Topical Melatonin for Treatment of Androgenetic Alopecia

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DOI: 10.4103/0974-7753.111199 · Source: PubMed
Cite this publication
Abstract
Background: In the search for alternative agents to oral finasteride and topical minoxidil for the treatment of androgenetic alopecia (AGA), melatonin, a potent antioxidant and growth modulator, was identified as a promising candidate based on in vitro and in vivo studies. Materials and methods: One pharmacodynamic study on topical application of melatonin and four clinical pre-post studies were performed in patients with androgenetic alopecia or general hair loss and evaluated by standardised questionnaires, TrichoScan, 60-second hair count test and hair pull test. Results: FIVE CLINICAL STUDIES SHOWED POSITIVE EFFECTS OF A TOPICAL MELATONIN SOLUTION IN THE TREATMENT OF AGA IN MEN AND WOMEN WHILE SHOWING GOOD TOLERABILITY: (1) Pharmacodynamics under once-daily topical application in the evening showed no significant influence on endogenous serum melatonin levels. (2) An observational study involving 30 men and women showed a significant reduction in the degree of severity of alopecia after 30 and 90 days (P < 0.001) based on questionnaires completed by investigators and patients. (3) Using a digital software-supported epiluminescence technique (TrichoScan) in 35 men with AGA, after 3 and 6 months in 54.8% to 58.1% of the patients a significant increase of hair density of 29% and 41%, respectively was measured (M0: 123/cm(2); M3: 159/cm(2); M6: 173/cm(2);) (P < 0,001). (4) In 60 men and women with hair loss, a significant reduction in hair loss was observed in women, while hair loss in men remained constant (P < 0.001). (5) In a large, 3-month, multi-center study with more than 1800 volunteers at 200 centers, the percentage of patients with a 2- to 3-fold positive hair-pull test decreased from 61.6% to 7.8%, while the percentage of patients with a negative hair-pull test increased from 12.2.% to 61.5% (P < 0.001). In addition, a decrease in seborrhea and seborrheic dermatitis of the scalp was observed. Conclusions: Since safety and tolerability in all of the studies was good, the topical application of a cosmetic melatonin solution can be considered as a treatment option in androgenetic alopecia.
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236 International Journal of Trichology / Oct-Dec 2012 / Vol-4 / Issue-4
INTRODUCTION
Having a full head of hair represents physical
attractiveness and youthfulness to men and women,
which is why hair loss can have significant negative
impacts on the self‑esteem and quality of life of those
affected.[1,2] By far the most common cause of hair loss in
men and women is androgenetic alopecia (AGA), which
is a genetically determined, age‑dependent, progressive
hair‑loss condition with gender‑specific differences
in frequency and severity.[2,3] AGA prevalence among
men aged 18 to 29 years is approximately 12% and
approximately 50% among men between the ages of 40
Address for correspondence:
Tobias W. Fischer,
Department of Dermatology,
Clinic for Dermatology,
Allergology and Venereology,
University of Lübeck,
Raeburger Allee 160,
23538 Lübeck, Germany.
E‑mail: Tobias.scher@
uk‑sh.de
Original Article Topical Melatonin for Treatment of
Androgenetic Alopecia
Tobias W Fischer, Ralph M Trüeb1, Gabriella Hänggi2,
Marcello Innocenti3, Peter Elsner4
Department for Dermatology, Allergology and Venereology, University of Lübeck,
Lübeck, Germany, 1Center for Dermatology and Hair Diseases, Wallisellen/Zurich,
2Thalwil, Switzerland, 3European Dermatology Institute, Milan, Italy, 4Department
for Dermatology, Clinic for Skin Diseases, Jena University Hospital, Jena, Germany
ABSTRACT
Background: In the search for alternative agents to oral nasteride and topical minoxidil for
the treatment of androgenetic alopecia (AGA), melatonin, a potent antioxidant and growth
modulator, was identied as a promising candidate based on in vitro and in vivo studies.
Materials and Methods: One pharmacodynamic study on topical application of melatonin
and four clinical pre-post studies were performed in patients with androgenetic alopecia or
general hair loss and evaluated by standardised questionnaires, TrichoScan, 60-second
hair count test and hair pull test. Results: Five clinical studies showed positive effects of a
topical melatonin solution in the treatment of AGA in men and women while showing good
tolerability: (1) Pharmacodynamics under once-daily topical application in the evening
showed no signicant inuence on endogenous serum melatonin levels. (2) An observational
study involving 30 men and women showed a signicant reduction in the degree of severity of
alopecia after 30 and 90 days (P<0.001) based on questionnaires completed by investigators
and patients. (3) Using a digital software-supported epiluminescence technique (TrichoScan)
in 35 men with AGA, after 3 and 6 months in 54.8% to 58.1% of the patients a signicant
increase of hair density of 29% and 41%, respectively was measured (M0: 123/cm²; M3: 159/
cm²; M6: 173/cm²) (P<0,001). (4) In 60 men and women with hair loss, a signicant reduction
in hair loss was observed in women, while hair loss in men remained constant (P<0.001). (5)
In a large, 3-month, multi-center study with more than 1800 volunteers at 200 centers, the
percentage of patients with a 2- to 3-fold positive hair-pull test decreased from 61.6% to
7.8%, while the percentage of patients with a negative hair-pull test increased from 12.2.%
to 61.5% (P<0.001). In addition, a decrease in seborrhea and seborrheic dermatitis of
the scalp was observed. Conclusions: Since safety and tolerability in all of the studies
was good, the topical application of a cosmetic melatonin solution can be considered as a
treatment option in androgenetic alopecia.
Key words: Androgenetic alopecia, melatonin, seborrhea, seborrheic dermatitis
and 49 years.[4] Among women, AGA affects approximately
17% of women between the ages of 30 and 49, while
postmenopausal prevalence increases signicantly and
can affect 23‑25% of women aged 50 to 69 years.[4] In
men, AGA typically begins with a receding hairline and
progresses as the hairline continues to recede above the
forehead accompanied by a balding pattern on the crown
of the head. As the condition progresses, the bald areas
can become larger until the top of the head is completely
bald with only a fringe of hair remaining at the back of
the head and at the temples.[5,6] AGA usually progresses
more slowly in women than in men and is accompanied
by a gradual, diffuse thinning of the hair on the top
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Fischer, et al.: Melatonin and androgenetic alopecia
International Journal of Trichology / Oct-Dec 2012 / Vol-4 / Issue-4 237
of the head with preservation of the hairline along the
forehead.[7]
Only two therapeutic agents have been approved to date
by the Federal Drug Administration (FDA) and European
Medicines Agency (EMEA) for treatment of AGA: Oral
nasteride (for men) and topical minoxidil (for women
and men).[4] Since the active ingredients in these substances
have limited efcacy and can involve adverse effects, which
compel patients to discontinue the treatment (e.g., rarely
gynecomastia in the case of nasteride,[8] and frequently
hypertrichosis in the case of minoxidil[9]), it seems
appropriate to identify alternative active substances for
the treatment of AGA.
According to our current pathogenetic understanding of
the condition, AGA is related to genetic peculiarities of
androgen metabolism as they relate to the hair follicle. The
most signicant factor in men is elevated activity of Type II
5‑alpha reductase enzymes, which metabolize testicular
testosterone circulating in the blood into dihydrotestosterone
(DHT) in the genetically predisposed hair follicles of
the temporal and vertex regions.[2,3] In women, decreased
aromatase activity, which converts ovarian testosterone
circulating in the blood into 17 beta‑estradiol, tends to play a
greater role.[3] An increase in the local concentration of DHT,
which binds to the highly expressed androgen receptors
in predisposed hair follicles,[2,4] results in a progressive
shortening of the anagen phase in favor of a longer telogen
phase, which is accompanied by a progressive miniaturization
of the hair follicles. This results in the gradual replacement
of thick, pigmented terminal hairs with ne, non‑pigmented
vellus hairs (miniaturized hairs).[10]
In addition to androgen‑dependent changes in the
morphology and growth dynamics of hair follicles, the
pathogenesis of AGA also appears to involve follicular
microinammation and brosis,[11] which may be triggered
by resident microbial flora in the case of seborrhea,
toxins and oxidative stress.[12] Other factors include the
aging process, ultraviolet radiation,[13,14] smoking,[15,16] and
environmental pollutants.[17] These stressful inuences
lead to the formation of free radicals, which are no longer
able to be sufciently scavenged by the cell’s defense
mechanisms, resulting in damage to the hair follicles.[10,12]
It was recently proven that the papillary broblasts exhibit
increased sensitivity to oxidative stress in cases of AGA.[18]
Melatonin (N‑acetyl‑5‑methoxy‑tryptamine) is a possible
candidate to counteract the oxidative stress associated with
general hair loss as well as AGA because of the strong
anti‑oxidant properties that have been described for this
substance.[19] Originally discovered as a neurohormone
formed and released by the pineal gland with a circadian
rhythm,[20] melatonin regulates a variety of physiological
processes, such as seasonal biorhythms and daily sleep‑wake
cycles, and inuences the aging process.[21‑23] However,
melatonin is most notable for its protective and anti‑apoptotic
effects, which can ensure the functional integrity of
non‑neoplastic cells, due to its strong anti‑oxidant properties
and ability to actively capture free radicals.[24‑28]
According to recent ndings, numerous peripheral organs
are not only the target of melatonin bioactivity, but are also
simultaneously the site for extrapineal melatonin synthesis,
regulation and metabolism of melatonin. Human skin
has been shown to have a melatoninergic enzyme system,
which completely expresses the specic enzymes necessary
for melatonin biosynthesis.[29] In addition, keratinocytes,
melanocytes, and broblasts feature functional melatonin
receptors, which are involved in phenotypic effects, such
as cellular proliferation and differentiation.[30] An active
melatoninergic anti‑oxidative system has been identied
in the skin, which protects against damage caused by
ultraviolet (UV) rays.[31]
Like human skin, human hair follicles have been
shown to synthesize melatonin and express melatonin
receptors, and an inuence on hair growth cycles has been
observed.[32‑34] In human anagen hair follicles cultivated
in vitro at a concentration of 30 µM melatonin results in a
signicantly faster rate of hair follicle growth in comparison
to the culture medium alone or even at signicantly higher
millimole concentrations (1‑5 mM).[35] A receptor‑mediated
mechanism of action involving melatonin seems very
likely because stimulation of the hair follicles can
be suppressed by the potent melatonin antagonist,
4‑phenyl‑2‑propionamidotetralin.[35] The regulation of
melatonin receptors during the course of the hair cycle
phases has already been shown, at least in the mouse
model.[34] These preclinical data on melatonin‑mediated
hair growth stimulation are supported by the results from a
double‑blind, placebo‑controlled pilot study, in which topical
treatment with 1 ml of a 0.1% melatonin‑alcohol solution
in women with AGA and diffuse alopecia resulted in a
signicant increase in detectable anagen hairs in the occipital
and frontal areas after six months compared with placebo.[36]
MATERIALS AND METHODS
Development of a pharmacological formula
Based on the positive effects of melatonin on hair growth,
Fischer, et al.: Melatonin and androgenetic alopecia
238 International Journal of Trichology / Oct-Dec 2012 / Vol-4 / Issue-4
ASATONA AG (Zug, Switzerland) developed a topically
applied cosmetic hair solution with a melatonin content
of 0.0033%, which was intended to slow the hair’s aging
process and be used as an adjuvant treatment for AGA. In
addition to melatonin, this formulation also included ginkgo
biloba, which also has pronounced anti‑oxidative properties
and a positive impact on hair growth by providing the hair
roots with better nutrients, as well as biotin, which is an
important micronutrient to support cellular functions.
Implementation of the studies
Between January 2003 and October 2006 ve studies
were performed on behalf of ASATONA AG using the
cosmetic melatonin solution described above; of these, the
rst study looked at the pharmacokinetics of the melatonin
solution and the other four studies evaluated the effect of
the melatonin solution on hair loss within various patient
groups based on various study parameters. The study
parameters and study designs are listed together with the
results from the individual studies for the purposes of
better organization. The studies were named as follows:
MEL‑COS‑1 (Study 1), MEL‑COS‑AS01 (Study 2),
MEL‑COS‑AS03 (Study 3), MEL‑COS‑AS04 (Study 4),
and MEL‑COS‑AS05 (Study 5).
RESULTS
Pharmacokinetics of the cosmetic melatonin
solution (Study 1; MEL‑COS‑1)
In order to assess the biological and clinical tolerability of the
cosmetic melatonin solution (0.0033%) the pharmacokinetic
parameters of the cosmetic hair solution, which was applied
once daily to the scalp before going to bed, were analyzed
in a double‑blind, placebo‑controlled cross‑over study on
four fertile and four postmenopausal healthy women.[37]
The study was conducted from January 2003 to April 2003
at the Forenap Centre Hospitalier in Rouffach, France,
following review and approval by the corresponding
Ethics Committee. Patients received an orientation based
on written materials and signed an informed consent form
prior to being enrolled. On Day 14 of the study blood
samples were collected at 30‑min intervals for 8 h following
application and at 10, 12, 16 and 20 h following application
in order to determine the pharmacokinetics of melatonin.
The analysis of the blood samples revealed that repeated
application of the cosmetic melatonin solution had no
negative inuence with respect to an increase or reduction
in physiological endogenous melatonin secretion. The
mean serum melatonin level over 20 h was similar to the
serum level with placebo; the maximum serum melatonin
concentration in the melatonin group was somewhat higher
than in the placebo group (83.4 pg/ml vs. 71.2 pg/ml) and
was reached somewhat earlier [Figure 1]. It was observed
that the mean serum melatonin concentration in the fertile
women was considerably higher than in the postmenopausal
women. The cumulative amount of 6‑hydroxy‑melatonin
sulfate, the most important melatonin metabolite and
melatonin measurement equivalent, excreted in the urine
within 24 hwas similar in both groups, whereas the values
also showed a considerable variability between individuals in
each group. No changes were detected in the vital parameters
(blood pressure, heart rate) or the electrocardiogram during
treatment with melatonin. Following completion of the
two‑week treatment period two neurocognitive tests, the
“critical icker fusion” and the “multiple choice reaction
time” test, were performed and the results showed that
repeated application of the cosmetic melatonin solution
had no signicant inuence on reaction time and cortical
arousal in comparison with the placebo solution.
Treatment with the cosmetic melatonin solution was shown
to be well tolerated because no signicant changes were
detected in the various laboratory tests and circulatory system
parameters nor were any effects on the central nervous
system identied in comparison with placebo. There were
only a few adverse reactions during the course of the study,
such as moderately severe headache and gastrointestinal
problems; their incidence was identical within the melatonin
and placebo groups and no causal connection was identied
with the use of the study medication.
Effect on early‑stage AGA (Study 2; MEL‑COS‑AS01)
Following clarification of the safety aspects of the
cosmetic melatonin solution in the pharmacokinetic
Figure 1: Mean serum concentration after two‑week treatment with
the cosmetic melatonin solutionmn
0
150
120
90
60
30
0
Time after application (h)
246810 12 14 16 18 20
Melatonin
Placebo
mean serum melatonin
concentration (pg/ml)
Fischer, et al.: Melatonin and androgenetic alopecia
International Journal of Trichology / Oct-Dec 2012 / Vol-4 / Issue-4 239
study (Study 1; MEL‑COS‑1) the efcacy of the cosmetic
melatonin hair solution to be applied at night was
evaluated in an open‑label observational study on 15
women with Stage I or II AGA (Ludwig scale)[7] and on 15
men with Stage I or II AGA (Hamilton/Norwood scale)
[5,6] aged 18‑40 years.[38] The study was carried out from
March 2003 to June 2003 at the Instituto Dermatologico
Europeo (European Dermatological Institute)(IDE)
in Milan, Italy following review and approval by the
corresponding Ethics Committee in accordance with
Good Clinical Practice(GCP). Prior to participating in
the study the patients gave written informed consent.
Based on objective examination forms for the medical
investigators and subjective questionnaires for the patients
a signicant reduction in the degree of severity of the
alopecia was identied after just 30 days with a further
signicant drop in the degree of severity after 90 days
(P< 0.001) [Figure 2]. Out of a maximum of 3 points
the cosmetic properties "scent", "consistency", and
"absorption" scored 2.67, 2.52, and 2.57, respectively;
out of a maximum of 1 point the effect of the product
on the overall greasiness of the hair scored 0.43, while its
effect on comb‑ability scored 0.76. Out of a maximum
of 2 points satisfaction with the product scored 1.80; out
of a maximum of 3 points intolerability scored 0.54 after
30 days and 0.52 after 90 days.
TrichoScan study to evaluate efficacy (Study 3;
MEL‑COS‑AS03)
In order to provide a reliable, technically and
methodologically objective assessment of the therapeutic
benets of the cosmetic melatonin solution a further
open‑label, clinically controlled study was carried out
based on the TrichoScan method to determine the efcacy
and tolerability of the melatonin hair solution, which was
applied to the scalp each night by 35 men (aged 18‑41 years)
with Stage I or II AGA (Hamilton/Norwood scale) for a
period of 6 months.[39] The study was carried out from
April 2004 to April 2005 at the Instituto Dermatologico
Europeo (European Dermatological Institute) (IDE)
in Milan, Italy following review and approval by the
corresponding Ethics Committee in accordance with
GCP. Prior to participating in the study the patients
signed a written informed consent form. TrichoScan is
a digital software‑supported epiluminescence technique
for measuring hair count (number of hairs/0.7cm²), hair
density (number of hairs/cm²), hair diameter, anagen/
telogen ratio, and vellus hair/terminal hair ratio.[40,41] The
results of this study showed an increase in the hair count
(number of hairs/0.7cm²) in 54.8% of participants after 3
and 6 months, respectively, and improved hair density
(number of hairs/cm²) in 54.8% and 58.1% of participants
after 3 and 6 months, respectively.
The increase in the hair count was 29.2% (3 months vs.
0 month) and 42.7% (6 months vs. 0 month); both values were
statistically signicant (P<0.001) (Month 0: 85.76±27.0;
Month 3: 110.82±31.7; Month 6: 122.35+40.5). In the case of
hair density an increase of 29.1% and 40.9% was determined
after 3 and 6 months, respectively (Month 0: 123.15±39.0;
Month 3: 159.03 ± 46.8; Month 6: 173.56 ± 58). The
differences among the hair density values were also
signicant (P<0.001).
Objective assessment of treatment with the cosmetic
melatonin solution by the medical investigator at each visit
found improved hair loss in 26.6% (Day 30), 48.2% (Day 90)
and 32.1% (Day 180) of patients, whereby the proportion
of patients showing improvement was greatest after 90 days
and even included a small group of patients with new hair
growth. In addition, the proportion of patients exhibiting no
change in hair loss during the period from Day 30 to Day 90
decreased from about 73.3% to 48.2% and this value was
maintained through Day 180. Hair loss continued in 3.4%
of patients (at 90 days) and in 19.3% (at 180 days) [Figure 3].
Based on the subjective patient questionnaires, 30%, 34.5%
and 29% of patients were satised with the treatment after
a treatment duration of 30, 90 and 180 days, respectively,
while 70%, 58.6% and 58.0%, respectively, were mostly
satised; conversely, the proportion of patients who were
dissatised with treatment was relatively small over the
course of the study with 0% (at 30 days), 6.8% (at 90 days)
and 12.9% (at 180 days). The patient questionnaire also
included an evaluation of cosmetic characteristics, such as
scent, consistency, absorption, greasiness, and combability
following use of the product.
Figure 2: Objective and subjective assessment of the severity of the
alopecia
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Fischer, et al.: Melatonin and androgenetic alopecia
240 International Journal of Trichology / Oct-Dec 2012 / Vol-4 / Issue-4
The scent was described by 83.8% of patients as above
average and by 6.4% of patients as excellent, while 9.6% were
dissatised with the scent. The consistency was described
by 77.4% as above average, by 9.6% as excellent, and by
12.9% as below average. The absorption of the product
into the scalp was considered to be above average by 80.6%,
excellent by 12.9%, and poor by 6.4%. Ninety‑three percent
of patients observed no greasiness of the scalp following
application and combability was classied as above average
by 96.7%. Only one patient reported occasional itchiness
following application of the product. Overall, 93.5% of
patients classied the cosmetic melatonin solution as above
average (80.6%) or excellent (12.9%).
Comb test at hair salons (Study 4; MEL‑COS‑AS04)
The efcacy of the cosmetic melatonin solution was evaluated
at four hair salons within the framework of an open‑label
observational study, which included 40 male and 20 female
patients (mean age 41 years) with early‑stage hair loss or
hair‑thinning, who applied the melatonin hair solution each
evening for 90 days.[42] The study was conducted as an
open‑label, “non‑FDA‑related” cosmetic study at 4 hair salons
in Tampa, FL, USA from June 2005 to September 2005.
Prior to participating in the study the patients given written
informed consent. Based on a 4‑point scale the hair stylists
reported an improvement in hair texture during treatment
with the cosmetic melatonin hair solution, which achieved a
statistically signicant level in both the female as well as the
male patients (P=0.002 and P=8 * 10‑5, respectively). In
addition, the hair stylists identied a reduction in hair loss,
which was also statistically signicant among both women
and men (P=4 * 10‑6 and P=3 * 10‑5, respectively) [Table 1].
Mean hair loss, as determined by the patients during a timed
60‑second hair count test performed while combing their hair
each morning,[43] fell signicantly among women during the
rst 40 days and continued to drop signicantly during the
next 40 days, while mean hair loss in men remained almost
constant throughout the course of the study, though it was
considerably lower than the mean value for women. With
respect to satisfaction with the treatment, the entire group
exhibited a trend toward improvement, whereby satisfaction
among women increased signicantly (P=0.002) and remained
almost constant among the men [Table 1]. Four patients
experienced mild side effects during the course of the study,
including temporary reddening, sensitivity, itching or burning.
However, none of these patients discontinued the study.
Multicenter study proves efcacy (Study 5;
MEL‑COS‑AS05)
A large, open‑label, multi‑center study, which included
Figure 3: Reduction of the hair loss assessed by means of objective
questionnaires completed by medical investigators. Percent values
above the bracket: Sum of the percent values for “minor improvement
with reduction in hair loss”, “moderate improvement with cessation of
hair loss” and “hair growth”
Table 1: Improvement of hair condition
Entire group Women Men
Hair texture
(4-point scale)
0.74 (P=7.10-9) 1.08 (P=0.002) 0.58 (P=8.10-5)
Hair loss
(5-point scale)
0.59 (P=1.10-7) 0.69 (P=4.10-6) 0.55 (P=3.10-5)
Satisfaction
(4-point scale)
0.22 (P=0.045) 0.46 (P=0.002) 0.10 (P=0.50)
Dierence from the mean value at 60 and 90 days minus value at 30 days. All the values are
increases of the values on a 4-point and 5-point scale, respectively; Statistical test: Paired t-test
0.0 3.4
19.3
73.3
48.2 48.3
13.3
31.0
16.0
13.3 13.8 16.1
0.0 3.4 0.0
0
10
20
30
40
50
60
70
80
30 days 90 days 180 days
Proportion of patients (%)
Treatment duration
Continued hair loss
No change in hair loss
Minor improvement with reduction in hair loss
Moderate improvement with cessation of hair loss
Hair growth
48.2%
26.6% 32.1%
901 men (47.6%) with stage I or II AGA (Hamilton scale)
and 990 women (52.4%) with stage I or II AGA (Ludwig
scale), all of whom applied a cosmetic hair solution
containing melatonin each evening for 90 days, was
carried out at 200 dermatology centers and practices
in order to provide a comprehensive assessment of
the therapeutic benefits of the cosmetic melatonin
solution.[44] The study was carried out from March 2004
to October 2006 under the guidance of the Instituto
Dermatologico Europeo [European Dermatological
Institute] (IDE) in Milan, Italy following review and
approval by the corresponding Ethics Comittee in
accordance with GCP. Prior to participating in the study
the patients gave written informed consent.
Clinical response was evaluated based on hair pull tests, a
semi‑quantitative method for the assessment of hair‑loss
activity.[4,45] Each hair pull test was classied as positive
based on three levels (+, ++, +++) or negative (‑). Over the
course of the study the results from the tests performed by
the medical investigators at Day 30 and Day 90 revealed a
signicant decrease—from 61.6% to 33.7% (after 30 days)
and 7.8% (after 90 days)—in the proportion of patients
Fischer, et al.: Melatonin and androgenetic alopecia
International Journal of Trichology / Oct-Dec 2012 / Vol-4 / Issue-4 241
with severe and moderately severe hair loss (P< 0.001).
In addition, the proportion of patients in whom no hair
loss was identied, rose signicantly from 12.2% to 25.5%
(after 30 days) and 61.5% (after 90 days) during treatment
with the cosmetic melatonin solution (P<0.001; Student’s
t‑test) [Figure 4].
According to the objective assessment of the medical
investigators, treatment with the cosmetic melatonin
solution resulted in significantly improved hair loss
in 59.4% and 66.4% of patients after 30 and 90 days,
respectively (P < 0.001), while new hair growth was
identied in 4.5% and 22.5% of patients at the same
respective intervals (P<0.001) [Figure 5].
According to the subjective self‑assessment performed by
the patients, the proportion of patients suffering from mild
or severe hair loss rose initially after 30 days from 71.4%
to 82.0%, but then dropped signicantly to 60.0% after
90 days. Consequently, the proportion of patients reporting
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7.7 2.0 0.5
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4.9
31.8 36.6
27.0
32.5
45.4
67.6
0
20
40
60
80
0 days 30 days90 days
Proportion of patients (%)
Treatment duration
Severe
Moderately severe
Slight
None
5.4%
35.7% 18.0%
Figure 7: Seborrhea
no hair loss dropped from 27.7% to 18% after 30 days,
but then rose considerably to 40% after 90 days [Figure 6].
In addition to a reduction in hair loss, treatment with
the melatonin solution also improved seborrhea. The
proportion of patients with moderately severe or severe
seborrhea was initially 35.7% and dropped to 18% and
5.4% after 30 and 90 days, respectively. Meanwhile, the
correspondingly signicant increase in the proportion
of patients reporting no seborrhea went from 32.5%
(at baseline) to 45.4% (after 30 days) and 67.6% (after
90 days) (P<0.001) [Figure 7].
The presence of seborrheic dermatitis was included as
another study parameter. At the start of the study the
proportion of patients with seborrheic dermatitis was
34.5%; this value dropped to 22.4% and 9.9% following
application of the cosmetic melatonin solution for 30 days
and 90 days, respectively. Consequently, the proportion
of patients reporting no seborrheic dermatitis increased
Fischer, et al.: Melatonin and androgenetic alopecia
242 International Journal of Trichology / Oct-Dec 2012 / Vol-4 / Issue-4
from 65.5% to 77.6% and 90.1% at the same respective
intervals [Figure 8].
A majority of the patients (74.4%) was satised with the
cosmetic results following 90 days of treatment, while 23.3%
were moderately satised, and a small proportion (2.3%)
was dissatised with the results. Based on the assessments
by the medical investigators and the patients, treatment
with the cosmetic melatonin hair solution was considered
to be well tolerated by a majority of investigators (88.0%)
and users (82.7%), while both the investigators as well as
the patients classied the treatment as poorly tolerated in
only 2.0% and 3.0% of the cases, respectively. According
to the overall assessment by the medical investigators and
the patients, the melatonin solution was found to be more
highly effective in improving hair loss than other previously
used products in 85.3% and 80.8% of cases, respectively,
while only 0.7% of the medical investigators and 1.0% of
the patients found the cosmetic hair solution to be less
effective than other previously used products.
DISCUSSION
It is known based on in vitro testing in the hair organ
culture model that the neurohormone melatonin is able to
stimulate growth in human hair follicles.[35] On the basis of
ve clinical studies referred to, this paper examined whether
the results from the in vitro data could be conrmed under
in vivo clinical conditions.
The rst study on pharmacodynamics and tolerability
found a slightly elevated, yet not signicantly different
serum melatonin level following topical application
of a 0.0033% melatonin solution as compared with a
melatonin‑free placebo solution.[37] The cumulative amount
of the melatonin metabolite 6‑hydroxymelatonin, which
provides an indirect indication of serum melatonin levels,
was comparable in both groups. Neurocognitive changes
and effects on vital signs were not observed.
In the second study involving 30 patients with early‑stage
AGA, melatonin achieved a signicant reduction in hair
loss after 30 and 90 days. In evaluating the study it must
be borne in mind that the value of the results is limited
because they are not based on objective image‑supported
measuring methods but instead on objective examination
forms for the medical investigators and subjective
questionnaires for the patients; in addition, the observed
effect was not placebo‑controlled. Nevertheless, it should
be noted that a signicant before‑and‑after effect was
observed.[38] Tolerability was relatively good (18% of cases
reported intolerability) and acceptance of the product was
high at 90%.
The third study, an open‑label, clinically controlled study
involving 35 men with AGA, demonstrated that 6 months
of topical melatonin treatment resulted in a signicant
increase in hair density in 54.8% and 58.1% of the men after
3 and 6 months, respectively; these results were observed
using TrichoScan, an objective, digital software‑supported
epiluminescence technique.[40,41] The hair density value
was+29% (after 3 months) and+41% (after 6 months).[39]
The assessment by the medical investigators also found
an improvement in hair loss (27% to 48%; Month 1
and 3). A stabilization of hair loss was observed in 75%
of the patients at Month 1 and in 50% at Month 3 and 6,
respectively. The cosmetic characteristics of the hair
treatment were considered relatively good and tolerability
was also good in all but one of the 35 study participants.
In the fourth study, an observational study involving four
hair salons and 60 male and female patients with early‑stage
hair loss, hair stylists performed a before‑and‑after
comparison of hair texture and hair loss based on a 4‑ and
5‑point scale, respectively; in this study the hair texture
was found to have signicantly improved and hair loss
was found to have signicantly decreased. Based on a
standardized combing test (60‑second hair count test)[43]
the female patients demonstrated a signicant reduction in
hair loss, while hair loss in men remained constant, but at
a low level.[42] Side‑effects included temporary reddening,
sensitivity, itching or burning, none of which resulted in
discontinuation of the study.
Finally, in the fth study, a 3‑month, large‑scale, open‑label,
multi‑center study involving 1891 female and male patients
with Stage I and II AGA, the proportion of patients with
34.5
22.4
9.9
65.5
77.6
90.1
0
20
40
60
80
100
0 days 30 days90 days
Proportion of patients (%)
Treatment duration
Present Not present
Figure 8: Sebohhheic dermatitits
Fischer, et al.: Melatonin and androgenetic alopecia
International Journal of Trichology / Oct-Dec 2012 / Vol-4 / Issue-4 243
2‑ and 3‑fold positive hair pull tests dropped from 61.6%
at baseline to 7.8% after 3 months, while the proportion
with negative hair pull tests (no hair loss) rose from 12.2%
to 61.5%.[44] Based on objective standardized examination
forms for the medical investigators a reduction in hair
loss of up to 66% was able to be identied, while new
hair growth was identied in up to 22.5% of patients
after 3 months. In addition, the medical investigators
observed a reduction in the proportion of patients with
severe and moderate seborrhea from 35.7% to 5.4%.
This was observed in association with a simultaneous
reduction in seborrheic dermatitis from 34.5% to 9.9%.
Eighty‑eight percent of the medical investigators and
82.7% of the patients classied the tolerability of the
melatonin‑containing solution as above average, while 2%
and 3%, respectively, classied it as poor.
The designs for the studies on the effect of melatonin
on AGA and on hair loss, respectively, must be evaluated
using different approaches. The rst study by Lorenzi and
Caputo (Study 2)[38] made exclusive use of examination
forms for the medical investigators and questionnaires
for the patients; while the examination forms enabled an
objective clinical evaluation based on training at least in the
case of the medical investigators, they were still subject to
higher variability than objective measurement methods.
In contrast the second study by Lorenzi (Study 3)[39] used
an objective, instrument‑based method, the TrichoScan,
and included 35 men. The intra‑investigator correlation
coefcient for the TrichoScan method is reported to be
91% and the intra‑investigator correlation coefcient
97%.[41] Thus, the TrichoScan method provides a
reliable before‑and‑after comparison and is highly
reproducible during the course of a clinical study.[40,41,46]
The increase in the measured hair count from 123 hairs/
cm² at baseline to 159 and 173 hairs/cm² after 3 and
6 months, respectively, must be considered clinically
relevant. Study 4 was conducted as an observational study
including 60 patients, in which signicant improvements
were identied in the before‑and‑after comparisons of
hair texture and hair loss; however, the study included
no placebo group. The 60‑second hair count test is a
relatively standardized method performed by the patients
themselves, in which the patients are required to comb
their hair continuously for 60 seconds. The method
is easy to perform and reproduces daily hair loss in a
standardized manner.[43] The multi‑center study (Study 5)
with over 1800 participants at 200 centers is the largest
study on the use of melatonin in early‑stage AGA[44]
and in terms of the number of patients it exceeds the
large‑scale study on the use of nasteride in male AGA
with 1500 patients.[47] The semi‑quantitative methodology
of the pull test is subject to relatively major inter‑
investigator variability. However, it should be noted
that the individual investigators usually achieve a high
level of intra‑individual standardization.[4,45] While the
method is considerably inferior by quality with respect
to variance and reproducibility as compared with the
TrichoScan method, the blinded hair count method
or global photography evaluation by a blinded panel
of investigators, the method still provides results with
a certain level of reliability based on intra‑individual
standardization by the individual investigators. In the
case of the multi‑center study with 200 centers under
consideration here, the high number of centers reduces
the inuence of inter‑investigator variability on the
study results to a relatively low level. However, this study
was not placebo‑controlled either, which still decreases
its signicance. Nevertheless, the study included two
further study parameters, seborrhea and the presence
of seborrheic dermatitis, which represent signicant
negative impacts on patients and which responded well
to treatment with melatonin.
The positive effects of melatonin on hair growth in
patients with AGA were conrmed by the results from
a pilot study on melatonin, which was conducted as a
placebo‑controlled, randomized, double‑blind study on
40 patients with androgenetic and/or diffuse alopecia.[36]
Although melatonin’s exact mechanism of action in the
stimulation of growth in human hair is not yet clearly
understood, studies on animals and on in vitro[33] animal and
human organ culture models with hair follicles offer some
clues. Research in the animal sciences especially has shown
that melatonin can increase wool and cashmere production
and modulate the development and cycle regulation of
outer coats, molting, and hair color.[48,49]
Receptor‑mediated melatonin effects are theoretically
possible because the MT1 membrane receptor has been
detected in both human hair follicle keratinocytes and
broblasts of the dermal hair papillae by means of Real
Time Polymerase Chain Reaction (RT‑PCR)[30] as well as
in situ in the human scalp at the center of the outer and
inner root sheath of the hair follicle.[28] An aberrant form
of the MT2 membrane receptor has also been detected in
human broblasts of the dermal hair papillae.[30] A specic,
hair cycle‑dependent expression of MT2 in the skin has
been demonstrated in the C57BL/6 mouse model.[34] Thus,
this receptor could have a functional inuence on the hair
cycle if the knowledge gained from the mouse model can be
applied to humans. To date only weak expression of MT2 in
the human hair follicle has been detected in the inner root
sheath using immunohistochemical techniques.[28] While
Fischer, et al.: Melatonin and androgenetic alopecia
244 International Journal of Trichology / Oct-Dec 2012 / Vol-4 / Issue-4
individual human skin cells (keratinocytes, melanocytes,
broblasts) contain the MT3 receptor or NQO2, it has
not been detected to date in individual hair follicle cells
or in situ in the hair follicle.[27] MT3/NQO2 could play a
role in the prevention of oxidative stress in HF catagen
regression or in oxidative stress‑induced hair aging.[12] The
nuclear melatonin receptor RORα performs a biological
function in hair growth because RORα‑knock‑out mice
had signicantly thinner coats.[33] Hair cycle‑dependent
regulation of the nuclear receptor in the inner and outer
root sheath was also able to be identied in C57BL/6
mice.[34] The melatonin receptors identied to date are all in
the root sheath of the hair, which assists in the regulation of
hair growth in addition to mechanically stabilizing the hair
shaft. Thus, it can be inferred that the growth‑promoting
properties of melatonin are at least partially regulated by
its receptors in the root sheath of the hair.
The effect of melatonin on hair growth may also be
mediated by interaction with androgens and estrogens as
well as their receptors, as evidenced by the antiandrogenic
effect of melatonin on benign prostate cells.[50] While the
antiandrogenic effect on prostate cells is accompanied by
an inhibition of proliferation, antiandrogenic effects on
hair follicles include prolongation of the hair cycle and
decreased miniaturization.[2] Human benign prostate cells
and human skin express functionally active melatonin
receptors (MT1),[30,51] making it possible to also assume a
melatonin receptor‑mediated, antiandrogenic effect in the
skin and hair follicles.
Melatonin has also demonstrated a modulating effect on
the aromatase activity and gene expression necessary for
the formation of estrogen in mammary cancer cell lines.[52]
Melatonin performs hair cycle‑dependent regulation of
α‑estrogen receptor gene expression in murine hair
follicles.[34] Relevance to human hair follicles will need to
be claried in functional studies.
In summary, it can be stated that multiple studies with
different study designs observed mostly positive effects
resulting from the topical application of a cosmetic
melatonin solution in women and men with early‑stage
AGA (Phase I and II, Hamilton and Ludwig scales,
respectively) or general hair loss with a partial reduction
in hair loss, as well as new hair growth in some cases.
Although the mechanism of action has not yet been
claried in detail, it appears highly likely that it is based
on a melatonin receptor‑mediated antiandrogenic effect
and/or an antioxidative effect. Due to the fact that the
application of the melatonin solution has been shown to
be very well tolerated in a total of 5 studies and because
positive effects on hair growth were observed in the
before‑and‑after comparisons, the cosmetic melatonin
solution represents a possible option for delaying hair
aging, hair loss in general, and for the treatment of
early‑stage AGA in men and women.
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How to cite this article: Fischer TW, Trüeb RM, Hänggi G,
Innocenti M, Elsner P. Topical Melatonin for Treatment of
Androgenetic Alopecia. Int J Trichol 2012;4:236-45.
Source of Support: Nil, Conict of Interest: None declared.
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  • ... The miniaturization of terminal hairs is frequently associated with activated T-cell infiltrates about the follicular bulge, and progressive fibrosis of the perifollicular sheath [1,44]. The potential trigger factors for the microinflammation might be resident microbial flora in the case of associated seborrhea, toxins and oxidative stress, the aging process in general, ultraviolet radiation exposure, smoking, and/or environmental pollutants [45]. Indeed, increased stress, increased smoking, having more children, and having a history of hypertension and cancer, may all be associated with increased hair thinning [46]. ...
    ... Melatonin in low doses enhances in vitro human hair follicle proliferation, though it inhibits hair growth in high doses. Stimulation of hair follicles can be suppressed by potent melatonin antagonists indicating a specific receptor-mediated mechanism of melatonin action on hair follicles [45]. Keratinocytes, melanocytes, and fibroblasts all feature functional melatonin receptors [139], the melatonin receptors are located in the root sheath of the hair, which may assist in the regulation of hair growth and stabilization of the hair shaft [140]. ...
    ... Clinical trials with topical application of melatonin (0.0033%) have been performed in patients with AGA. At 3 and 6 months, patients exhibited significant increases in hair density of 29% and 41%, respectively [45]. ...
    Article
    Full-text available
    Introduction: Treatments for androgenetic alopecia constitute a multi-billion-dollar industry, however, currently available therapeutic options have variable efficacy. Consequently, in recent years small biotechnology companies and academic research laboratories have begun to investigate new or improved treatment methods. Research and development approaches include improved formulations and modes of application for current drugs, new drug development, development of cell-based treatments, and medical devices for modulation of hair growth. Areas covered: Here we review the essential pathways of androgenetic alopecia pathogenesis and collate the current and emerging therapeutic strategies using journal publications databases and clinical trials databases to gather information about active research on new treatments. Expert opinion: We propose that topically applied medications, or intra-dermal injected or implanted materials, are preferable treatment modalities, minimizing side effect risks as compared to systemically applied treatments. Evidence in support of new treatments is limited. However, we suggest therapeutics which reverse the androgen-driven inhibition of hair follicle signaling pathways, such as prostaglandin analogs and antagonists, platelet-rich plasma (PRP), promotion of skin angiogenesis and perfusion, introduction of progenitor cells for hair regeneration, and more effective ways of transplanting hair, are the likely near future direction of androgenetic alopecia treatment development.
  • ... [42] Melatonin has been found to modulate hair growth, pigmentation, and molting in many species including humans. [43] The topical application of the melatonin 0.1% solution was shown to significantly increase anagen hair in male and female AGA with good compliance in a controlled study [44] 5) Platelet-rich plasma: it is an autologous concentration of human platelets contained in a small volume of plasma and is composed of several different growth factors-platelet-derived growth factor, transforming growth factor-alpha, vascular endothelial growth factor, insulin-like growth factor 1, epidermal growth factor, basic fibroblast growth factor, transforming growth factor-beta1, and platelet-activating factor that are released through degranulation. Various studies have reported improvement in regrowth rates after five local treatments of 3 mL of platelet-rich plasma (PRP) at 2-3-week intervals and histology examinations showed thickened epithelium, the proliferation of collagen fibers and fibroblasts, and increased vessels around follicles [45] ...
    Article
    Full-text available
    Female pattern hair loss (FPHL) is nonscarring progressive thinning of hair with gradual decrease in the number of hair, especially in the frontal, central, and parietal scalp, due to a process known as follicular miniaturization. The etiopathogenesis of FPHL is complex with multiple factors such as genetics, inflammation, hormones, and environment playing role in it. It usually manifests as slowly progressive hair thinning, mainly over the vertex and upper parietal scalp, the frontal hairline is often spared and the miniaturization is also not as severe as in men. A thorough history, clinical examination, hair loss evaluation tests, dermoscopy, and scalp biopsy can help in establishing the diagnosis. Various biochemical tests may be needed in patients with hyperandrogenism. The treatment includes medical and surgical modalities. Topical minoxidil is still considered the first line of treatment. Along with medical therapy, cosmetic camouflage may also be needed in some cases.
  • ... Several studies have revealed that mammalian skin possesses a melatoninergic system [4,5], where melatonin synthesis decreases with aging. However, topical melatonin has been shown to improve the clinical signs of skin aging [6], promote skin wound healing [7][8][9], and to treat many skin pathologies such as atopic dermatitis [10][11][12][13], seborrheic dermatitis [14], and vitiligo [15,16]. Thus, the pleiotropic biochemical action of melatonin at the skin level could represent an effective anti-aging strategy as well as an excellent therapeutic treatment for skin pathologies. ...
    Article
    Full-text available
    When exposed to hostile environments such as radiation, physical injuries, chemicals, pollution, and microorganisms, the skin requires protective chemical molecules and pathways. Melatonin, a highly conserved ancient molecule, plays a crucial role in the maintenance of skin. As human skin has functional melatonin receptors and also acts as a complete system that is capable of producing and regulating melatonin synthesis, melatonin is a promising candidate for its maintenance and protection. Below, we review the studies of new metabolic pathways involved in the protective functions of melatonin in dermal cells. We also discuss the advantages of the topical use of melatonin for therapeutic purposes and skin protection. In our view, endogenous intracutaneous melatonin production, together with topically-applied exogenous melatonin and its metabolites, represent two of the most potent defense systems against external damage to the skin.
  • ... Sus propiedades antitumorales se han comprobado en diferentes modelos tumorales, que incluyen el melanoma y tumores de origen epitelial (11,12). También se ha visto la influencia de la melatonina en el crecimiento del pelo (13,14) y en algunos estudios se ha visto que puede jugar un papel en la etiología del eccema atópico (15) y la psoriasis (16). ...
  • ... Hair density improved 29.1% in 54.8% of patients, and 40.9% in 58.1% of patients after 3 and 6 months, respectively. Continued research using 0.0033% topical melatonin solution, including a large multicenter study, demonstrated improvements in hair texture, decreased hair loss, and a reduction in seborrheic dermatitis [53,54]. ...
    Article
    The treatment of alopecia is limited by a lack of therapies that induce and sustain disease remission. Given the negative psychosocial impact of hair loss, patients that do not see significant hair restoration with conventional therapies often turn to complementary and alternative medicine (CAM). Although there are a variety of CAM treatment options on the market for alopecia, only a few are backed by multiple randomized controlled trials. Further, these modalities are not regulated by the Food and Drug Administration and there is a lack of standardization of bioactive in gredients in over-the-counter vitamins, herbs, and supplements. In this article, we provide a comprehensive review of the efficacy, safety, and tolerability of CAM, including natural products and mind and body practices, in the treatment of hair loss. Overall, there is a need for additional studies investigating CAM for alopecia with more robust clinical design and standardized, quantitative outcomes.
  • ... In this context, melatonin modulates hair growth, pigmentation, and molting in many species including humans (Fischer et al., 2008;Singh and Jadhav, 2014). The topical application of the melatonin 0.1 % solution was shown to significantly increase anagen hair in male and female AGA with a good compliance in a controlled study (Fischer et al., 2012). ...
    Article
    Full-text available
    Female pattern hair loss (FPHL) is the most common form of alopecia in women. Affected women may experience psychological distress and impaired social functioning. Early diagnosis and initiation of treatment are desirable because treatments are more effective to avoid the progression of hair loss than stimulating regrowth. Typically, a diagnosis of FPHL can be confirmed by review of a patient's medical history and a physical examination alone. Testing a scalp biopsy is diagnostic but usually not required. In women with signs of hyperandrogenism, an investigation for ovarian or adrenal disorders should be performed. Treatment for FPHL is obscured by myths. The aim of FPHL treatment could be two-fold: Reverse or stabilize the process of hair follicle miniaturization. Mild-to-moderate FPHL in women can be treated with oral antiandrogen therapies (cyproterone acetate and spironolactone) and/or topical minoxidil with good results in many cases. If used correctly, available medical treatments arrest the progression of the disease and reverse miniaturization in most patients with mild-to-moderate FPHL. Hair systems and surgery may be considered for selected cases of severe FPHL.
  • ... For a detailed overview on the different miscellaneous products, please refer to the long version of the guidelines. 1 When looking at the includes studies, 21 trials examined a single product, 37,39,50,[115][116][117][118][119][120][121][122][123][124][125][126][127][128][129][130][131][132] while five trials investigated combinations of different products. 36,40,45,116,133 Evaluation of individual ingredients is limited, as most of the tested products contain multiple different substances. ...
    Article
    Androgenetic alopecia is the most common hair loss disorder, affecting both men and women. Initial signs of androgenetic alopecia usually develop during teenage years leading to progressive hair loss with a pattern distribution. Moreover, its frequency increases with age and affects up to 80% Caucasian men and 42% of women. Patients afflicted with androgenetic alopecia may undergo significant impairment of quality of life. The European Dermatology Forum (EDF) initiated a project to develop evidence-based guidelines for the treatment of androgenetic alopecia. Based on a systematic literature research the efficacy of the currently available therapeutic options was assessed and therapeutic recommendations were passed in a consensus conference. The purpose of the guideline is to provide dermatologists with an evidence-based tool for choosing an efficacious and safe therapy for patients with androgenetic alopecia.
  • ... [25] Human skin and hair follicles have a melatonergic enzyme system, which expresses the specific enzymes necessary for melatonin biosynthesis. [27] Melatonin acts as a potent antioxidant, direct radical scavenger, and anti-aging factor and protects against damage caused by UV rays. [5] Melitane, a biomimetic peptide agonist of α-MSH, stimulates melanin synthesis, inducing skin pigmentation via the activation of its receptor MC1-R. ...
    Article
    Full-text available
    In today’s world, physical appearance and the desire to look young are very important. Skin and hair play a powerful role in this as they impart much information, not only about our race, ethnicity, and health but also about gender and age. We experience a significant change in pigmentation during our journey of life from birth to puberty and then to young adulthood, middle age, and beyond. Graying of hair is a conspicuous sign of aging. It is said that 50% of the people have 50% gray hair by the age of 50. Premature graying or premature canities is defined as graying that occurs before the age of 20 in Caucasians, before 25 in Asians, and before 30 in Africans. The pathogenesis of premature canities is not yet clear but various hypotheses have been suggested including alteration in pH and cysteine levels in melanosomes, the role of trace metal ions, vitamin B12 and folic acid, vitamin D3, and oxidative stress. Along with increased awareness, there is an increased demand for treatment modalities but the options are limited and unsatisfactory. Various topical preparations containing phytic acid, amino acids, peptides, acetyl hexapeptide-1, melitane, capixyl, pea proteins, etc. are already available in the market. Currently, research is focusing on topical liposome targeting melanins, genes, and proteins selective to hair follicles for therapeutic and cosmetic modification of hair. Keywords: Melanosomes, melitane, oxidative stress, canities, premature graying
  • Article
    Die androgenetische Alopezie gehört bei vielen Männern zum Älterwerden, aber auch bei Frauen tritt Alopezie auf. Für die Behandlung kommen etablierte und aufstrebende Optionen infrage — wenn der Haarausfall gestoppt ist, zudem auch eine Haartransplantation.
  • Article
    Melatonin, an evolutionarily ancient derivative of serotonin with hormonal properties, is the main neuroendocrine secretory product of the pineal gland. Although melatonin is best known to regulate circadian rhythmicity and lower vertebrate skin pigmentation, the full spectrum of functional activities of this free radical-scavenging molecule, which also induces/promotes complex antioxidative and DNA repair systems, includes immunomodulatory, thermoregulatory, and antitumor properties. Because this plethora of functional melatonin properties still awaits to be fully appreciated by dermatologists, the current review synthesizes the main features that render melatonin a promising candidate for the management of several dermatoses associated with substantial oxidative damage. We also review why melatonin promises to be useful in skin cancer prevention, skin photo- and radioprotection, and as an inducer of repair mechanisms that facilitate the recovery of human skin from environmental damage. The fact that human skin and hair follicles not only express functional melatonin receptors but also engage in substantial, extrapineal melatonin synthesis further encourages one to systematically explore how the skin's melatonin system can be therapeutically targeted in future clinical dermatology and enrolled for preventive medicine strategies.