel are the initial values of the number of hairs and the colour of the hair. For this reason it was checked whether these factors were distributed proportionally among both study groups. Furthermore at the beginning of the study a number of prognostic variables which might influence the effect of Dabao were recorded for all participants, viz. the participants’ age, the duration of baldness and the type of baldness. These variables permit the selection of men likely to derive more than the average benefit from Dabao. Because it is assumed that these variables only interfere with an increased number of hairs in the Dabao group, they are merely
considered as putative modifiers of the effect of Dabao. Analysis For each participant the increase of the number in hairs was first of all recorded by determining the difference between the hair count at the first and last contacts. However, the hair was counted four times. Linear regression was used to fit a straight line through these four measuring points for each participant. The rise of the regression line over a period of 6 months is based on these four measuring values and probably will result in a more accurate estimation of the increase in the number of hairs. Of the outcome measurements, two are of a continuous nature, viz. the change in the number of hairs and the score of the panel. For these outcome measurements the difference between the Dabao and placebo groups was tested onesided assuming Student’s distribution. Besides, for these differences 95% confidence intervals were established. The influence of confounding variables was furthermore corrected with a
The Effectiveness of a Hair-restorer on Alopecia Androgenetica
multiple linear regression model. By introducing interaction terms in this linear regression model, the influence of the prognostic factors on the effect of Dabao was determined. The opinion the participants recorded on a 5-point scale was dichotomized into a positive result, and a combined negative and neutral result. The difference in the proportions of positive results between the Dabao and placebo groups was tested in the standard way and in addition 95% confidence intervals were computed for the difference between these proportions. For participants who withdrew prematurely, not all outcome measurements could be carried out. If it could be reasonably assumed that a participant dropped out for reasons not related to the (expected) results but to events such as an accident or a change of residence, he was excluded from the analysis. If disappointment about the results could not be excluded as a reason for withdrawal, the last result measured was regarded as the final outcome for these participants. Each participant who ceased participation was asked to state his reasons for doing so. The decision whether a connection between the stated reason and the supposed effect could be reasonably rejected was taken by a blinded independent jury. RESULTS
Prior to a description of the results of the outcome measurements, the following matters will be discussed: premature withdrawal, blinding, compliance and the distribution of confounding variables among the two study groups, Of the original 396 participants, 23 (6%) participants quit the study prematurely. For 13 participants the reasons for withdrawal were factors such as serious traffic and sports accidents or a new job elsewhere (10 Dabao, 3 placebo). For 10 participants a connection with the expected result could not be ruled out (3 Dabao, 7 placebo). One participant who had to stop using Dabao because of a possible side effect has also been excluded from further analysis. This person developed a contact dermatitis for Dabao after 3 months. Some other participants, Dabao as well as placebo users, reported isolated inflamed follicles. After 2 months 192 participants (48%) indicated they had no idea which preparation (Dabao or placebo) they had been using so far. Of the 89 participants who thought they had
443
100%
80% 5 5 I) ; ‘; d
E
2
60%
40%
E z 20%
0.40
1 .oo
0.80
0.60
compliance Fig. 2. Cumulative distribution of the degree of compliance for the Dabao and placebo groups.
been using Dabao, 54% has used Dabao and 46% placebo. Of the 111 participants who thought they had been using placebo, 45% had used Dabao and 55% placebo. After 6 months these answers showed almost the same distributions over both study groups. At both moments the persons conducting the hair count specified in almost all cases that they did not know which preparation the participants were using. In Fig. 2 the cumulative distribution of the indicated compliance for both study groups has been plotted. The vertical axis of the graph represents the percentage of the study group in question, with a compliance larger than the corresponding value on the horizontal axis. The figure shows that 90% of the participants used more than 90% of the prescribed quantity of tonic. Table 2 represents the distribution over the two study groups of variables that might distort Table 2. Distribution of the participants among both research groups according to the hair colour, to the initial value of the hair count and to the tellers of the hair count Dabao Placebo (n = 188) (n = 194) Colour of hair
Light brown Brown Dark brown/black
35% 32% 33%
33% 37% 30%
Initial value of the hair count
< 100 hairs 101-200 hairs 201-300 hairs > 300 hairs
13% 33% 31% 23%
10% 38% 31% 21%
82% 18%
85% 15%
Teller
Doctor A Doctor B
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350 0) .b 2 5
325 300
$ ? 2
275 250
2 time
4
6
in months
Fig. 3. The average number of nonvellus hairs in the Dabao and placebo groups in a 5 cm* marked area (see text) as a function of time.
the outcome measurements, viz. the hair colour and the initial values of the hair count. In addition, this distribution has also been given for both the doctors who carried out the hair count. There is not much difference between the distributions in terms of percentages, which means that the influence on the result is probably small. E&cts The number of hairs were counted every 2 months, thus four times altogether. By determining the average number of hairs for each of the two study groups per measuring moment a global progress during the study period can be outlined (Fig. 3). In both the Dabao and the placebo group, the average amount increases over the time similar to a flattened S-curve. In 6 months, the average number of hairs increases by about 110 hairs per 5 cm2 in the placebo
et al.
group and by about 135 hairs per 5 cm2 in the Dabao group. Tables 3-5 display the differences between the Dabao and placebo groups with their 95% confidence intervals. Dependent on the method of computation, the hair increase in the Dabao group amounted to 24 or 29 more hairs per 5 cm3 than the placebo group (Table 3). The evaluation of the panel about the certainty of a change in the number of hairs on a scale of - 10 to + 10 is 0.49 higher for the Dabao group than for the placebo group and on an equal scale the cosmetic result is 0.24 higher in the Dabao group (Table 4). With the aid of a linear multiple regression model the hair count and the evaluation of the panel have, moreover, been corrected for a possible confounding influence of the initial value of the number of hairs and the colour of the hair. The results of the hair count have been additionally corrected for the doctor who conducted the count. The results hardly change at all, or they become marginally more favourable for Dabao. Among Dabao users the percentage reporting positively about the increase in the number of hairs was 13% higher than among placebo users (Table 5). The percentage of Dabao users having a positive opinion about the cosmetic result was 5% higher than the corresponding percentage in the placebo group. Table 6 represents the differences between the Dabao and placebo groups for the change in hair count and for the cosmetic result as scored by the panel, both stratified for the type of baldness, the duration of baldness and for different age categories. The results of the hair counting are not very consistent with the evaluation of the cosmetic result by the panel. The 95% confidence intervals are very large; a part of this discrepancy may be due to chance.
Table 3. The increase of the amount of hair after 6 months computed by taking the difference between the hair count in the sixth month and the initial value (subtraction) and comouted with the aid of a reeression line (reeression)
Subtraction Regression
Dabao
Placebo
Difference
95% CI
p-Value one-sided
133 148
109 119
24 29
- 1/+50 +3/+56
0.03 0.02
Table 4. Average score of the panel with regard to the certainty about the change in the amount of hair and with regard to the cosmetic result on a scale of -10 to +10
Amount of hair Cosmetic result
Dabao
Placebo
Difference
95% CI
p-Value one-sided
0.94 0.46
0.45 0.21
0.49 0.24
-0.24/c 1.21 -0.03/+0.51
0.10 0.04
The Effectiveness of a Hair-restorer on Alopecia Androgenetica
445
Table 5. Percentages of participants with a positive opinion about an increase in the amount of hair and the cosmetic result
. Amount of hair Cosmetic result
Dabao
Placebo
Difference
95% CI
p-Value one-sided
39% 42%
26% 37%
13% 5%
4%/22% -5%/15%
0.002 0.08
Table 6. The differences between the Dabao and placebo groups in the increase of the hair count and in the cosmetic result (on a scale of - 10 and + 10) with the 95% CI, stratified for type of baldness, duration of baldness and age Number of participants
Hair count
95% CI
Cosmetic result
95% CI
59 132 18lt
55 0 24
-9/+119 -59/+60 -11/+59
0.6 0.1 0.2
-0.6/+ 1.9 -0.3/+0.5 -0.0/+0.4
Type of baldness
Front* Vertex* Crown*
Duration of baldness O-5 yr 90
30
-29/+89
0.0
-o.s/+o.s
6lOyr 11-20yr
180 112
3 53
-32/+39 2/+104
0.3 0.3
-0.2/+0.7 -0.2/+0.7
Age 18-34 yr 35-39 yr 40-50 yr
139 105 138
10 24 24
-37/+58 -21/+68 -16/+63
0.3 0.0 0.3
-0.2/+0.7 -0.7/+0.8 -0.1/+0.7
*According to the Hamilton’s classification: front = type II + II, + III + III,; vertex = type III,,,,, + IV + V; crown = IV, + V, + VI. tTen participants could not be classified according to Hamilton.
As demonstrated by both effect measurements, the participants with a frontal baldness (Hamilton type II, IIa, III and IIIa), those with a duration of baldness of more than 10 years and those older than 40 years show a noticeable difference in effect between the Dabao and placebo groups. In order to determine the influence of the previously mentioned confounders on these results, a stratified analysis has also been done with the aid of a linear regression model including interaction terms. The outcome of this analysis did not essentially deviate from the results given in Table 6. DISCUSSION
Because the interpretation of the results depends on the proportion of the participants completing the study, the blinding and the compliance, these issues will be discussed first. Compared to other studies about the effectiveness of hair-restorers, the 94% completion rate scored in this study can be considered very high. If the participants who withdrew for reasons which were very probably unrelated to the expected results are not taken into account, the completion rate even reaches 97%. This high percentage is probably the result of the motivation of the participants and of the efforts to
ensure a correct and attentive relationship with the participants. After 2 months the percentages of the participants indicating correctly the preparation they used was hardly different from what can be expected from chance. Based on these findings, it can be concluded that during the study the blinding was not broken. As Fig. 2 shows, the compliance in an absolute sense, as well as the difference in compliance between the study groups, does not give any cause for concern as to a systematic manipulation of the results by insufficient use of lotion. The compliance in the placebo group is slightly better, which is an additional check on the blinding in this group. Side-effects of Dabao have only been reported once. A dermatologist diagnosed this as an allergic dermatitis, which was treated successfully. Inflamed follicles, which were reported a few times, were possibly the result of daily mechanical friction, through massage. It is also possible that there was no actual increase of inflamed follicles, but that the daily massage heightened the chance of discovering any. Figure 3 displays a significant increase of the amount of hair for the placebo group, viz. an average of 109 hairs on a surface of approximately 5 cm2. There are various ways of accounting for this.
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-The density of the hair depends on the season [ 161. It reaches its lowest value [ 171 in the month of November, followed by a gradual increase. This study started in September and ended in April. -There are indications [16] that the process of balding proceeds according to an alternating pattern. The chance to enrol as a participant of the study is therefore partly determined by the phase in which the person in question happens to be. According to this line of thought, a relatively large number of people will apply in a phase of increasing hair loss. The increase of the number of hairs setting in after the commencement of this study would consequently be a normal process, independent of the preparation administered. -The placebo preparation contained 50% alcohol. The treatment requires the scalp to be warmed before applying the preparation. It is possible that regular massage with alcohol of the warmed scalp has a stimulating effect on the growth of nonvellus hair. -Furthermore, it is possible that the prescribed treatment stimulates the growth of vellus hair instead of nonvellus hair. To distinguish objectively between vellus and nonvellus hair was not as easy as had been expected. Part of the increase in the amount of hair may be due to vellus hair growth. -Lastly, the positive but unintentional influence of the persons engaged in the counting should be mentioned [12]. Two aspects of the counting procedure should be considered. The count takes place on the edge of hair and baldness. A slight shift of the marking point will strongly influence the number of hairs counted. By (unintentionally) putting the point a bit more in the hairy area at subsequent contacts, an artificial increase can be created. Furthermore, an optimistic disposition in relation to the expected outcome on the part of the people involved with the hair count cannot be excluded. For this reason, the results of previous counts were not disclosed to these people. In spite of the large number of participants the measured difference of 25 hairs is just statistically significant. This is caused by the relatively large dispersion of the value of the hair count. The standard deviation of the hair count for the placebo group was 120 hairs. That means that the increase of the number of hairs after 6 months ranges between - 140 and +340 hairs
per 5 cm2 for 95% of the participants. An explanation for this substantial spread could lie in biological variability. A varying natural course, possibly under the influence of the Dabao and placebo treatment, is then the cause of the large dispersion in the changes of the number of hairs per 5 cm2. A second and more likely explanation is a substantial measurement variability. To position the marking point less accurately during the hair count could be a source of large measurement errors, both positively and negatively. In addition, the hair count itself is very labour-intensive and can easily lead to errors, although not on such a large scale. The objectives of this study can be translated into the following questions: -Did the amount of hair increase after 6 months of using Dabao? -1s there a visible cosmetic improvement under the influence of Dabao? -Do the type of baldness, duration of baldness and age have an influence on the effect of Dabao? These questions will now be discussed in turn. In the original research protocol, the hair count was proposed as the most important and most objective outcome measurement. Dependent on the method of computation, the difference between the average amount of hair in the Dabao and placebo groups amounts to 24 or 29 hairs per 5 cm2 (see Table 3). The differences are statistically significant. The panel and the participant have also given their opinion about possible changes in the number of hairs. In both cases the Dabao treatment scores higher than the placebo treatment. On a scale of - 10 to + 10, the panel rated the Dabao group 0.49 higher than the placebo group (see Table 3). The percentage of participants reporting an increase is 39% in the Dabao group and 26% in the placebo group. If the outcomes of all three methods of computation are pooled, it may be concluded that Dabao affects the hair growth and that the amount of hair increases by an average of 24-29 hairs per 5 cm2, over a period of 6 months. The second question is whether this increase in the number of hairs is sufficient for a satisfactory cosmetic result. This has been evaluated by an independent panel and by the participants themselves. Compared to the judgement of the participants, the evaluation of the panel will be more objective and more detached. The
The Effectiveness of a Hair-restorer on Alopecia Androgenetica
judgement of the participants will be coloured by hopes of a positive result and by involvement in the study. On the other hand their attitude towards the problem of baldness will be more in accordance with the one of the future user. About 40% of the participants reported a positive cosmetic result, but the difference between the Dabao and the placebo users is small (42% and 37% respectively). The proportion of participants who mentioned an increase in the number is less than the proportion that mentioned a cosmetic improvement. The most likely explanation appears that a number of participants regard a stabilization of the amount of hair as a positive cosmetic effect. The panel is more modest in its judgement. On a scale of - 10 to + 10, the average values for the Dabao group and the placebo group are 0.46 and 0.21, respectively. The difference of 0.24 is statistically significant, but it is not impressive. The last issue concerning the influence of the prognostic factors, such as type of baldness, duration of baldness or age, on the effect of Dabao, remains unclarified. There is an indication that men with a frontal baldness (Hamilton type II, IIa, III and IIIa), those with a duration of baldness of at least 10 years and those older than 40 years may expect a better result from Dabao. Further studies are necessary to confirm this outcome. The question remains whether the cosmetic effect in particular will improve, stabilize or decrease after a longer use of Dabao. In addition, it is not yet clear what will happen if the treatment with Dabao is stopped. We expect that the results of a follow-up study, in which all participants receive Dabao for 12 months and then stop any treatment for 6 months, will provide the answers to these questions. Acknowledgement-The Minerals.
study was supported
by Vialle
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Clin Exp Dermatol
1989; 14: 40-46.
12. De Groot AC, Nater JP, Herxheimer A. Minoxidil for male pattern baldness [letter]. Lancet 1987; 2: 563. 13. Prinsen MK. Acute dermal irritation/corrosion and acute dermal phototoxicity study with “Dabao” in albine rabbits. TN0 reports V 89.011/290032/ 88.516/280061. Zeist, The Netherlands: TNO-CIVO Institutes; 1988. 14. Wilmer JWGM. Examination of “Dabao” for mutagenic activity in the Ames test. TN0 report number V 89.096. Zeist, The Netherlands; TNO-CIVO Institutes; 1988. 15. Koperski JA, Orenberg EK, Wilkinson DI. Topical minoxidil therapy for androgentic alopecia. A 30 month study. Arch Dermatol 1987; 123: 1483-1487. 16. Orphan01 CE. Haar und Haarkrankheiten. Gustav Fischer Verlag; 1979; 577-584. JDR. Dynamivc Aspects of Hair Growth and Diagnostics of Hair Growth Disorders. Proc Symp. Rotterdam: Erasmus University; 1987:
17. Peereboom-Wynia
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1991
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Copyright 0 1991Pergamon Press plc
THE EFFECTIVENESS OF THE HAIR-RESTORER “DABAO”@ IN MALES WITH ALOPECIA ANDROGENETICA. A CLINICAL EXPERIMENT A. G. H. KESSELS,‘* R. L. L. M. CARDYNAALS,* R. L. L. BORGER,’ M. J. T. H. Go,’ J. C. C. A. LAMBERS,~ J. A. KNOTTNERUS~ and P. G. KNIPSCHILD’ ‘Department of Epidemiology/Health Care Research, University of Limburg, Maastricht, ‘Vialle Minerals, Venlo, 3Department of Dermatology, De Wever Hospital, Heerlen, and 4Department of
General Practice, University of Limburg, Maastricht, The Netherlands (Received 31 May 1990; received for publication 30 October 1990)
Abstract-In
a randomized, double-blind trial the effectiveness of 6 months’ use of a Chinese herb extract (Dabaoa) as a hair-restorer was studied on 396 males with alopecia androgenetica. The effect was evaluated by nonvellus hair counts, participants’ opinions and a panel’s judgement of a photo-report. Twenty-three participants withdrew prematurely from the study. In both the Dabao and placebo groups an increase in the amount of hair was observed; 133 and 109 hairs on a 5 cm* marked area, a difference of 24 hairs (p = 0.03, one-sided). Participants as well as the panel reached a similar conclusion. Regarding cosmetic effect, 42% of the participants in the Dabao group and 37% in the placebo group reported positive results. The average panel score for the cosmetic result on a scale of - 10 to + 10 was 0.46 in the Dabao and 0.21 in the placebo group, a difference of 0.24 (p = 0.04, one-sided). It appears from our study that, although the cosmetic effect over 6 months is modest, Dabao does have a certain effect on the growth of nonvellus hair. Alopecia androgenetica iment Male Age Photo-report Esthetics
Hair-restorer Administration topical Clinical experHamilton type Duration of baldness Hair count Dabao
INTRODUCTION
herb extracts. Several uncontrolled studies by means of photo-reporting suggest a positive action. Furthermore a randomized double-blind trial [8] was conducted in Japan in 1987. In this study, involving 109 persons, Dabao was compared with another hair-restorer on its subjective effect. Eighty-three percent of the Dabao users and 50% of the users of the alternative preparation demonstrated favourable results. For 2 years Dabao has been distributed free to a number of inhabitants of the city of Venlo, in The Netherlands. Here too a before/after comparison by means of photo-reporting revealed positive results. In order to assess the effect of Dabao, from September 1988 until April 1989 a clinical
Medicine has long viewed hair-restorers with a good deal of scepticism [l, 21. Tests concerning the effectiveness of minoxidil [3-71 have revived hopes for a solution to the age-old problem of baldness. For 7 years now, in a number of hospitals in China, such as the Peking Friendship Hospital, patients suffering from alopecia androgenetica and alopecia areata have been treated with Dabao@, a hair tonic with a base of Chinese *All corresnondence should be addressed to: A. G. H. Kessels,-Department of Epidemiology/Health Care Research, University of Limburg, P.O. Box 616, 6200 MD Maastricht,
The Netherlands. 439
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experiment was conducted on men suffering from alopecia androgenetica. In the literature about studies on the effect of hair-restorers, hair count is used as the most objective measure to determine a possible increase of hair growth. According to Koperski [9], however, an increase of the amount of hair does not necessarily give information about its cosmetic results. The future user will probably be especially interested in this qualitative aspect of hair growth. Therefore the most important outcome measurements of this study were counts of the number of nonvellus hair and the judgement of the cosmetic effect. In addition, the influence of the type of baldness (according to Hamilton’s classification [lo]), the duration of the baldness, and age on the effect of Dabao were investigated. Except for the prevailing scepticism about the effects of hair-restorers, the study methods as used in most trials have also been disputed [l l-131. Issues especially criticized were the method of effect measurements, the unexplained high effect of the placebo treatment, and the high number and insufficient documentation of the drop-outs. For this reason special attention will be paid to a precise description of the method of the effect measurement and factors that could possibly distort the results.
MATERIALS AND METHODS
The study was conducted as a randomized, placebo-controlled, double-blind experiment. Three hundred and ninety-six participants in the study were divided at random into two groups. The participants in one group used Dabao for 6 months, while those in the other used a placebo over the same length of time. Participants
Participants were recruited via advertisements in two local newspapers and their selection was based on several considerations. Preference was given to participants offering a high prospect of Dabao acting effectively. To reduce the influence of factors of disturbance, the test population was kept as homogeneous as possible. Furthermore, factors affecting compliance and the reliability of the outcome measurement were taken into account during selection. All this resulted in the following criteria for participation: -male -age 18-50 years
et al.
-type of baldness: alopecia androgenetica -maximum duration of baldness: 20 years -no previous therapy against baldness (hairrestorer, laser or transplant) -for a minimum period of 6 months, no other therapy that could affect the growth of the hair, such as cytostatic drugs, sex hormones, thyroid hormones, adrenocorticoids and growth hormones, heparin and high doses of salicylic acids -no skin diseases, in particular alopecia areata and psoriasis dark hair -good health (no serious or chronic diseases) -willingness to comply with the research procedure -no signs of a markedly irregular way of life -residence within 100 km of the study centre. Of the 8000 persons who showed interest in participating, 3000 completed application forms, and of these, 900 prospective participants were invited for an interview and a preliminary examination. Eventually 396 persons were selected. All participants confirmed in writing that they had been sufficiently informed about the procedures of the study. After selection and informed consent, randomization into two groups was performed in blocks of 10 consecutive participants, by means of a computer programme. The inflow was completed in 1 month. Treatment and compliance
Regardless ~of the degree of baldness, the participants received one 100 ml bottle of the preparation, sufficient for 1 month’s use. The Dabao preparation contained ethanol, water and herbal extracts and the placebo contained ethanol, water, artificial odours and colouring agents (Table 1). These agents were only added to achieve the closest possible resemblance, as to scent, colour and viscosity, between the placebo preparation and the Dabao preparation. A measuring cup and a syringe were supplied to measure the dose of 1.7 ml. This quantity had to be massaged into the dry scalp twice a day, for 4-5 minutes, after warming the scalp with a warm towel or with warm water. Regular application of the lotion was stimulated by making regular entries in a specially supplied therapy calendar. This calendar was also used to answer questions concerning compliance as accurately as possible. In order to monitor the degree of compliance indicated, the
The Effectiveness of a Hair-restorer on Alopecia Androgenetica
441
Table 1. The components of Dabao and of the placebo preparation Dabao 50% Ethanol 42% Water 8% Chinese herbal extracts consisting of (as far as known): -Saffron flowers (F/OS carrhami) -Mulberry leaves (Folium mori) --Stemona root (Radix stemonae) -Fruits of the pepper plant (Frucfus cap&i) -Sesame leaves (Folium sesami) -The skin of the fruit of Sechuan pepper
Placebo 50% Ethanol 48% Water 2% Odour and colouring agents* consisting of: --Cherry laurel water (Aqua laurocerusi art) Xinnamon water (Aquacinnamoni) -Licorice syrup (Sir Liquiritiae) -Sugar syrup (Sir simplex) -An aqueous solution of burned sugar (Solutio fusca FNA)
(Sichuan pericarpium zanthoxyli) qinger root (Rhizoma zingiberis recens) Chinese angelica root (Radix angelicae sinesis) -Bark of the Pseudolarix (Corfex pseudohzricis) -Fruits of the hawthorn (Fructus crafaegi)
*As far as is known, the placebo does not contain active substances with an allergic or pharmacological action.
participants were questioned about the quantity of lotion left. Side effects The Dabao preparation meets the requirements of the Cosmetics provisions 1979 under Dutch Commodities legislation. On the basis of toxicological studies [ 14, 151, and earlier experiences in China, Japan and The Netherlands, no side effects were known. At each consultation, participants were asked about any special experiences with the product and their scalp was examined by a doctor. In case side effects were suspected, a dermatologist was consulted. Blinding The participants as well as the persons performing the outcome measurement were blinded. The preparation was handed out in a closed non-transparent packaging. The participants were told not to bring the (partly empty) bottles to the follow-up consultations. Furthermore, in order to prevent possible recognition by the persons performing the effect measurements, participants had to wash their hair before each consultation. After 2 and 6 months the blinding was checked by asking each participant which preparation he thought he was using. The persons carrying out the outcome measurement also recorded their opinion of which preparation was being used. Effects During the first consultation the participant was asked about the spot where hair loss occurred most recently. On this spot, if possible at the intersection of hair and baldness, a mark was drawn. In view of its labour-intensive
nature, the hair count on this marked spot was carried out once every 2 months (see Fig. 1). In order to avoid inaccurate counting results, due to interobserver variability, each participant was always counted by the same doctor. Only nonvellus hair, i.e. hair longer than 2 cm and pigmented, was counted. To prevent the data obtained during previous contacts being a source of potential influence, such data were not disclosed to the people involved with the effect measurements. The cosmetic result was judged by a blinded independent panel, by means of a standardized slide report, displaying one general and one detailed picture, taken before and after treatment. The panel was composed of three women and three men. Half of the panel consisted of professionals involved in problems concerning baldness, viz. a dermatologist, a representative of the hairdresser’s association, and a beautician. The other half of the panel consisted of individuals uninvolved professionally and presumably capable of an objective and unbiased judgement, viz. an epidemiologist, a journalist and a health educator. The panel was requested to score a possible change in the cosmetic aspect and the certainty of hair decrease or increase, on a visual analogue scale. The average, computed from the scores of all panel members, was taken as the final outcome measurement. A third important outcome measurement was the participant’s opinion about the increase or decrease of the amount of hair and about the cosmetic aspect, both scored on a Spoint scale. Confounding variables and efect -mod@ers Factors which interfere with the outcome measured can distort the result if unevenly
A.G. H.
KESSELS et al.
0
.
Fig. 1. Description of the hair count. Every 2 months the number of nonvellus hairs is determined in the same marked area. Nonvellus hairs are pigmented and longer than 2cm. During the first contact, the participant points out the area where according to him he lost hair most recently and here, at the intersection of hair and baldness, a mark is drawn with a fine-liner. By means of the apparatus shown in (A) and (B) the coordinates of this point are determined. This apparatus makes it possible to reproduce this point for each count accurate to less than 2 mm. When the participant is sitting on a chair, the head rest is adjusted. Next, the head (B) is secured by means of two elastic ear tubes (B, 3), provided with earplugs. The head can now only rotate in the sagittal plane. This movement is prevented by securing the nose by means of a nose plate (B, 4). The head rest and marker (B, 1) can be adjusted for height, cross position and angle; the ear tubes and the nose support are only adjustable for height. After marking the scalp, a circle is drawn round the point (B, 2) with the help of a disc (C) having a surface of 5 cm*. The illumination is standardized by fixing the strength and the angle of the light source. The hairs are counted according to the Dallwitz method. This means that the comb is inserted about 1cm from the outline circle. Hereafter the comb is moved against the hair implantation, towards the circle. If the comb has crossed the edge of the circle, it is kept stationary. With a small hook the hairs are then removed from under the comb and counted. As soon as a row of hairs has been counted, the comb is shifted slightly and the next row is counted. This process is repeated until all hairs within the circle have been counted.
distributed among the study groups. If one of the two doctors counts with a more positive disposition, he will obtain a larger increase in the number of hairs in both the Dabao group and the placebo group. However, if, among the participants counted by this particular doctor, there is by chance a higher proportion of Dabao users, the result will be distorted in favour of Dabao. Other factors which can influence the hair count as well as the opinion of the panel are the initial values of the number of hairs and the colour of the hair. For this reason it was checked whether these factors were distributed proportionally among both study groups. Furthermore at the beginning of the study a number of prognostic variables which might influence the effect of Dabao were recorded for all participants, viz. the participants’ age, the duration of baldness and the type of baldness. These variables permit the selection of men likely to derive more than the average benefit from Dabao. Because it is assumed that these variables only interfere with an increased number of hairs in the Dabao group, they are merely
considered as putative modifiers of the effect of Dabao. Analysis For each participant the increase of the number in hairs was first of all recorded by determining the difference between the hair count at the first and last contacts. However, the hair was counted four times. Linear regression was used to fit a straight line through these four measuring points for each participant. The rise of the regression line over a period of 6 months is based on these four measuring values and probably will result in a more accurate estimation of the increase in the number of hairs. Of the outcome measurements, two are of a continuous nature, viz. the change in the number of hairs and the score of the panel. For these outcome measurements the difference between the Dabao and placebo groups was tested onesided assuming Student’s distribution. Besides, for these differences 95% confidence intervals were established. The influence of confounding variables was furthermore corrected with a
The Effectiveness of a Hair-restorer on Alopecia Androgenetica
multiple linear regression model. By introducing interaction terms in this linear regression model, the influence of the prognostic factors on the effect of Dabao was determined. The opinion the participants recorded on a 5-point scale was dichotomized into a positive result, and a combined negative and neutral result. The difference in the proportions of positive results between the Dabao and placebo groups was tested in the standard way and in addition 95% confidence intervals were computed for the difference between these proportions. For participants who withdrew prematurely, not all outcome measurements could be carried out. If it could be reasonably assumed that a participant dropped out for reasons not related to the (expected) results but to events such as an accident or a change of residence, he was excluded from the analysis. If disappointment about the results could not be excluded as a reason for withdrawal, the last result measured was regarded as the final outcome for these participants. Each participant who ceased participation was asked to state his reasons for doing so. The decision whether a connection between the stated reason and the supposed effect could be reasonably rejected was taken by a blinded independent jury. RESULTS
Prior to a description of the results of the outcome measurements, the following matters will be discussed: premature withdrawal, blinding, compliance and the distribution of confounding variables among the two study groups, Of the original 396 participants, 23 (6%) participants quit the study prematurely. For 13 participants the reasons for withdrawal were factors such as serious traffic and sports accidents or a new job elsewhere (10 Dabao, 3 placebo). For 10 participants a connection with the expected result could not be ruled out (3 Dabao, 7 placebo). One participant who had to stop using Dabao because of a possible side effect has also been excluded from further analysis. This person developed a contact dermatitis for Dabao after 3 months. Some other participants, Dabao as well as placebo users, reported isolated inflamed follicles. After 2 months 192 participants (48%) indicated they had no idea which preparation (Dabao or placebo) they had been using so far. Of the 89 participants who thought they had
443
100%
80% 5 5 I) ; ‘; d
E
2
60%
40%
E z 20%
0.40
1 .oo
0.80
0.60
compliance Fig. 2. Cumulative distribution of the degree of compliance for the Dabao and placebo groups.
been using Dabao, 54% has used Dabao and 46% placebo. Of the 111 participants who thought they had been using placebo, 45% had used Dabao and 55% placebo. After 6 months these answers showed almost the same distributions over both study groups. At both moments the persons conducting the hair count specified in almost all cases that they did not know which preparation the participants were using. In Fig. 2 the cumulative distribution of the indicated compliance for both study groups has been plotted. The vertical axis of the graph represents the percentage of the study group in question, with a compliance larger than the corresponding value on the horizontal axis. The figure shows that 90% of the participants used more than 90% of the prescribed quantity of tonic. Table 2 represents the distribution over the two study groups of variables that might distort Table 2. Distribution of the participants among both research groups according to the hair colour, to the initial value of the hair count and to the tellers of the hair count Dabao Placebo (n = 188) (n = 194) Colour of hair
Light brown Brown Dark brown/black
35% 32% 33%
33% 37% 30%
Initial value of the hair count
< 100 hairs 101-200 hairs 201-300 hairs > 300 hairs
13% 33% 31% 23%
10% 38% 31% 21%
82% 18%
85% 15%
Teller
Doctor A Doctor B
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350 0) .b 2 5
325 300
$ ? 2
275 250
2 time
4
6
in months
Fig. 3. The average number of nonvellus hairs in the Dabao and placebo groups in a 5 cm* marked area (see text) as a function of time.
the outcome measurements, viz. the hair colour and the initial values of the hair count. In addition, this distribution has also been given for both the doctors who carried out the hair count. There is not much difference between the distributions in terms of percentages, which means that the influence on the result is probably small. E&cts The number of hairs were counted every 2 months, thus four times altogether. By determining the average number of hairs for each of the two study groups per measuring moment a global progress during the study period can be outlined (Fig. 3). In both the Dabao and the placebo group, the average amount increases over the time similar to a flattened S-curve. In 6 months, the average number of hairs increases by about 110 hairs per 5 cm2 in the placebo
et al.
group and by about 135 hairs per 5 cm2 in the Dabao group. Tables 3-5 display the differences between the Dabao and placebo groups with their 95% confidence intervals. Dependent on the method of computation, the hair increase in the Dabao group amounted to 24 or 29 more hairs per 5 cm3 than the placebo group (Table 3). The evaluation of the panel about the certainty of a change in the number of hairs on a scale of - 10 to + 10 is 0.49 higher for the Dabao group than for the placebo group and on an equal scale the cosmetic result is 0.24 higher in the Dabao group (Table 4). With the aid of a linear multiple regression model the hair count and the evaluation of the panel have, moreover, been corrected for a possible confounding influence of the initial value of the number of hairs and the colour of the hair. The results of the hair count have been additionally corrected for the doctor who conducted the count. The results hardly change at all, or they become marginally more favourable for Dabao. Among Dabao users the percentage reporting positively about the increase in the number of hairs was 13% higher than among placebo users (Table 5). The percentage of Dabao users having a positive opinion about the cosmetic result was 5% higher than the corresponding percentage in the placebo group. Table 6 represents the differences between the Dabao and placebo groups for the change in hair count and for the cosmetic result as scored by the panel, both stratified for the type of baldness, the duration of baldness and for different age categories. The results of the hair counting are not very consistent with the evaluation of the cosmetic result by the panel. The 95% confidence intervals are very large; a part of this discrepancy may be due to chance.
Table 3. The increase of the amount of hair after 6 months computed by taking the difference between the hair count in the sixth month and the initial value (subtraction) and comouted with the aid of a reeression line (reeression)
Subtraction Regression
Dabao
Placebo
Difference
95% CI
p-Value one-sided
133 148
109 119
24 29
- 1/+50 +3/+56
0.03 0.02
Table 4. Average score of the panel with regard to the certainty about the change in the amount of hair and with regard to the cosmetic result on a scale of -10 to +10
Amount of hair Cosmetic result
Dabao
Placebo
Difference
95% CI
p-Value one-sided
0.94 0.46
0.45 0.21
0.49 0.24
-0.24/c 1.21 -0.03/+0.51
0.10 0.04
The Effectiveness of a Hair-restorer on Alopecia Androgenetica
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Table 5. Percentages of participants with a positive opinion about an increase in the amount of hair and the cosmetic result
. Amount of hair Cosmetic result
Dabao
Placebo
Difference
95% CI
p-Value one-sided
39% 42%
26% 37%
13% 5%
4%/22% -5%/15%
0.002 0.08
Table 6. The differences between the Dabao and placebo groups in the increase of the hair count and in the cosmetic result (on a scale of - 10 and + 10) with the 95% CI, stratified for type of baldness, duration of baldness and age Number of participants
Hair count
95% CI
Cosmetic result
95% CI
59 132 18lt
55 0 24
-9/+119 -59/+60 -11/+59
0.6 0.1 0.2
-0.6/+ 1.9 -0.3/+0.5 -0.0/+0.4
Type of baldness
Front* Vertex* Crown*
Duration of baldness O-5 yr 90
30
-29/+89
0.0
-o.s/+o.s
6lOyr 11-20yr
180 112
3 53
-32/+39 2/+104
0.3 0.3
-0.2/+0.7 -0.2/+0.7
Age 18-34 yr 35-39 yr 40-50 yr
139 105 138
10 24 24
-37/+58 -21/+68 -16/+63
0.3 0.0 0.3
-0.2/+0.7 -0.7/+0.8 -0.1/+0.7
*According to the Hamilton’s classification: front = type II + II, + III + III,; vertex = type III,,,,, + IV + V; crown = IV, + V, + VI. tTen participants could not be classified according to Hamilton.
As demonstrated by both effect measurements, the participants with a frontal baldness (Hamilton type II, IIa, III and IIIa), those with a duration of baldness of more than 10 years and those older than 40 years show a noticeable difference in effect between the Dabao and placebo groups. In order to determine the influence of the previously mentioned confounders on these results, a stratified analysis has also been done with the aid of a linear regression model including interaction terms. The outcome of this analysis did not essentially deviate from the results given in Table 6. DISCUSSION
Because the interpretation of the results depends on the proportion of the participants completing the study, the blinding and the compliance, these issues will be discussed first. Compared to other studies about the effectiveness of hair-restorers, the 94% completion rate scored in this study can be considered very high. If the participants who withdrew for reasons which were very probably unrelated to the expected results are not taken into account, the completion rate even reaches 97%. This high percentage is probably the result of the motivation of the participants and of the efforts to
ensure a correct and attentive relationship with the participants. After 2 months the percentages of the participants indicating correctly the preparation they used was hardly different from what can be expected from chance. Based on these findings, it can be concluded that during the study the blinding was not broken. As Fig. 2 shows, the compliance in an absolute sense, as well as the difference in compliance between the study groups, does not give any cause for concern as to a systematic manipulation of the results by insufficient use of lotion. The compliance in the placebo group is slightly better, which is an additional check on the blinding in this group. Side-effects of Dabao have only been reported once. A dermatologist diagnosed this as an allergic dermatitis, which was treated successfully. Inflamed follicles, which were reported a few times, were possibly the result of daily mechanical friction, through massage. It is also possible that there was no actual increase of inflamed follicles, but that the daily massage heightened the chance of discovering any. Figure 3 displays a significant increase of the amount of hair for the placebo group, viz. an average of 109 hairs on a surface of approximately 5 cm2. There are various ways of accounting for this.
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-The density of the hair depends on the season [ 161. It reaches its lowest value [ 171 in the month of November, followed by a gradual increase. This study started in September and ended in April. -There are indications [16] that the process of balding proceeds according to an alternating pattern. The chance to enrol as a participant of the study is therefore partly determined by the phase in which the person in question happens to be. According to this line of thought, a relatively large number of people will apply in a phase of increasing hair loss. The increase of the number of hairs setting in after the commencement of this study would consequently be a normal process, independent of the preparation administered. -The placebo preparation contained 50% alcohol. The treatment requires the scalp to be warmed before applying the preparation. It is possible that regular massage with alcohol of the warmed scalp has a stimulating effect on the growth of nonvellus hair. -Furthermore, it is possible that the prescribed treatment stimulates the growth of vellus hair instead of nonvellus hair. To distinguish objectively between vellus and nonvellus hair was not as easy as had been expected. Part of the increase in the amount of hair may be due to vellus hair growth. -Lastly, the positive but unintentional influence of the persons engaged in the counting should be mentioned [12]. Two aspects of the counting procedure should be considered. The count takes place on the edge of hair and baldness. A slight shift of the marking point will strongly influence the number of hairs counted. By (unintentionally) putting the point a bit more in the hairy area at subsequent contacts, an artificial increase can be created. Furthermore, an optimistic disposition in relation to the expected outcome on the part of the people involved with the hair count cannot be excluded. For this reason, the results of previous counts were not disclosed to these people. In spite of the large number of participants the measured difference of 25 hairs is just statistically significant. This is caused by the relatively large dispersion of the value of the hair count. The standard deviation of the hair count for the placebo group was 120 hairs. That means that the increase of the number of hairs after 6 months ranges between - 140 and +340 hairs
per 5 cm2 for 95% of the participants. An explanation for this substantial spread could lie in biological variability. A varying natural course, possibly under the influence of the Dabao and placebo treatment, is then the cause of the large dispersion in the changes of the number of hairs per 5 cm2. A second and more likely explanation is a substantial measurement variability. To position the marking point less accurately during the hair count could be a source of large measurement errors, both positively and negatively. In addition, the hair count itself is very labour-intensive and can easily lead to errors, although not on such a large scale. The objectives of this study can be translated into the following questions: -Did the amount of hair increase after 6 months of using Dabao? -1s there a visible cosmetic improvement under the influence of Dabao? -Do the type of baldness, duration of baldness and age have an influence on the effect of Dabao? These questions will now be discussed in turn. In the original research protocol, the hair count was proposed as the most important and most objective outcome measurement. Dependent on the method of computation, the difference between the average amount of hair in the Dabao and placebo groups amounts to 24 or 29 hairs per 5 cm2 (see Table 3). The differences are statistically significant. The panel and the participant have also given their opinion about possible changes in the number of hairs. In both cases the Dabao treatment scores higher than the placebo treatment. On a scale of - 10 to + 10, the panel rated the Dabao group 0.49 higher than the placebo group (see Table 3). The percentage of participants reporting an increase is 39% in the Dabao group and 26% in the placebo group. If the outcomes of all three methods of computation are pooled, it may be concluded that Dabao affects the hair growth and that the amount of hair increases by an average of 24-29 hairs per 5 cm2, over a period of 6 months. The second question is whether this increase in the number of hairs is sufficient for a satisfactory cosmetic result. This has been evaluated by an independent panel and by the participants themselves. Compared to the judgement of the participants, the evaluation of the panel will be more objective and more detached. The
The Effectiveness of a Hair-restorer on Alopecia Androgenetica
judgement of the participants will be coloured by hopes of a positive result and by involvement in the study. On the other hand their attitude towards the problem of baldness will be more in accordance with the one of the future user. About 40% of the participants reported a positive cosmetic result, but the difference between the Dabao and the placebo users is small (42% and 37% respectively). The proportion of participants who mentioned an increase in the number is less than the proportion that mentioned a cosmetic improvement. The most likely explanation appears that a number of participants regard a stabilization of the amount of hair as a positive cosmetic effect. The panel is more modest in its judgement. On a scale of - 10 to + 10, the average values for the Dabao group and the placebo group are 0.46 and 0.21, respectively. The difference of 0.24 is statistically significant, but it is not impressive. The last issue concerning the influence of the prognostic factors, such as type of baldness, duration of baldness or age, on the effect of Dabao, remains unclarified. There is an indication that men with a frontal baldness (Hamilton type II, IIa, III and IIIa), those with a duration of baldness of at least 10 years and those older than 40 years may expect a better result from Dabao. Further studies are necessary to confirm this outcome. The question remains whether the cosmetic effect in particular will improve, stabilize or decrease after a longer use of Dabao. In addition, it is not yet clear what will happen if the treatment with Dabao is stopped. We expect that the results of a follow-up study, in which all participants receive Dabao for 12 months and then stop any treatment for 6 months, will provide the answers to these questions. Acknowledgement-The Minerals.
study was supported
by Vialle
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