In Search of Human Skin Pheromones

Bruce A. Cohn, MD

pheromone was first designated by Karlson and L\l=u"\scher1 in 1959 as a sub-

The
term
stance secreted by an animal to the outside of that individual, which was then re-
ceived by another individual, classically of the same species, and which then elicited
some behavioral or developmental response in the latter. They composed the term
from the Greek words pherein, which means to bring or to transfer, and hormon, which means to
excite. In the usual context, this response in the second individual is of a sexual or of a reproduc-
tive physiologic nature, although sometimes the definition might even be extended to include other
social responses such as when a dog uses pheromones in urine to mark territory. Classically, phero-
mones are thought of as being olfactory, but these chemicals may also be received by contact. Phero-
mones may be present in many different sites in animals, such as in the skin, including some of its

glands, saliva, urine, vaginal discharge, and feces.

Pheromones are known to function in
many different animals from arthropods
to mammals. Classically, many animals'
pheromones are secreted by the male to
be received by the female to help induce
puberty, or to stimulate ovulation, or to
cause the latter to be sexually receptive.
The pig pheromone androsterone (5a-16-
androst-16-en-3-one), for example, which
is synthesized in the testes and then stored
in sites including the submaxillary glands,
is known to stimulate a sow to position
herself for coitus when it is secreted from
the saliva of the boar.2 Similarly, female
pheromones may be secreted to cause
copulatory behavior in the male and may
at times function to cause an earlier sexual
maturation in the male. One example of
a female-produced pheromone is aphro-
disin in the hamster's vaginal discharge that
causes male sexual behavior.3
In humans, the status of phero¬
mones does not seem to be universally ac¬
cepted in the scientific community, and,
quite whimsically, is the manner in which
From the Department of Dermatology, University of California\p=m-\SanFrancisco.
the subject seems to be mainly discussed
by the lay media. Still, the perfume indus¬
try has for a long time been adding syn¬
thetic mammalian pheromonal chemi¬
cals to their products, such as that based
on the well-known musk from musk deer
glands. However, this seems to have been
done more for the use of these chemicals
as fixatives and as carriers for the other fra¬
grances, as well as to give some scent, and,
of course, also for marketing purposes,
rather than there really being an expecta¬
tion of eliciting some behavioral or physi¬
ologic response.4
Nevertheless, it has been postulated
that pheromones may come from the hu¬
man integument itself. That is, it has been
speculated that they can come from skin
keratinocyte desquamations themselves in
the form of metabolites that are delivered
from one person to another, possibly by
airborne contact.4 It has also been specu¬
lated that the sebum of the mouth and lips
may have pheromonal properties that can
be transmitted from one person to an¬
other.5 Pheromones certainly have also
been postulated to be in human apocrine

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 sweat gland secretion, which will be a major focus of this
presentation, because much of the evidence for the pres¬
ence of human skin pheromones pertains to these glands.
For example, the above-mentioned androsterone, plus
its alcohol androsterol (5a-androst-16-en-3a-ol), have
also been found in the human axilla, in concentrations
higher in the male than in the female, and these steroids
are thought to come from the secretion of the apocrine
sweat glands.6"8
Thus, in humans the presence of these or other
chemicals from the apocrine glands in at least the
axilla has been a source of interest for their possible
influence on reproductive physiology. For example,
there are studies that have suggested that the presence
of chemicals in apocrine gland secretion may have an
effect on the menstrual cycle. More specifically, it has
been shown that women who have regular sexual
activity with men seem to have more regular men¬
strual cycles than women who lack such regular activ¬
ity.9 This has been thought to quite possibly be due to
the more frequent exposure of the former women to
substances in male apocrine gland secretion. Similarly,
exposure of extract from the male axillae to the upper
lips of females has been shown to create more regular
menstrual cycles.10 On the other hand, it has been
shown that women often synchronize their menstrual
cycles after having lived together, such as in college
dormatories, for a duration of a few months, which is
thought to quite possibly be due to substances in the
apocrine gland secretion among them.11 Similarly, it
has been shown that exposure to the upper lips of
females of axillary extract from other females can syn¬
chronize the recipients' menstrual cycles to that of the
donors.12
Several
studies have been done in an
attempt todetermine if the behavior of
either sex regarding sexual attraction, or
at least social mood, can be influenced by
the presence of some chemicals including
androsterone and androsterol. Certainly studies such
as these can have an inherent potential of being diffi¬
cult to interpret, with, perhaps, at times, even their
interpretation reflecting the bias of the observer. In
any regard, differing results and conclusions have
been reported from these studies, but still some of
these articles have suggested some actual behavioral
response.13
Also, the presence of the vomeronasal (Jacob-
son's) organ, a small tubular structure in the mucosa
of the nasal septum, with its bilateral pits that enter
into the anterior nasal cavity, has recently become
more substantiated in humans, which adds to the
concept of human pheromones possibly being a
reality.14"16 The vomeronasal organ (VMO), which is
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present in most terrestrial vertebrates, is a component
of the accessory olfactory system (AOS). In animals,
the VMO commonly serves the function of the recep¬
tion of pheromonal chemicals and then the transmis¬
sion of this information through the AOS into the
brain for processing. The VMO and AOS were previ¬
ously thought to not be present, or else they were
thought to be vestigial, in humans. The VMO is
thought to act through receptors that receive olfactory
or contact stimuli. In this way, it is thought that
chemicals that are volatile, as well as some that are
nonvolatile, or even particulate, and sometimes odor¬
less, are received by the receptors of the VMO. The
AOS is considered to be a separate system from the
main olfactory system, the latter which has its recep¬
tors in the olfactory epithelium in the nasal cavity, and
which processes the more standard olfactory stimuli.
The possibility of the human VMO having truly func¬
tional receptors along with a functional sensory path¬
way via an accessory olfactory system into the brain
still awaits clarification.
Nevertheless, the situation remains that phero¬
mones have not often been discussed in the dermato¬
logie literature. Also, a relative paucity has been writ¬
ten in the dermatologie literature regarding any
possible function of human apocrine sweat glands.
Hurley and Shelley,17 in their book that presented
their very informative studies from 1951 through 1956
on human apocrine glands, simply stated that they
were atavistic "scent" glands, and that these glands
were important primarily because of local disease.
However, in these studies, Hurley and Shelley did not
specifically seek the presence of pheromonal attributes
to human apocrine glands. However, Craigmyle18 has
been more accepting of the concept that there may be
pheromonal properties in human apocrine glands.
Also, Ebling19 20 has been quite supportive of the possi¬
bility that there may be an actual human pheromonal
contribution from these glands.
It might even be said that there are some simple
implications that pheromonal qualities do exist in
human apocrine gland secretion, which come from
some basic anatomic and physiologic information
regarding these structures. Apocrine glands are dif¬
fusely present and do serve a thermoregulatory func¬
tion in many hoofed hairy mammals, such as horses
and cows. In humans, there is diffuse distribution of
apocrine glands in utero, but they completely resolve
before birth, except for their retention in the axilla,
where they are most prevalent, the anogenital area, the
aerolae, and, on occasion, in a few other sites. It might
be assumed that the generalized resolution in utero of
these apocrine glands is that of phylogenetically ther¬
moregulatory glands. The fact that apocrine glands do
not resolve in humans in the few remaining sites cer¬
tainly might in itself be thought of implying that they
 have some other function. Also, these apocrine glands
do not significantly develop in humans until puberty,
and this seems to be due to the influence of hormones.
These glands may also manifest some diminution after
menopause. In addition, the fact that these apocrine
glands may be under the influence of emotional
stimuli might also be thought to imply some func¬
tional significance.
A not surprising correlation has evolved in
human evolution with apocrine glands and hair, ie, it
is not unexpected that apocrine glands would involute
in the course of evolution as hair loss occurred, simply
because all apocrine glands develop from the primary
epithelial germ, as does hair, and apocrine glands thus
develop in association with hair follicles and do their
secreting into these follicles. In humans diffuse hair
loss has evolved, except in a few sites. This generalized
hair loss is thought to have occurred for the purpose
of facilitating the diffusely present eccrine sweat
glands to serve their vital function of thermorégula¬
tion.21 The evaporative heat loss from eccrine gland
sweating is more able to be accomplished from rela¬
tively bare skin than from densely hairy skin.21 Thus,
humans are relatively hairless diffusely, with, of
course, some racial variations and with also a few sites
of exception, such as the scalp, in which hair at least
serves a function of preventing the too-direct UV light
damage; the eyebrows, which, at least, may help to
prevent foreign materials and sweat from getting into
the eyes; lashes, which also protect the eyes from for¬
eign materials and sweat; and the male beard and
some of the male body hair, which might only be
assumed to have the social role of simply emphasizing
the difference between the sexes. Of course, these
above-mentioned sites are areas in which hair reten¬
tion has occurred but in which the apocrine glands
have largely disappeared, meaning that the generalized
evolutionary apocrine gland loss in humans was not
solely a consequence of hair loss.
There remains only the postpubertal axillary and
anogenital skin that are relatively dense hairy areas in
association with apocrine gland retention. This situa¬
tion presents a couple of questions, at least. Is it pos¬
sible that the human axilla and the human anogenital
area have retained these relatively dense large hairs
with their large hair follicles to permit the needed
large apocrine glands to be present for the latter to be
able to serve some function, namely, that of phero¬
monal production? Is it also possible that the large
retained hairs in these two sites actually serve a direct
physical function themselves, that of giving at least
temporary site for the retention of apocrine gland
pheromones after they have been secreted?
Also, is it possible that this milieu needs the pres¬
ence of the copious clear eccrine sweat gland secretion,
especially in the axilla, as a source to bathe and dis-
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perse, plus at times to help to volatilize these chemi¬
cals? Apocrine secretion itself is minute, milky, and vis¬
cous, and this secretion would, by itself, form into small
gluey droplets without the presence of the eccrine sweat.
With this in mind, it can be added here that the eccrine
sweat glands in the axilla are also under emotional in¬
fluence as well as thermal influence, although the situ¬
ation from most of the remainder of the skin is just that
of thermoinduced eccrine sweating. Also, there are the
recently discovered apoeccrine glands, which may be only
in the human axilla. These glands develop in puberty,
probably from eccrine glands or eccrinelike precursor
glands, and they do enter directly to the skin surface just
as do eccrine glands.22 These glands provide a copious
clear sweat contribution.23 It may be that the apoeccrine
glands serve a special function in helping in the delivery
of axillarypheromones.
Itmight also be wondered whether the presence
of the abundant sebaceous glands in the axilla has
some role in pheromonal functioning. It is known that
in some animals some sebaceous glands do produce
pheromones. It is only in chimpanzees, gorillas, and
humans in which the so-called axillary organ is pres¬
ent, which is an abundance of sebaceous glands in
association with abundant apocrine glands and eccrine
glands, all of this suggesting the possibility that, in
these great apes and humans, the axilla may be a
major site of pheromonal contribution.
Humans are unique among the primates in being bi¬
pedal. In addition, it might be postulated that the unique
bipedal stance of humans offers a very advantageous way
of presenting and delivering axillary pheromones from
one sex to the other. The reality may be that the human
axilla is an extremely specialized functional unit.
IT
is ALSO KNOWN that there are particular bac¬
teria present in the axillae, which are the aero¬
bic coryneforms, that seem to play a role in pro¬
ducing the odor of apocrine sweat, which by
itself is odorless.24,23 These bacteria may, through
metabolic processes, be needed to produce the active states
of some pheromones themselves.25,27 It is thus interest¬
ing that, in many cleanliness-oriented societies, there is
often meticulous washing of these sites, sometimes in
which there is even the inclusion of antibacterial ingre¬
dients to cleansers. This might then be diminishing needed
bacteria and pheromones. Similarly, the shaving away of
the axillary hairs may be removing a structure that is
needed to help produce the proper pheromonal environ¬
a ment. Ironically, hyperhidrosis of the axilla may cause a
somewhat analogous situation to careful washing and
shaving, in that the secretion of too much eccrine and
apoeccrine sweat may actually wash away these phero¬
mones. Recently, it has also been found that chemicals
such as trans-3-methyl-2-hexenoic acid may be a major
 contributor to axillary odor.28 However, the presence of
any specific odor-causing chemical in the axilla or else¬
where does not necessarily imply that it has phero¬
monal properties.
In summary, this discussion has really only been in¬
tended to ask a few questions pertaining to a subject,
which, despite a large but mainly nondermatologic lit¬
erature that has been developing, seems to need much
more information and understanding than has been at¬
tained so far. The question of the presence and possible
role of human pheromones and the question as to what
significance the apocrine gland contribution is to all of
this still await clarification.
Humans have a uniquely developed cerebral cor¬
tex that gives them cognitive abilities to such an extent
that they are able to modulate their sexual behavior as
well as at times some aspects of their reproductive en¬
docrine physiology. Despite this situation, the potential
of learning if there is any pharmacologie role for phero¬
monal chemicals, even if it be a minor one, in affecting
this physiology, seems to be determinable.
Accepted for publication September 13, 1993.
Reprint requests to 2100 Webster St, San Francisco,
CA 94115 (DrCohn).
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