human diets needs further corroboration, prudence in describing the fatty acids in natural and in proc-

favors their provisional inclusion in the group of essed fats than is afforded by the general terms, ani-
nutrients required by man.
The problem of the nutritive value of the triglycér-
ides of common fatty acids is complicated by the fact
that man uses appreciable quantities of triglycérides of
other and unnatural fatty acids in his diet. This hap-
pens because of the commercial hardening of plant
oils by the process of hydrogénation. This procedure
not only forms saturated bonds from unsaturated
bonds but also may transform the natural "eis" isomers
to unnatural "trans" isomers. The latter have higher
melting points but remain unsaturated. Other un-
natural isomers may result from a shifting of the
double bonds along the carbon chain. At the present
time it is virtually impossible to describe chemically
some of the commercial hydrogenated plant oils be-
cause of their complexity.
Some plant oils such as corn, cottonseed, safflower,
soybean, and peanut oils are rich sources of trilinolein.
As noted before, hydrogénation replaces a significant
part of the linoleic acid with stearic acid and with
unnatural, unsaturated fatty acids. Arachidonic acid
occurs in small amounts in some animal fats. Olive oil,
although unsaturated, is a poor source of linoleic acid;
coconut oil, a plant fat, is saturated. Chicken fat is an
unusual animal fat because of its relatively large con-
tent of linoleic acid; fish oils are highly unsaturated
and are characterized by other polyunsaturated fats
in addition to some trilinolein. These illustrations
demonstrate the need of a more definitive terminology
mal or plant, hard or soft, saturated or unsaturated,
and low iodine or high iodine number.
Considerable evidence exists to show that, under
certain circumstances, sources of linoleic acid may
lower elevated serum cholesterol levels in man. The
evidence favors the concept that essential unsaturated
fatty acids are required for the normal transport of
cholesterol as lipoprotein and, possibly, phospholipid
complexes. Clarification of the circumstances under
which hypercholesteremia can be prevented, however,
remains to be delineated. Valid experimentation has
not yet determined the relative influence on serum
cholesterol of surplus dietary calories, of an excess of
the total dietary fat, of abnormal ratios of linoleic
acid to other fatty acids in the diet, or of numerous
other nutritive factors that may influence adversely
the physical and chemical characteristics of lipids in
the blood and in the walls of the vascular system.
Until a clear-cut solution of the problem of the pre-
vention of arteriosclerosis and of its sequelae is forth-
coming, it seems wise to assume that a faulty diet
may be one of the causative agents. Whether or not
dietary fat is, in some fashion, the culprit remains to
be proved. In the meantime, one may recommend the
dietary control required to attain and maintain opti-
mum body weight and the choosing of a varied diet
containing adequate amounts of those foods, includ-
ing fats, shown by experience and by experiment to
have special nutritive value.

COMMITTEE ON COSMETICS

Report to the Committee

The following paper was presented at the symposium, "The Rational Use of Cosmetics in
Medical Practice," in Chicago, June 13, 1956. This symposium toas sponsored by the Com-
mittee on Cosmetics, in cooperation with the Section on Dermatology, at the 105th Annual
Meeting of the American Medical Association. This is the third in a series of papers, the
others of which appeared in The Journal, March 2, page 740, and March 16, page 943.
Veronica Lucey Conley, Secretary.
ACTION OF EMOLLIENT CREAMS AND THEIR ADDITIVES
I. H. Blank, Ph.D., Boston
Some confusion exists among physicians, pharma- itching. If emollients and dryness are so defined, it
cologists, and cosmetic chemists as to just what con- becomes apparent at once that the emollient creams
stitutes an emollient. For the purpose of this discus- and lotions produced by the cosmetic manufacturer
sion, an emollient is defined as any externally applied and the simple emollient ointments and lotions pre-
material that tends to prevent or counteract the symp- scribed by the physician have much in common. Their
toms and signs of dryness of the skin. Very mild dry- functions are the same. The cosmetic manufacturer
ness may be apparent only as superficial scaling of the and the physician probably can learn from each other.
skin, but severe dryness may be accompanied by con- The majority of emollients, cosmetic or pharmaceu-
siderable scaling, fissuring, inflammation, pain, or tical, are mixtures of an oil and water. In addition,
an emulsifying agent is used to keep the oil and water

From the Dermatological Research Laboratories, Department

well mixed, and a perfume may be added. Any one or
of Dermatology, Harvard Medical School, Massachusetts Gen- more of a large variety of oils may be used. If the oil
eral Hospital. has a low melting point, the emollient will feel greasy

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 on the skin; if it has a high melting point, the resid-
ual oily film will not feel greasy. Because it does not
feel greasy, and because, as it is rubbed onto the sur-
face, its color probably changes from white to colorless,
it seems to "vanish." The external, continuous phase of
the emollient may be either oil or water; that is, the
emollient may be either a water-in-oil or an oil-in-
water emulsion, depending on the type of emulsifying
agent used. When the continuous phase is oil, water
is the dispersed phase and vice versa.
After these emollients are applied to the cutaneous
surface, some of the water may be taken up by the
stratum corneum, but most of it evaporates into the
air. The nonvolatile oil of the emollient remains on the
skin. It has been assumed, therefore, that the residual
oily layer serves as a "lubricant," since most of the
emollients have the physical characteristics of lubri-
cants. In order to act as a "lubricant," the oil should
locate between the lamellas of the stratum corneum,
thus allowing the lamellas to slip over one another and
permitting the skin to flex without breaking the stratum
corneum. With this in mind, attempts have been made
to find oily substances that would penetrate the strat-
um corneum. Lanolin and lanolin mixtures have been
said to penetrate the skin better than do other oils,
particularly petrolatum.
Indeed, lubrication might be one of the mechanisms
by which emollients act, but it does not seem to be
the major mechanism involved. It can be easily shown
that neither an externally applied oil nor the natural
oils can keep the stratum corneum flexible without
the aid of water.1 If the cornified epithelium (a piece
of callus or the top of a sunburn blister) is removed
from the skin and allowed to lose its water but none
of its natural oils, it becomes inflexible and brittle.
Immersion of this dry, brittle cornified epithelium in
various anhydrous oils for long periods of time, even
two or three years, will not make the cornified epithe-
lium flexible again. If the brittle callus is immersed
in water, however, it becomes quite flexible in a very
short time. Currently, water is the only known plasti-
cizer for keratinized tissue.
The application of a film of oil to the cutaneous sur-
face relieves the symptoms of dryness, however. This
film functions in two ways. First, the oil replaces a
roughened, scaly surface with a smooth film, and small
spicules of cornified epithelium, which extend above
the surface and produce roughness, are "cemented
down." Thus, the cutaneous surface seems smoother.
Second, and more important perhaps, if the oily films
are occlusive, they will retard the evaporation of water
from the cutaneous surface and help keep the stratum
corneum hydrated and flexible.
The natural lipid film on the surface is not an oc-
clusive barrier, and the major barrier in the skin is be-
low the stratum corneum. Winsor and Burch 2 showed
that the natural lipids do not prevent water loss to the
environment, and Rothman3 stated that it is not
difficult to get water into the stratum corneum from
the environment through whatever lipid film there is
on the surface. In 1924, Rein4 pointed out that the
stratum lucidum and stratum granulosum are respon-
sible for the impermeability of the skin to electrolytes.
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Later Rothman 5 stated that, at this same anatomic
position in the skin, the Übergangsschichten act as the
barrier against the penetration of water molecules be-
cause the proteins in these layers are buffered at a pH
corresponding to their isoelectric points and therefore
take up a minimum quantity of water. Szakalls showed
that it is necessary to strip intact human skin six times
with adhesive tape before the barrier is broken suffi-
ciently to allow water to escape rapidly enough to
produce a moist surface.
Quantitative measurements
of the rate of water loss through pieces of excised
human skin, which have been stripped various num-
bers of times, have been correlated with histological
sections of the stripped skin and support the hypothe-
sis that the major barrier against diffusion of water
molecules is near the base of the cornified epithelium.7
Thus, since the surface film of natural lipids is not
an adequate barrier to prevent loss of water from the
stratum corneum and because there is a barrier be-
tween the cornified epithelium and the underlying
moist tissues, the cornified epithelium loses water to
the environment more rapidly than it receives water
from the underlying tissues. It tends to dry out, but
fortunately it is a hygroscopic material and does not
dry out completely in atmospheres of normal or high
relative humidity; however, when the relative humid-
ity is low, as during the winter months, the stratum
corneum may dry out, become brittle, and break or
scale when flexed unless it is adequately protected by
a film of occlusive oil. The action of the simple emolli-
ents, therefore, is primarily a surface phenomenon,
and possibly the importance of the penetration of the
oil into the skin has been overemphasized. An effective
emollient must be so constituted that it will help the
stratum corneum maintain an adequate water content.
It is at once apparent that the thicker the stratum
corneum, the less flexible it will be if and when it
becomes dehydrated. Not only does the water content
of the stratum corneum influence the condition of the
skin, but the thickness of the cornified epithelium also
plays a role. When the stratum corneum becomes
thicker, the symptoms of dryness increase. Physical
stimuli such as friction and exposure to ultraviolet
radiation, chemical stimuli, and certain pathological
states thicken the stratum corneum. On frequent ex-
posure to warm solutions of a soap or detergent, the
skin receives both physical and chemical stimuli. Such
a process might evoke thickening. If thickening is ab-
normal because of an added external stimulus, it may
be corrected just by removing this stimulus, but, if it
is abnormal because of some diseased state and ab-
normal keratinization, correction may be much more
difficult.
Vitamin A
Some evidence suggests that vitamin A alters keratin-
ization. Fell and Mellanby 8 and Weiss and James 9
have shown that keratinization of epidermal cells from
the chick embryo growing in tissue culture can be com-
pletely suppressed by the use of vitamin A. Flesch lu
has shown that ethers and esters of vitamin A inacti-
vate sulfhydryl groups of mouse liver homogenates and
the sulfhydryl enzyme dehydrogenase and cause hair
loss when externally applied to mice. Other investi-
 gators
n
have stated that large oral doses of vitamin
A correct the abnormal keratinization in such diseases
as keratosis follicularis, keratosis pilaris, and ichthyosis.
Reasoning that this effect is exerted directly on the
end-organ and that therefore systemic administration
would not be necessary, some physicians have applied
vitamin A topically, and cosmetic manufacturers have
used this vitamin occasionally in emollient creams.
There is fairly good evidence 12 to prove that vita-
min A can penetrate normal, intact animal skin, and
Mandelbaum and Schlesinger 13 indicate a systemic
effect after external application in humans. It is prob-
able that it penetrates intact human skin slowly and
that only a small portion of the amount applied reaches
the granular and Malpighian layers of the epidermis
where any faulty keratinization might be corrected.
There is still little evidence, however,14 to show that
abnormal keratinization in skin diseases is altered by
the external application of a vitamin A ointment any
more than it would be altered by the application of the
vehicle alone. Very little evidence has been found to
show that the use of cosmetics containing vitamin A
is any more beneficial for controlling symptoms of
dryness than are simple emollient creams not contain-
ing any vitamin A. In support of this statement, a rep-
resentative of the cosmetic industry, in 1954, com-
mented on a paper by Conley 15 and said, "I agree with
our able contemporary that there is some boloney
being handed out in publicity on the need for and
value of vitamins in skin creams....
"Whether the vitamins help the skin or not is some-
thing that clinical trials can establish easily enough.
So it is hoped the industry has done the work, or if
not, it should get started. Methinks we have loads to
learn about the skin." 16
Estrogens
Indiscussing estrogens, perhaps it is not justifiable to
ask whether they function only by increasing the
emollient action of a cream. The estrogens are said to
cause hydration of the skin, but this refers to hydra-
tion of the dermis and not of the stratum corneum.
They are supposed to delay or reverse some of the
changes that occur in the skin during normal aging,
only one of which is dryness. During aging, there are
changes in both the epidermis and dermis. The epi-
dermis and stratum corneum do not become thicker
with age; if they change at all, they become thinner.
There may be a decrease in the activity of the seba-
ceous glands, and less sebum may be produced. As has
already been indicated, however, the sebum is prob-
ably not the major factor in skin dryness. Some at-
rophy occurs in the skin of elderly people; the entire
skin feels thinner, and it is less elastic and less resilient.
Many elderly people describe their skin as "dry." The
question arises as to whether these changes are revers-
ible and whether they can be prevented. From what
is known of the action of simple emollients, it would
appear that they could not prevent or reverse such
changes in the aging skin.
It is easy to understand why estrogens have been
added to simple emollients in an attempt to control
aging of the skin in women, for these changes in the
skin occur at a time when the normal production of
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estrogen decreases. Other physiological changes also
occur at menopause, and it is asked whether simple
replacement of estrogen will control the cutaneous
changes, and, if so, whether this replacement can be
accomplished by topical application of estrogen.
It seems well established that estrogens
reasonably
can penetrate normal human skin.17 Because this is
true, undesirable systemic effects from the topical
application of estrogen creams might occur. Scattered
reports in the literature, such as that of Goldberg and
Harris,18 seem to support this point of view. However,
there is a dearth of evidence concerning the absolute
rate of penetration of estrogen through normal and ab-
normal skin from various concentrations of estrogen in
different types of vehicles. More evidence is needed.
Most estrogen creams currently available do not con-
tain more than 10,0001. U. of estrogen per ounce. When
such creams are used according to directions, they
appear to be free of any abnormal systemic effects.19
There is probably a factor of safety in a cream of this
concentration. Peck, Klarmann, and Spoor20 state that
concentrations of estrogens in excess of 50,000 I. U.
per ounce may produce undesirable systemic effects.
Early fears of carcinogenic action of these cosmetics
appear to be unwarranted.21
When estrogens in suitable vehicles are applied to
the surface of animal skins, the majority of reports in-
dicate that there are some local effects on the skin 22
as well as possible effects on distant organs.23 The
response of human skin, however, may not necessarily
be similar to that of animal skin when estrogens are
applied, for evidence that cutaneous effects occur in
humans is not as conclusive. Most investigators who
feel that they see histological changes in the skin of
aging women agree that there is very little evidence
of alteration of the skin of men or young women.24
Much of the evidence in support of the alteration of
aging skin by the local application of estrogens is his-
tological.25 The changes that have been observed-
thickening of the epidermis, extension of the papillae,
increase in the amounts of elastic tissue and in the
diameter of the collagen bundles—are difficult to quan-
titate. Some of the changes may be due to the angle at
which the histological section has been cut. Much of
this work seems to lack objectivity. Seldom have the
investigators used control sites of skin treated with
the vehicle alone, and seldom have they made their
observations on coded slides. Goldzieher, Roberts,
Rawls, and Goldzieher253 did observe coded slides.
Clinical evidence to support or contradict the opin-
ion that estrogen creams delay or reverse the aging
process in the skin is meager. Any change is likely to
be quite subtle and to develop slowly; thus, adequate
controls are very important. In one recent well-con-
trolled study26 27 women of various ages applied an
estrogen cream to side of the face and vehicle to
one
the other side for a period of 91 days; no difference
could be detected in the two sides of the face. A de-
cision as to whether the subjects of this clinical evalua-
tion represent the type of individuals for whom estro-
gen creams might be effective and whether the con-
clusions are justifiable must await further observations
of this kind.
 One should not dogmatically say at this time that
the external application of estrogen creams does noth-
ing to aging skin, but good clinical evidence to support
a statement to the contrary is not yet available. In
1948, Sevringhaus 27
said:
The whole field of percutaneous administration of estrogens
has had very little systematic study by qualified investigators.
Systemic as well as local effects are involved. A recent review
of the local activity of the sex hormones presents but little
helpful information on this part of the problem, but points out
the unfortunate exploitation of the public by the purveyors of
certain cosmetics. The remedy for such undesirable methods of
treatment lies in careful study of the field by the medical pro-
fession.
Eight years later, there is less concern about possible
systemic effects, but it is felt that the medical profes-
sion has not adequately responded to this challenge,
and it has not been proved conclusively that the estro-
gen creams either do or do not affect the aging skin.
Massachusetts General Hospital ( 14 ).
The original title of this report as presented at the Sym-
posium was "The Emollient Creams and Their Modern Addi-
tives."
References
1. Blank, I. H.: Mechanism of Action of Agents Used for
Relief of Dry Skin, Proc. Scient. Sec. Toliet Goods A. No. 23, pp.
19-23 (May) 1955; reprinted Drug & Cos. Ind. 76:758-760 (June)
1955; Am. Perfumer & Aromatics 67:35-39 (May) 1956.
2. Winsor, T., and Burch, G. E.: Differential Roles of Layers
of Human Epigastric Skin on Diffusion Rate of Water, Arch.
Int. Med. 74:428-436 (Dec.) 1944.
3. Rothman, S.: Principles of Percutaneous Absorption, J.
Lab. & Clin. Med. 28:1305-1321 (Aug.) 1943.
4. Rein, H.: Experimentelle Studien \l=u"\berElektroendosmose
an \l=u"\berlebendermenschlicher Haut, Ztschr. Biol. 81:125-140,
1924.
5. Rothman, S.: Resorption durch die Haut, Handb. norm. u.
path. Physiol. 4:107-151, 1929.
6. Szakall, A.: Hautphysiologische Forschung und Gesunder-
haltung der Haut, Fette u. Seifen 53:399-405 (July) 1951.
7. Blank, I. H.: Further Observations on Factors Which In-
fluence Water Content of the Stratum Corneum, J. Invest.
Dermat. 21:259-271 (Oct.) 1953.
8. Fell, H. B., and Mellanby, E.: Metaplasia Produced in
Cultures of Chick Ectoderm by High Vitamin A, J. Physiol.
119:470-488 (March 30) 1953.
9. Weiss, P., and James, R.: Vitamin A and Skin Keratiniza-
tion in Vitro: Experimental Dissociation of Induction and
Realization of Phases in Cytodifferentiation; abstracted, Science
119:587 (April 30) 1954.
10. Flesch, P.: Studies on Mode of Action of Vitamin A, J.
Invest. Dermat. 21:421-434 (Dec.) 1953.
11. Griesemer, R. D.; Frazier, C. N.; and Blank, I. H.:
Nutritional Influences on Physiology of Skin: Observations on
Metabolism of Vitamin A., Medicine 32:293-321 (Sept.) 1953.
Peck, S. M.; Chargin, L.; and Sobotka, H.: Keratosis Follicularis
(Darier's Disease) a Vitamin A Deficiency Disease, Arch.
Dermat. & Syph. 43:223-229 (Feb.) 1941. Peck, S. M.; Glick,
A. W.; Sobotka, H.; and Chargin, L.: Vitamin A Studies in
Cases of Keratosis Follicularis (Darier's Disease), ibid. 48:17\x=req-\
31 (July) 1943. Peck, S. M.; Glick, A. W.; and Chargin, L.:
Vitamin A Studies in Cases of Ichthyosis, ibid. 48:32-34 (July)
1943. Leitner, Z. A., and Ford, E. B.: Vitamin A and Pityriasis
Rubra Pilaris with Comment About Genetics, Brit. J. Dermat.
59:407-427 (Dec.) 1947.
12. Bern, H. A., and others: Influence of Vitamin A on Epi-
dermis, Am. J. Anat. 96:419-448 (May) 1955. Flesch, P.,
and Goldstone, S. B.: Local Depilatory Action of Unsaturated
Compounds: Effect of Human Sebum on Hair Growth, J.
Invest. Dermat. 18:267-287 (March) 1952. Montagna, W.:
Downloaded From: http://jama.jamanetwork.com/ by a New York University User on 06/15/2015
Penetration and Local Effect of Vitamin A on Skin of Guinea
Pig, Proc. Soc. Exper. Biol. & Med. 86:668-672 (Aug.-Sept.) 1954.
Sabella, J. D.; Bern, H. A.; and Kahn, R. H.: Effect of Locally
Applied Vitamin A and Estrogen on Rat Epidermis, ibid.
76:499-503 (March) 1951. Sobel, A. E., and Rosenberg, A.:
Transfer of Topically Applied Vitamin A Through Skin, in
Abstracts of Papers, American Chemical Society, 124th Meet-
ing, Chicago, Sept. 6-11, 1953, p. 62C.
13. Mandelbaum, J., and Schlesinger, L.: Absorption of
Vitamin A Through Human Skin, Arch. Dermat. & Syph.
46:431-442 (Sept.) 1942.
14. Flesch, P.: Inhibition of Keratin Formation with Un-
saturated Compounds, J. Invest. Dermat. 19:353-363 (Nov.)
1952.
15. Conley, V.: Vitamins in Cosmetics, Today's Health
32:33 (Jan.) 1954.
16. DeNavarre, M. G.: A. M. A. and Vitamin Cosmetics,
Am. Perfumer & Essen. Oil Rev. 63:173 (March) 1954.
17. MacBryde, C. M.: Production of Breast Growth in the
Human Female by Local Application of Estrogenic Ointment,
J. A. M. A. 112:1045-1049 (March 18) 1939. Shapiro, I.:
Topical Estrogens: Clinical Effects and Side Actions, J. Clin.
Endocrinol. 12:751-760 (June) 1952.
18. Goldberg, M. B., and Harris, F. I.: Use of Estrogen
Creams, J. A. M. A. 150:790-791 (Oct. 25) 1952.
19. (a) Davis, J. W., Jr.: Carcinogenic Action of Hormones,
South. Med. & Surg. 109:63-65 (March) 1947. (b) Larrick,
G. P.: Official Position on Hormone Creams Revaluated, Fed-
eral Security Administration, Am. Perfumer & Essen. Oil Rev.
57:276 (April) 1951. (c) Sulzberger, M.: Hearings Before
the House Select Committee to Investigate Use of Chemicals
in Foods and Cosmetics, pt. 3, Washington, 1952, p. 1066.
20. Peck, S. M.; Klarmann, E. G.; and Spoor, H. J.: Treat-
ment of Acne Vulgaris with Estrone, A. M. A. Arch. Dermat.
& Syph. 70:452-467 (Oct.) 1954.
21. Dunbar, P. B.: Cosmetics Containing Hormones, New
England J. Med. 233:198 (August 16) 1945. Footnote 19 a.
22. Lapiere, C.: Studies of Modifications of Sebaceous
Glands by Cutaneous Application of Sex Hormones in New
Neutral and Penetrating Vehicle, Dermatologica 109:345-354
(Dec.) 1954; Cited in Drug & Cos. Ind. 77:107-109 (July)
1955. Pliske, E. C.: Histologic Changes in Skin of Female
Guinea Pig Following Percutaneous Application of Estrogen,
Anat. Rec. 115:673-689 (April) 1953. Reiss, F., and Gellis,
S.: Effects Produced on Pilosebaceous System and Adrenals
of Rabbit by Inunction of Sex Hormones, J. Invest. Dermat.
12:159-172 (March) 1949. Williams, W. L.; Gardiner, W.
U.; and DeVita, J.: Local Inhibition of Hair Growth in Dogs
by Percutaneous Application of Estrone, Endocrinology 38:368\x=req-\
375 (June) 1946. Wheeler, C. E.; Cawley, E. P.; and Curtis,
A. C.: Effects of Topically Applied Hormones on Growth,
Pigmentation and Keratinization of Nipple and Aureola, J.
Invest. Dermat. 20:385-399 (May) 1953.
23. Dunaif, C. B., and Finerty, J. C.: Effects of Estrogen
Administration upon Epidermal Proliferation, J. Invest. Dermat.
15:363-371 (Nov.) 1950. Kroeger, R.; Sperandio, G. J.; and
Jenkins, G. L.: Study of Comparative Absorption of Estrone
from Hydrophobic and Hydrophilic Ointment Base, J. Am.
Pharm. A. (Scient. Ed.) 42:501-504 (Aug.) 1953.
24. (a) Eller, J. J., and Eller, W. D.: Estrogenic Ointments:
Cutaneous Effects of Topical Applications of Natural Estrogens,
with Report of 321 Biopsies, Arch. Dermat. & Syph. 59:449\x=req-\
464 (April) 1949. (b) Goldzieher, J. W.: Direct Effect of
Steroids on Senile Human Skin: Preliminary Report, J. Gerontol.
4:104-112 (April) 1949.
25. (a) Goldzieher, J. W.; Roberts, I. S.; Rawls, W. B.;
and Goldzieher, M. A.: Local Action of Steriods on Senile
Human Skin, A. M. A. Arch. Dermat. & Syph. 66:304-315
(Sept.) 1952. (b) Peck, S. M., and Klarmann, E. G.: Hormone
Cosmetics, Practitioner 173:159-165 (Aug.) 1954. (c) Traub,
E. F.: Hearings Before the Louisiana State Board of Health,
1946. (d) Footnote 24 a.
26. Behrman, H. T.: Hormone Creams and Facial Skin,
J. A. M. A. 155:119-123 (May 8) 1954.
27. Sevringhaus, E. L.: Use of Estrogens in Medicine, Ann.
Int. Med. 29:595-600 (Oct.) 1948.