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doi: 10.1111/ics.12501
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MRS. LUISA ZOE COLLINS (Orcid ID : 0000-0002-4117-3499)
DR. GRAHAM ANDREW TURNER (Orcid ID : 0000-0002-6051-7947)
Article type : Original Article
Sex-related differences in response to zinc pyrithione shampoo versus non-
anti-dandruff shampoo
L. Z. Collins*, F. L. Baines*, J. R. Matheson*, G. A. Turner*, Y. Diao†, Y. Li† and
Y. Pi†
*Unilever Research and Development Port Sunlight Laboratory, Bebington, Merseyside, UK and
†Unilever Research and Development Centre Shanghai, Changning District, Shanghai, P.R. China
Correspondence: Luisa Z. Collins, Unilever Research and Development Port Sunlight Laboratory,
Quarry Road East, Bebington, Wirral, Merseyside, CH63 3JW, UK. Tel: +44 (0)151 641 3980; e-mail:
luisa.z.collins@unilever.com
Co-author contact details:
F. L. Baines
Unilever R&D Port Sunlight, Quarry Road East, Bebington, Merseyside, CH63 3JW, UK; Tel: +44 151
641 3001; Fax: N/A; E-mail: fiona.baines@unilever.com
J. R. Matheson
Unilever R&D Port Sunlight, Quarry Road East, Bebington, Merseyside, CH63 3JW, UK; Tel: +44 151
641 3633; Fax: N/A; E-mail: jane.matheson@unilever.com
G. A. Turner
Unilever R&D Port Sunlight, Quarry Road East, Bebington, Merseyside, CH63 3JW, UK; Tel. +44 151
641 3705; Fax: N/A; E-mail: graham.turner@unilever.com
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Y. Diao
Unilever Research and Development Centre Shanghai, 66 LinXin Road, Changning District, 200335
Shanghai, P.R. China; Tel: + 86 21 22125926; Fax: N/A; E-mail: harbor.diao@unilever.com
Y. Li
Unilever Research and Development Centre Shanghai, 66 LinXin Road, Changning District, 200335
Shanghai, P.R. China; Tel: + 86 22 22125249; Fax: N/A; E-mail: ryan.lee@unilever.com
Y. Pi
Unilever Research and Development Centre Shanghai, 66 LinXin Road, Changning District, 200335
Shanghai, P.R. China; Tel: + 86 21 22125513; Fax: N/A; E-mail: echo.pi@unilever.com
Keywords: ceramides, dandruff, protein loss, sex, Total Weighted Head Score Adhered Flake (TWHS-
AF), zinc pyrithione
Presentations: Ceramide and total protein findings have been previously presented at 12th World
Congress of Cosmetic Dermatology, Bengaluru (2017) and 10th World Congress of Hair Research,
Kyoto (2017).
Abstract
OBJECTIVE: Sex-related differences in skin properties may be expected to impact on dandruff
formation and treatment. A meta-analysis approach was undertaken to investigate potential
differences between males and females in response to zinc pyrithione (ZnPT) treatment versus non-
anti-dandruff (AD) shampoo. A separate pooled statistical analysis of ceramide and total protein loss
endpoints was also undertaken to assess potential sex-related differences in stratum corneum
properties that might influence response to ZnPT versus non-AD shampoo in subjects with dandruff.
METHODS: The meta-analysis approach included data from 17 half-head, double-blind, randomized
studies (N=2088) undertaken in Asia to assess the effectiveness of 1% ZnPT shampoo and/or non-AD
shampoo in reducing dandruff severity, as assessed by Total Weighted Head Score Adherent Flake
(TWHS-AF) methodology. Treatment duration was 4 weeks, with TWHS-AF measured at weekly
intervals. Data from an additional three studies (N=143) conducted in Asia were included in the
pooled analysis of ceramide levels and protein loss from scalp skin of subjects with dandruff.
RESULTS: Response to 1% ZnPT versus non-AD shampoo was greater in males than in females at all
time points; after 4 weeks, the between-treatment difference in TWHS-AF was −17.5 (95%
confidence interval [CI] −19.5, −15.5) in males and −11.1 (−13.2, −8.9) in females. Sex-related
differences were observed between males and females in response to both 1% ZnPT and non-AD
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shampoos. Males had a stronger response than females to treatment with 1% ZnPT shampoo, while
dandruff decreased to a greater extent in females than in males when using non-AD shampoo.
Statistically significant sex-related differences in ceramide levels and total protein loss were
observed (both P<0.01). Ceramide levels were 0.76 times lower (95% CI 0.60, 0.97) in males than in
females, while total protein loss was 1.4 times greater (95% CI 1.1, 1.9) in males than in females.
CONCLUSION: Males show a greater response than females to 1% ZnPT shampoo, while females
show a greater response than males to non-AD shampoo. These findings may in part be explained by
the sex-related differences observed in stratum corneum properties, which may make males more
prone to dandruff than females.
Introduction
Dandruff is a common scalp disorder that affects at least half of the adult population worldwide at
some time [1]. Dandruff is generally characterized by stratum corneum flaking and scaling, and is
often accompanied by itch, skin tightness and erythema [2]. While the precise aetiology of dandruff
has still to be confirmed, the current scientific consensus is that dandruff development is influenced
by three major factors: Malassezia colonization, sebum production and individual predisposition.
However, the relative contributions of these factors as a trigger for dandruff formation remain the
subject of debate [3].
It is well documented that the commensal yeast Malassezia is a strong contributory factor to
dandruff development. In particular, the incidence of dandruff has been associated with an
increased abundance of Malassezia restricta [4]. However, the presence of Malassezia species on
healthy scalps indicates that this alone is not a sufficient cause for dandruff formation; more recent
evidence suggests that disruption of the stratum corneum may facilitate dandruff generation by
affecting susceptibility to metabolites from Malassezia species. A healthy stratum corneum forms a
protective barrier to prevent water loss, maintain hydration of the scalp and protect against external
insults [3]. Severe or chronic barrier damage can impair proper hydration, leading to atypical
epidermal proliferation, keratinocyte differentiation and stratum corneum maturation, which may
underlie some dandruff symptoms [5]. Measurement of total protein, recovered from the scalp
surface, can be used as marker of stratum corneum cohesion [6]. The depleted and disorganized
structural lipids of the stratum corneum in individuals with dandruff are consistent with a weakened
barrier, as indicated by elevated transepidermal water loss [7] and measurement of diminished
levels of total ceramides [6, 8, 9]. Further evidence of weakening of the protective barrier in
individuals with dandruff includes subclinical inflammation and greater susceptibility to topical
irritants [3]. The response to topically applied histamine has been shown to be greater in subjects
with dandruff than controls, also suggesting compromised barrier integrity [9].
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Dandruff is usually treated with anti-fungal agents such as zinc pyrithione (ZnPT), applied topically
through shampoo. Studies have demonstrated sex-related differences in a number of skin properties
that might be expected to impact dandruff formation and treatment, such as stratum corneum
hydration and skin barrier function as measured by transepidermal water loss [10]. In addition, there
may be differences in hair washing and styling methods between males and females that could
influence dandruff development [11]. A previous meta-analysis found no sex-related difference in
the efficacy of ZnPT treatment [12]; however, the authors did not consider the relative contribution
of detergency from non-anti-dandruff (AD) shampoo versus ZnPT shampoo. Furthermore,
therapeutic efficacy was only evaluated at a single time point compared with baseline.
This paper presents the results of a more recent meta-analysis undertaken to further investigate
potential differences between males and females in response to ZnPT treatment, taking into account
possible cleansing effects and examining treatment effects over several time points. The results of a
pooled analysis from an additional three clinical studies undertaken to assess potential sex-related
differences in levels of ceramide and total protein loss (as a marker of corneocyte loss) are also
presented, in order to explore possible underlying mechanisms that might influence response to
ZnPT.
Materials and methods
Meta-analysis of clinical trials assessing sex-related differences in response to ZnPT and non-AD
shampoos
Study design
Data from 17 Unilever-sponsored, half-head, double-blind, randomized studies conducted in Asia
since 2010 were included in four separate meta-analyses (Table I). Studies were included if they
assessed the effectiveness of 1% ZnPT shampoo (CLEAR, Unilever) and/or a non-AD shampoo in
reducing dandruff severity.
To be eligible for study inclusion, subjects were required to be 18–60 years of age and in good
general health, and to have qualifying levels of dandruff [7] not currently treated with an AD
shampoo. Exclusion criteria included: use of any medicine that could affect the study outcome; use
of ketoconazole-containing treatments within the last 6 months; use of treatments containing
selenium sulphide within the last 3 months; use of AD products within the last 2 months; hair
colouring or perming within the last 2 weeks; other medical skin conditions; any known allergies or
sensitivities to the ingredients in study shampoos; and pregnancy.
In all studies, dandruff severity was assessed using the Total Weighted Head Score Adherent Flake
(TWHS-AF) methodology; this is a well-defined approach for assessing the efficacy of AD treatment
[7, 9, 13]. All studies involved a 2- to 3-week pre-treatment washout period, followed by a test phase
of at least 4 weeks and a 0- to 4-week regression phase, with dandruff scored at weekly intervals
throughout. During the pre-treatment washout period, there were two dandruff assessments
(TWHS-AF): screening and rescreen. If the subject’s screening score and other conditions met the
inclusion/exclusion criteria, they were given a bottle of non-AD shampoo and instructed to wash
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their hair every other day for 2–3 weeks at home. At the end of the pre-treatment washout period,
subjects were rescreened to evaluate if they should progress onto the test phase. Qualifying subjects
were allocated two different test products, one for each side of the scalp (random allocation to side
of scalp). In studies involving two products, the rescreen score was treated as baseline; in studies
involving more than two products, there was a separate baseline visit following the washout period
to ensure balance of dandruff score and sex across the product groups. During the test phase,
subjects had their hair washed three times per week using the assigned product at the study site.
All studies were conducted according to the principles of good clinical practice and in compliance
with local government regulations, guidelines and standards applicable to such studies. All studies
were reviewed and approved by an independent ethics committee before initiation. All study
participants provided written informed consent.
Statistical analysis
To compare the effects of the test product (1% ZnPT shampoo) and non-AD shampoo over time and
by sex, analysis of covariance was conducted for each study using PROC MIXED in SAS (SAS Institute
Inc., Cary, North Carolina, USA). The baseline value was included as a covariate, with both a side-
level and a subject-level average to avoid any cross-level bias in product comparisons [14].
Additional factors were included as fixed effects to adjust for any potential effects of the product,
namely time point, sex and their interactions, and subject as a random effect. The protocol-
recommended UN@CS covariance structure and the ddfm=KR option were used. Four separate
meta-analyses were conducted using R [15] with the metafor package [16], using random-effects
models. Results are the combined estimate of the difference between and within groups at each
time point. If the 95% confidence interval (CI) did not enclose zero, then the difference was
considered to be statistically significant. The four meta-analyses were conducted to estimate:
I. Difference between males and females when treated with 1% ZnPT shampoo
II. Difference between males and females when treated with non-AD shampoo
III. Difference between 1% ZnPT and non-AD shampoo treatment in males
IV. Difference between 1% ZnPT and non-AD shampoo treatment in females
Pooled analysis assessing sex-related differences in ceramides and protein loss
Study design
Data from three Unilever-sponsored studies conducted in Asia were included in the pooled analysis.
Inclusion and exclusion criteria were as described above. In all studies, subjects used a non-AD
shampoo at home for 3–4 weeks, after which the dandruff score was re-assessed (2 days after the
last home wash). In subjects with TWHS-AF remaining at or above the study entry level after the
washout period, buffer scrubs were collected for measurement of ceramides and protein loss; two
buffer samples were collected from each subject (one from each side of the scalp). A section of scalp
skin was exposed by making a straight parting in the hair and securing the hair with standard salon
clips. To obtain a buffer scrub sample, a sterile plastic ring of 18 mm internal diameter and 60 mm
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height was placed on the parting and held steady by both the person carrying out the sampling and a
second operator. Using a sterile plastic disposable pipette, 2.0 mL of collection medium (sterile
phosphate-buffered saline, pH 7.9, containing 0.1% Triton X-100) was applied to the sample site. The
scalp was then gently massaged with a round-ended Teflon rod for 1 min. This was repeated with a
further aliquot of 2.0 mL of collection medium for a further 1 min.
All studies were conducted following the principles of good clinical practice and in compliance with
local government regulations, guidelines and standards applicable to such studies. All studies were
reviewed and approved by an independent ethics committee before initiation. All study participants
provided written informed consent.
Buffer scrub extractions
Buffer scrub samples were centrifuged and the corneocyte pellet retained. Lipid content from the
corneocyte pellet was extracted with 1 mL chloroform/methanol (2:1, high-performance thin-layer
chromatography grade) for 2 h at room temperature (referred to as ‘lipid extract’). The lipid extract
was dried at 37°C under nitrogen. Excess chloroform/methanol was allowed to evaporate from the
remaining lipid-depleted corneocytes.
Total protein loss assay
Lipid-depleted corneocytes were extracted in 10 mmol/L phosphate buffer, pH 7.8, containing 1%
(w/v) sodium dodecyl sulphate (SDS) and 20 mmol/L β-mercaptoethanol at 60°C for 1 h. The samples
were centrifuged for 10 min at 13,000 rpm, and the SDS/mercaptoethanol protein extract was
removed and analysed using the BCA™ Protein Assay Kit (Fisher Scientific, Loughborough, UK).
Ceramide levels
The lipid extracts were reconstituted in chloroform/methanol. Extracts were placed in duplicate
wells of a deep-well plate, and the volume was made up to 800 µL with methanol. HCl (1 mol/L) was
added to each well and the samples were dried overnight at 60°C. Samples were reconstituted in 80
mmol/L imidazole, 8 mmol/L triethylamine and 6.4 mmol/L acetic acid in 80% isopropanol, pH 8.3,
for 30 min at room temperature. Fluorescamine (2 mg/mL) in isopropanol was added, and 150 µL
was transferred to a microtitre plate. Fluorescence was read immediately at 360 nm (excitation) and
460 nm (emission) using a Millipore fluorescence plate reader. The ceramide signal generated after
hydrolysis was expressed as µg/µg extracted protein. Standard curves were created using Ceramide
2 (0–20 µg/mL; Givaudan [formerly Quest International], Ashford, UK) and sphingosine (0–10 µg/mL;
Sigma, Poole, UK) treated in the same manner as the samples.
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Statistical analysis
Total protein loss and ceramide (normalized by extracted protein) data from the three studies were
included in the statistical analysis. Regression analysis of log-transformed data was conducted to
include data from both sides of the head; consequently, the effect of subject-level variables (e.g. sex
and age) and study-level variables (e.g. study number) could be explored. A separate regression
model was fitted for total protein loss and ceramide to assess which of the exploratory variables
might have an effect. Subject ID was added as a random effect in all models. Only results for the
effect of sex are presented in this paper. Differences were considered statistically significant if they
had a P-value of less than 0.05; where a difference was found to be significant, the direction of this
significance is also given.
Results
Meta-analysis of clinical trials assessing sex-related differences in response to ZnPT and non-AD
shampoos
Key features of the 17 studies included in this meta-analysis are shown in Table I. Data were
available for a total of 2088 subjects, all of whom were of Asian race and 53% of whom were female.
Mean age at baseline ranged among studies from 30.6 to 46.9 years. Three studies directly
compared 1% ZnPT versus non-AD shampoo in males and females (n=374), and one study made the
comparison in females alone (n=86). The remaining 13 studies investigated either 1% ZnPT (eight
studies) or non-AD shampoo (five studies) in both males and females (n=1628).
Meta-analysis I included both males and females treated with 1% ZnPT (11 studies), whereas meta-
analysis II included both males and females treated with non-AD shampoo (8 studies). Comparisons
between meta-analyses I and II demonstrated a clear difference between female and male subjects
in terms of response to both 1% ZnPT and non-AD shampoo (Fig. 1). The difference in response to
1% ZnPT (females minus males) was statistically significant at Week 2 (1.4 [95% CI 0.3, 2.6]) and
Week 3 (2.0 [95% CI 0.6, 3.4]), indicating that males have a stronger response than females to
treatment with 1% ZnPT shampoo. In contrast, dandruff decreased to a greater extent in females
than in males when using non-AD shampoo; the difference (females minus males) was statistically
significant at Week 3 (−2.6 [95% CI −4.4, −0.8]) and Week 4 (−1.8 [95% CI −3.4, −0.2]).
Results from meta-analyses III and IV showed the response to 1% ZnPT versus non-AD shampoo to
be greater in males than in females at all time points evaluated (Table II). After 4 weeks, the
between-treatment difference in TWHS-AF was −17.5 (95% CI −19.5, −15.5) in male subjects and
−11.1 (−13.2, −8.9) in female subjects.
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Pooled analysis assessing sex-related differences in ceramides and protein loss
The pooled analysis included data from a total of 143 subjects (98 females and 45 males). All
subjects were of Asian race; mean age at baseline ranged from 24.5 to 25.4 years among the studies.
Statistically significant sex-related differences in ceramide levels and total protein loss (as assessed
in buffer scrub samples) were observed (both P<0.01). Ceramide levels were 0.76 times lower (95%
CI 0.60, 0.97) in males than in females (Fig. 2), while total protein loss was 1.4 times greater (95% CI
1.1, 1.9) in males than in females (Fig. 3).
Discussion
The results from the four meta-analyses, using data from 17 clinical studies, confirm the
effectiveness of 1% ZnPT-containing shampoo products in improving dandruff in both male and
female Asian subjects. The results also showed sex-related differences for ZnPT effectiveness
compared with non-AD shampoos in Asian consumers, driven by opposing sex-related responses to
AD versus non-AD shampoo. Our findings contrast with those of a previous meta-analysis of seven
studies that found no sex-related differences in response to ZnPT-containing shampoo [12].
However, this previous analysis did not take into account any effects of washing alone on dandruff
over time beyond the pre-treatment washout period. The current meta-analysis approach also
demonstrates a difference in the placebo effect between males and females, with dandruff in
females improving over time to a greater extent than in males in the absence of ZnPT. The
mechanism(s) for this difference are not clear, but may involve a long-term impact on barrier
function of different behavioural aspects of hair washing between males and females, as well as
possible differences in scalp skin physiology.
These findings are supported by the results of the pooled analysis undertaken to assess sex-related
differences in scalp stratum corneum ceramide levels and total protein loss in subjects with
dandruff. The results showed males to have significantly lower scalp ceramide levels and significantly
greater protein loss (in response to gentle scrubbing) compared with females. The stratum corneum
is an important element in scalp protection against external insults (e.g. microbes, pollution,
ultraviolet light, dirt, chemical residues) and acts as the primary epidermal barrier to water loss,
maintaining hydration, flexibility and integrity of the scalp [3]. This outer protective layer consists of
protein cells, lipids and water [17, 18]. Total protein loss is a marker of flakes adhered to the scalp
and of a weak barrier. Lipids, composed of ceramides, cholesterol and fatty acids, also play an
important role in maintaining the integrity of the scalp stratum corneum. Ceramides are critical to
the skin barrier structure and have been shown to be decreased in the scalps of subjects with
dandruff [6, 8, 9]. The finding that, compared with females, males have significantly lower ceramide
levels per corneocyte and significantly more protein loss (i.e. corneocyte loss) in response to gentle
abrasion implies an impaired skin barrier in males, which could make their scalps more prone to
dandruff.
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With a weaker scalp barrier, it is also possible that males do not benefit from the detergent effect
when using non-AD shampoo. Detergents in the shampoo will help to physically remove external
irritants, such as microbes, pollutants, dirt and chemical residues, and temporarily reduce their load.
After washing, the external irritants reaccumulate. It is possible that males, with a weaker scalp
barrier, are more sensitive to external irritant load than females, which might explain the lesser
reduction in dandruff levels seen in males following thrice-weekly washing with non-AD shampoo.
Subjects’ perception of changes in their dandruff relative to the subjective TWHS-AF measurement
was not evaluated in the studies included in these analyses. However, the observation of sex-related
differences in response to shampoos containing 1% ZnPT is consistent with a consumer poll
conducted in China (Unilever, data on file), which found that a higher percentage of men (68%) than
women (55%) were satisfied with their scalp condition after using shampoos containing 1% ZnPT.
A key strength of the current analyses is the large number of subjects included; the largest pool of
data was available for meta-analysis I (N=1714) for assessing sex-related differences in response to
ZnPT, with 143 subjects included in the pooled analysis assessing sex-related differences in
ceramides and protein loss. Although only studies in Asian subjects were included in the current
analyses, results of a previous meta-analysis found no differences in response to ZnPT between
Asian and Caucasian populations [12], suggesting that the sex-related differences observed in the
current analyses are widely applicable.
In summary, the results of these analyses suggest that males may be more prone to dandruff than
females because of lower ceramide levels and a greater propensity for protein loss in the stratum
corneum. These physiological differences may explain the finding that males experience less benefit
than females from the detergency of non-AD shampoo and show a greater response than females to
1% ZnPT shampoo. These findings warrant further research.
Acknowledgements
All studies and analyses reported in this paper were performed and funded by Unilever Research &
Development. Editorial assistance was provided by Jennifer Coward of Anthemis Consulting, funded
by Unilever Research & Development. The authors would like to thank Yajun Luo and Yingjie Li
(Unilever R&D Shanghai, P.R. China) for conducting the studies. Luisa Collins, Fiona Baines, Jane
Matheson, Graham Turner, Yuanyuan Diao, Yuanpei Li and Yingying Pi are employees of Unilever
Research & Development.
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Legends
Table I Summary of studies included in the meta-analysis.
Table II Between-treatment difference in TWHS-AF (1% ZnPT shampoo minus non-AD shampoo) for
males and females over time.
Figure 1 Mean (95% confidence interval) between-sex difference in TWHS-AF (females minus males)
for 1% ZnPT and non-AD shampoo over time.
Figure 2 Ceramide levels in buffer scrub samples from males and females with dandruff before
initiation of anti-dandruff treatment. Data are presented as back-transformed least-square means
with 95% confidence intervals.
Figure 3 Total protein extracted from buffer scrub samples in males and females with dandruff
before initiation of anti-dandruff treatment. Data are presented as back-transformed least-square
means with 95% confidence intervals.
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Table I Summary of studies included in the meta-analysis
Study
Year
Age
(years),a
mean (SD)
Test phase
duration
(weeks)
Treatment
Sample size,
n
(female/male)a
Meta-
analysis
groupsb
1
2010
33.0 (8.1)
4
Four products, including
1% ZnPT and non-AD
shampoo
174 (102/72)
I, II, III, IV
2
2013
31.5 (9.3)
6
Two products: 1% ZnPT
and non-AD shampoo
86 (86/0)
IV
3
2013
34.0 (8.8)
6
Two products, including
1% ZnPT
200 (100/100)
I
4
2013
30.6 (10.0)
4
Two products, including
1% ZnPT
208 (104/104)
I
5
2014
46.1 (11.0)
4
Two products, including
non-AD shampoo
57 (33/24)
II
6
2014
31.3 (9.5)
4
Two products, including
1% ZnPT
139 (55/84)
I
7
2014
33.3 (10.7)
4
Two products, including
1% ZnPT
119 (48/71)
I
8
2014
43.0 (12.0)
4
Two products, including
non-AD shampoo
48 (29/19)
II
9
2014
35.7 (10.0)
4
Three products,
including 1% ZnPT
132 (78/54)
I
10
2015
31.6 (9.8)
4
Five products, including
1% ZnPT
228 (114/114)
I
11
2015
32.2 (10.4)
4
Four products, including
1% ZnPT
186 (108/78)
I
12
2015
33.3 (11.0)
4
Two products, including
1% ZnPT
128 (64/64)
I
13
2015
33.3 (10.9)
4
Two products: 1% ZnPT
and non-AD shampoo
100 (51/49)
I, II, III, IV
14
2016
31.2 (10.5)
4
Two products, including
non-AD shampoo
99 (51/48)
II
15
2016
35.0 (11.9)
4
Two products: 1% ZnPT
and non-AD shampoo
100 (52/48)
I, II, III, IV
16
2016
46.9 (10.5)
4
Two products, including
non-AD shampoo
35 (15/20)
II
Accepted Article
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17
2016
33.9 (9.0)
4
Two products, including
non-AD shampoo
49 (27/22)
II
aAt baseline; bSee text for explanation of groups
AD, anti-dandruff; ZnPT, zinc pyrithione
Accepted Article
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Table II Between-treatment difference in TWHS-AF (1% ZnPT shampoo minus non-AD shampoo) for
males and females over time.
Time (weeks)
Mean between treatment difference in TWHS-AF
(95% confidence interval)
Males
Females
1
−7.3 (−8.7, −6.0)
−4.0 (−5.0, −2.9)
2
−13.1 (−15.0, −11.3)
−7.4 (−8.6, −6.1)
3
−17.3 (−19.2, −15.5)
−9.2 (−10.9, −7.5)
4
−17.5 (−19.5, −15.5)
−11.1 (−13.2, −8.9)
TWHS-AF, Total Weighted Head Score Adherent Flake
Accepted Article
This article is protected by copyright. All rights reserved.
Accepted Article
This article is protected by copyright. All rights reserved.
Accepted Article
This article is protected by copyright. All rights reserved.
