U.S. patent application number 10/130297 was filed with the patent office on 2002-12-05 for use of melatonin for treating androgenetic and diffuse alopecia.
Invention is credited to Elsner, Peter.
Application Number | 20020183377 10/130297 |
Document ID | / |
Family ID | 7930930 |
Filed Date | 2002-12-05 |
United States Patent
Application |
20020183377 |
Kind Code |
A1 |
Elsner, Peter |
December 5, 2002 |
Use of melatonin for treating androgenetic and diffuse alopecia
Abstract
The invention relates to the use of melatonin and
melatonin-containing preparations for the treatment of androgenetic
and diffuse alopecia of the female type.
Inventors: |
Elsner, Peter; (Meilen,
CH) |
Correspondence
Address: |
Arent Fox Kintner
Plotkin & Kahn
Suite 400
1050 Connecticut Avenue NW
Washington
DC
20036-5339
US
|
Family ID: |
7930930 |
Appl. No.: |
10/130297 |
Filed: |
May 30, 2002 |
PCT Filed: |
November 29, 2000 |
PCT NO: |
PCT/EP00/11976 |
Current U.S.
Class: |
514/415 |
Current CPC
Class: |
A61K 8/492 20130101;
A61P 5/28 20180101; A61Q 7/00 20130101; A61P 17/14 20180101; A61K
31/4045 20130101; A61P 5/26 20180101 |
Class at
Publication: |
514/415 |
International
Class: |
A61K 031/405 |
Foreign Application Data
Date |
Code |
Application Number |
Nov 30, 1999 |
DE |
19557710.2 |
Feb 18, 2000 |
US |
09506442 |
Claims
1. The use of melatonin for producing a composition for the
treatment of androgenetic and diffuse alopecia of the female
type.
2. The use as claimed in claim 1, wherein the composition can be
applied topically.
3. The use as claimed in claim 1 or 2, wherein the composition can
be applied as a spray, solution, lotion, cream or ointment.
4. The use as claimed in one of the preceding claims, wherein the
melatonin preparation has an active compound concentration of 0.001
to 1% (wt/wt).
5. The use as claimed in one of the preceding claims, wherein the
amount of the composition applied daily contains an active compound
dose of 0.01 to 10 mg per day.
6. The use as claimed in one of the preceding claims, wherein a
reduction in the telogenic rate is achieved.
7. The use as claimed in one of the preceding claims, wherein an
increase in the anagenic rate is achieved.
8. The use as claimed in one of the preceding claims, wherein an
enlargement of the hair diameter and/or an increase in the breaking
force of the hair is achieved.
9. The use of melatonin for producing a composition for enlarging
the hair diameter and/or increasing the stretching ability in the
case of diffuse alopecia.
10. The use as claimed in claim 9. in the case of occipital
hair.
11. The use as claimed in claim 9 or 10 in female patients.
Description
DESCRIPTION
[0001] The invention relates to the use of melatonin and
melatonin-containing preparations for the treatment of androgenetic
alopecia of the female type. Melatonin
(N-acetyl-5-methoxytryptamine) is a hormone with a broad spectrum
of action [1,2], produced and secreted from the pineal gland under
the influence of .beta.-adrenergic receptors having a circadian
rhythm. Although the mechanisms of the action of melatonin are
still not comprehensively clarified in detail, melatonin appears to
control the adaptation of the organism to environmental stimuli, in
particular light and temperature. The toxicity of melatonin is not
detectable, even on oral administration of several grams per day
[3]. In the case of topical application in a nanocolloid
preparation, and of alcoholic solutions, no local or systemic side
effects were seen in over 60 subjects. Animal experimental studies
indicate that the systemic administration of melatonin improves the
thickness and structure of coat hair [4,5].
[0002] The influence of the duration of daylight exposure to the
seasonal change of coat has been described for the sheep [6], the
Cashmere goat and some other species of goat [7], red deer [8] and
mink [9]. The mitotic activity of the secondary follicles and the
hair growth resulting therefrom increases from the beginning of
summer until the winter, to stop in the spring. After a resting
stage, in which the hairs of the primary and secondary follicles
fall out, a new growth cycle begins with induction of a new
anagenic phase.
[0003] This cycle of hair growth and of molting is disturbed if the
pineal gland is removed [5]. Welch [10] was able to show that by
administration of melatonin in cashmere goats the initialization of
the growth activity of the secondary follicles in the spring can be
accelerated. In New Zealand, goats were treated with melatonin over
a period of 14 days in order to initiate the spring growth, and
compared with untreated goats. The histological examination of
biopsies of the skin which were taken during the 14 days showed, in
the goats which had been treated with melatonin, an induction of
hair growth by changeover of the hair follicle from the telogenic
phase to the proanagenic phase, while the hair follicles of the
untreated goats remained in the telogenic phase [11].
[0004] In in-vitro investigations of hair follicles of the cashmere
goat in the hair organ culture model, it was likewise possible to
detect the influence of melatonin on the hair growth of the
follicle. In the 24 hour interval, the administration of melatonin
in concentrations from 150 mg/ml led to a greater growth of the
hair shafts than the lower dose and the control. Over the total
period of 120 hours, the differences in the longitudinal growth
were significant (p=0.05). The best growth rates and maximal total
growth after 120 hours were recorded with the administration of the
melatonin concentration of 300 ng/l [12].
[0005] U.S. Pat. No. 4,476,674 discloses the use of melatonin for
the treatment of various disorders in humans which are accompanied
by hair loss, namely the treatment of toxic alopecia, e.g. alopecia
induced by treatment with medicaments, and the treatment of
alopecia of the male type. A reference to the use of melatonin for
treatment in the case of androgenetic alopecia of the female type
is not found.
[0006] Androgenetic alopecia of the female type differs
significantly from toxic alopecia. Significant differences also
exist with respect to androgenetic alopecia of the male type,
namely with respect to the clinical intensity, the mechanism of
action and the treatability.
[0007] 1. Differences in the Clinical Intensity
[0008] Although androgenetic alopecia occurs in both sexes, the
clinical intensity is typically different.
[0009] The hair loss pattern of the male type (male pattern
alopecia) has already been described by Hamilton in 1942 and
modified by Eblin and Rook in 1972. In this, marked receding of the
hairline is seen in stage 1, which is accompanied from stage 2 with
increasing thinning of the occipital hair and then with increasing
confluence of both areas in stage 4 results in the appearance of a
largely bald scalp with a residual fringe of hair in the occipital
region [13, 14].
[0010] The hair loss pattern of the female type (female pattern
alopecia) differs markedly from the male type, as in this form no
receding of the hairline occurs and complete baldness of the scalp
never results. This form was divided into three stages by Ludwig,
with especially the centroparietal (crown of the head) region
diffusely thinning out as the stages progress. Even in the case of
advanced alopecia in women, there is usually still a thin fringe of
hair of 1 to 2 cm between the forehead and thinned crown region
[15].
[0011] 2. Differences in the mechanism of action
[0012] The term "androgenetic alopecia" is understood as meaning
forms of hair loss which occur under the influence of androgens in
the presence of a genetic disposition. They are associated with an
acceleration of the hair cycle, which leads to the proliferation of
telogenic hairs and increasing occurrence of thin miniature
hairs.
[0013] In men, the high androgen levels, together with a given
constitutional sensitivity of the hair roots to androgens,
regularly lead to male alopecia.
[0014] In women, who have 10 times lower androgen levels than men,
the absolute amount of androgen is less responsible for the
development of hair loss than the increased end organ sensitivity
to androgens. In over 90% of women, this mechanism leads to female
pattern alopecia, while in the other cases male pattern alopecia
can also occur. In this case, increased androgen levels are often
found [16]. Likewise, a rare female pattern alopecia can occur in
men, which in this case too has no similarity to male pattern
alopecia and also does not change into this.
[0015] 3. Differences in Treatability
[0016] Differences are also seen in the therapeutic mechanisms of
action.
[0017] The studies extensively carried out in recent years on
alopecia in men showed a very good response of a 5-alpha-reductase
inhibitor (finasteride), which inhibits the conversion of
testosterone to dihydrotestosterone. It was possible to achieve
stopping of the hair loss in 80% of the cases and a slight to
marked improvement in the hair density in 66% of the cases [17].
Thus the pathological mechanism of the male hair loss type still
seems to be limited rather by the amount of androgens reacted than
by the sensitivity of the roots.
[0018] Up to now unpublished data on experiments with finasteride
in postmenopausal women did not show any superior efficacy compared
with placebo. This gives the decisive reference to the increased
sensitivity of the hair roots to the small amounts of androgens
present in women.
[0019] Moreover, the use of finasteride in women of childbearing
age is contraindicated, as reduced levels of dihydrotestosterone,
the active metabolite of testosterone, in a male fetus can lead to
malformations of the external genitals.
[0020] In a scientific investigation leading to the present patent
application, it has now been found that melatonin is a suitable
active compound for the treatment of androgenetic alopecia of the
female type. Significantly better results from the use of melatonin
in androgenetic alopecia in women compared with those of diffuse
alopecia in women were found with respect to the telogenic rates.
The use of melatonin in androgenetic and diffuse alopecia in women
is thus to be delineated as a specific medicinal indication from
androgenetic alopecia in men and implies a novel principle of
action. It can be presumed that melatonin, in the androgen-mediated
mechanism in women, develops modulating properties which are not
effective in men on account of the high androgen concentration.
[0021] For the treatment of androgenetic alopecia of the female
type, a melatonin preparation is preferably applied topically.
Application can take place here in the form of sprays, solutions,
lotions, creams or ointments. In addition to the active compound,
the preparations can contain suitable vehicles, diluents or
excipients and, if appropriate, further pharmacologically active
compounds such as, for example, vitamins, e.g. vitamins C, E and/or
H. Examples of suitable vehicles are water, aqueous buffers,
alcohol or lipophilic substances. If appropriate, excipients can be
employed which improve the absorption and penetration of the active
compound (see U.S. Pat. No. 4,746,674).
[0022] The melatonin preparation can have, for example, an active
compound concentration of 0.001 to 1% (wt/wt). Preferably, the
active compound concentration lies in ranges from 0.01 to 0.5%
(wt/wt). The active compound dose applied daily depends on the
severity of the disorder and the type of application. Thus active
compound doses of 0.001 to 10 mg, preferatly of 0,01 to 10 mg and
in especially prefered of 0.1 to 5 mg, per day and patient have
proven suitable.
[0023] By means of the administration of melatonin, a reduction in
the telogenic rate is surprisingly achieved. The telogenic rate in
the range of below 20% characterizes a physiological hair loss,
i.e. hair falling out is replaced by newly growing hair. A
telogenic rate of 20% is to be considered here as an upper limit of
a normal range, the majority of the findings varying in a range
from 5% to 15%. If the telogenic rate exceeds 20%, a net loss of
hair occurs, in which hair falling out can no longer be completely
replaced by newly growing hair. An increasing thinning of the hair
results from this. By administration of melatonin, it was possible
to achieve a reduction in the telogenic rate of a value increased
above the norm in the normal range, i.e. below 20%.
[0024] Furthermore, in patients having androgenetic alopecia of the
female type an enlargement of the hair diameter and/or an increase
in the power of resistance of the hair, in particular in the case
of frontal hair, but also in the case of occipital hair, is found
due to the administration of melatonin.
[0025] Even in the case of diffuse alopecia of the female type, an
action of the melatonin preparation was found. This action was
admittedly not so pronounced as in androgenetic alopecia,
nevertheless a significant enlargement of the hair diameter and an
increase in the extensibility were observed, in particular in the
case of occipital hair.
[0026] In addition, a statistically significant effect (p=0,02) of
the melatonin treatment, particularly in view of the amount of
anagen hair follicles could be detected.
[0027] The invention thus also relates to the use of melatonin for
the enlargement of the hair diameter and/or increase in the
extensibility and/or for the increase in the number of anagenic
hair follicles in the case of diffuse alopecia, in particular in
the case of occipital hair and female patients.
[0028] While the melatonin plasma levels admittedly increase under
administration of melatonin compared with a placebo treatment, they
do not exceed the physiological night level of 250 pg/ml. In the
subjects treated with melatonin, no increased occurrence of
tiredness was seen compared with the placebo group, such that the
safety profile of the melatonin application used could be
classified as good.
[0029] The invention will furthermore be illustrated in the context
of the following examples.
EXAMPLES
[0030] 1. Methodology
[0031] Study Design
[0032] The trial was carried out as a randomized,
placebo-controlled double-blind study on 40 female patients having
diffuse or androgenetic, non-epulotic alopecia, who, after
clarification, declared themselves willing to participate in the
investigation.
[0033] Trial Procedure
[0034] A daily evening topical treatment of the scalp with 8
strokes of 0.128 ml of 0.1% melatonin spray, corresponding to 1.024
ml daily, or administration of melatonin-free alcoholic solution
(placebo) was carried out. The treatment period was 6 months. The
hair growth and the mechanical hair quality were determined by
means of trichograms and also measurements of the hair shaft
diameter and the tensile strength. Checks on the plasma melatonin
level were carried out.
[0035] Subjects
[0036] 40 women of 20 to 70 years of age with healthy skin and good
general health and having androgenetic or diffuse alopecia were
tested. Care was taken that none of the women were pregnant or
lactating, there was no dermatological local therapy on the scalp
and no epulotic alopecia was present. Furthermore, no hair-cosmetic
measures were carried out during the study.
[0037] Washing Phase
[0038] Before the beginning of the study, each patient had to carry
out a one-week washing phase using a neutral shampoo
(Every-Day-Shampoo.RTM., Sebapharma, Boppard, Germany).
[0039] Test Substance
[0040] 0.1% melatonin in alcoholic solution (30% ethanol, 70%
water, v/v) in light-protected aluminum bottles having a
standardized spray head and placebo in alcoholic solution (30%
ethanol, 70% water; v/v) in light-protected aluminum bottles having
a standardized spray head were in each case used in a number-coded
randomized distribution.
[0041] The test products were handed over at the beginning of the
study as a packet having 6 spray bottles for the treatment period
of 6 months. One bottle in each case contained 33 ml corresponding
to a month's supply.
[0042] Target Parameters
[0043] Trichogram:
[0044] For the investigation of the anagenic and telogenic rates,
trichograms were prepared. In this procedure, 5 days in each case
after the last hair wash 30 to 50 hairs were obtained frontally
approximately 2 cm from the forehead/hair boundary and laterally
from the sagittal line in a standardized manner by epilation using
a special hairgrip. A 2nd epilation was taken occipitally 2 cm
laterally of the protuberantia occipitalis. The trichograms were
carried out before the beginning of the study, and after 3 and 6
months' treatment. The hair roots obtained were mounted on slides,
analogously counted by means of a light microscope at 20-times
magnification and the percentage ratios of the anagenic, telogenic
and dystrophic hairs were calculated.
[0045] Hair Shaft Measurements:
[0046] From the hair samples obtained for the trichogram, frontally
and occipitally at least 10 hairs in each case were used for the
hair shaft measurements. These samples were investigated before the
beginning of the preparation application and after 3 and 6 months'
treatment.
[0047] Diameter
[0048] For the measurement of the diameter and of the mechanical
properties of the hair, 5 hairs from the frontal and occipital
taking region of the trichograms were in each case used.
[0049] Breaking Force
[0050] For the measurement of the force which had to be used in
order to break the hair, the hairs were first stretched, by means
of a computer-controlled measuring and control unit at a constant
force (Newton), to breaking point.
[0051] Breaking Distance
[0052] In a manner analagous to the determination of the breaking
force, it was possible to determine the stretching distance up to
the breaking point by means of the measuring unit. The stretching
distance was measured in mm.
[0053] Melatonin Plasma Levels:
[0054] Melatonin plasma levels were determined by means of a
commercially obtainable radioimmunoassay (RIA, DPC Biermann GmbH,
Bad Neuheim, Germany).
[0055] Patient Questionnaire
[0056] Undesirable pharmaceutical side effects were determined by
means of a patient questionnaire. At the end of the study, an
additional termination questionnaire was filled in by the patients,
in which they could express their views on the success of the
therapy, on the chronological occurrence of side effects and on the
administration form of the preparation.
[0057] Data and Statistics
[0058] All the individual data from the trichogram investigations,
the hair shaft measurements and the melatonin measurements were
recorded in Microsoft Excel and mean values and standard deviations
were calculated. The statistical analysis of the measured values at
the various points in time in the two treatment groups was carried
out by the SPSS statistics program.
[0059] 2. Results
[0060] Study Population
[0061] A total of 40 female patients were admitted into the study,
12 women having androgenetic alopecia and 28 women diffuse
alopecia. The clinical severity of the androgenetic alopecia ranged
from the stage Ludwig I to III, that of diffuse alopecia from
slightly to moderately pronounced. In none of the patients was
there an internal condition or another local condition of the scalp
apart from alopecia.
[0062] Trichograms
[0063] The trichograms were carried out according to plan at the
beginning of the 6-month investigation period, after the 3rd month
and the 6th month (final measurement). For the overall analysis,
the anagenic and telogenic rates of both condition groups were
combined.
[0064] Frontal Trichograms
[0065] In the placebo group, the analysis of the frontal
trichograms showed a relatively constant anagenic rate of 82.2%
before therapy, 82% after two months and 82.2% after six months.
The telogenic rate correspondingly behaved similarly, a slight
decrease from 17.2% to 16.8% being recorded at the end of the
investigation period. The rate of dystrophic hairs varied in the
normal range of below 4%. In the drug group, a slight increase in
the anagenic rate from 80.4% to 82.6% was observed. The telogenic
rate decreased from 18.9% to 16.8% and 15.9%. The dystrophic hairs
had a normal rate with a proportion of 0.6% to 2.2%. The
differences in the anagenic and telogenic rates after 3 and 6
months' treatment compared with the starting values were not
significant either in the placebo group or in the drug group.
[0066] Occipital Trichograms
[0067] On inspection of the occipital trichograms, the placebo
group initially showed a decrease in the anagenic rate from 80.4%
to 79.5% up to month 3 and a subsequent increase to 84.1% by month
6.
[0068] The telogenic rate increased up to month 3 from 16.8% to
19.2% and by month 6 decreased to 14.0%.
[0069] The changes in the placebo group were not significant either
for the anagenic rates or for the telogenic rates.
[0070] The anagenic rates of the drug group, however, showed a
marked continuous increase from 76.3% to 78.8% (month 3) and 85% to
month 6. The difference in the anagenic rate between the starting
result and month 6 was significant (p.ltoreq.0.021).
[0071] Still more pronounced changes were seen both after 3 months'
and after 6 months' treatment in the telogenic rate of the drug
group. It fell from 23.03% to 18.1% from month 1 to month 3. Up to
month 6, a decrease to 12.5% was achieved. Thus, by means of 6
months' treatment with drug, a reduction in the telogenic rate to
approximately half was achieved. At p.ltoreq.0.048, the difference
from month 3 to month 6 was significant and over the entire
observation period of 6 months it was highly significant
(p.ltoreq.0.005).
[0072] Analysis of the Diagnostic Groups (Alopecia Androgenetica
vs. Alopecia Diffusa)
[0073] On account of the significant differences in the occipital
trichograms of the drug group, a division was carried out as a
function of the various diagnoses.
[0074] Androgenetic Alopecia
[0075] The 12 patients having androgenetic alopecia showed constant
anagenic and telogenic rates of 78.22% to 82.11% or 17.6% and 17.2%
under placebo (n=6). The anagenic rates in patients of the drug
group (n=6) increased from 73.6% to 87.8%. Even more marked
differences in the telogenic rates were found with a decrease from
26.5% to 18.3% (month 3) and 10.8% (month 6). In this case, the
decrease from the starting result to month 6 was significant with
p.ltoreq.0.035.
[0076] Diffuse Alopecia
[0077] In the 28 patients with diffuse alopecia, under placebo
administration (n=14) a slight increase in the anagenic rate from
81.39% to 84.89% and a decrease in the telogenic rate from 16.4% to
12.66% was seen. In patients of the drug group (n=14), an increase
in the anagenic rate from 77.4% to 83.7% was recorded. The
telogenic rate decreased from 21.6% to 13.2%. A comparison between
the melatonin and placebo group showed statistically significant
differences in patients having diffuse alopecia (p=0,02) regarding
an increase in the anagenic rate.
[0078] Measurement of the Physical Hair Parameters
[0079] Measurements of the hair diameter of hair taken frontally
showed an enlargement of the diameter in 67% of the patients of the
drug group having the diagnosis androgenetic alopecia. The power of
resistance of hair of patients under melatonin treatment increased
from 0.56 N to 0.61 N after 6 months' treatment. In the frontal
hair, no further improvements were otherwise seen compared with the
placebo group with respect to the physical hair parameters.
[0080] In investigations on hair taken occipitally, an enlargement
of the hair diameter was seen in 55% of patients treated with
melatonin and an increase in the stretching force in 70% of the
patients. The improvements due to melatonin were observed
particularly in the group having diffuse alopecia (86%).
[0081] Melatonin Plasma Levels
[0082] The melatonin plasma levels in the placebo group lay at
values between 2 and 10 pg/ml with individual peak values of up to
80 pg/ml. In some cases considerable intra- and inter-individual
differences were found.
[0083] In the drug group, the melatonin plasma levels at the
measurement time 1 before application lay in the range from 2 to 10
pg/ml and increased at the following measurement times to values of
on average 30 to 50 pg/ml. Individual peak values lay at 180 pg/ml.
In this group too, considerable intra- and inter-individual
differences in the measured values were seen. Despite the
application of melatonin, the physiological average melatonin peak
in the night of 250 pg/ml was not exceeded in this group.
[0084] Furthermore, an accumulation in the melatonin serum level
did not occur. The melatonin plasma levels remained constant
between 30 and 50 pg/ml over the investigation period of 6
months.
[0085] Patient Questionnaire
[0086] Success of the Therapy
[0087] The hair loss was classified in the placebo group by a total
of 56% of the patients as improved, by 36% as stopped and by 13% as
worsened.
[0088] In the drug group, 69% of the patients stated that the hair
loss had improved, in 23% the hair loss had stopped and only in 8%
had the hair loss worsened.
[0089] Acceptance of the Preparation
[0090] The preparation size was classified as good by the majority
of the users (85%). The spray form was indicated as suitable by 91%
and the application was generally classified as practical by almost
all patients (97%).
[0091] 3. Discussion
[0092] In the present study, a significant efficacy of the topical
0.1% strength melatonin preparation at a dose of 1 ml daily was
shown on the telogenic rate in the occipital region. While the
quality of the hair with respect to its diameter and its stretching
properties was not significantly influenced by the melatonin
preparation in contrast to the placebo, clear differences between
verum and placebo were seen in the trichogram results. In the
overall analysis of the findings of all patients, a significant
increase in anagenic hair (p.ltoreq.0.021) and a decrease in
telogenic hair (p.ltoreq.0.005) was seen, especially in the
occipital trichograms at the end of the 6-month treatment period.
On examination of the telogenic hair, a significant difference was
seen even from month 3 to month 6 (p.ltoreq.0.048). The rate of the
dystrophic hair was always in the normal range, such that no
harmful actions of the preparation on the physiological hair root
were observed. As the determination of the hair root status by the
trichogram shows a percentage ratio of anagenic, telogenic and
dystrophic hairs, it inevitably results that changes in one hair
type in turn also cause changes in the other type. In spite of
this, the determination of the telogenic rate as a parameter of the
hair loss is to be classified as particularly important, since the
light-microscopic assessment of the telogenic hair as pigment-free,
club-shaped hair without a root sheath is clearly to be carried
out. The anagenic hair class, on the other hand, subsumes various
hair types such as, for example, anagenic hairs with and without
root sheaths, broken-off hairs and dysplastic anagenic hair.
Difficulties in discrimination sometimes result here with the
dystrophic hair, which is not to be included in the anagenic hair.
For this reason, all trichograms which had an inconclusive result
with respect to the dystrophic hair and anagenic hair were
subjected to a plausibility check and complete counting again.
[0093] In the region of below 20%, the telogenic rate characterizes
physiological hair loss, i.e. the hair falling out is replaced by
newly growing hair. The rate of 20% is to be considered as an upper
limit of a normal range, in which the majority of the results vary
in a range from 5% to 15%. If the telogenic rate exceeds 20%, a net
loss of the hair occurs, in which the hair falling out can no
longer be completely replaced by newly growing hair. An increasing
thinning of the hair results from this. In the present study, it
was possible to detect the significant reduction in the telogenic
rate in the occipital region, where a decrease from 23% to 12.5%
occurred. The telogenic rate, which was increased slightly above
the norm at the beginning of the study, thus lay completely in the
normal range at the end of the 6-month treatment period. In the
analysis separated according to diagnostic groups, it was seen that
the group having androgenetic alopecia profited most from the use
of the preparation, in particular in the occipital scalp region. At
a starting rate of 26.5% telogenic hair, the melatonin preparation
achieved a reduction to 18.3% after 3 months use and to 10.8% after
6 months. The differences were significant from month 1 to month 6
at p.ltoreq.0.035.
[0094] The positive effects on the telogenic rates of the frontal
hair samples were likewise stronger than those of the placebo, and
showed statistically significant differences, in particular in the
patients with diffuse alopecia.
[0095] In the case of diffuse alopecia, the action of the melatonin
preparation is admittedly present, but not pronounced to such an
extent as in androgenetic alopecia. Diffuse alopecia represents a
symptom-orientated diagnosis which is not specified in greater
detail, in which various causes such as nutritive factors, noxae
and perfusion disorders of the scalp disturb the physiological
equilibrium of the hair growth. Here, melatonin can likewise be
effective as a promoter of anagen induction, but only under the
condition that other harmful factors do not predominate.
[0096] The melatonin plasma levels admittedly increased under
melatonin administration, compared with the placebo treatment, but
not over the physiological night level of 250 pg/ml. The effect to
be expected of increased melatonin plasma levels on the vigilance
of the subjects has been recorded by the patient questionnaires.
Compared with the placebo group, no increased occurrence of
tiredness is seen, such that the safety profile of the melatonin
preparation used is to be classified as good in the case of topical
application to the scalp.
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