ARTICLE
Seborrhea is a cosmetic skin problem for which topical treatment is often
ineffective. In our experience, there are very few substances which are
active in reducing sebum production when applied to the surface of the
skin [1-5]. Moreover, detecting and quantitating reduced sebum production
is difficult by simple physical examination, so more sophisticated measurement
techniques have to be used.
The overall strategy in identifying products with anti-seborrheic activity
may include identifying those which stimulate sebum absorption by the
stratum corneum. The aim of this work was to quantify the anti-seborrheic
activity of Effidrate® cream (produced by the La Roche
Posay company), a product which is based on a glycerol alkyl-ether which
has well-characterized activity against Propionibacterium acnes.
An open study was conducted to compare treated and untreated areas of
the skin of the subjects' foreheads.
Subjects
Twenty healthy men of between 25 and 39 years of age were included in
the study after they had signed an Informed Consent Form. The main inclusion
criterion was a measured level of over 250 µg/cm2 of sebum
on the forehead. All subjects were required to abstain from taking drugs,
applying cosmetic products to their skin and exposing themselves to sunlight
or any other source of ultraviolet radiation throughout the duration of
the study.
Experimental design
For a total of 12 weeks, each subject applied Effidrate®
cream twice a day to a 5 x 3 cm area on one side of his forehead. A template
was used to map out the area to be treated. The untreated area on the
opposite side was used as the control.
The method used to evaluate seborrhea has been described elsewhere [4].
Sebum excretion was measured at three-week intervals (T0, T3, T6, T9 and
T12) using a SM810® Sebumeter (C + K Electronics, Cologne)
and lipid-absorbent Sebutape® (Cuderm Corporation, Dallas).
At least 14 hours elapsed between the last application of the cream and
the measurements. Throughout the period of the study, both the outside
temperature and that inside the clinic were below 21° C. In order
to avoid problems associated with circadian variation in the number of
actively secreting sebaceous follicles in the forehead, all measurements
were made between 10 and 12 a.m. Subjects were instructed not to wash
their foreheads on the morning of the day on which measurements were made.
The sebum casual levels (µg/cm2) were recorded using
a Sebumeter® and the sebum excretion rate (SER, µg/cm2/h)
was derived from a second set of readings made exactly one hour after
the skin of the forehead had been thoroughly cleaned by wiping with pads
soaked in 70% ethanol. Other measurements were made using Sebutape®.
Again, the skin surface was cleaned with ethanol-soaked pads before application
of a strip of Sebutape®. This first strip was removed after
one hour and a second strip was applied to exactly the same area for the
same period of time. This cycle was repeated four times to harvest the
total cumulative sebaceous output over a 4 hour period. All samples were
subjected to image analysis to quantitate the total spot area (TSA, expressed
in arbitrary units) on the lipid-absorbent strips. The spots were formed
by sebum secreted from infundibular reservoirs. Each 4h-TSA value corresponds
to the sum of the 4 TSA values for the strips successively applied to
one part of the forehead: these values were used to compare treated and
untreated skin. In addition, since sebum excretion from the infundibular
reservoir is linear for several hours after the removal of lipids from
the surface of the skin, the slope of this correlation could be calculated
to derive the Follicular Reservoir Evacuation Rate (FRER) (Fig.
1).
Statistics
For each variable, the mean, the standard deviation, the median and
the percentage variation with respect to the starting median value were
all calculated. Friedman's non-parametric test followed by a Dunn test
were used to compare sebum secretion over time in treated and untreated
skin. In addition, a paired Student-t test was used to compare treated
and untreated skin at the T0 and T12 time points.
Results
Effidrate® cream was well tolerated and did not appear
to affect skin physiology. However, sebum measurements revealed that the
cream did affect sebum levels at the surface of the skin.
Sebum casual levels
At T0, no difference was observed between the sebum casual levels measured
on treated (321.5 ± 45 µg/cm2) and untreated skin
(320.4 ± 44.1 µg/cm2). Between T0 and T12, the amount
measured on untreated skin did not change. However, at T12, the amount
measured on treated skin was observed to be significantly lower than that
measured on control skin (by a factor of 5%, p = 0.01). This corresponds
to a significant decrease in the sebum casual level on treated skin between
T0 and T12 (a decrease of 5%, p < 0.01) (Fig.
2a).
Sebum excretion rate
At T0, similar SER were measured for treated (95.1 ± 8.4 µg/cm2/h)
and untreated skin (95.8 ± 8.2 µg/cm2/h). The rate
for untreated skin did not change between T0 and T12 but, over the same
period, a significant decrease in SER was observed for treated skin (a
decrease of 7%, p < 0.01) (Fig.
2b).
Cumulative follicular sebaceous output
No difference was detected in 4h-TSA measurements of follicular secretion
rates at T0 between treated (4547 ± 576 AU) and control skin (4540
± 523 AU). Between T0 and T12, significant reductions in the total
area of sebum spots was recorded for both control (a decrease of 4%, p
< 0.02) and treated skin (a decrease of 5%, p < 0.01) (Fig.
2c). At T12, the 4h-TSA reading for treated skin was slightly
lower than that for untreated skin (1% lower).
Follicular reservoir evacuation rate
No significant difference in FRER was detected between treated and untreated
skin, either at T0 or at T12. How-ever, this rate was observed to decrease
significantly between T0 and T12 in both control (a decrease of 2%, p
< 0.05) and treated skin (a decrease of 3%, p < 0.01) (Fig.
2d).
Discussion
In order to enhance the value of the data, two different methods were
used to measure the amount and dynamics of sebum at the skin surface.
This strategy is all the more necessary given that it is well recognized
that physical examination is of limited value in this field.
At the beginning of the study, all parameters relevant to seborrhea
were comparable between the treatment and control sites. This is consistent
with the well-documented fact that sebum excretion is symmetrical on the
forehead [7]. During the 12 week study, seborrhea was reduced all over
the forehead, but excretion in the area treated with Effidrate®
cream was reduced to a moderately greater extent than that in the untreated
part. A statistically significant difference was revealed by both photometric
and Sebumeter®-based measurements. In contrast, measurements
based on lipid-absorbent tape failed to demonstrate any sebosuppressive
activity on the part of the cream.
Why the two methods give different results is
not known. In practice, not all authors accept that the Sebumeter®-based
and Sebutape®-based techniques measure the same thing [8-10].
Analysis of the correlation between the two methods has given coefficients
as disparate as r = 0.5 [8] and r = 0.8 [9]. In our experience, correlation
is good for intermediate levels of sebum secretion but the results diverge
as secretion levels become more extreme (i.e. hypo- and hypersecretion).
One possible explanation for some of the differences between the two types
of result depends on the fact that sebum is collected in a different way
in each method. Lipid-absorbent tape only absorbs the free sebum present
in the upper part of the infundibulum [4, 11-14] and not the lipid material
spread out on the stratum corneum. In contrast, the photometric method
is based on a substrate which collects all the sebum present in the follicular
reservoir plus any on the interfollicular skin surface [7, 15]. This hypothesis
is based on the fact that the absorption of sebum onto Sebutape®
can be observed to result in spots whereas the Sebumeter®
head registers a relatively even layer of lipid. If this is the true explanation,
any reduction in sebum secretion which is detected by the Sebumeter®
but not by Sebutape® could be due to a dynamic effect on
sebum resorption, a mechanism which has already been observed and reported
[16].
On the basis of the results of these experiments, we conclude that the
cosmetic formulation tested may be acting by stimulating sebum absorption
by the stratum corneum.
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