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Hiu ng tm l ca cc hp cht x hng :


So snh cc Androstadienone
vi androstenol v Muscone
Suma Jacob , Sheila Garcia , Davinder Hayreh ,
v Martha K. McClintock1
Khoa Tm l , Vin Tm v Sinh hc , i hc
Chicago ,
Chicago, Illinois 60637
Nhn c ngy 07 thng 6 nm 2001 , sa i
ngy 18 thng 1 nm 2002 , chp nhn 11 thng 4
2002
Trc y, chng ti ch ra rng ? 4,16 androstadien - 3
mt iu bin trng thi tm l , gim tiu cc
tm trng v tng cng tm trng tch cc
( Jacob v Mc Clintock , 2000 , Jacob v cng s, 2001) . .
xc nh
liu hp cht x hng tng t cng sn xut
nhng
hiu ng, chng ti so snh hiu qu ca
androstadienone
nhng androstenol v muscone , o lng tm l
quc gia ca 37 ngi tham gia. androstenol v
muscone c chn v chng cng c mt musky
mi hi nng cao , trong khi androstenol l
mt steroid
nh androstadienone v muscone khng phi l .
Trong mt kim sot
phng th nghim , chng ti tin hnh mt
nghin cu m i ,
trong -mn, lp i lp li , cc bin php th
nghim i trng
cho t trnh by . Di mi ngi tham gia
mi , mt s lng nanomolar ca mi hp cht
c trnh by , eo mt n bng du inh
hng gim thiu cm nhn
s khc bit khu gic . Ngi tham gia hon
thnh mt
c s tm l pin v hai ln mt ln na 25 pht
khong thi gian sau khi tip xc . Hiu ng
Androstadienone v
trng thi tm l rt c o so vi
nhng androstenol v vi muscone . tip xc
thng qua ng h hp th ng , ch khng
phi l tip xc qua da ,
1

Psychological Effects of Musky Compounds:


Comparison of Androstadienone
with Androstenol and Muscone
Suma Jacob, Sheila Garcia, Davinder Hayreh,
and Martha K. McClintock1
Department of Psychology, Institute for Mind and Bio
The University of Chicago,
Chicago, Illinois 60637
Received June 7, 2001, revised January 18, 2002, acc
April 11, 2002
Previously, we have shown that 4,16-androstadien-3one modulates psychological state, reducing negative
mood and increasing positive mood (Jacob and McClintock, 2000; Jacob et al., 2001a). In order to determ
whether similar musky compounds also produce these
effects, we compared the effects of androstadienone to
those of androstenol and muscone, measuring the
psychological
states of 37 participants. Androstenol and
muscone were chosen because they too have a musky
odor at high concentrations, while androstenol is a ste
like androstadienone and muscone is not. In a control
laboratory setting, we conducted a double-blind,
within-subject, repeated-measures experiment
counterbalanced
for order of presentation. Under each participants
nose, a nanomolar amount of each compound
was presented, masked by clove oil to minimize perce
olfactory differences. Participants completed a
baseline psychological battery and twice again at 25-m
intervals after exposure. Androstadienones effects on
psychological state were unique in comparison with
those of androstenol and with muscone. Exposure
through passive inhalation, rather than dermal contact
was sufficient for these effects. Although this is additi
evidence that androstadienone may be a pheromone,
it is yet to be determined whether humans exude
concentrations into the air adequate for social
communication
or process this chemical information within natural
social contexts. 2002 Elsevier Science (USA)

l cho nhng hiu ng ny . Mc d y l


thm
bng chng cho thy androstadienone c th l
mt pheromone ,
l cha c xc nh liu con ngi chy ra
nng trong khng kh thch hp cho truyn
thng x hi
hoc x l thng tin ha cht ny trong t nhin
bi cnh x hi . 2002 Elsevier Science (M)
T kha: chemosignals ; pheromone ; mi , tm
trng ;
cc hp cht x hng ; steroid .
Tn hiu ha hc x hi nh hng n sinh l
hc, tm l
nh nc , v hnh vi nhiu loi ng vt
( McClintock , 2000, 2002 ) . Nghin cu nh
hng ca
tn hiu ha hc i vi con ngi l c bit kh
khn
v hnh vi con ngi c xc nh nhn
v c chemosignals tim nng v . nhng
bao gm mi x hi , c hai u c thc v v
thc,
cng nh kch thch t ( McClintock , 2001). cu
tr li
nhng chemosignals c th phn nh cht lng
mi ca h ,
nh cay , quen thuc , hng th valance , mc
pht hin c thc , v ngun c cng nhn
ca
kch thch kinh t . Trc y, chng ti chng
minh rng mt
c bit steroid , ? 4,16 - androstadien - 3-one
( chung
tn : androstadienone ) , iu bin tm l
v thay i sinh l m khng pht hin c thc
nh mi ( Jacob v McClintock , 2000), Gia-cp
v cng
al . , 2001a) . Mc tiu ca nghin cu ny l
bt u nh gi
ha cht v c hiu kch thch khu gic ca
androstadienone .
Lng nanomolar ca androstadienone nh hng
chung
trng thi cm xc v hng phn, nh lng bng
wellvalidated
2

Key Words: chemosignals; pheromone; odor; mood;


musky compounds; steroids.
Social chemical signals influence physiology,
psychological
state, and behavior in many animal species
(McClintock, 2000, 2002). Studying the effects of
chemical signals on humans is particularly challengin
because human behavior is multiply determined
and there are myriad potential chemosignals. These
include social odors, both conscious and unconscious
as well as pheromones (McClintock, 2001). Response
to these chemosignals can reflect their odor qualities,
such as pungency, familiarity, hedonic valance, level
of conscious detection, and recognized source of the
stimulus. Previously, we have demonstrated that a
particular steroid, 4,16-androstadien-3-one (common
name: androstadienone), modulates psychological
and physiological variables without conscious detecti
as an odor (Jacob and McClintock, 2000); Jacob et
al., 2001a). The goal of this study was to begin evalua
the chemical and olfactory stimulus specificity of
androstadienone.
Nanomolar amounts of androstadienone affect genera
emotional and arousal states, quantified by wellvalida
measures of psychological state (POMS,
ARCI, and VAS scales; (Jacob and McClintock, 2000
Androstadienone prevents the drop in positive mood
and rise of negative mood, which typically occur unde
the odor carrier condition during our experimental
protocols. This suggests that androstadienone
modulates the physiological mechanisms of emotiona
states and attention. Indeed, androstadienone alters
cerebral glucose utilization in brain areas not typically
associated with olfaction, including subcortical region
and widespread areas of the neocortex, including
the prefrontal cortex, superior parietal area, and
visual cortex (Jacob et al., 2001b). These widely distr
changes are consistent with modulation of an
1 To whom correspondence and reprint requests shou
addressed
at Department of Psychology, The University of Chic

cc bin php ca trng thi tm l ( POMS ,


ARCI , v VAS quy m ; ( Jacob v McClintock ,
2000) ) .
Androstadienone ngn chn s st gim trong tm
trng tch cc
v pht trin ca tm trng tiu cc , thng xy
ra trong
iu kin nh cung cp mi trong qu trnh th
nghim ca chng ti
giao thc . iu ny cho thy rng
androstadienone
iu chnh cc c ch sinh l ca cm xc
cc quc gia v s ch . Tht vy,
androstadienone lm thay i
s dng glucose no cc vng no khng
thng
lin quan n khu gic , bao gm c vng di
v
v cc khu vc rng ri ca tn v no , bao gm
c
v no trc trn , khu vc nh cao , v
hnh nh v no ( Jacob et al. , 2001b) . Nhng
phn b rng ri
thay i ph hp vi iu ch ca mt
1 ngi th v in li yu cu cn c gii
quyt
ti Khoa Tm l , i hc Chicago ,
5730 S. Woodlawn Avenue, Chicago, IL 60637 .
Fax : 773-702-0320 .
E-mail : mkml@uchicago.edu .
Kch thch t v hnh vi 42 , 274-283 (2002)
doi: 10.1006/hbeh.2002.1826
0018-506X/02 $ 35,00
2002 Elsevier Science (M)
274 Tt c cc quyn .
tch hp mng li thn kinh iu tit cm xc
cc quc gia v s ch . Nhng tc ng quan
st ca androstadienone
khng phi l quan h tnh dc c th, theo
ngh ca ngi khc
( Monti - Bloch v Grosser , 1991 ; . Monti Bloch v cng s,
1994) , c hai ngi n ng v ph n phn ng
vi androstadienone
( Jacob v McClintock , 2000a ; . Jacob v cng
s,
3

5730 S. Woodlawn Avenue, Chicago, IL 60637. Fax:


702-0320.
E-mail: mkml@uchicago.edu.
Hormones and Behavior 42, 274283 (2002)
doi:10.1006/hbeh.2002.1826
0018-506X/02 $35.00
2002 Elsevier Science (USA)
274 All rights reserved.
integrated neural network for regulation of emotional
states and attention. The observed effects of
androstadienone
are not sex-specific, as suggested by others
(Monti-Bloch and Grosser, 1991; Monti-Bloch et al.,
1994); both men and women respond to androstadieno
(Jacob and McClintock, 2000a; Jacob et al.,
2001a). Moreover, effects on the autonomic nervous
system and mood are seen only in particular social
contexts (Jacob et al., 2001a).
Humans are, to date, the only species other than
pigs known to produce significant amounts of
androstadienone.
Androstadienone has been measured in
peripheral plasma of men at 0.010.06 g/100 ml
unconjugated, 0.050.1 g/100 ml sulfate-conjugated
(Brooksbank et al., 1969), 98 ng/100 ml (Brooksbank
al., 1972), and 2.05 pmol/ml (Fukushima et al., 1991)
is also found in mens sweat (Labows, 1988), semen
(Kwan et al., 1992), and axillary hair (Nixon et al., 19
Rennie et al., 1990). In women, androstadienone is
measurable in plasma at 36 ng/100 ml (Brooksbank e
al., 1972). Fragrance manufacturers claim to have iso
androstadienone from skin cells (Kodis et al.,
1998), although there is no peer-reviewed publication
stating how they were extracted, isolated, or identified
(Preti and Wysocki, 1999). Thus there are several site
of androstadienone production that would make it
available during human interactions.
Others have reported that androstadienone has
unique effects on the surface potentials of the vomero
epithelium and speculated that its behavioral
effects would also be unique and not generalize to

2001a) . Hn na, nh hng n thn kinh t tr


h thng v tm trng ca ngi ch nhn thy
trong x hi c bit
bi cnh ( Jacob et al. , 2001a) .
Con ngi , cho n nay, loi duy nht khc hn
ln bit sn xut mt lng ng k
androstadienone .
Androstadienone c o lng
plasma ngoi vi ca ngi n ng 0,01-0,06 ?
g/100 ml
unconjugated , 0,05-0,1 ? g/100 ml sulfate lin
hp
( Brooksbank et al. , 1969) , 98 ng/100 ml
( Brooksbank et
al . , 1972) , v 2.05 pmol / ml ( Fukushima et al. ,
1991). n
cng c tm thy trong m hi ca nam gii
( Labows , 1988) , tinh dch
. ; Lng nch ( Nixon v cng s, 1988 ( Kwan v
cng s, 1992 . ) , V
Rennie et al. , 1990). ph n, l
androstadienone
o lng c trong huyt tng 36 ng/100 ml (
Brooksbank et
al . , 1972). Cc nh sn xut nc hoa cho rng
h b c lp
androstadienone t cc t bo da ( Kodis et al. ,
1998) , mc d khng c cng b peer-xem xt
nu r cch h chit xut , c lp, hoc xc
nh
( Preti v Wysocki , 1999). Do c mt s cc
trang web
sn xut androstadienone lm cho n
c sn trong qu trnh tng tc ca con ngi.
Nhng ngi khc thng bo rng
androstadienone c
hiu ng c o v tim nng b mt ca
vomeronasal
biu m v suy on rng n hnh vi
hiu ng cng s l duy nht v khng khi qut

hp cht tng t (v d , 16 - androstenes


khc ) . ny
c hiu kch thch r rng c s dng bin
minh cho gi
androstadienone mt pheromone . do chng ti
4

similar compounds (e.g., other 16-androstenes). This


apparent stimulus specificity was used to justify callin
androstadienone a pheromone. We therefore
sought to evaluate the specificity of androstadienone
effect on psychological state. We chose psychological
changes as our basis of comparison, deferring any
questions or inferences about receptor specificity unti
we had demonstrated functional effects.
The effects of androstadienone could be associated
with its musky odor, detectable at high concentrations
even though at low concentrations it altered
psychological state without being consciously detecte
as an odor. If so, other compounds that have a
similar musky odor might produce the same psycholo
effects.
In the current experiment, we tested this hypothesis
by comparing androstadienone with two other musky
compounds, the pig pheromone androstenol (5-andros
16-en-3-ol) and the musk deer pheromone
muscone (3-methylcyclopentadecanone or methylexa
Androstenol and muscone, like androstadienone,
have a musky odor. Androstenol is in the same
steroid family of 16-androstenes, while muscone is a
15-carbon ring with a ketone functional group. All
three have been used in human perfumes as essential
musky ingredients (Engen, 1991). Such compounds
are also stable and effective fixatives used in many
different perfumes (Berliner et al., 1991). Thus, there
the opportunity for generalization of the effects of
androstadienone through its common associations
with musky odor and common perfumes and fragranc
products.
Androstenol is a mating releaser pheromone in the
pig (Sus scrofa) and a nonandrogenic 16-androstene
steroid like androstadienone. In humans, androstenol
and androstadienone are part of the same metabolic
pathway in humans (Gower and Ruparelia, 1993). In
addition, adrostenol is also excreted by humans in at
least three isomers (Brooksbank and Gower, 1964;
Brooksbank, 1970). Muscone is a territorial releaser

tm cch nh gi cc c trng ca
androstadienone ca
nh hng n trng thi tm l . Chng ti
chn tm l
thay i nh c s ca chng ti so snh, tr hon
bt k
cu hi hoc suy lun v th th c hiu cho n
khi
chng ti chng minh hiu qu chc nng.
Nhng nh hng ca androstadienone c th
c lin kt
vi mi x hng ca n , c pht hin nng
cao ,
mc d nng thp n thay i
trng thi tm l m khng b pht hin c thc
nh mi. Nu vy , cc hp cht khc m c mt
mi x hng tng t c th sn xut ra cng
mt tm l
hiu ng.
Trong th nghim hin ti , chng ti th nghim
gi thuyt ny
bng cch so snh androstadienone vi hai musky
khc
cc hp cht pheromone ln androstenol ( 5 ? androst 16 -en- 3 ? -Ol ) v hu x pheromone
muscone ( 3 methylcyclopentadecanone hoc
methylexaltone ) .
Androstenol v muscone , nh androstadienone ,
c mi x hng . Androstenol l trong cng mt
gia nh steroid 16 - androstenes , trong khi
muscone l mt
Vng 15 - cacbon vi mt nhm chc xeton . tt
c
ba c s dng trong nc hoa ca con ngi
l cn thit
thnh phn x hng ( Engen , 1991). cc hp
cht nh vy
cng l cht km hm n nh v hiu qu s dng
trong nhiu
nc hoa khc nhau ( Berliner et al. , 1991). Nh
vy, c
c hi cho s khi qut v tc ng ca
androstadienone thng qua cc hip hi chung ca
n
vi mi x hng v nc hoa ph bin v hng
5

pheromone in musk deer (Moschus moschiferus) (Par


et al., 1985; Agosta, 1992) and is not produced by
humans. Both androstadienone and androstenol have
been classified prematurely as human pheromones in
marketing claims for fragrances and in some basic
research (Monti-Bloch and Grosser, 1991; Monti-Blo
et al., 1994). These claims have been made prior to
amassing evidence that they fulfill all of the criteria
required to be termed a pheromone in any species
(Beauchamp, 1976; reviewed in Jacob et al., 2002; M
Clintock, 2002). Whether or not these claims are ultim
substantiated, the effects of androstadienone
might generalize to androstenol because they are prod
together in humans, but not to muscone, which
is a not produced by humans.
We exposed each participant to androstadienone,
androstenol, and muscone, masking their musky odor
with clove oil, the strong odor used in our previous
research (Monti-Bloch and Grosser, 1991; Jacob and
McClintock, 2000; Jacob et al., 2001a). Following the
comparison design typically used to compare the effe
of similar odorants (Lorig and Schwartz, 1988),
we made independent comparisons of androstadienon
with androstenol and with muscone (two repeatedmeasures within-subjects analyses). An odor
comparison design purposely omits no-odor carrier
conditions, in order to avoid several important confou
The dramatic difference between the odor
conditions and the control condition, which obvious
has no odor, creates an unconscious Hawthorne
effect. In addition, dramatically different
brain states between the no-odor carrier condition and
the presence of an odor can produce statistical artifact
Androstadienone, Androstenol, Muscone 275
(i.e., biasing omnibus F tests) simply as the result of
the difference in information between an odorantconta
condition and a no-odorant condition. This
comparison design is also used for clinical treatment
trials, in which the gold standard is showing significa
differences from comparable substances or protoco

thm
sn phm .
Androstenol l mt giao phi releaser pheromone
trong
heo ( Sus scrofa ) v mt nonandrogenic 16 androstene
steroid nh androstadienone . ngi,
androstenol
v androstadienone l mt phn ca trao i cht
cng
con ng ngi ( Gower v Ruparelia , 1993).
trong
Ngoi ra, adrostenol cng c bi tit ca con
ngi trong lc
t nht ba ng phn ( Brooksbank v Gower ,
1964 ;
Brooksbank , 1970). Muscone l mt releaser lnh
th
pheromone trong hu x ( Moschus
moschiferus ) ( Parrott
v cng s , 1985; . Agosta , 1992) v khng c
sn xut bi
con ngi. C hai androstadienone v androstenol
c
c phn loi sm nh kch thch t con ngi
trong
tuyn b tip th cho nc hoa v trong mt s c
bn
nghin cu ( Monti - Bloch v Grosser , 1991 ;
Monti - Bloch
et al. , 1994). Nhng tuyn b ny c thc
hin trc khi
tch ly bng chng cho thy h thc hin y
tt c cc tiu ch
yu cu c gi l mt pheromone trong bt
k loi
( Beauchamp , 1976; xem xt trong Gia-cp v
cng s, 2002; . Mc Clintock , 2002). C hay khng nhng cng b
ny l cui cng
chng minh, nhng nh hng ca
androstadienone
c th khi qut vi androstenol bi v chng
c sn xut
cng nhau trong con ngi , nhng khng
muscone , m
6

Nonetheless, it is important to verify that the


effect sizes in this study are comparable to those in
studies where there were carrier controls. Therefore,
we confirmed that androstadienone in the current
study had effects similar in size to those in previous
studies (Jacob and McClintock, 2000).
Finally, in our previous experiments, we had always
applied androstadienone directly on the skin under
the nose, enabling continuous exposure. This exposur
method has always left open the possibility that
our observations derived from either direct transcutan
transmission of the steroid into the bloodstream
or the sustained exposure to the steroid remaining on
the skin. In this experiment, we determined whether
brief passive inhalation of the air space above a small
amount androstadienone solution was sufficient to
produce its psychological effects. We exposed each
subject to the odorants using two methods: (1) simply
holding a small amount of the stimulus solution near
the nose on a swab for only 4 s and (2) applying the
solution to the skin under the nose with a soaked
swab, as we had done in our previous studies.
MATERIALS AND METHODS
Participants
Thirty-seven nonsmoking volunteers (18 women
and 19 men) participated in a study that we described
as investigating a variety of common household odora
including compounds in perfumes. Participants
were blind to our specific hypotheses and the identity
of all compounds. The participants were between the
ages of 18 and 35 years (means: women, 25.7 years;
men, 22.2 years). Participants were students or associ
with the medical science community at the University
of Chicago. All participants identified themselves
as heterosexual and all but 3 were righthanded.
Eight women and eleven men described
themselves as Caucasian or White, 4 women and 3
men described themselves as African-American,
Black, or of African descent, 4 women and 3 men
described themselves as of Asian descent, while the
rest were of Latin descent or had multiple ethnic

l mt khng sn xut ca con ngi.


Chng ti tip xc vi mi ngi tham gia
androstadienone ,
androstenol, v muscone , mt n mi x hng
ca h
vi du inh hng , mi mnh m c s dng
trong trc ca chng ti
nghin cu ( Monti - Bloch v Grosser , 1991 ,
Jacob v
McClintock , 2000 , Jacob v cng s, 2001) . .
sau
thit k so snh thng c s dng so snh
cc tc ng
ca Cht hng tng t ( Lorig v Schwartz ,
1988) ,
chng ti so snh c lp ca androstadienone
vi androstenol v vi muscone ( hai lp i lp li
cc bin php trong -mn phn tch ) . mi
thit k so snh c tnh b qua "khng mi " tu
sn bay
iu kin , trnh nhiu confounds quan trng .
S khc bit ng k gia cc mi
iu kin v "kim sot" tnh trng , m r rng l
khng c mi , to ra mt cch v thc
"Hawthorne
nh hng . "Ngoi ra, ng k khc nhau
trng thi no b gia cc iu kin vn chuyn
khng c mi v
s hin din ca mi c th sn xut cc to
tc thng k
Androstadienone , androstenol, Muscone 275
(v d , xu hng th nghim F omnibus ) ch n
gin l kt qu ca
s khc bit trong thng tin gia mt
odorantcontaining
iu kin v iu kin khng c mi . ny
thit k so snh cng c s dng iu tr lm
sng
th nghim , trong tiu chun vng ang cho
thy ngha
s khc bit t "so snh " cht hoc cc giao
thc .
Tuy nhin, iu quan trng l xc minh rng
nh hng trong nghin cu ny c so snh
vi nhng ngi trong
7

backgrounds.
This sample represented the ethnic diversity
of the community, but did not enable comparisons of
ethnic differences. Participants were in good health,
with no sinus problems, and no history of any respirat
or reproductive disease. Subjects provided
written consent, as required by the Institutional Revie
Board at the University of Chicago, and were
paid for their participation.
Testers and Testing Facility
Two testers (one male age 24 years, of Scottish/
Indian descent, and one female age 22 years, of Filipi
descent) ran the data-collection sessions. Testers
were assigned randomly to subjects and ran all three
sessions of a given subject. The testers were trained to
adhere closely to a written script and demonstrated
high inter-tester reliability before being approved for
data collection by the primary study directors (S.J. an
M.M.). The testers wore no strongly scented products
during study sessions. We confirmed that there were
no significant differences in any of our measures betw
the two testers (0.32 all P values 0.96 based
on analyses of data with tester as a between-subjects
variable).
Participants were tested in an isolated testing room
(10 10 ft in size, 74.3 2F, with 15 air changes per
hour) that was carpeted, with neutral color walls, and
well lit with fluorescent light. Two desks were positio
side by side facing the wall to the left of the
entrance. Throughout the session the participant sat
by the desk farther from the doorway in a comfortable
chair.
Stimulus Solutions and Odor Masking
Because we successfully masked awareness of steroid
chemosignals in our previous studies using clove
oil as a strong-odor olfactory mask (Jacob and McClintock, 2000), we decided to use clove oil as the
olfactory masking component in this experiment as
well. The three musky compounds were androstadien
(4,16-androstadien-3-one, Steraloids, Inc.),

nghin cu , ni c iu khin tu sn bay. do ,


chng ti khng nh androstadienone trong
hin ti
nghin cu c tc dng kch thc tng t cho
nhng ngi trc
nghin cu ( Jacob v McClintock , 2000).
Cui cng, trong th nghim trc y ca chng
ti , chng ti lun lun
p dng androstadienone trc tip trn da di
mi , cho php tip xc lin tc . tip xc ny
phng php lun lun ng kh nng
quan st ca chng ti bt ngun t hoc trc tip
xuyn qua da
truyn ca steroid vo mu
hoc tip xc lu di vi steroid cn li trn
da. Trong th nghim ny , chng ti xc nh liu
ht th ng ngn gn v cc khng gian pha trn
mt nh
gii php androstadienone lng l
to ra hiu ng tm l ca n . Chng ti tip xc
vi mi
chu s Cht hng s dng hai phng php : ( 1
) ch n gin
nm gi mt lng nh cc gii php kch thch
kinh t gn
mi trn mt tm ch c 4 s v (2) p dng
gii php cho da di mi vi mt ngm
tm bng , nh chng ti lm trong nghin cu
trc y ca chng ti .
Vt liu v phng php
tham gia
Ba mi by tnh nguyn vin ( 18 ph n khng
ht thuc
v 19 nam) tham gia vo mt nghin cu m
chng ti m t
nh iu tra mt lot cc h gia nh Cht hng
chung ,
bao gm cc hp cht trong nc hoa. tham gia
b m n gi thuyt c th ca chng ti v bn
sc
ca tt c cc hp cht . Nhng ngi tham gia l
gia
tui t 18 n 35 nm ( c ngha l: ph n , 25,7
nm ;
nam gii, 22,2 nm ) . Ngi tham gia l sinh
vin hoc c lin quan
8

androstenol (5-androst-16-en-3-ol, Sigma-Aldrich


Co.), and muscone (3-methyl-cyclopentadecalactone,
Firmenich). The stimulus solutions were composed of
one of the musky compounds at 250 Mconcentration
in a 10% clove oil/90% propylene glycol (by volume)
carrier solution. The participants could not discrimina
the three solutions as different odors, either in
open-ended verbal description or in olfactory
characteristics.
The subjects described the three solutions as
smelling the same. To further validate our olfactory
276 Jacob et al.
masking of all three compounds, we asked participant
to use Likert scales to describe each solutions
intensity (0 to 5), familiarity (0 to 5), and pleasantnes
(5 to 5). There were no significant differences in
perception of these olfactory qualities (0.33 all Ps
0.97). Moreover, to assess possible trigeminal nerve
effects, we asked participants to rate any sensations o
itching (0 to 5) or burning (0 to 5). Again, there were
no significant differences among all three stimuli in
perception of these somatosensory qualities (0.45 all
Ps 0.55).
Psychological Measures and Testing Procedures
We employed psychological measures that have detec
effects of androstadienone exposure in several
previous studies (Jacob and McClintock, 2000; Jacob
al., 2001a). These were the Addiction Research Cente
Index (ARCI, cf. (Haertzen, 1974a,b) composed of 49
True/False responses which collapse into scores for
five families of drug effects); the Profile of Mood Sta
(POMS, McNair et al., 1971) composed of 72 5-point
Likert scale responses which are scored as eight emot
arousal factors; the De Wit Visual Analog Scale
(VAS) items derived from earlier androstadienone (Ja
and McClintock, 2000) and psychopharmacological
(de Wit et al., 1990) research. Each VAS is a 100-mm
line paired with an adjective. Its ends are labeled
extremely and not at all. A subject indicates how
much the adjective applies to their state by placing a
mark on the line at the appropriate point; Bond VAS

vi cng ng khoa hc y khoa ti i hc


Chicago. Tt c ngi tham gia t nhn mnh
l d tnh v tt c nhng 3 c thu n tay m t .
Tm ph n v mi mt ngi n ng c m
t
mnh l Ngi Da trng , 4 ph n v 3
ngi n ng t cho mnh l ngi M gc Phi ,
en hoc gc Phi , 4 ph n v 3 ngi n ng
m t mnh l ngi gc chu , trong khi cc
cn li l ngi gc Latin hoc c nhiu bn sc
dn tc .
Mu ny i din cho s a dng dn tc
ca cng ng, nhng khng cho php so snh
dn tc khc nhau . Ngi tham gia c sc khe
tt ,
khng c vn v xoang , v khng c tin s
ca bt k h hp
hoc bnh sinh sn . i tng quy
vn bn tha thun , theo yu cu ca Institutional
Review
Hi ng qun tr ti i hc Chicago , v l
tr tin cho s tham gia ca h .
C s xt nghim v kim tra
Hai th nghim (mt tui nam 24 nm , ca
Scotland /
Gc n , v mt ph n tui 22 nm ,
Philippines
gc ) chy phin thu thp d liu . xt nghim
c phn ngu nhin cho cc i tng v chy
tt c ba
phin hp ca mt ch nht nh . Cc xt
nghim c o to
tun th cht ch vi mt kch bn c vit v
chng minh
cao tin cy gia cc th nghim trc khi c
chp thun
thu thp d liu do Gim c nghin cu chnh
( SJ v
M.M. ) . Cc xt nghim khng mc cc sn phm
c mi thm mnh m
trong cc bui hc . Chng ti xc nhn rng
c
khng c khc bit ng k trong bt k cc bin
php ca chng ti gia
hai th nghim ( 0,32 ? tt c cc gi tr P ? 0.96
da
9

items created from the first reported use of VAS meas


(Bond and Lader, 1974). These are the same as
the De Wit VAS, but, rather than representing a contin
of intensity for a single adjective, they are
marked with antonymic adjectives at either end of the
line.
The four psychological measures yielded 62 scores
(5 ARCI subscales 7 POMS subscales 20 De Wit
VAS items 30 Bond VAS items 62 total scores). To
minimize potential Type I errors from statistically test
each score individually, the data were combined
into discrete factor scores. Based on our previous find
(Jacob and McClintock, 2000; Jacob et al., 2001a),
we expected there to be several factors covering posit
and negative emotion as well as states of arousal
or drug-like euphoria. To confirm these factors in the
current study, factor analyses were performed separat
on the ARCI/POMS data and on the Lab/Bond
VAS data. These two data sets were analyzed
independently
because they are different types of measures.
The ARCI and POMS have well-established
subscales (McNair et al., 1971; Haertzen, 1974a,b). B
the ARCI and the POMS are widely used and validate
measures. In contrast, the VAS (Bond and
Lader, 1974; de Wit et al., 1990) measures do not hav
any preestablished subscales.
As expected, factor analyses and varimax rotation
confirmed the robustness of previously derived factor
structures. Only one of the factors was unique to this
study (anxiousness-irritability) and it did not reveal
any treatment effects. We confirmed that the factor
analysis output corresponded to strongly intercorrelat
clusters of questionnaire scores (all linear association
and correlation P values less than 0.0001).
A measure for each derived factor was calculated
using methods described previously (Jacob and McClintock, 2000). A factor score for each time interval
was obtained by calculating a mean of the measures
for each of the factors that had a varimax rotated
factor loading 0.5. Measures with a negative factor

10

trn phn tch d liu vi th nghim nh mt


gia cc i tng
bin ) .
Ngi tham gia c kim tra trong mt phng
th nghim c lp
( 10 ? 10 ft trong kch thc, 74,3 ? 2 F , vi 15
thay i khng kh mi
gi ) c tri thm , vi nhng bc tng
mu trung tnh , v
cng thp sng bng n hunh quang . Hai bn
c b tr
bn cnh phi i mt vi bc tng bn tri ca
li vo . Trong sut phin giao dch ngi tham
gia ngi
bi bn xa hn t cc ca trong mt thoi mi
gh .
Gii php kch thch kinh t v Mi mt n
Bi v chng ta che giu thnh cng nhn thc v
steroid
chemosignals trong nghin cu trc y ca
chng ti s dng inh hng
du nh mt mt n mnh mi khu gic ( Jacob
v Mc Clintock , 2000) , chng ti quyt nh s dng
du inh hng l
thnh phn mt n khu gic trong th nghim ny
nh
tt. Ba hp cht x hng l androstadienone
( ? 4,16 - androstadien - 3-one , Steraloids , Inc ) ,
androstenol ( 5 ? - androst -16 -en- 3 ? -ol ,
Sigma- Aldrich
Cng ty TNHH ) , v muscone ( 3 -methylcyclopentadecalactone ,
Firmenich ) . Cc gii php kch thch kinh t
c bao gm
mt trong nhng hp cht x hng ti 250
Mconcentration ?
trong mt inh hng oil/90 % propylene glycol
(theo khi lng ) 10 %
gii php vn chuyn. Nhng ngi tham gia
khng th phn bit i x
ba gii php nh mi khc nhau, hoc trong
m m t bng li ni hoc trong c im khu
gic .
Cc i tng c m t ba gii php nh
ngi " nh vy. " Tip tc xc nhn khu gic ca
10

loading were subtracted from the sum of the measures


with positive loadings. This sum was then divided by
the total number of measures within each factor. The
individual factors and measures used to calculate each
factor score are listed in Tables 1 and 2.
Finally, the psychological responses were quantified
as a change from their value at baseline, prior to
exposure to the olfactory stimuli. A change in factor
score from the baseline was calculated for each subse
time interval and these values were used in
analyses. Since the focus of our experiment is on the
psychological effects of androstadienone, one
repeatedmeasures
ANOVA was done in comparison with androstenol
and a second in comparison with muscone.
Menstrual Cycle Status
To maximize the ability to discriminate odors, we
tested subjects during the periovulatory phase of their
menstrual cycle when olfactory sensitivity is highest
(Doty, 1981). Menstrual cycle information was gather
by all 18 women for two consecutive cycle
months based on dates of menses onset. The 18
women also collected detailed daily basal body
temperature,
vaginal secretions, menses, and urinary LH
data. Basal body temperature was measured before
getting out of bed in the morning. Vaginal secretions
and LH measures were collected at 6 PM in the eveni
to maximize detection of LH rise (Stern and McClintock, 1996). During the first cycle month, we
determined
the day when their preovulatory LH surge
began (LH surge onset) using a commercially availab
kit (OvuQuik) and used this information to
Androstadienone, Androstenol, Muscone 277
schedule the testing during the subsequent cycle
(Stern and McClintock, 1996). The testing sessions
were scheduled during the late follicular/periovulatory
phase of the menstrual cycle (i.e., within a few
days of LH surge onset).
Design and Procedures

11

chng ti
276 Jacob et al.
mt n ca tt c ba hp cht , chng ti yu cu
ngi tham gia
s dng thang o Likert m t ca mi gii
php
cng ( 0-5 ) , quen thuc ( 0-5 ) , v
pleasantness
( ? 5-5 ) . Khng c khc bit ng k trong
nhn thc v nhng phm cht khu gic ( 0.33 ?
tt c P ?
0,97) . Hn na, c th nh gi thn kinh sinh
ba
hiu ng, chng ti yu cu ngi tham gia
nh gi bt k cm gic ca
nga ( 0-5 ) hoc t ( 0-5 ) . Mt ln na , c
khng c khc bit ng k trong s tt c ba tc
nhn kch thch trong
nhn thc v nhng phm cht somatosensory
( 0,45 ? tt c
P ? 0,55 ) .
Cc bin php tm l v cc th tc kim tra
Chng ti s dng cc bin php tm l pht
hin
nh hng ca tip xc vi androstadienone trong
nhiu
nghin cu trc y ( Jacob v McClintock ,
2000; Jacob v cng
al . , 2001a) . y l Trung tm Nghin cu
Nghin
Ch s ( ARCI , xem . ( Haertzen , 1974a , b ) bao
gm 49
True / False phn ng m sp vo im s cho
nm gia nh ca tc dng ca thuc ) , cc h s
ca Hoa Tm trng
( POMS , McNair v cng s . , 1971) gm 72 5
im
p ng quy m Likert c ghi nh tm cm
xc /
cc yu t kch thch , cc Wit De trc quan tng
t quy m
(VAS) cc mt hng c ngun gc t
androstadienone trc ( Jacob
v McClintock , 2000 ) v psychopharmacological
( de Wit v cng s . , 1990) nghin cu . Mi
VAS l 100 mm
11

We used a within-subjects, double-blind design that


was randomized for order of exposure to the three
stimulus solutions. Participants were asked to come to
our human subject room for three sessions, scheduling
1 day between sessions. With the exception of the
stimulus solutions, sessions were identical in procedu
environment, time of day (1 h), and experimenter
interaction. Each participant was tested with
the same tester for each of the three sessions. Which
tester ran a subjects sessions was determined on the
basis of availability. We confirmed that this resulted in
random assignment of participants to each of the two
testers.
One half hour before each scheduled session, odorant
were aliquotted by a laboratory member not involved
in the study. Six standard 1.5-ml polypropylene,
flat top microcentrifuge tubes were used in a
session. These have a surface area less than 5 mm in
diameter. All tubes were labeled by colored tape,
identifying
them according to when in the session they
were to be used. Two tubes were empty for practicing
demonstrating the passive inhalation exposure
procedure, two tubes contained 50 l of the solution
for the passive inhalation, and two tubes contained
130 l of the odorant for epidermal application. The
six tubes were placed on a rack outside the human
subject room.
Each session followed the same protocol. When
participants
arrived for a session, they first washed their
hands with the nonodorous liquid soap. They were
then seated in the human subject room approximately
1.25 m to the right of the tester, who gave them
introductory
instructions. Participants were asked to limit
movement and talking throughout the session, but
were free to make observations specific to the session
The sessions were exactly timed and were divided
into three intervals: baseline, passive inhalation
(nonepidermal

12

dng kt hp vi mt tnh t . Kt thc ca n


c dn nhn
"Cc k " v " khng g c. " Mt ch ch ra
cch
nhiu tnh t p dng i vi nh nc ca h
bng cch t mt
nh du trn ng ti thi im thch hp ;
VAS Bond
mc c to ra t vic s dng bo co u tin
ca VAS bin php
(Bond v lader , 1974). y l nhng ging nh
VAS De Wit, nhng , ch khng phi l i din
cho mt lin tc
cng cho mt tnh t duy nht, h l
nh du bng antonymic tnh t hai u ca
dng .
Bn bin php tm l mang li 62 im
( 5 ARCI bng phn ? 7 POMS bng phn ? 20 De
Wit
VAS mc ? 30 Bond VAS mc ? 62 tng s im )
. n
gim thiu kh nng sai st loi I t th nghim
thng k
mi im c nhn , d liu c kt hp
vo im yu t ri rc . Da trn nhng pht
hin trc y ca chng ti
( Jacob v McClintock , 2000; . Jacob v cng s,
2001) ,
chng ti d kin s c c mt s yu t bao
gm tch cc
v cm xc tiu cc cng nh trng thi kch thch
hoc thuc nh hng phn. xc nhn cc yu
t trong
nghin cu ny, phn tch yu t c thc hin
ring
trn cc d liu ARCI / POMS v Phng th
nghim / tri phiu
VAS d liu. Hai tp hp d liu c phn tch
mt cch c lp
bi v h l cc loi khc nhau ca cc bin php .
Cc ARCI v POMS c thit lp tt
bng phn ( McNair v cng s, 1971; .
Haertzen , 1974a , b ) . c hai
cc ARCI v POMS c s dng rng ri v xc
nhn
cc bin php . Ngc li, VAS ( tri phiu v
12

application), and epidermal application. In


the baseline interval, the participants were administer
a baseline battery of psychological state questionnaire
presented on a computer screen. If the participants
completed the tests before the predetermined
end of the baseline interval, the tester provided them
with light nonstimulating reading material.
After 30 min, the passive inhalation exposure procedu
was demonstrated to reduce its novelty and
increase awareness and expectations. Using the empty
tubes, each of two cotton swabs, one to be held under
each nostril, was dipped into its own microcentrifuge
tube for 3 s. Each swab was then held approximately
TABLE 1
Factor Loadings (Varimax Rotation) of ARCI/POMS
Subscale Responses to Androstadienone, Androstenol, an
Muscone by Women and Men
Rotated variable
Rotated factor loadings
Uniqueness
Negative-confusion
(Factor 1)
5.62790
Elation-vigor
(Factor 2)
2.21673
Euphoric-stimulant
(Factor 3)
1.10372
Anxiety (POMS) 0.88472 0.14538
Depression (POMS) 0.91899 0.07420
Anger (POMS) 0.90218 0.10500
Fatigue (POMS) 0.69119 0.33678
Confusion (POMS) 0.83143 0.18067
Vigor (POMS) 0.86228 0.17408
Friendliness (POMS) 0.67307 0.42081
Elation (POMS) 0.82285 0.21888
Intellectual efficacy (BG-ARCI) 0.74104 0.255
Stimulant (A-ARCI) 0.87428 0.18383
Euphoric (MBG-ARCI) 0.76266 0.23800
Note. Chart of items from the Addiction Research Cen

13

Lader , 1974; . De Wit v cng s, 1990) bin


php ny khng c
bt c bng phn preestablished .
Theo d kin, phn tch nhn t v quay varimax
khng nh s vng mnh ca cc yu t c
ngun gc trc y
cu trc . Ch c mt trong nhng yu t rt c
o ny
nghin cu ( lo u , d b kch thch ) v n
khng tit l
bt k tc dng iu tr. Chng ti xc nhn rng
cc yu t
sn lng phn tch tng ng vi intercorrelated
mnh
cm im cu hi ( tt c cc lin kt tuyn tnh
v mi quan h P c gi tr nh hn 0,0001).
Mt bin php cho mi yu t ngun gc c
tnh ton
phng php s dng m t trc y ( Jacob v
Mc Clintock , 2000). Mt s yu t cho mi khong
thi gian
thu c bng cch tnh trung bnh ca cc bin
php
cho mi trong nhng yu t c th xoay varimax
yu t ti? 0.5 . Cc bin php vi mt yu t tiu
cc
loading c tr vo s tin ca cc bin php
vi ti trng tch cc . S tin ny sau c
chia
tng s cc bin php trong tng yu t . cc
cc yu t v cc bin php c s dng tnh
ton mi c nhn
im yu t c lit k trong Bng 1 v 2 .
Cui cng, nhng phn ng tm l c nh
lng
nh mt s thay i t gi tr ca h lc ban u,
trc khi
tip xc vi cc tc nhn kch thch khu gic .
Mt s thay i trong yu t
im t ng c s c tnh ton cho mi
tip theo
khong thi gian v nhng gi tr ny c s
dng trong
phn tch . K t khi tp trung th nghim ca
chng ti l trn
13

Index (ARCI) and Profile of Mood States (POMS)


questionnaire items grouped by
factor membership. Factors were identified based on s
plot inspection. Items within each factor were included g
varimax rotated
factor loading 0.5 without rounding.
Eigenvalue:
278 Jacob et al.
0.5 in. underneath the nostril for 4 s. This baseline
presentation contained no odorant and the subjects
were asked to continue breathing normally. The
participants
were then asked a series of questions about
what they smelled.
After a minute, the same exposure procedure was
repeated but with swabs dipped into tubes with 50 l
of the test solution assigned for that session and held
just under each nostril. The participants were again
asked to breathe normally without sniffing, resulting
in passive inhalation of the stimulus solution. They
were then given the second battery of questionnaires.
Twenty-five minutes after the initial exposure, the
participants were exposed again, except that the two
swabs were dipped into microcentrifuge tubes with
130 l of solution and then swiped twice on the upper
lip below the nose, once with each side of the swab
head. The participants continued to breathe normally
and were then given the same battery of psychologica
tests. After each application, the tester placed the used
cotton swabs and closed microcentrifuge tubes in a
sealed plastic bag to prevent any additional ambient
exposure.
The entire session lasted approximately 90 min.
RESULTS
Main Effects of Treatment Condition
Although participants could not identify any olfactory
differences between the three masked comTABLE 2
Factor Loadings (Varimax Rotation) of VAS Item
Responses to Androstadienone, Androstenol, and Muscon
Women and Men

14

nh hng tm l ca androstadienone , mt
repeatedmeasures
ANOVA c thc hin so vi androstenol
v th hai so vi muscone .
Chu k kinh nguyt trng
ti a ha kh nng phn bit mi hi , chng
ti
i tng kim tra trong giai on periovulatory
ca h
chu k kinh nguyt khi nhy cm khu gic l cao
nht
( Doty , 1981). Thng tin chu k kinh nguyt
c thu thp
tt c 18 ph n cho hai chu k lin tip
thng da trn s ngy ca chu k kinh nguyt bt
u . 18
ph n cng thu c nhit c th c bn hng
ngy chi tit ,
dch tit m o , chu k kinh nguyt , v tiu LH
d liu. Nhit c th c bn c o trc
khi ra khi ging vo bui sng. dch tit m o
v cc bin php LH c thu thp ti 6:00 vo
bui ti
ti a ha pht hin ca LH tng ( Stern v Mc
Clintock , 1996). Trong thng chu k u tin ,
chng ti xc nh
ngy trc khi rng trng khi LH tng ca h
bt u (LH tng khi pht) bng cch s dng c
sn thng mi
kit ( OvuQuik ) v s dng thng tin ny
Androstadienone , androstenol, Muscone 277
lch trnh kim tra trong chu k tip theo
( Stern v McClintock , 1996). Cc bui th
nghim
c ln k hoch trong thi gian cui nang /
periovulatory
giai on ca chu k kinh nguyt (ngha l , trong
vng vi
ngy LH tng khi pht) .
Thit k v th tc
Chng ti s dng mt trong -mn , thit k m
i m
l ngu nhin cho tip xc vi ba
cc gii php kch thch kinh t . Ngi tham gia
c yu cu n
14

(DeWit Unipolar Scale, Bond Bipolar Scale)


Rotated variable
Rotated factor loadings
Uniqueness
Clearheaded-lucid
(Factor 1)
15.61533
Anxious irritability
(Factor 2)
3.83290
Alert/(drowsy) 0.86643 0.18117
Clear-headed/(fuzzy) 0.86333 0.12044
Clear-headed/(light-headed) 0.82417 0.18773
Sharp 0.77590 0.24290
Energetic 0.67552 0.25321
Light-limbed/(heavy) 0.59988 0.39754
Stimulated 0.55563 0.32992
Incompetent/(proficient) 0.52578 0.20386
Sedated 0.55626 0.37952
Clumsy/(well-coordinated) 0.58305 0.25693
Bored/(interested) 0.62878 0.26281
Stimulated/(sedated) 0.63037 0.25427
Spacy 0.66088 0.26230
Dreamy/(attentive) 0.75140 0.18719
Mentally slow/(quick-witted) 0.75599 0.16933
Lethargic/(energetic) 0.77844 0.15754
Discontented/(contented) 0.53272 0.30262
Irritated 0.54226 0.31374
Excited/(calm) 0.60360 0.40230
Anxious 0.60526 0.38443
Antagonistic/(amicable) 0.61784 0.26146
Tense/(relaxed) 0.75969 0.24224
Tranquil/(troubled) 0.74731 0.23617
Peaceful/(irritated) 0.72438 0.23701
Mellow/(irritable) 0.69088 0.32690
Well/(sick) 0.52124 0.31989
Note. Chart of items from the Visual Analog Scale (V
questionnaire items grouped by factor membership. Items
listed with a slash (/)
between them are ends of bipolar VAS items. Single
descriptor items are from VAS items which rated a single

15

phng ch nhn ca chng ti trong ba phin , lp


k hoch
1 ngy gia phin. Vi ngoi l ca
cc gii php kch thch kinh t , cc bui ging
nhau trong th tc ,
mi trng , thi gian trong ngy ( 1 gi ) , v th
nghim
tng tc . Mi ngi tham gia c th
nghim vi
cc th nghim tng t cho mi trong ba phin .
m
th chy phin ca i tng c xc nh
trn
c s sn c . Chng ti xc nhn rng iu ny
dn n
phn cng ngu nhin ngi tham gia mi hai
xt nghim .
Mt na gi trc khi mi phin theo lch trnh,
Cht hng
c aliquotted bi mt thnh vin trong phng
th nghim khng lin quan n
trong nghin cu. Su tiu chun 1,5 ml
polypropylene ,
ng microcentrifuge nh bng phng c s
dng trong mt
phin . Nhng c mt din tch b mt t hn 5
mm
ng knh . Tt c cc ng c dn nhn bng
bng mu , xc nh
h theo khi trong phin giao dch h
c s dng . Hai ng trng rng thc
hnh /
th hin s tip xc vi ng h hp th ng
th tc , hai ng cha 50 lt dung dch ?
cho ng h hp th ng , v hai ng cha
130 l ? Ca mi cho ng dng ca biu b . cc
su ng c t trn mt gi bn ngoi con
ngi
phng.
Mi phin theo giao thc tng t. khi tham gia
n cho mt phin lm vic, h ln u tin ra
sch ca h
tay vi x phng nonodorous . h
sau ngi trong phng ch th nhn khong
1,25 m bn phi ca cc th nghim , ngi
cho h gii thiu
15

adjective from not at all to


extremely. Factors were identified based on scree p
inspection. Items within each factor were included given
varimax rotated factor
loading 0.5 without rounding.
Eigenvalue:
Androstadienone, Androstenol, Muscone 279
pounds, androstadienone had unique effects on positiv
and negative moods as well as mental acuity (see
Fig. 1a for androstadienone vs androstenol effects and
Fig. 1b for androstadienone vs muscone). The magnit
of the effect of androstadienone was consistent
with that in our previous studies, i.e., it prevented the
drop in positive mood observed during the androsteno
and muscone conditions, which was the same as
the drop seen during exposure to the odor carrier
alone (Jacob and McClintock, 2000). In this study,
androstadienone prevented the drop in elation-vigor
that did occur in the presence of androstenol (main
effect of treatment, F(1, 35) 6.6, P 0.01) and
muscone (main effect of treatment, F(1, 35) 10.4, P
0.003). This change mirrors the changes in the POMS
Positive Mood measure observed in earlier work and
was a virtually identical effect size (Jacob and McClintock, 2000; a minimal drop in the androstadienon
condition vs a 0.35 standard unit drop in the odor
carrier condition). Similarly, androstadienone prevent
the rise in clearheaded-lucid factor that occurred
in the presence of androstenol (main effect of
treatment, F(1, 35) 5.0, P 0.03) and muscone
(main effect of treatment, F(1, 35) 4.3, P 0.04).
Again, this was an effect size similar to those of previ
studies.
Androstadienone also affected negative mood.
Androstadienone
prevented the increase in negative-confusion
that occurred during exposure to muscone
(main effect of treatment, F(1, 35) 6.2, P 0.02),
although its effects were not significantly different
from those of androstenol (F (1, 35) 0.84, P 0.37).
This effect was specific to negative-confusion, as

16

hng dn. Nhng ngi tham gia c yu cu


hn ch
di chuyn v ni chuyn sut phin giao dch ,
nhng
c t do quan st c th cho cc phin .
Cc phin hp c chnh xc gi v c
chia
vo ba khong: ban u, ht th ng
( nonepidermal
ng dng ) , v ng dng biu b . trong
khong thi gian ban u, nhng ngi tham gia
c qun l
mt pin c bn ca cu hi trng thi tm l
trnh by trn mt mn hnh my tnh . Nu nhng
ngi tham gia
hon thnh cc bi kim tra trc khi c xc
nh trc
cui khong thi gian ban u, cc th nghim
cung cp cho h
vi nh sng nonstimulating c ti liu .
Sau 30 pht , cc th tc tip xc vi ng h
hp th ng
c chng minh gim mi l v n
nng cao nhn thc v k vng. Bng cch s
dng trng
ng, mi hai ming gc bng , mt s c t
chc di
mi l mi , c nhng vo microcentrifuge
ring ca mnh
ng cho 3 s . Mi ming gc sau c t
chc khong
BNG 1
Yu t ti trng ( Varimax xoay ) ca ARCI /
POMS subscale hi p ti Androstadienone ,
androstenol, v Muscone ca ph n v nam gii
lun chuyn bin
Lun chuyn ti trng yu t
c o
m nhm ln
( H s 1 )
5,62790
Hng khi , sc sng
( H s 2 )
2,21673
Phn khch , kch thch
( Yu t 3 )
16

androstadienone
had no effect on anxious-irritability
(main effect of treatment, androstenol, F(1, 36) 0.03,
and P 0.85; muscone, F(1, 36) 0.58, P 0.45).
Effect of Exposure Methods
Passive inhalation and dermal application had
indistinguishable
effects on mood, indicating that direct
skin contact and prolonged exposure are not necessar
for the psychological effects of androstadienone.
Moreover, exposure method did not interact with
treatment in any of the factors. This occurred when
male and female subjects were combined in a single
analysis, both with and without a sex of subject intera
term, and when males and female were analyzed
separately (0.0003 all Fs 3.32; .077 all
Ps 0.99).
Effect of Sex of Subject
Independent of treatment, the sex of the subject was
significant in only one analysis. When androstadienon
and muscone data were analyzed together (i.e.,
when androstenol data were excluded), male subjects
reported a greater average increase in Anxious irritabi
during our study than did the female subjects
(F(1, 36) 6.13, P 0.02). As a result, we included
sex of subject as a potential interaction factor in our
analyses of treatment effect. However, there were no
significant sex differences in response to the compoun
for any measure (0.04 all Fs 1.55, 0.22 all P
values 0.85).
DISCUSSION
Androstadienone had unique effects on the participan
mood in comparison with androstenol and
muscone, even though they could not distinguish any
of the compounds as an odor. It prevented both the
drop in positive mood and the rise in the negative
mood that has previously occurred with our experime
protocol (Jacob and McClintock, 2000). These
results on mood correspond in both type and effect
size with our previous findings that compared
androstadienone

17

1,10372
Lo lng ( POMS ) 0,88472-0,14538
Trm cm ( POMS ) 0,91899-,07420
Tc gin ( POMS ) 0,90218-,10500
Mt mi ( POMS ) ,69119-,33678
Nhm ln ( POMS ) 0,83143-,18067
Vigor ( POMS ) - ,86228-,17408
Thn thin ( POMS ) - 0,67307-,42081
Hng khi ( POMS ) - ,82285-0,21888
Hiu qu tr tu ( BG- ARCI ) - 0,74104 0,25530
Cht kch thch ( A- ARCI ) - 0,87428 0,18383
Phn khch ( MBG - ARCI ) - 0,76266 0,23800
Lu . Biu cc mt hng t Trung tm
Nghin cu Nghin Index ( ARCI ) v h s ca
Hoa Tm trng ( POMS ) Cc cu hi c nhm
theo
thnh vin yu t . Cc yu t c xc nh
da trn kim tra m mu Scree . Cc mt hng
trong mi yu t c a cho mt xoay varimax
yu t ti? 0.5 m khng lm trn.
gi tr c trng :
278 Jacob et al.
0,5 in bn di l mi trong 4 s . ng c s ny
trnh by khng c mi v cc i tng
c yu cu tip tc th bnh thng. nhng
ngi tham gia
sau hi mt lot cc cu hi v
nhng g h ngi thy mi .
Sau mt pht , cc th tc tip xc cng l
lp i lp li nhng vi gc nhng vo ng vi
50 ? l
dung dch th giao cho phin hp v t chc
di mi l mi . Nhng ngi tham gia mt
ln na
yu cu th bnh thng m khng cn nh hi,
kt qu
trong ng h hp th ng ca cc gii php
kch thch kinh t . h
sau c a ra pin th hai ca cu hi .
Hai mi lm pht sau khi tip xc ban u,
ngi tham gia c tip xc mt ln na, ngoi
tr hai
bnh phm c nhng vo ng
microcentrifuge vi
130 l ? Ca gii php v sau qut hai ln pha
trn
17

in its strong clove-scented carrier to its


carrier alone. Androstadienone also had unique effect
on mental acuity in this study. It should be noted,
however, that our previous studies have not consisten
identified similar factors measuring mental
acuity, arousal, or alertness, nor has androstadienone
had consistently significant effects on this aspect of
psychological function (Jacob and McClintock, 2000;
Jacob et al., 2001a).
During sustained exposure, androstadienone has local
but widely distributed cerebral effects in areas
associated with emotion and attention (Jacob et al.,
2001b). The degree to which these effects were distrib
throughout the brain suggests that the neural
effects of androstadienone cannot be conceptualized
strictly in terms of olfactory perception and categoriza
The current findings provide additional evidence
that androstadienone is a chemosensory stimulus
categorically distinct from simple odorants, with
psychologically unique effects on humans different
from those of two other musky compounds, similar in
odor at high concentrations and use in common perfu
and fragrances. It is noteworthy that the effects
of androstadienone did not generalize to another 16androstene, which is similar in structure and also
found in a variety of human secretions.
280 Jacob et al.
FIG. 1. Effects of androstadienone, androstenol, and
muscone on psychological factors derived from the test b
Responses are expressed
as change from baseline and standardized within subj
(mean SEM). No effects of exposure method were obser
Data from male (N
19) and female (N 18) subjects are combined in these
figures as there were no significant sex differences in resp
(a) Comparison of
androstadienone and androstenol. (b) Comparison of
androstadienone and muscone.
Androstadienone, Androstenol, Muscone 281
The psychological effects did not require direct epide
application (Jacob and McClintock, 2000) or

18

mi di mi , mt ln vi mi bn ca ming
gc
u . Nhng ngi tham gia tip tc th bnh
thng
v sau c a ra cng mt b pin ca tm l
kim tra . Sau mi ng dng , my o t s dng
gc bng v ng microcentrifuge ng trong mt
ti nha kn ngn chn bt k tip xc vi mi
trng xung quanh b sung.
Ton b phin ko di khong 90 pht .
KT QU
Tc dng chnh ca iu tr iu kin
Mc d tham gia khng th xc nh bt k khu
gic
s khc bit gia ba eo mt n com BNG 2
Yu t ti trng ( Varimax xoay ) ca VAS mc
hi p ti Androstadienone , androstenol, v
Muscone ca ph n v nam gii
( Dewit Quy m n cc , lng cc tri phiu
quy m )
lun chuyn bin
Lun chuyn ti trng yu t
c o
Thanh tnh , sng sut
( H s 1 )
15,61533
kh chu lo lng
( H s 2 )
3,83290
Cnh bo / ( bun ng ) ,86643-0,18117
Nhy bn / ( m ) 0,86333-,12044
Nhy bn / ( chong vng ) ,82417-0,18773
Sharp ,77590-,24290
Nng lng ,67552-0,25321
nh sng - tay chn / ( nng ) ,59988-0,39754
Kch thch ,55563-,32992
Khng nng lc / ( thnh tho ) 0,52578 0,20386
An thn 0,55626 - 0,37952
? Vng v / ( phi hp tt ) 0,58305-,25693
Chn / ( quan tm ) 0,62878 - 0,26281
Kch thch / ( thuc an thn ) 0,63037 - 0,25427
Spacy 0,66088 - 0,26230
M mng / ( chu o ) 0,75140 - 0,18719
? Tinh thn chm / ( nhanh tr ) ,75599-,16933
18

presentation at the opening of the vomeronasal organ


(Monti-Bloch and Grosser, 1991). Airborne presentati
of nanomolar amount during passive inhalation
was sufficient. In addition, we found no evidence that
androstadienone has exclusive effects on women, as
suggested by others (Berliner et al., 1991; Monti-Bloc
and Grosser, 1991; Monti-Bloch et al., 1994). This ne
finding is consistent with our previous studies
comparing androstadienone with the odor carrier
alone (Jacob and McClintock, 2000). Estratetraenol,
which has psychological effects similar to androstadie
(Jacob and McClintock, 2000), may well show
similar stimulus specificity in comparison to androste
and muscone.
Given the current findings and previous work,
androstadienone
is clearly a human social chemosignal.
Others have claimed that it is a pheromone (Berliner e
al., 1991; Monti-Bloch and Grosser, 1991; Monti-Blo
al., 1994). We believe this claim to be premature with
directly testing each of the various criteria that a comp
must meet to be called a mammalian pheromone
(reviewed by (Beauchamp et al., 1976; Jacob et al., 20
The current study is the first to test the criterion that
androstadienone has specific effects that are unique in
comparison with similar compounds, not just differen
from the carrier solution (a criterion set forth by
Beauchamp, 1976). Indeed, androstadienones effects
were unique in comparison with two similar compoun
even though they were chemically similar
(androstenol) or had similar musky odors at high
concentrations
(muscone and androstenol).
An additional criterion is that animal pheromones
operate independently of their odor properties (criteri
set forth by Beauchamp et al., 1976; McClintock,
2000). Although it is true that some people are able to
detect androstadienone at higher concentrations as an
odor, in this study and in all previous studies,
androstadienone
produced its effects without being detected

19

Hn m / ( nng lng ) 0,77844 - 0,15754


Bt mn / ( hi ) - 0,53272 0,30262
Kch thch - 0,54226 0,31374
Vui mng / ( bnh tnh ) - 0,60360 0,40230
Lo lng - 0,60526 0,38443
i khng / ( thn thin ) - 0,61784 0,26146
Cng thng / ( thoi mi ) - 0,75969 0,24224
Yn tnh / ( kh khn ) - 0,74731 0,23617
Ha bnh / ( kch thch ) - 0,72438 0,23701
m du / ( kh chu ) - 0,69088 0,32690
Tt / ( bnh ) - 0,52124 0,31989
Lu . Biu ca cc mc t Analog Scale
Visual ( VAS) mc cu hi c nhm theo thnh
vin yu t . Cc mt hng c lit k vi mt
du gch cho ( / )
gia chng l kt thc ca lng cc VAS mc .
Mc m t duy nht l t VAS hng mc nh gi
mt tnh t duy nht t " khng tt c "
Cc yu t " v cng . " c xc nh da
trn kim tra m mu Scree . Cc mt hng trong
mi yu t c a cho mt nhn t xoay
varimax
ti ? 0.5 m khng lm trn.
gi tr c trng :
Androstadienone , androstenol, Muscone 279
pound , androstadienone c tc dng duy nht trn
dng
v tm trng tiu cc cng nh s bn nhy (xem
V . 1a cho androstadienone vs androstenol hiu
ng v
V . 1b cho androstadienone vs muscone ) . ln
v hiu qu ca androstadienone l ph hp
vi iu trong nghin cu trc y ca chng
ti , tc l , n ngn chn s
th trong tm trng tch cc quan st thy trong
androstenol
v iu kin muscone , l tng t nh
th nhn thy trong thi gian tip xc vi cc tu
sn bay mi
mt mnh ( Jacob v McClintock , 2000). Trong
nghin cu ny ,
androstadienone ngn chn s st gim hng khi
, sc sng
iu xy ra trong s hin din ca
androstenol ( chnh
hiu qu iu tr , F ( 1 , 35 ) ? 6.6 , P ? 0.01 ) v
19

as an odor.
Androstenol and muscone are both animal pheromone
and did not have effects on humans comparable
to those of androstadienone. This observation is
important for evaluating previous claims that androste
is a human as well as a pig pheromone. However,
although species-specificity has traditionally
been a criterion for classifying a compound as a
pheromone,
current data indicate that a number of pheromones
may serendipitously exert effects on multiple
species, and so this additional classic criterion should
be dropped. For example, airborne chemosignals from
female hamsters affect ovarian function in rats
(Weizenbaum
et al., 1977). Thus, the fact that androstadienone
has specific effects on humans does not preclude
that possibility that it may play a part in sows
pheromonal responses to boars along with androsteno
particularly because it shares a metabolic pathway.
In sum, our findings provide additional evidence
that androstadienone may be a human pheromone.
Nonetheless, it still needs to be determined whether
its psychological effects play a role in human social
behavior in the context of everyday life. If it does not
function under normal, nonexperimental social condit
then it is not a pheromone.
If so, what do we call the effects of androstadienone
when it is presented in nanomolar quantities? In this
miniscule amount, that which is contained in 1/10th
of a drop of sweat, it cannot be called or classified as
a social odor because subjects were unable to perceiv
it as a smell or odor, either unmasked or masked,
under the conditions of this and all previous experime
It could be termed an unconscious odor or
a low concentration odorant of which there is
no conscious awareness (Lorig et al., 1990; Lorig,
1991). However, unconscious odor and unconscio
odorant are self-contradictory terms. An odor is by
definition a conscious percept in humans and so cann
also be unconscious. Thus, we use the term vasana

20

muscone ( tc dng chnh ca iu tr , F ( 1 ,


35 ) ? 10.4, P ?
0,003) . S thay i ny phn nh nhng thay i
trong POMS
Tm trng bin php tch cc quan st thy trong
cng vic trc v
l mt kch thc hiu ng hu nh ging ht
nhau ( Jacob v Mc Clintock nm 2000; gim ti thiu trong
androstadienone
iu kin vs gim 0,35 n v tiu chun trong cc
mi
iu kin tu sn bay) . Tng t nh vy ,
androstadienone ngn chn
s gia tng yu t u c sng sut , minh mn
xy ra
trong s hin din ca androstenol ( tc dng
chnh ca
iu tr, F ( 1 , 35 ) ? 5.0, P ? 0,03) v muscone
(hiu ng chnh tr , F ( 1 , 35 ) ? 4.3, P ? 0,04).
Mt ln na, y l mt kch thc hiu ng
tng t nh trc
nghin cu .
Androstadienone cng nh hng n tm trng
tiu cc . Androstadienone
ngn chn s gia tng trong m nhm ln
xy ra trong qu trnh tip xc vi muscone
(hiu ng chnh tr , F ( 1 , 35 ) ? 6.2 , P ? 0,02) ,
mc d nh hng ca n khng khc bit ng
k
t nhng ngi androstenol ( F ( 1 , 35 ) ? 0.84 , P
? 0,37 ) .
Hiu ng ny c c th m nhm ln , nh
androstadienone
khng nh hng lo lng , kh chu
(hiu ng chnh tr , androstenol, F ( 1 , 36) ? 0.03
,
v P ? 0,85 ; muscone , F ( 1 , 36) ? 0.58 , P ? 0,45
).
nh hng ca phng php phi sng
Ht th ng v ng dng da c th phn bit
nh hng n tm trng , ch ra rng trc tip
tip xc vi da v tip xc ko di khng cn thit
cho cc hiu ng tm l ca androstadienone .
Hn na, phng php tip xc khng tng tc
vi
20

as a category for the effects of chemosignals that


function neither as odors nor pheromones, yet do have
effects on psychological state and behavior without
being consciously detected (McClintock, 2001, 2002)
How can further work determine whether androstadie
in nanomolar amounts functions as a modulatory
pheromone or a social signal or is simply a
vasana? One step will be to compare the reactivity of
normal participants, anosmics, and individuals with
specific anosmias for androstadienone or other
nonandrogenic
steroids (Labows and Wysocki, 1984; Pause
et al., 1999). Another will evaluate the natural dispers
androstadienone as a chemosignal and verify its role i
normal human social interactions. Whichever type of
chemosignal androstadienone ultimately proves to be,
this study has demonstrated uniquivocally that brief
passive inhalation of androstadienone, simply from
the headspace above a small surface, is sufficient exp
to produce its psychological effects.
ACKNOWLEDGMENTS
This work was supported by NIH MERIT Award R37
MH41788
and a grant from the Mind-Body Network of the John
and
282 Jacob et al.
Catherine T. MacArthur Foundation to Martha K.
McClintock, as
well as the Olfactory Research Funds Tova Fellowsh
NIH
MD/Ph.D. Training Grant HD-07009 to Suma Jacob.
thank Tyler
Lorig for insightful discussions of olfactory study des
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21

iu tr trong bt k ca cc yu t . iu ny xy
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i tng nam v n c kt hp trong mt n
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22

trong mnh m hng inh hng thm ca n


n
tu sn bay mt mnh . Androstadienone cng c
hiu ng c o
trn s bn nhy trong nghin cu ny. Cn lu
,
Tuy nhin , cc nghin cu trc y ca chng
ti khng nht qun
cc yu t tng t nh xc nh o tinh thn
sc so , kch thch , hoc s tnh to, v cng
khng c androstadienone
c tc dng ng k nht qun trn kha cnh ny
ca
chc nng tm l ( Jacob v McClintock , 2000;
Jacob et al. , 2001a) .
Trong qu trnh tip xc lu di , androstadienone
bn a ho
nhng phn b rng ri trong khu vc nh hng
no
lin quan n cm xc v s ch ( Jacob v cc
cng s . ,
2001b) . Mc m nhng hiu ng ny c
phn pht
trong no cho thy thn kinh
nh hng ca androstadienone khng c th
c khi nim
cht ch v nhn thc khu gic v phn loi.
Cc kt qu hin ti cung cp bng chng b sung
m androstadienone l mt s kch thch gic
quan
khot khc bit Cht hng n gin , vi
hiu ng tm l duy nht trn con ngi khc
nhau
t nhng ngi ca hai hp cht x hng khc ,
tng t nh trong
mi hi nng cao v s dng trong nc hoa
ph bin
v nc hoa . Cng cn lu rng nhng tc
ng
ca androstadienone khng khi qut n 16 khc
androstene , tng t nh trong cu trc v cng
tm thy trong mt lot cc dch tit ca con
ngi.
280 Jacob et al.
FIG . 1 . nh hng ca androstadienone ,
22

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23

androstenol, v muscone trn yu t tm l bt


ngun t pin kim tra . Phn ng c th hin
nh thay i so vi ban u v tiu chun ha
trong ch (SEM ngha l g? ) . Khng c tc
dng ca phng php tip xc c quan st .
D liu t nam ( N ?
19) v n ( N ? 18) i tng c kt hp trong
nhng con s ny l khng c khc bit gii tnh
ng k p ng . ( a) So snh
androstadienone v androstenol . ( b ) So snh cc
androstadienone v muscone .
Androstadienone , androstenol, Muscone 281
Nhng tc ng tm l khng yu cu trc tip
biu b
ng dng ( Jacob v McClintock , 2000)
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