STARLING REVIEW The endocrinology of sexual arousal

17 Pages·2005·0.18 MB·English

411
STARLING REVIEW
. .
The endocrinology of sexual arousal
J Bancroft
TheKinseyInstitute,IndianaUniversity,MorrisonHallthirdfloor,Bloomington,Indiana47405,USA
(RequestsforoffprintsshouldbeaddressedtoJBancroft;Email:[email protected])
Abstract
The relevance of testosterone, oestradiol and certain pep- tion hypothesis’ to account for the striking gender differ-
tides (oxytocin (OT), (cid:1)-endorphin and prolactin (PRL)) encesisoffered.Thereislimitedevidenceofadirecteffect
to sexual arousal in humans is reviewed. In addition to of oestradiol on sexual arousability in women. The extent
behavioural studies, evidence of distribution of gonadal to which testosterone in women acts by conversion to
steroid receptors in the brain and the limited evidence oestradiol or by increase of free oestradiol is not yet clear.
frombrainimagingarealsoconsidered.Testosteroneplays The role of peptides in sexual arousal remains uncertain,
a key role in the adult male, with clear, consistent partly because of the multiple roles and sites of action of
evidencefromstudiesofhypogonadalandeugonadalmen. most peptides. OT and (cid:1)-endorphin appear to have both
The roles of testosterone in the development of sexual excitatory and inhibitory effects. PRL has been proposed
arousability, and in the aging male, are less clear. The asaninhibitoryfactorviadirectinhibitionofdopaminergic
relevance of aromatization and of non-sexual effects of activity,buttheevidenceforthisisinconclusive.Whereas
testosterone which might indirectly influence sexual thetraditionalconceptof‘hormone’continuestoapplyto
arousalarenotwellunderstood.Testosteroneinthefemale the role of testosterone and oestradiol in sexual arousal,
presents a more complex, less consistent picture. One peptides present a more complex role.
possible explanation is a much greater variability across JournalofEndocrinology(2005)186,411–427
women in responsiveness to testosterone. A ‘desensitiza-
Introduction This paper will review the role of hormones in influ-
encing sexual arousal, sexual arousability, orgasm and the
The term ‘sexual arousal’ is used with variable meanings. post-orgasm inhibition of arousability. Its focus will be on
It is commonly equated with genital response; thus the the human experience, but reference to the animal
manwhohasanerectionissaidtobesexuallyaroused.As literaturewillbemadewhenhelpfulinunderstandingthe
used in this paper, the concept of sexual arousal involves human condition.
more than genital response (Bancroft 2002a), covering a
state motivated towards the experience of sexual pleasure
Current concepts
andpossiblyorgasm,andinvolving(i)informationprocess-
ing of relevant stimuli, (ii) arousal in a general sense, (iii)
Gonadal steroids
incentive motivation and (iv) genital response. ‘Sexual
arousal’appliestothestate,and‘sexualarousability’tothe Androgens in the male
capacity for experiencing sexual arousal, which varies Hypogonadal and eugonadal men Most controlled studies of
across individuals, and within individuals across time. In testosterone replacement in hypogonadal men have used
thispaper,sexualinterestisconceptualizedasanaspectof a period of withdrawal as a baseline, followed by the
sexualarousal,whenallfourcomponentsmaybeinvolved administration of testosterone and placebo, using a
to some extent, but where at least sexual information double-blind cross-over design (for review see Bancroft
processing (e.g. sexual thoughts) is associated with some 2003). Such studies consistently show a reduction in the
degree of incentive motivation. Orgasm needs to be level of sexual interest during testosterone withdrawal,
considered,bothasagoaloftheincentivemotivation,and usually evident within 3 to 4 weeks, consistent with
as a process associated, at least in males, with a temporary testosterone being necessary for normal levels of sexual
suspension or inhibition of sexual arousability. interest (and arousability). If testosterone withdrawal lasts
JournalofEndocrinology(2005)186,411–427 DOI:10.1677/joe.1.06233
0022–0795/05/0186–411 (cid:1)2005SocietyforEndocrinology PrintedinGreatBritain Onlineversionviahttp://www.endocrinology-journals.org
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412 JBANCROFT · Sexualarousal
long enough, seminal emission will eventually be level of testosterone needed to avoid the sexual effects of
impaired. Typically, in male studies of this kind, placebo testosterone withdrawal was substantially lower than the
has only a modest effect, but testosterone replace- pre-treatment baseline level. This is consistent with most
ment restores sexual interest and arousability. Effects on men having more circulating testosterone than they need
sexual activity with a partner are less consistent, partly for the maintenance of normal sexual function.
because they depend on partner and relationship The exploration of testosterone as a method of male
characteristics. Frequency of masturbation tends to contraception has led to further studies of the effects of
follow the level of sexual interest, although cultural increasing circulating testosterone above a normal base-
factors may influence this pattern of sexual expression line by means of exogenous testosterone administration.
(Anderson et al. 1999). Anderson et al. (1992), using weekly injections of either
Psychophysiologicalstudieshavebeenusedtoassessthe placeboortestosteroneenanthate(200mg)over8weeks,
effects of testosterone withdrawal and replacement on found no effect of the exogenous testosterone on sexual
genital response (erection) to sexual stimuli. Early studies activity, either with a partner or as masturbation, but a
werebasedonthemaximumchangeinpenilecircumfer- significant increase in a measure of sexual interest inde-
ence as a measure of erectile response; they found little pendent of sexual interaction with the partner. Bagatell
difference between hypogonadal men with and without et al. (1994b) and Yates et al. (1999), in eugonadal men,
testosterone replacement. More recently, such assessment foundnoeffectsofincreasingtestosteroneonfrequencyof
has also included penile rigidity as well as duration of sexual activity, or in the latter study, daily measures of
penile response. This showed significantly more rigid sexual interest.
and longer duration erectile responses with testosterone Buena et al. (1993) explored the effect of varying
replacement. Without testosterone, the erectile response testosterone levels within the normal range. They first
was ‘stimulus bound’, i.e. would recede as soon as the suppressed testicular function with a GnRH agonist
stimulus was switched off. With testosterone replace- (Lupron), followed by exogenous testosterone admin-
ment, the response would not only show greater rigidity, istration in either high or low dosage, to produce testos-
but would also last beyond the sexual stimulus (Carani terone levels that were either at the high end or low end
et al. 1995). of the normal range. They found no difference in sexual
Nocturnal penile tumescence (NPT), the occurrence activity, sexual interest or NPT, although the rigidity of
of spontaneous erections during rapid eye movement NPT was not measured.
(REM) sleep, is relevant. The neurophysiological basis
of NPT is still disputed, but one plausible explanation Androgens in male sexual development Whereas the impor-
is that REM sleep is associated with a ‘switching off’ of tanceoftestosteroneinsexualdifferentiation,bothinearly
the noradrenergic cells in the locus coeruleus (l.c.) development and around puberty, is beyond dispute, the
(Parmeggiana & Morrison 1990) which, via their spinal impact of testosterone on the emergence of sexual arous-
projections, are probably associated with inhibitory tone ability is less clear. Udry and colleagues carried out two
in the penis. Thus, the reduction of inhibitory tone studies in teenage boys in which testosterone levels were
duringREMpermitswhatcanbecalled‘excitatorytone’ related to various aspects of sexuality. In the first (Udry
to be expressed as erection. NPT is clearly impaired in et al. 1985), a cross-sectional study, the free testosterone
hypogonadal men, and restored to normal with testoster- index was found to be a strong predictor of ‘sexual
one replacement. The l.c. has testosterone receptors motivation’, whereas stage of pubertal development was
(Parmeggiana & Morrison 1990), and this putative ‘exci- not predictive. In the second (Halpern et al. 1993), a
tatory tone’ can be regarded as testosterone dependent. longitudinal study over 3 years, with 6-monthly assess-
Carani et al. (1995) evaluated the effects of exogenous ments, they found the reverse; the stage of pubertal
testosterone on NPT in eugonadal men. Intramuscular developmentwasmuchmorepredictiveofsexualinterest
testosterone enanthate had no effect on sleep parameters, and behaviour than the free testosterone index. One
and did not affect frequency, degree or duration of NPT, possible explanation for this apparent contradiction is that
when assessed as penile circumference, but did increase, the impact of testosterone on sexual arousability (and
modestly but significantly, penile rigidity during NPT. hencebehaviour)hastogothroughstagesofdevelopment,
Testosterone manipulation in eugonadal men has pro- which may involve changes in receptor numbers or
duced results consistent with the earlier hypogonadal sensitivity, a process which will also be influenced by
studies. Bagatell et al. (1994a) used the gonadotrophin- individual differences in receptor sensitivity. Gooren
releasing hormone (GnRH) antagonist, NalGlu, to sup- (1988), in a study of hypogonadal teenage males, found
press testosterone levels in eugonadal men over a 6-week that boys with primary hypogonadism showed less
period. This lowered sexual interest and associated sexual response to testosterone replacement than boys with
activity. An additional feature was the administration of secondaryhypogonadism.Otherstudiescomparinghyper-
varyingdosesofexogenoustestosteroneorplaceboduring gonadotrophic and hypogonadotrophic hypogonadism
theNalGluadministration.Thissuggestedthattheplasma have not shown such clear differences, but have all
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Sexualarousal · JBANCROFT 413
involvedmaleswellbeyondtheageofnormalpuberty(for thelevelsoftestosteroneinthecirculationaresubstantially
review see Bancroft 2003). higher than required to maintain sexual arousability,
suggestingthatothereffectsoftestosterone,mostprobably
AndrogensandaginginmenSchiavietal.(1990),inastudy in the periphery, require higher levels than are needed in
of healthy, medication-free men aged 45 to 74 years, thecentralnervoussystem(CNS).Theroleoftestosterone
found a clear decline in sexual interest, arousability and in the emerging sexual arousability of the peri-pubertal
activity with age. The relatively predictable effects of maleisnotwellunderstood.Intheoldermale,thepicture
testosteronewithdrawalandreplacementinyoungeradult is complicated by various aging effects, including altered
men gives way to a more complex, or at least less well- hypothalamo–pituitary feedback, increased testosterone
understoodpictureinoldermen.Anumberofage-related binding and reduced receptor sensitivity.
changes may be relevant: altered negative feedback of
testosterone and hence less increase in luteinizing hor- Androgens in the female In the female, in comparison
mone (LH) with falling testosterone levels, increased sex with the male, we find inconsistent and often contradic-
hormone binding globulin (SHBG) and hence relatively tory evidence. This is in spite of the fact that we have
reduced free testosterone and the likelihood of an age- many more studies in women, usually involving larger
relateddeclineintestosteronereceptorsensitivity.Schiavi samples, than are found in the male literature. This may
et al. (1990) also found an age-related decline in NPT. result from the greater complexity of the reproductive
This suggested an age-related decline in testosterone- endocrine system in women, who experience menstrual
dependent central arousability (i.e. ‘excitatory tone’). It cycles, pregnancy and lactation and a clearly identifiable
is noteworthy that, as yet, there has been no adequate menopause. At the same time, these endocrine variations
placebo-controlled evaluation of the effects of testoster- offer more opportunities for studying hormone/sexual
one replacement on sexuality in older men (Institute of arousal relationships than is the case with men.
Medicine 2004).
DevelopmentalaspectsIncreasinglevelsoftestosteroneoccur
Clinical studies – relevance of testosterone to low sexual desire in the development of girls as they approach and go
anderectiledysfunction(ED)Inonesmallplacebo-controlled through puberty. However, the changes are much less
studyofeugonadalmenwiththeprimarycomplaintoflow substantialthaninthemale.Testosteronestartsatalower
sexualdesire,O’Carroll&Bancroft(1984)foundamodest level in the infant girl, and effectively doubles through
but significant increase in sexual desire with testosterone pubertal maturation, compared with an 18-fold increase
treatment. The limited evidence of the effectiveness of in testosterone for boys. The most substantial evidence of
testosterone in treating ED is inconsistent. O’Carroll & therelationshipbetweentestosteroneandemergingsexual
Bancroft (1984) found no improvement in erections with arousability in females comes again from Udry et al.
testosterone treatment in eugonadal men with ED. In (1986). As with their studies on adolescent boys, they
studies of men showing some degree of hypogonadism in found discrepant results between their cross-sectional
association with ED, Carani et al. (1990a) and Morales study of eighth to tenth grade girls (approximately 13–15
etal.(1994a)foundimprovementinerectilefunctionina years of age), where they found a relation between
minority of cases. So far it has been difficult to predict testosterone levels and measures of sexual interest and
which cases of ED are likely to benefit from testosterone, masturbation, but not with the likelihood of having
although low baseline levels of testosterone certainly experienced sexual intercourse, and their longitudinal
increase the likelihood. Based on a large clinical series of studyofgirlspost-menarchewherethereverserelationsto
suchcases,Buvat&Lemaire(1997)recommendedthatin testosterone were found (Halpern et al. 1997). Similar
men under 50 years of age, measurement of serum explanationsasdiscussedfortheirmalestudiescouldapply
testosterone should only be done when there was an here,butinadditionthereisacrucialmethodologicalissue
associated loss of sexual interest, whereas in men over 50 of timing of blood sampling for testosterone in relation to
years of age with ED, testosterone should be measured in theovariancycle(forafullerdiscussionoftheseissuessee
all cases. Bancroft 2003).
Conclusions about the role of testosterone in the male The ThemenstrualcycleThereisalackofevidenceoftestoster-
evidenceisfairlyclearthatinmenwhohavegonethrough one levels during the early cycles of post-menarcheal
normal puberty and who have not yet been affected by adolescents,whichtendtobeirregularandnotpredictably
aging, testosterone plays an important role in their sexual ovulatory.However,onceawomansettlesintoapatternof
interest and associated sexual arousability. The evidence regular ovulatory cycles, testosterone levels typically rise
points mainly to the effects of testosterone on central duringthefollicularphaseandareatamaximumapproxi-
arousal mechanisms; the peripheral effects of testosterone mately for the middle third of the cycle, declining during
in the human male, relevant to sexual arousal, are as yet thefinalthirdtoreachanadirduringthefirstfewdaysof
unclear. It is also apparent that, in adult eugonadal men, thenextfollicularphase.Giventhispattern,iftestosterone
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414 JBANCROFT · Sexualarousal
is important for sexual arousability in women, we should combined OC users? Graham et al. (1995), in a placebo-
expect to find related temporal patterns of arousability controlled study of women who had been sterilized or
throughthecycle.However,themid-cycleriseintestos- whosepartnershadbeensterilized,foundthatasubstantial
terone is associated with other hormonal changes, and minority of women on the combined OC reported a
hence correlational studies may not discriminate between decline in sexual interest and enjoyment, an effect not
direct effects of mid-cycle testosterone levels, and the observed with a low-dose progestagen only method. In
effects of other mid-cycle changes, such as the rise in a subsequent study of women starting on OCs, where
oestradiol. a pre-OC baseline was established, negative effects on
In the substantial literature on the pattern of sexual sexual interest and mood were the best predictors of
interest and behaviour through the menstrual cycle there discontinuationoftheOC(Sandersetal.2001).Inbothof
are many inconsistencies, and Hedricks (1994) has dis- these studies, lowered testosterone levels could be the
cussed various methodological explanations for them. explanation.Asyet,however,wehavenodirectevidence
There is a relatively consistent finding that sexual activity of the relation between testosterone levels and sexual
is lowest during the menstrual phase. However, this does interest.Otherexplanationsfortheseadversesexualeffects
notnecessarilymeanthatsexualarousabilityisatitslowest need to be considered (e.g. progestagenic effects). But if
at that stage; there are a number of other non-hormonal lowered free testosterone is the explanation this illustrates
explanations for the drop in sexual activity during men- once again that such reduction is only relevant in a
struation.Thereisalsoatendencyacrossstudiesforindices proportion of women.
of sexual interest to be highest during the follicular phase
or around ovulation, though with considerable individual Effects of anti-androgens Cyproterone acetate (CPA) is an
variability in this respect. This mid- to late-follicular anti-androgen with both negative feedback and direct
patterniscompatiblewithaneffectoftherisingtestoster- androgen receptor antagonism, and which has been used
one during the follicular phase, although one might have for the treatment of androgen-dependent conditions such
expectedacontinuationofthistestosteroneeffectintothe as acne and hirsutism in women. Appelt & Strauss (1986)
first part of the luteal phase. Clearly, other hormonal studied 36 women who had not had sexual problems
explanations have to be considered. before starting on CPA, and of these 16 (44%) reported
A much more limited literature looks at the correlation negativeeffectsontheirsexlife;thisrisesto61%ifwomen
between testosterone level and sexuality through the not in sexual relationships are excluded.
cycle, and it is very inconsistent (for review see Bancroft
2003). In part, there may be methodological reasons for Lactation Reduction in sexual interest and enjoyment is
this, especially variability in the aspects of sexuality common during the post-partum period, and is more
measured. But these inconsistent findings, involving marked in breast-feeding than bottle-feeding mothers
studieswithrelativelysmallnumbersofparticipants,could (Alder&Bancroft1988,Hyde&DeLamater2000).Alder
result from substantial individual variability in et al. (1986) assessed women prospectively for 6 months
testosterone/behaviour relationships. post-partum. Not surprisingly, given the effects of lacta-
Onlyonestudyaddressesthetimingoftheeffectsofan tion on ovarian function, bottle feeders had higher testos-
increase in testosterone on sexual arousal. Eight healthy teroneandandrostenedionelevelsthanthebreast-feeding
women with normal testosterone levels, given sublingual mothers. Of more relevance, five of the breast feeders
doses of testosterone in a placebo-controlled experiment, reported reduced sexual interest, and their testosterone
showed effects of increased testosterone on genital re- and androstenedione levels were consistently and signifi-
sponse to erotic stimuli occurring 3–4h after the peak cantly lower than the breast feeders who reported no
increaseinplasmatestosterone(Tuitenetal.2000).These reduction in sexual interest. This finding needs to be
results suggest that, at least in those women in whom replicated.
testosterone has an effect on their sexuality, cyclical
variation in testosterone levels should be manifested by Aging and the menopause Adrenal androgens have been
cyclical patterns of sexual interest and/or responsiveness. shown, in a number of studies (Crilly et al. 1979, Orent-
reichetal.1984,Bancroft&Cawood1996,Sulcováetal.
Steroidal contraceptives There is consistent evidence that 1997, Burger et al. 2000) to decline with age over a
combined low-dose oral contraceptives (OCs) lower free relatively wide age span. Ovarian androgens start to
testosterone (e.g. Bancroft et al. 1991). Two principle declineafewyearsbeforethemenopause,probablydueto
mechanisms are involved: the mid-cycle rise in testoster- a reduction in the mid-cycle rise of testosterone (Roger
one is blocked by suppression of ovulation and the et al. 1980, Zumoff et al. 1995, Mushayandebvu et al.
associated pattern of gonadal steroid change and the 1996).However,thereisnopredictabledeclineinovarian
combined OC increases SHBG levels and hence reduces androgens following the menopause (Bancroft & Cawood
the free testosterone available. Given this predictable 1996, Burger et al. 2000). A crucial change in the
hormonal effect, what happens to sexual arousability in function of the interstitial cells of the ovary from pre- to
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Sexualarousal · JBANCROFT 415
post-menopause complicates the picture. Whereas in All subjects then received 1 month of placebo following
pre-menopausalwomen,gonadotrophicstimulationofthe which they were crossed-over to one of the other three
interstitial cells is regulated by the negative feedback of treatment groups. The oestrogen+testosterone and testos-
ovarian steroids, the rise in LH that accompanies the terone only conditions showed significantly higher levels
menopausal transition, resulting from the reduction in of sexual interest, fantasy and arousal than either the
oestrogen-induced negative feedback, may stimulate the oestrogen only or placebo conditions. They did not differ
interstitial cells to produce testosterone and androstenedi- in measures of sexual activity with a partner or orgasm.
one, sometimes excessively. In addition, factors such as Thisistheonlystudyinwhichtestosteroneadministration
body weight and insulin resistance influence this ovarian on its own has been evaluated. It is also noteworthy
androgen production (for a brief review of the evidence becauseitfocusedontheimmediatepost-operativeperiod
see Bancroft & Cawood 1996). in women who were not reporting significant sexual or
Anumberofbehaviouralstudieshavereportedadecline mood problems pre-operatively. Mood was significantly
insexualinterestinwomenastheyage(seeBancroft1989, better with all three hormone regimes (testosterone,
Bancroft et al. 2003). Studies have varied in the extent to oestrogen+testosterone and oestrogen) compared with
which the menopause per se contributes to this decline, placebo (Sherwin & Gelfand 1985a) and energy level,
although there is consistent evidence of an increase in well-being and appetite were significantly higher in the
vaginal dryness related to the change in oestradiol levels two groups receiving testosterone than in the oestrogen
(Dennerstein et al. 2003). only or placebo groups (Sherwin & Gelfand 1985b).
Dotestosteronelevelscorrelatewithmeasuresofsexual Shifren et al. (2000) studied women who had under-
interest or activity as women get older? A number of gone surgical menopause from 1–10 years previously. In
cross-sectional studies, using multivariate methods of contrast to the previous study, all had impaired sexual
analysis, have found no relation between testosterone and function and all had been on Premarin, at least 0·625mg
changing levels of sexual interest (Cawood & Bancroft daily for at least 2 months, when recruited for the study.
1996,Kirchengastetal.1996,Dennersteinetal.1997).In All subjects continued on the same dose of oral oestrogen
their longitudinal study of women going through the throughout the study. After a 4-week baseline assess-
menopausal transition, assessed over a 9-year period, with ment, they were all given daily transdermal patches with
an average starting age of 48 years, Dennerstein et al. placebo,or150µgor300µgtestosteroneasthedailydose,
(2003)foundnorelationbetweenandrogenlevelsandany eachfor12weekswiththeorderofpresentationrandom-
aspect of sexual functioning. However, in none of these ized. There was a substantial placebo response; however,
studies was there any assessment of the pre-menopausal therewassignificantlymoreimprovementwiththehigher
testosterone decline. To adequately test the androgen– testosterone dose than with placebo on measures of
behaviour relationship during the mid-life period, longi- frequencyofsexualactivity,andpleasure/orgasm,though
tudinalstudiesareneededinwhichthebaselinetestoster- not for sexual desire or arousal (the opposite pattern
onelevelsareassessedbeforethepre-menopausaldecline. reported by Sherwin et al. 1985). Mood was significantly
improved with the higher testosterone dose for ratings of
The effects of ovariectomy and hormone replacement With both depression and ‘positive well-being’. The transder-
surgical removal of the ovaries there is an immediate and malrouteusedinthisstudyhastheadvantageofproducing
substantial drop in circulating androgens. Androgen pro- more physiological and more stable serum testosterone
duction by the interstitial cells of the post-menopausal levels than the intramuscular routes used in most other
ovary is an important source of oestrogen from peripheral studies, where supra-physiological peaks soon after injec-
conversion. Whether pre- or post-menopausal, therefore, tion are followed by gradual decline.
the woman with both ovaries removed is in a state of A third study also warrants attention. Nathorst-Böös
relative gonadal steroid deficiency. et al. (1993) were unusual in this literature in taking a
Most of the literature on hormone replacement, with sample of women who had been oophorectomized and
both natural and surgical menopause, has assessed the reporting the proportion who had experienced loss of
effects of testosterone in combination with oestradiol, sexual interest. Approximately 50% of women came into
compared with oestradiol alone or placebo. The evidence this category, which suggests that around 50% of women
from such studies on the role of testosterone in sexual can undergo this depletion of ovarian steroids and not
interest and response is inconsistent. Two studies will be experience loss of sexual interest.
considered closely. (For a more comprehensive review of
this literature see Bancroft 2003.) Hormone replacement of adrenal androgens Androstenedione
Sherwin et al. (1985) investigated women who were has a substantial capacity for conversion to both oestradiol
about to undergo hysterectomy and bilateral oophorec- and testosterone; dehydroepiandrosterone (DHEA) has a
tomy. Post-operatively, women were assigned randomly verylimitedcapacityforconversiontotestosterone.There
to one of four 3-month treatment groups: oestrogen only, islittleevidence,however,thatDHEAisdirectlyrelevant
testosterone only, oestrogen plus testosterone or placebo. to sexuality in either men or women, whereas it may be
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416 JBANCROFT · Sexualarousal
relevant to well-being and energy, and hence secondarily of women is powerfully influenced by mood, energy and
to sexual arousability (Cawood & Bancroft 1996). In a well-being,aswellasbyotherpsychologicalmechanisms.
placebo-controlledevaluationofDHEAadministrationto This may account for why, in several studies of younger
women between 40 and 70 years (Morales et al. 1994b), women, the relationship between testosterone and sexu-
there was significant improvement in a somewhat crude ality was most apparent in women whose sexuality was
measure of well-being, but no effect on ‘libido’. In a unproblematic (e.g. Bancroft et al. 1980, Tuiten et al.
placebo-controlled study of women with adrenal insuffi- 1996, Riley & Riley 2000). Thus, whereas testosterone
ciency, the addition of DHEA to the corticosteroid mayplayaroleinthesexualityofmanywomen,itseffects
replacement improved measures of sexual interest and can easily be obscured by the co-existence of other
responsiveness as well as mood and general well-being, psychologicaloraffectivefactors.Testosteronealsoappears
although the effects on mood were more substantial to have a mood and energy-enhancing effect in women.
(Arlt et al. 1999). The sexual effects could therefore have Hence, some of the sexual effects of testosterone may
been secondary to improvements in general well-being indirectly result from these mood effects.
and energy.
Where do androgens act in the brain?
Clinicalstudiesofwomenwithlowsexualinterestorarousability
AndrogenreceptorstudiesForobviousreasons,wearelargely
Stuartetal.(1987)andSchreiner-Engeletal.(1989)found
dependentonanimalstudiesonthistopic,althoughmainly
no difference in testosterone levels between women
primate studies will be considered here. Research on the
presenting with low sexual interest and controls; Riley &
site of action of testosterone in the non-human primate
Riley (2000) found a marginally lower free androgen
brain has been ongoing for more than 30 years, during
index(FAI)inwomencomplainingoflife-longabsenceof
which time there have been major changes in the tech-
sexual drive than in controls. Controlled studies of the
nologies used, and these have to be kept in mind when
treatment with testosterone of women presenting with
comparing findings across studies.
sexual problems have been few. Although Carney et al.
Michael et al. (1989), using autoradiography in male
(1978)foundsomebenefitoftestosteronewhencombined
rhesus monkeys, looked at aspects of both androgenic and
with counselling for couples whose main problem was
oestrogenic activity. They found 5(cid:2)-reductase activity to
sexual unresponsiveness of the woman, other comparable
be fairly evenly distributed in the brain, whereas, in
studies failed to replicate this effect (Mathews et al. 1983,
contrast, aromatase activity was much more localized.
Dow & Gallasher 1989).
They assumed that in areas of high aromatase activity,
In a more experimental study, Tuiten et al. (1996)
testosterone was acting by conversion to oestradiol. By
studied eight young amenorrhoeic women with low
identifying brain areas where there was overlap in
weight, although none had the diagnosis of anorexia
androgen- and oestrogen-concentrating neurons, they
nervosa. They showed lower levels of sexual interest and
concluded that the medial pre-optic and ventro-medial
activity, and lower testosterone levels than a comparison
hypothalamic nuclei, the bed nucleus of the stria termi-
group of normally menstruating aged-matched women.
nalis, and the cortical, medial and accessory amygdaloid
The amenorrhoeic group was given testosterone unde-
nuclei were the main sites at which the effects of testos-
canoate(40mg)dailyfor8weeks,andplacebofor8weeks
terone are mediated predominantly by oestradiol. In con-
in a double-blind cross-over study. They were evaluated
trast, testosterone activity was thought to be mediated by
in a psychophysiology laboratory with measurement of
androgenreceptorsinthelateralseptal,pre-mamillaryand
vaginal pulse amplitude (VPA) in response to erotic
intercalated mamillary nuclei.
fantasiesanderoticfilms.VPAwassignificantlygreaterin
Roselli et al. (2001) used in situ hybridization histo-
response to film in the testosterone-treated condition.
chemistry to locate cytochrome P450 aromatase mRNA
However,thiseffectwasnotreflectedinsubjectiveratings
andandrogenreceptormRNA(ARmRNA)inthehypo-
of arousal. Nor did the two treatments differ in terms of
thalamus and amygdala of cynomolgus monkeys. Their
dailyratingsofsexualityormood.Thisexperimentthere-
findings were broadly similar to those of Michael et al.
fore demonstrated an effect of increasing testosterone on
(1989). They concluded that testosterone acts through
physiologicalresponsetoeroticstimulation,whichwasnot
signallingpathwaysthatdiffereitherinspecificbrainareas,
apparent in any subjective or mood measures.
or within different cells from the same area.
Summary of androgen effects in women Whereas there is Abdelgadir et al. (1999) studied the distribution of
evidencethattestosteronewithdrawaland/orreplacement ARmRNA,usingaribonucleaseprotectionassay,inmale
can have effects on women’s sexuality, the evidence is rhesusmonkeys.TheirlocalizationoftheARmRNAwas
inconsistent and sometimes contradictory. One obvious again broadly similar to the distribution of androgen
explanation is that women vary in the extent to which activity reported by Michael et al. (1989). In this study,
their sexuality is influenced by testosterone, and several intactanimalswerecomparedwithcastratedanimalswith
examplesofevidencesupportingthishavebeenpresented. and without testosterone replacement. They found little
It is also becoming increasingly clear that the sexuality difference between these three groups in the distribution
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Sexualarousal · JBANCROFT 417
orconcentrationofARmRNA,andconcludedthatinthe androgens have in these areas is not yet clear, but in
monkey brain this androgen receptor is not regulated at addition to more specifically reproductive actions, other
the transcriptional level by androgen. relativelynon-specificandrogen-mediatedbrainfunctions
For both non-human primates and humans, the ma- need to be considered, including activation or general
jority of evidence is from males. However, Finley & arousal as well as stimulation of neuronal growth and
Kritzer(1999),reportingthepresenceofandrogenrecep- gender differentiation of brain function (Kelly 1991).
tor protein in the pre-frontal cortex of rhesus monkeys,
Brain imaging Functional brain imaging promises to throw
found no differences between their male and female
considerable light on brain activity related to sexual
monkeysinthisrespect.Inastudyofhumans,Fernandez-
function, but is still at an early stage of development,
Guasti et al. (2000) used immunochemical methods to
withmethodologicalinconsistenciesacrossstudiesmaking
examine the distribution of androgen receptors in the interpretation of the findings more difficult (Sumich
hypothalamus, involving post-mortem samples from five
et al. 2003, Mouras & Stoleru 2005). So far, only two
men and five women. In men, intense androgen receptor
studiesprovideevidenceofdirectrelevancetotestosterone
immunoreactivity was found in neurons of the horizontal
activity. Park et al. (2001) reported on two hypogonadal
limb of the diagonal band of Broca, and of the lateral
men,assessedwithfunctionalmagneticresonanceimaging
mamillary and medial mamillary nuclei. Intermediate
in their response to sexual stimuli, with and without
staining was found in other parts of the diagonal band of
testosterone replacement. In both men, activation of the
Broca, the sexually dimorphic nucleus of the pre-optic
inferior frontal lobe, cingulate gyrus, insula and corpus
area, paraventricular, suprachiasmatic, ventromedial and
callosum was greater with testosterone replacement.
infundibularnuclei.Weakerstainingwasfoundinthebed
Redoute et al. (2005) compared positron emission tom-
nucleusofthestriaterminalis,medialpre-opticarea,dorsal
ographyscanevidenceofbrainactivityduringresponseto
andventralzonesoftheperiventricularnucleus,supraoptic
sexualstimuliinninehypogonadalmenwithandwithout
nucleus and nucleus basalis of Meynert. In most areas,
testosteronereplacement,andeighteugonadalmen.They
women revealed less staining of receptor protein. This
found greater activation in the controls and the treated
gender difference was particularly marked in the lateral
hypogonadal men than the untreated, in the right orbito-
andmedialmammillarynuclei.Therewasalsostainingin
frontal cortex, insula and claustrum. They also found
the paraventricular and supra-optic nuclei in the males,
deactivationoftheleftinferiorfrontalgyrus,suggestiveof
whichwasapparentlyabsentinthefemales.Overall,there
reduced inhibition of sexual arousal, but only in the
wasgreaterindividualvariabilityintheintensityofrecep-
controls and treated patients. There is some consistency
tor staining in the women than in the men.
acrossthesetwostudies,andandrogenreceptorshavebeen
Asyet,therearenocomparativedataonthedistribution
reportedintheorbito-frontalcortexofprimates(Finley&
ofaromataseactivityinwomenorfemaleprimates,though
Kritzer 1999) and to a limited extent, in the cingulate
in the rat greater amounts of aromatase activity are found
cortex (Abdelgadir et al. 1999). As yet, however, there is
in the male than the female, in all areas examined except
no evidence of androgen receptors in the insula or
the medial preoptic nucleus (Roselli & Resko 1993).
claustrumofprimatesorhumans.Sofar,therefore,thereis
Furthermore, Roselli & Klosterman (1998) concluded
only limited overlap between localization of testosterone
from their findings that this male pattern of aromatization effects in the brain when comparing androgen receptors
in the rat is established perinatally, and probably forms a
and functional brain-imaging studies. This may in part
fundamental component of masculinization.
reflect methodological limitations of brain imaging; some
Thelimitedevidenceofandrogenreceptordistribution
relevant areas of the brain, especially the hypothalamus,
in humans includes two studies of the temporal cortex, aremoredifficulttoimageinthisway.Butweshouldalso
both of which found substantial amounts of androgen
keepinmindthatthesetwotechniquesarelookingatvery
receptor protein (Sarrieau et al. 1990, Puy et al. 1995). different markers of brain activity – steroid receptors and
Bothstudiesinvolvedmaletemporalcortextissuebecause
localized oxygen uptake. Physiological levels of testoster-
it was available from surgical interventions in men with
one may be necessary for a more generalized pattern of
intractable epilepsy, not because the temporal cortex was
interactivebrainactivity,muchofwhichisnotdependent
regardedasaparticularlylikelysiteforandrogenreceptors. on direct testosterone effects.
Whereasmuchofthereportedlocalizationisconsistent
withandrogeniceffectsonsexualandreproductivebehav- Oestrogens and male sexuality Evidence of the effects
iour, it is important to keep in mind that much of the of oestrogens on the sexuality of the human male, while
research has been restricted to the hypothalamus and, limited, consistently suggests a negative effect of exogen-
where more extensive studies have been done, androgen ousoestrogens.Oestradiolappearstoplayakeyroleinthe
receptors appear to be widespread in the primate and negative feedback control of testosterone. In long-term
human brain, including various cortical areas (e.g. pre- castrated rhesus monkeys, physiological doses of testoster-
frontal cortex: Finley & Kritzer 1999, temporal cortex: onedonotreduceLHunlessasmallamountofoestradiol
Sarrieau et al. 1990, Puy et al. 1995). What specific role isalsogiven(Reskoetal.1977).Also,menwitharomatase
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418 JBANCROFT · Sexualarousal
deficiency or oestrogen resistance show raised LH and EE, l-norgestrel, combination of EE and l-norgestrel,
follicle-stimulating hormone (see Roselli et al. 2001). and placebo. The EE only regime was significantly better
In the past, oestrogens were used as a treatment for than the others in improving sexual interest, enjoyment,
prostatic carcinoma, based on their assumed anti-andro- orgasmic frequency and also mood. Also found were
geniceffect,andreductionofsexualinterestandresponse correlations between measures of sexual desire and of
wasatypicalside-effect.Oestrogenshavealsobeenusedas mood, particularly ‘feelings of well-being’.
a treatment of sexual offenders. Bancroft et al. (1974) Only one study of hormone replacement has incor-
compared the effects of ethinyl oestradiol (EE) and CPA, porated different doses of oestradiol. Sherwin (1991)
an anti-androgen, in 12 incarcerated sexual offenders. randomlyassigned‘perimenopausal’womentofourtreat-
Both compounds reduced sexual interest, masturbatory ment regimes, involving either a low (0·625mg) or
activity and erectile response to erotic fantasies and slides high (1·25mg) dose of Premarin, combined with either
producingapatternverysimilartothatfoundinhypogo- Provera (5mg) or placebo. After a baseline month of
nadalmen.However,althoughCPAsubstantiallyreduced assessment, each woman took the assigned regime for 12
total testosterone, with no change in SHBG, EE substan- months, and was assessed with daily ratings during the
tiallyincreasedbothtotaltestosteroneandSHBG(Murray 3rd, 6th, 9th and 12th months. The main purpose of
et al. 1975). the study was to evaluate the effects of the progestagen
How can we reconcile these negative effects with the on mood and sexuality, not to compare the different
widespread interaction between testosterone and oestra- doses of oestradiol. However, apparent from the graphed
diol in the male brain? Is it possible that, in addition to sexualinterestdata,womeninthehighoestradiol+placebo
interactionbetweentestosteroneandoestradiolinnegative group had substantially lower levels of sexual interest at
feedbackcontrolofLH,someoftheeffectsoftestosterone baseline (i.e. pre-treatment), than the low oestradiol+
onsexualinterestandarousabilityaremediatedbyaroma- placebo group, yet by the 6th month of treatment and
tizationoftestosteronetooestradiol?Gooren(1985)found continuing through the 12th month they were showing
that,ineugonadalmen,theoestrogenreceptorantagonist, noticeably higher levels of sexual interest. This was not
tamoxifen, and the aromatase inhibitor, testolactone, had commented on in the paper. It would appear to indi-
no adverse sexual effects, and that dihydrotestosterone cate that the effects of oestradiol on sexual interest are
(DHT) was as effective as testosterone in maintaining dose related.
sexuality in hypogonadal men. He took this to mean that So to what extent are the effects of testosterone,
the sexual effects of testosterone within the CNS are discussedearlier,theresultofaromatizationoftestosterone
mediated by DHT but not by oestradiol. to oestradiol or, alternatively, of increased levels of free
Whereas in other species, the role of oestradiol in oestradiol resulting from testosterone-induced reduction
mediating many of the central nervous system effects of in SHBG? Wallen & Parsons (1998) have strongly advo-
testosterone on male sexual behaviour is well established cated that the sexual effects of testosterone in women
(Lindzey&Korach2003),itsroleinhumanmalesexuality result from the consequent increase in free oestradiol,
remains unclear, with the possibility that exogenous and supporting this conclusion with experimental data from
endogenous sources of oestradiol have fundamentally dif- rhesus monkeys. At this stage we should keep an open
ferenteffects,particularlywhentheendogenousoestradiol mind about the role of testosterone and oestradiol in
resultsfromaromatizationoftestosteronewithinthebrain. female sexuality.
Oestrogens and female sexuality There is consistent Mode of action of androgens and oestrogens in the
evidenceoftheimportanceofoestradiolfornormalvaginal brain The conventional view is that androgens act in the
lubrication. However, whether oestradiol has a direct brain via genomic effects (Rommerts 1990). It has been
effect on sexual interest and arousability remains unclear. known for some time, however, that oestradiol and pro-
Anumberofstudiesofthesymptomsofeithernaturalor gesterone can, in addition, have much more rapid effects
surgical menopause, reviewed above, have either taken directlyonthecellmembrane(Dufy&Vincent1980).As
women on oestradiol replacement, who continue to have yet we have few directly relevant data on the speed of
lossofsexualinterestorresponse,andevaluatedtheeffect action of androgens in the human, although one study in
of adding testosterone, or have compared oestradiol re- women, discussed earlier (Tuiten et al. 2000), showed an
placement with a combination of oestradiol and testoster- effectongenitalresponsewithin3to4h.Caldwell(2002)
one,ortestosteronealone.Muchlessattentionhasfocused has proposed a model of steroid-influenced sexual arous-
on the effects of oestradiol itself on sexual interest and ability, which depends on membrane-associated receptors
arousal in post-menopausal women. linkedtoamoreenduringchangeinG-proteincoupling.
Dennerstein et al. (1980) studied 49 surgically meno- However, the evidence he cites is largely restricted to
pausal women, all of whom had stable, satisfying sexual oestradiol and progesterone. It remains a possibility that
relationships, using a double-blind cross-over design in androgens may produce a relatively rapid membrane-
which they spent 3 months on each of four treatments, mediated effect by means of aromatization.
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Sexualarousal · JBANCROFT 419
Comparison of gonadal steroid effects in men and peripheral, classically ‘hormonal’ effects that may occur.
women As yet, there is little evidence that would allow Towhatextenttheseintra-cerebraleffectsinvolvesynap-
comparisonoftheeffectsofoestradiolonmaleandfemale tic transmission, ‘parasynaptic’ transmission through local
sexuality. With testosterone, there is much more relevant diffusionordisseminationviathecerebrospinalfluidisnot
evidence, allowing the following conclusions. clear,butallmaybeinvolved,togetherwithconsiderable
(1) The evidence is more consistent for the male than potential for interaction with other neurotransmitters as
for the female. Apart from methodological considerations, well as steroid hormones. The limbic system is character-
which are more complex in women than in men, poten- ized by peptidergic neurotransmission, contrasting with
tiallythemostimportantfactoraccountingforthisgender the synaptic neuronal structure of the cortex (Herbert
differenceisagreatervariabilityofbehaviouralresponsive- 1993)andconsistentwiththemoreprimitivephylogenetic
ness to androgens among women. origins of the brainstem. The specific effect of a peptide
(2) Those women who are behaviourally responsive to may depend on its site of action, or even the context in
testosteronerespondtolevelsoftestosteronewhichwould which it is acting. In this review, attention will be
be totally ineffective in men. This greater sensitivity to restricted to oxytocin (OT), (cid:1)-endorphin and prolactin
testosteroneinwomenismostapparentinbehaviouraland (PRL) as representatives of the main types of peptides
other CNS responses and may be less marked in the relevant to sexual arousal, and most of the cited evidence
anabolic and skin effects of testosterone. is from animal studies.
(3) In the male, the evidence points to a threshold,
below the normal physiological range, above which in- OxytocinItisgenerallyacceptedthatOTplaysakeyrole
creased testosterone levels have little behavioural effect, during lactation, facilitating the milk ejection reflex. It
andbelowwhichsignsofandrogendeficiencyarelikelyto may also play a role in facilitating uterine contraction
occur.Thisthresholdconceptdoesnotappeartoapplyto during parturition. For such purposes, OT is produced in
women. The most convincing behavioural effects of the the magnocellular neurons of the paraventricular nucleus
administration of exogenous androgens to women have (PVN)ofthehypothalamus,whichprojectaxonsintothe
involved supra-physiological levels, although in a number posterior pituitary and thence into the peripheral circula-
of studies sensitivity to these levels appears to decrease tion (Kupfermann 1991). OT has also been proposed as a
overtime.Ontheotherhand,itremainspossiblethatsigns key factor in affiliative behaviour (Insel 1992). The evi-
ofandrogendeficiencywilloccurinwomenifcirculating dence for OT being important in sexual arousal, response
levelsoftestosteronefalltoolow,thecriticalleveldepend- and behaviour is, however, less consistent. In animal
ing on a particular woman’s sensitivity. studies, centrally administered OT has induced erection,
(4) A fundamental difference in male and female an effect which is apparently testosterone dependent, and
mechanisms of androgen production needs to be kept in OT receptor antagonists can prevent non-contact erec-
mind. More than 90% of testosterone in the male is tions, considered an index of sexual arousal (Argiolas
producedbythetestes.Inwomen,asubstantialproportion 1999).Dopamineagonistsmayenhancesexualresponseby
of androgen production is from the adrenal glands and increasing central oxytocinergic transmission (Argiolas
hence increased adrenal androgens can be expected in 1999).Infemalerats,studieswithOTantagonistsindicate
states associated with increased adrenal activity, such as thatOTfacilitateslordosis,aneffectapparentlydependent
anxiety, stress or depression (e.g. Weber et al. 2000). on progesterone priming. Less striking effects on procep-
Given the strong relationship between mood and sexual- tive female behaviour (hopping and darting) were also
ity, which has been demonstrated particularly in women reported.Therewasalsoanincreaseinvocalizationswhen
(e.g. Bancroft et al. 2003), this aspect of testosterone mounted,consistentwiththetactilestimulationleadingto
function warrants closer attention. lordosis and mounting becoming aversive (Insel 1992).
This may be related to the effects of vagino-cervical
stimulation (VCS), which has been shown to induce
Peptides
analgesia in rats. Komisaruk & Sansone (2003) have
Notonlyisthereaseeminglylimitlessnumberofpeptides proposed that this analgesic mechanism, which may have
tobefoundacrossspecies,itisapparentthattheyactina a fundamental role in reproduction by making mounting
varietyofways;functioninglikeclassical‘hormones’being and intromission less noxious for the female, in part
released into the circulation to act at a distance, but also involvesOT.TheyalsopresentevidencethatVCSresults
acting as neurotransmitters or local regulators, leading in a release of OT from PVN neurons, which project to
Polak & Bloom (1982) to call them ‘regulatory peptides’. thebrainstemandspinalcord,activatingthesympathetic
Although peptides are released in many different parts division of the autonomic nervous system in the process.
of the body, neuropeptides are produced in substantial Cantoretal.(1999)examinedtheinteractionofOTand
amounts within the CNS. With the evolution of the serotonin. Having demonstrated that fluoxetine, a selec-
blood–brain barrier, the mammalian brain has been able tive serotonin re-uptake inhibitor, impaired ejaculation
to develop peptidergic communication independent of in male rats and also reduced appetitive behaviours
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420 JBANCROFT · Sexualarousal
(level changing), they found that OT administration (cid:1)-endorphinTherehasbeen,formanyyears,widespread
reversedtheeffectoffluoxetineonejaculationbutnoton awareness of the negative effects of exogenous opiates,
appetitive behaviour. The authors concluded that sero- suchasmorphineandheroin,onthesexualityofmaleand
tonin suppresses ejaculation by interrupting the action of female drug addicts, reducing sexual interest, impairing
OT.TheysuggestedthattheeffectsofOTadministration genitalresponseandblockingejaculationandorgasm,with
could have been mediated by a central stimulation of active and spontaneous reversal of such effects often
sympatheticoutflow,orperipherallybyfacilitatingsmooth occurring during opiate withdrawal (for review see Pfaus
muscle contraction in the reproductive tract. & Gorzalka 1987). In general, the subsequent animal
Thus, so far the animal evidence is consistent with researchhasshownsimilarnegativeeffectsofbothexogen-
both a peripheral and central role for OT; the most ous and endogenous opiate administration, in male and
obvious peripheral effect being facilitation of smooth femaleanimals,withconfirmatoryevidencefromblocking
muscle contraction – the central role being more as a such effects with opiate antagonists such as naloxone, as
neuromodulator in a variety of response systems. Both well as withdrawal effects comparable with those in
peripheral and central mechanisms, however, appear to humans.Thepictureiscomplicatedbythefactthatopiates
be steroid hormone dependent. The enhancement of inhibitLH-releasinghormone,andhencereduceLHand
erections is unlikely to result from the peripheral effects testosterone. However, the animal evidence shows that
of OT given that they most obviously facilitate muscle thesexuallyinhibitingeffectsarepredominantlyindepen-
contraction (necessary for ejaculation), whereas erection dent of this reduction of testosterone.
is dependent on muscle relaxation. However, whereas (cid:1)-endorphinistheendogenousopiatethathasreceived
the central role of OT in lactation remains the most research attention. Apart from the anterior
unchallenged, its fundamental role in sexual behaviour is pituitary, the synthesis of (cid:1)-endorphin is limited to two
questioned by the effects of OT gene ablation studies. cell groups in the brain, one in the arcuate nucleus of the
OT knockout mice show clear impairment of milk hypothalamus,theotherinthenucleusofthesolitarytract
let-down, but no apparent impairment of either mating in the brainstem. The relevant neurons in the arcuate
or parturition (Nishimori et al. 1996, Young et al. 1996). nucleus project anteriorly to other parts of the hypothala-
What evidence do we have for humans? Carmichael mus, including the medial pre-optic area, and also to the
et al. (1987) found that plasma OT increased around the amygdala. Dorsally, neurons run to the PVN of the
time of orgasm in men and women, remaining raised for hypothalamus and then on to the brainstem to structures
at least 5min after orgasm. The authors postulated that involvedintheautonomicnervoussystem(Herbert1995).
OT has a facilitatory role on sperm and egg transport by The sexual inhibiting effects of (cid:1)-endorphin, and related
increasing smooth muscle contractility in the reproduc- opiatepeptides,arebelievedtooccurmainlythroughtheir
tive tracts. In a recent study of men, OT increased in actiononthepre-opticareaandtheamygdala,theprecise
some subjects following ejaculation, but the individual inhibiting effect depending on the site of infusion. Thus
variability was such that the group effect was not (cid:1)-endorphininfusedintothemedialpre-opticareainhib-
significant (Kruger et al. 2003a). Murphy et al. (1987) its consummatory mounting and intromission, providing
reported an increase in OT in men during sexual that mounting has not already started with a particular
arousal, which persisted beyond ejaculation, but with no female;inotherwords,inhibitionisoftheactivationofthe
obvious increase at ejaculation. In a study of women, consummatory sequence rather than its completion. On
Blaicher et al. (1999) found an increase in OT 1min the other hand, infusion of (cid:1)-endorphin into the medial
after orgasm, but levels were close to baseline by 5min amygdala inhibits the initial appetitive phase (Herbert
post-orgasm. 1995).AccordingtoArgiolas(1999)theinhibitoryeffectis
It is difficult to draw clear conclusions from this dose dependent, with low doses of opiate having facilita-
literature on OT and sexual arousal. Whether the tory and high doses inhibitory effects. (cid:1)-endorphin may
increase of OT around orgasm, which has been facilitate appetitive behaviour by acting on the ventral
somewhat inconsistently observed in the human tegmental area to activate the mesolimbic dopaminergic
literature, has any specific function, rather than being an system. This raises a crucial question, at least about
epiphenomenon of other changes, remains uncertain, exogenous opiates in humans, which remains largely
though it is possible that this OT rise will affect the unanswered. Exogenous opiates can induce an intense
experience of orgasm by influencing uterine and other feeling of pleasure, which has been likened to an orgasm,
reproductive tract smooth musculature. The possibility followed by a state of relaxation and calm. What are the
that a peri-orgasmic increase in OT contributes to the mechanisms underlying this? Is the activation of the
post-orgasmic refractory period, at least in males, should mesolimbicdopaminergicsystem,whichisassociatedwith
also be considered. Caldwell (2002) has proposed that ‘appetite’ for a variety of behaviours, including sexual
OT is a satiety hormone that acts by de-coupling the (Hull et al. 1998), relevant? ‘Appetite’, however, is not
G-protein (see above) and hence reducing sexual the same as intense pleasure, the origins of which, and
arousability. The reader is entitled to feel confused. of sexual orgasm also, remain obscure. A fair amount of
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