2637

REVIEW

Physiology of Women’s Sexual Function: Basic Knowledge and

New Findings jsm_1810 2637..2660

Andrea Salonia, MD,* Annamaria Giraldi, MD, PhD,† Meredith L. Chivers, PhD,‡
Janniko R. Georgiadis, PhD,§ Roy Levin, PhD,¶ Kenneth R. Maravilla, MD,** and
Margaret M. McCarthy, PhD††
*University Vita–Salute San Raffaele—Department of Urology, Milan, Italy; †Rigshospitalet University
Hospital—Sexological Clinic, Psychiatric Centre, Copenhagen, Denmark; ‡Queen’s University—Department of
Psychology, Kingston, Ontario, Canada; §University Medical Center Groningen, University of Groningen—Department of
Neurosciences, Section Anatomy, the Netherlands; ¶Porterbrook Clinic—Sexual Physiology Laboratory, Sheffield,
Yorkshire, UK; **University of Washington—Department of Radiology, Seattle, WA, USA; ††University of Maryland School
of Medicine—Department of Physiology and Program in Neuroscience, Baltimore, MA, USA

DOI: 10.1111/j.1743-6109.2010.01810.x

ABSTRACT

Introduction. Data concerning the physiology of female sexual functioning are still obtained from animal studies,
but an increasing amount of novel evidence comes from human studies.
Aim. To gain knowledge of psychological and biologic physiology of women’s sexual functioning, mainly addressing
sexual arousal and orgasm.
Methods. A broad-based literature review of current knowledge of the psychological and biologic physiology aspects
of women’s sexual functioning.
Results. A comprehensive understanding of the anatomical, neurobiological, and psychological mechanisms behind
sexual function and responses is of paramount importance. A biopsychological paradigm was considered when
reviewing currently available data, thus considering aspects of: (i) sexual differentiation of the brain, which is critical
for sex differentiation in behavior; (ii) central neurobiology of sexual function, highlighting specific and innovative
findings from neuroimaging methods that enable visualization of active brain areas during arousal and orgasm; and
(iii) peripheral functional anatomy, mainly addressing genital arousal and orgasm. Translational science was also
covered, providing data about the actual role of sexual arousal in women in both procreation/reproduction and
recreation/pleasure. The interaction between physiological and psychological states of women’s sexual response,
nonspecific sexual response, interoceptive awareness, and flexibility of sexual interests have also been addressed.
Conclusion. Further research on normal physiology of women’s sexual function is needed in order to expand and
“translate” current knowledge into the pathophysiological clinical setting. This manuscript encompasses data
presented at the 3rd International Consultation on Sexual Medicine in Paris, France, July 10–13, 2009. Salonia A,
Giraldi A, Chivers ML, Georgiadis JR, Levin R, Maravilla KR, and McCarthy MM. Physiology of women’s
sexual function: Basic knowledge and new findings. J Sex Med 2010;7:2637–2660.
Key Words. Female; Arousal; Orgasm; Physiology; Biology; Brain

Introduction female sexual function (FSF) and dysfunction

(SD), mainly driven by more and more sophisti-

S ince the early descriptions of the sexual

response cycle by Masters and Johnson [1]
and, later, Kaplan [2], the stages have been chal-
lenged [3]; substantial advances have occurred in
the understanding of physiological aspects of
cated methods of their measurement. The recent
application of neuroimaging methods has signifi-
cantly improved our knowledge of central mecha-
nisms; similarly, research on peripheral pathways
and the interaction between central and peripheral

© 2010 International Society for Sexual Medicine J Sex Med 2010;7:2637–2660

2638
mechanisms have provided a better understanding
of female desire, arousal, and orgasm. Likewise, an
increased awareness of the interaction between
anatomical, physiological, neurobiological, and
endocrine mechanisms, along with psychological/
behavioral factors and their influence on FSF, has
grown in parallel.
By reviewing the most recent peer-reviewed
data, according to the basic principles of evidence-
based medicine, whenever possible, this manu-
script addresses central and peripheral anatomical
and physiological aspects of women’s sexual arousal
and orgasm, also highlighting their interactions
with psychological factors in a “biopsychological
paradigm.” Because of ethical constraints and
experimental limitations, much of our current
knowledge is still obtained from animal studies;
these have been included in the article when no
human data are available.
Physiology of Women’s Sexual Function
Definitions of Female Sexual Arousal and Orgasm
When describing the physiological fundamentals of
arousal and orgasm, it is noteworthy to stress that it
is difficult to retrieve an exhaustive definition for
female sexual arousal (FSA) [4]; in the literature, this
is often based on what is considered dysfunctional. It
is mandatory to stress that in women, changes in
physiology do not necessarily induce SD, while
sexual problems may occur despite an apparent
normal sexual physiology. In this context, it has been
suggested to subdivide FSA into an objective
(namely, both genital and “extra-genital”) and a sub-
jective part. Genital sexual arousal may be described
as “a combination of objective and subjective signs;
the bodily reactions as vulvar swelling, vaginal lubri-
cation, heavy breathing and increased sensitivity of
the genitalia, combined with the subjective experi-
ence of feeling pleasure and excitement” [4].
Orgasm, in contrast, may be defined as “a variable,
transient peak sensation of intense pleasure, creating
an altered state of consciousness, usually accompa-
nied by involuntary, rhythmic contractions of the
pelvic striated circumvaginal musculature, with con-
comitant uterine and anal contractions and myoto-
nia that resolves the sexually induced vasocongestion
(sometimes only partially), usually with an induction
of well-being and contentment” [5].
Development and Determination of Female Sexual
Physiology and Anatomy
Biological Principles of Sexual Behavior
Understanding the physiology of adult female
sexual behavior requires knowledge of events that
J Sex Med 2010;7:2637–2660
Salonia et al.
occur early in development and the understanding
of brain regions essential to motivation, consum-
mation, and reward. The basic principles of the
neural control of sexual behavior apply to an
impressively broad range of species, from fish to
nonhuman primates; the importance of the bio-
logical mechanisms regulating reproduction in
animals is much greater than that in humans. Ste-
reotyped sexual behavior and coitus occur nor-
mally only in estrous, while human female
receptivity or proceptivity can occur over the
entire ovarian cycle, during pregnancy, and in the
postmenopausal period, thus demonstrating first
the relative freedom from hormonal control [6],
and, second, the epigenetic influence of both cog-
nitive and sociocultural factors. In this context,
several basic cellular mechanisms establishing the
physiological and neuronal parameters upon
which other variables act to influence human
female sexuality may be often only available from
studies in animals, by means of observation,
experimentation, and hypothesis testing.
Sex Determination and Differentiation. In mam-
mals, phenotypic sex is determined by a single
gene—called Sry—on the Y chromosome. This
sex-determining region of the Y chromosome
codifies for the protein tdf, for testis determining
factor, a transcription factor which initiates a
cascade of gene expression and protein products
that will direct the development of the bipotential
gonadal anlage toward a testis [7]. In the absence
of the Sry gene, this same gonadal anlage will
become an ovary. The brain is also sexually differ-
entiated in males and females by gonadal steroid
hormones and this process occurs during a
restricted developmental window termed the sen-
sitive period. In rodents, the sensitive period is
during the last few days of gestation and first week
of life, and the critical hormone for masculiniza-
tion is estradiol (E2), derived from testicular
androgens. In primates, including humans, the
sensitive period is largely prenatal, beginning in
the 2nd trimester, and the critical hormone for
masculinization is testosterone (T).
Female Sex Behavior is Controlled by a Hormonally
Responsive Neuronal Network. Sexual behavior rep-
resents a complex set of behaviors which includes
motivation to seek partners, evaluation of critical
stimuli, motor execution of the behavior, and
rewarding physiological processes, which eventu-
ally reinforce the behavior so it will be subse-
quently repeated. Each component of the behavior
involves multiple brain regions, with a number of
Psychophysiology of Women’s Sexual Arousal and Orgasm
critical nodes that are essential for gating informa-
tion in order to produce a functional behavioral
output. Neurons in each of the critical brain
regions express high levels of steroid receptors,
thereby creating a hormonally sensitive neuronal
network. The fundamental core of the network is
represented by those regions that control motor
execution of the behavior itself. In rodents, for
instance, the female adopts a sexually receptive
posture, referred to as lordosis, which allows the
male to mount and intromit. The ventromedial
nucleus (VMN) of the hypothalamus is an essential
brain region for the executing of this behavior; if
VMN is damaged or destroyed, the female will not
exhibit sexual receptivity. The estrogen receptor
expressing neurons of the VMN then project to
the estrogen sensitive neurons of the midbrain
central gray, and—in turn—those neurons project
on down to the spinal cord, thus activating the
motor neurons which innervate the critical muscle
groups on the back. The sensory information asso-
ciated with mating is then received at the spinal
cord and passed on back up the line to activate the
same regions, as well as those associated with
reward, such as the ventral tegmental area and the
nucleus accumbens. The VMN receives critical
input from the amygdala, which has in turn
received olfactory information, an important
evaluative signal in the rodent setting. The preop-
tic area (POA) is another critical hormonally-
sensitive region that shares reciprocal connections
with the VMN and other brain regions relevant to
mating. The POA—which is considered the criti-
cal area for male sexual behavior—influences
female behavior, in part, by exerting an inhibitory
influence over the expression of sexual behavior
[8].
Since the motor patterns involved in male vs.
female sexual behavior are so notably different,
particularly in our animal models, it is usually
assumed that separate neuronal networks exist
within the brain to specifically regulate the expres-
sion of each. However, no male vs. female circuit
has been identified to date; it might be hypoth-
esized that the reality is that the neuronal under-
pinnings of male vs. female sex behavior are largely
the same, but critical nodes are weighted
differently—although this is not a regulatory
mechanism that has been proven yet.
The Organizational/Activational Hypothesis of Sexual
Differentiation of the Brain. Phoenix et al. [9] in
1959 popularized the so-called “organizational/
activational hypothesis” stating that early actions
2639
of gonadal steroids act to organize the neural
architecture regulating sexual behavior and that
secretion of gonadal steroids in adulthood will
activate this previously organized substrate to
permit sex-specific sexual behavior in response to
appropriate stimuli. Accordingly, the differences
between males and females are largely determined
by the exposure to steroid hormones during a
perinatal sensitive period that alters subsequent
hormonal and nonhormonal responses through-
out the life span [10]. The onset of testicular ste-
roidogenesis in the fetus marks the beginning of
this sensitive period with a subsequent sexual dif-
ferentiation of the brain [10,11]. In this context,
shortly after birth, the testis ceases androgen pro-
duction and both males and females are devoid of
circulating gonadal steroids until the onset of
puberty, weeks (rodents) or years (primates) later
[10,11].
The role of E2 in the masculinization of sexual
behavior in the rodent is undisputed [12], although
E2 has recently been challenged as being the sole
mediator of the differentiation process [13,14].
Converging evidence suggests that androgens are
also a key mediator under normal circumstances,
and although the entire process of differentiation
can be completed with exogenous E2 treatment,
the natural course of events necessarily involves
androgens as well. This highlights the complexity
of hormonal modulation of the differentiation
process, being particularly important when con-
sidering the hormonal modulation of sexual differ-
entiation in primates for whom the evidence for a
critical masculinizing effect of androgens is undis-
puted, and a role for estrogens is considerably
more controversial [15]. Consistent with the
importance of androgens and a lesser role of estro-
gens, human males with a mutated gene for the
estrogen receptor or the aromatase enzyme are
phenotypically and psychologically males, whereas
genetic males completely androgen insensitive—
due to a mutated androgen receptor—are psycho-
logically females. This does not negate the value of
animal models to understand sexual behavior in
humans, as the cellular mechanisms initiated by E2
vs. T frequently converge. Whether this is the case
for sexual differentiation of the primate brain is
currently unknown.
Mechanisms Establishing Sex Differences in the Brain
Relevant to Sexual Behavior. Sex differences in the
brain occur at the critical nodes regulating sexual
behavior and are considered the neuronal under-
pinnings of male vs. female sexual behavior.
J Sex Med 2010;7:2637–2660
2640
The cellular mechanisms by which steroids act
on the developing brain to induce sex differences
can be categorized into four key processes: (i) cell
birth; (ii) cell migration; (iii) cell death; and (iv) cell
differentiation [11]. Major components of the
weighting toward male vs. female sexual behavior
are cell differentiation, which includes the neuro-
chemical phenotype and synaptic patterning of the
cell, both of which are essential to its role in the
integrated neuronal network, and the cell death, as
well. Some nodal points in the network are larger
in the male as compared with female brain, or vice
versa. For critical nodes in the control of sex
behavior, the most celebrated sex difference is the
size of a subnucleus in the POA called the sexually
dimorphic nucleus; the number of neurons in this
region is 5–7 times greater in males. Although, the
cellular mechanisms of the differential cell death
are only partially known, they involve E2 inducing
or repressing the process of apoptosis [16]. In con-
trast, there are greater evidences concerning the
synaptic patterning of the cell, with the finding
that the number of inputs to a particular region
exerts an important effect on the execution of
sexual behavior [17]. Particular attention, in this
context, has been focused on the dendritic spine
synapse in rodents’ POA. Dendritic spine synapse
are small protrusions of neuronal dendrites acting
as the principle site of excitatory (glutamatergic)
input, which are differently represented in male
rats than in females, according to the greater
gonadal steroid production in males [18]. There is
an equally profound sex difference in the VMN,
the major brain region controlling female sexual
behavior, since the males have two to three more
dendritic spine synapses, and the dendrites them-
selves are longer and branch more frequently than
in the female brain. This sex difference is also a
function of gonadal steroids that are higher in
male rodents during the critical period of the first
few days of life [19].
Biological Principles of Sexual Behavior: The Take
Home Message. Multiple mechanisms are involved
in differentiating the male from the female brain at
distinct nodes throughout a neuronal network.
Genetic differences in specific kinases, enzymes,
and/or receptors can all be important contributors
to the manner in which hormones exert organiza-
tional influences toward the neuronal network. As
a result, the phenotypic variability is far greater
than that which would be achieved by a single
unifying mechanism of hormone action. There is
no male brain vs. female brain; instead, it was
J Sex Med 2010;7:2637–2660
Salonia et al.
hypothesized a mosaic of overlapping and varying
degrees of masculinization and feminization
within one brain, and the potential that any indi-
vidual male or female are highly similar in some
nodes on the network but highly divergent at
others, with differences from one person to the
next. The variety of the steroid hormone action
toward cellular mechanisms in the developing
brain contributes to individual variability in adult
sexual behavior.
Centrally based Physiology of Women’s
Sexual Function
There is strong evidence that human sexual behav-
ior is guided by the cerebral cortex [20–22],
although the central nervous system (CNS)
mechanisms which govern female sexual behavior
are largely unexplored in humans. Therefore,
most descriptions are based on neurophysiological
investigations in rodents; lordosis, for instance, has
served as an important animal model for neural
control of female sexual behavior [8,23–27].
However, since taxonomic differences between
primates and non-primates in mating-related
functional neuroanatomy have been shown [28], it
is still questionable if rodents should serve as a
model for all aspects of female sexual behavior. In
this context, human brain function—thus includ-
ing SF—can be assessed relatively easily using
neuroimaging techniques like positron emission
tomography (PET) and functional magnetic reso-
nance imaging (fMRI) [29].
Neuroimaging Methods: Neurovascular Coupling.
PET and fMRI are functional neuroimaging
methods that measure metabolic or vascular
parameters. The physiological basis of these
methods is the claim that local changes in meta-
bolic demand are coupled with local blood flow
and blood oxygenation changes [30]. The principle
behind PET is the use of radioactive positron-
emitting isotopes tagged to molecules of a biologi-
cal compound of interest, which are introduced
into the human body by intravenous injection.
The most widely applied radioactive “tracer” for
neuroimaging purposes is [15O]-H2O (oxygen-15-
labeled water) and its distribution is a measure of
regional cerebral blood flow (rCBF) [31]. Blood
oxygenation level-dependent fMRI (BOLD-
fMRI), in contrast, uses a series of magnetic reso-
nance (MR) images to assess changes in MR signal
intensity over time caused by changes in brain
activity. Changes in MR signal occur because
blood flow responses to neural activity exceed
metabolic demands [30]. This leads to an increase
Psychophysiology of Women’s Sexual Arousal and Orgasm
Table 1 Comparison of major brain activation sites in women during arousal
Arnow Karama
[41] [40]
Insular region x x
Corpus striatum x x
Anterior cingulate x x
Hypothalamus x x
Amygdala
Thalamus x x
Occipital-temporal cortex x x
Ventral premotor cortex x
Medial prefrontal cortex x
Orbito frontal cortex x x
Paracentral lobule
Secondary somatosensory cortex
in the local concentration of oxygenated hemoglo-
bin compared to deoxygenated hemoglobin, which
increases the local MR signal because of their dif-
ferent magnetic properties [32].
Visual Sexual Stimulation-Induced Brain Responses
During Women’s Arousal Phase. The stimulus most
used to elicit sexual arousal in PET and fMRI
studies is visual sexual stimulation (VSS), using
erotic or sexually explicit photos or film excerpts.
In this context, it is critical to consider that experi-
mental studies support that men generally respond
more to VSS than do women, although there is
substantial variability in this effect [33–35].
After initial reports only devoted to assess male
sexual arousal [36,37], fMRI studies conducted in
healthy women documented activation in multiple
cortical and subcortical areas of the brain during
VVS. Park et al. [38] originally found involvement
of extrastriate visual areas in the occipitotemporal
cortex, the lateral prefrontal cortex (PFC), the
insula, the cingulate cortex, the inferior temporal
lobe, the thalamus, and the basal ganglia during
FSA, with many of the sites of activation being the
same as previously demonstrated in men during
sexual arousal [37]. Interestingly, using an “erotic
video” vs. a “documentary video” study paradigm,
Park et al. showed that all women perceived sig-
nificantly more sexual arousal during the erotic
video, but no correlations were computed between
perceived sexual arousal (PSA) and brain activity
[38]. A very similar result was recently reported in
a small cohort of healthy women that served as
healthy controls for women suffering from major
depression [39].
Subsequently, Maravilla and Yang [29] studied a
group of healthy heterosexual women without SD
and found activation in many of the same areas
previously described by Park [38]; in addition,
2641
Hamann Jeong Maravilla
[39] [43] [28]
x x
x x x
x x
x x
x x
x x x
x
x
there was activation in the amygdala and hypo-
thalamus, areas not described by Park et al. but
thereafter shown by other fMRI investigators
[40,41]. Importantly, the study by Maravilla and
Yang [29] demonstrated decreased activation in
bilateral temporal lobe with the VSS arousal
stimulus, at sites that have been associated with
moral judgment or embarrassment. This led to
hypothesize that such a decreased activity was due
to lowering of activity in sites that normally exhibit
active inhibition to a sexual stimulus. A possible
inhibitory influence of the temporal cortex over
sexual arousal in women has been also recently
confirmed [42], with a peculiar greater activation
of the entorhinal cortex (part of the temporal
cortex) in women with hyposexual desire as com-
pared with healthy heterosexual women, when
watching VSS stimuli [42].
Table 1 shows areas shown to be activated
during arousal in women in different studies.
Although a different methodological paradigm was
used among studies, overall VSS induced increased
BOLD signal in the extrastriate visual cortex, the
inferior parietal lobule, the orbitofrontal cortex
(OFC), the anterior cingulate cortex, the ventral
striatum, and the amygdala. The same pattern of
activation is largely found with similar VSS
periods also in men [37,44].
Perceived emotional state of sexual arousal was
assessed in two studies [41,42], but only Arnow
et al. [42] correlated CNS findings and vaginal
photopletysmography (VPP), as an objective
measure of sexual arousal. Comparing women
with no history of SD to women with hypoactive
sexual desire disorder (HSDD), Arnow et al. [42]
observed that subjective arousal to erotic stimuli
was significantly greater in participants with no
history of SD as compared with women with
HSDD. Moreover, there were no between-group
J Sex Med 2010;7:2637–2660
2642
differences in VSS-correlated brain activation, and
peripheral sexual response was not significantly
associated with either subjective sexual response or
brain activation patterns [42]. Karama et al. [41]
did not find any significant correlation between
PSA and hypothalamic activity. Using a relatively
brief 4-second presentation of erotic (nude indi-
viduals or couples) and neutral photos instead of
longer period of VSS, Hamann et al. [40] showed
that PSA ratings were highest for the couples
stimuli, but no correlations with BOLD signal
were computed specifically within the hypothala-
mus and both amygdalae. However, longer VSS
periods with videos consistently activated the
female amygdale [29,41,42], and, in one instance,
also the hypothalamus [29]. This suggests that, in
heterosexual women, the amygdalae, and probably
also the hypothalamus, are not sensitive to brief
periods of still VSS. Outside these regions of inter-
est, women had increased BOLD signal in the
extrastriate visual areas, the inferior parietal
lobule, the anterior cingulate cortex, and the
ventral striatum, which they shared with men [40].
This pattern showed substantial overlap with that
found using longer periods of VSS using film
excerpts [21,41,42].
It is important to highlight that—when inter-
preting VVS-induced brain responses—attention
should be paid to the eventual “contaminating
effects” of general emotional arousal and atten-
tion, which are readily found in any given
“emotional” neuroimaging experiment. This is a
well-known (epi)phenomenon in visual paradigms
that reflects visual attention processes [45], occur-
ring most readily when emotionally laden stimuli
are used [46,47]. In this context, a few reports
showed that when VSS was controlled for “general
emotional” arousal and bodily content, only a
restricted amount of brain areas were significantly
correlated with both sexual contents and sexual
intensity [48,49].
Gender Differences in VSS Brain Responses. Consis-
tent effects of VSS-induced brain activation in
women were found across studies in the extrastri-
ate visual areas, the inferior parietal lobule, the
anterior cingulate cortex, and the ventral striatum.
However, only the ventral striatum can be con-
vincingly linked to FSA [48,49]. As previously
mentioned, overall VSS produces greater neural
activations in men than in women in both the
hypothalamus and the amygdala, which thus seem
to be less sensitive in the female gender even when
women reported greater arousal [40,41,50]. One
J Sex Med 2010;7:2637–2660
Salonia et al.
explanation is that in men, visual stimuli have fast
access to primordial systems underlying the sexual
response, and that this reflects men’s higher pro-
pensity to identify cues for sexual opportunity [40],
especially in the visual domain. In both the
amygdala [29,41,42] and the hypothalamus [29],
women showed significant activation only with
longer VSS samples, providing further support for
the idea that, in men, this system is more phylo-
genetically tuned toward sexual cues [51], thus
supporting the concept that while women, in
general, take a more thoughtful approach with
regard to sexual encounters, men have a more
instinctive sexual response.
Clitoral Stimulation, Clitorally induced Orgasm, and
Brain Activation. Neuroimaging techniques have
been also used to study the orgasmic phase in
women. In this context, Georgiadis et al. [52]
reported the results of a series of [15O]-H2O PET
experiments in healthy heterosexual women expe-
riencing sexual clitoral stimulation and clitorally
induced orgasm, with the contemporary measure-
ment of rectal pressure (RP) and the subjective
ratings of PSA in order to objectify women’s
reported orgasms. Compared to a passive non-
sexual resting state, increased rCBF during sexual
stimulation of the clitoris was found in bilateral
primary somatosensory cortex (SI), the left sec-
ondary somatosensory cortex (SII), and the left
supplementary motor area [52]. In their study,
Georgiadis et al. [52] confirmed that the somato-
topical representation for the clitoris—namely, of
the genital party of SI—is on the dorsal convexity
of the postcentral gyrus, such as it was previously
showed in men [53–55]. SII, which is located in the
inferior parietal lobule, serves a variety of higher-
level sensory modalities [56,57]. Sensory stimula-
tion in the pelvic region readily activated SII, for
instance, during distension of the anal canal
[58,59]. In addition, VSS activated the inferior
parietal lobule, which contains SII, in both men
[44], and women [40–42], possibly as a result of the
sensory input caused by genital arousal [44]. In this
context, women with vulvar vestibulitis syndrome
had more SII activation in response to pressure on
the posterior vaginal vestibulum as compared with
healthy controls, being this suggestive of aug-
mented central processing of sensory afferent
information in these patients who experience
vaginal pain [60]. Thus, it seems that SII activation
reflects the context of the sensory stimulus,
“weighting” the salience of somatosensory stimuli
before they enter the realm of consciousness.
Psychophysiology of Women’s Sexual Arousal and Orgasm
Relative to the nonsexual resting state, Georgia-
dis et al. [52] reported that rCBF decreases in the
inferomedial temporal lobe—including the
amygdala—during clitoral stimulation and during
orgasm. Activity levels in the left parahippocampal
gyrus and anterior temporal pole decreased even
further from clitoral stimulation to orgasm [52]. As
stated above, temporal lobe probably exerts a tonic
inhibition on sexual arousal [29,61], and a success-
ful release of this inhibition may be imperative in
the event of sexual opportunity. This was con-
firmed by a highly significant inverse relationship
between PSA ratings and temporal lobe blood flow
[52]. Clinical findings of temporal lobe lesions
causing hypersexuality [62], and temporal lobe
epilepsy-associated sexual (or even orgasmic) auras
[63,64] provide further support.
The female amygdala readily responded to long
periods of VSS [29,41,42,65]. However, Georgia-
dis et al. found clear deactivation in the amygdala
in response to sexual genital stimulation in men
and women alike [52,54,66]. This switch in
amygdala activity may be crucial for sexual
encounters to take place. The PFC is called OFC
where it overlies the orbita, and ventromedial pre-
frontal cortex (vmPFC) where it borders the mid-
sagittal plane. Orgasm-induced strong rCBF
decreases in the left OFC and vmPFC, in both
men and women [52,54,66]. In women, the largest
blood flow decrease in the OFC was measured
between clitoral stimulation and orgasm, while it
was observed between the nonsexual resting state
and orgasm for the vmPFC [52]. The PFC in
general is instrumental in social behavior and
executive function. The vmPFC constitutes a
crucial part of a neural network underlying self-
monitoring and self-referential thought [67],
being, therefore, the vmPFC deactivation unlikely
to represent orgasm-specific neurobiology.
The OFC deactivation certainly connects to
sexual consummation in a much more specific
way. The OFC consists of functionally distinct
lateral, middle, and medial parts [68]. The peak
of the orgasm-related OFC deactivation was
located on the border of lateral and middle OFC.
The middle OFC is believed to specifically
encode hedonic experience, as it becomes acti-
vated with increasing satisfaction and subjective
pleasantness, and deactivated with feelings of
satiety [69,70]. The lateral OFC is strongly
linked to urge suppression [71,72]. Georgiadis
et al. [52] suggested that the activity level of the
OFC reflects conscious control over the sexual
urge: high control during clitoral stimulation
2643
(because orgasm was not allowed), with increased
rCBF, and decreased rCBF during orgasm, thus
indicating the release of that conscious control.
The failed orgasm attempts, too, were associated
with increased rCBF in the OFC [52], providing
strong evidence that OFC activity levels signifi-
cantly determine sexual behavioral outcome. Pos-
sibly, the loss of conscious control and the release
of tension that people report when they describe
an orgasmic experience [73] relates to this
decreased OFC activity.
Orgasm-related Activity of the Cerebellum. Although
the precise contribution of the cerebellum to
orgasm remains unclear, it has been shown that the
left anterior lobe of the cerebellar vermis and adja-
cent deep cerebellar nuclei activate during orgasm
in both sexes [52,54,66]. Women showed a strong
positive association between blood flow in the left
anterior vermis and RP fluctuations [52], a
measure of pelvic and abdominal muscular con-
tractions. The vermis takes part not only in axial
motor control, but also in autonomic regulation
and affect [74]. Indeed, orgasms are characterized
by substantial cardiovascular and respiratory
arousal [73], and vast emotional changes [75].
Table 2 shows areas shown to be activated and
deactivated in women during orgasm and clitoral
stimulation.
Gender Differences in Brain Responses During Sexual
Consummation. When directly compared to acti-
vation patterns for penile stimulation, women
showed significantly more activation in left fronto-
parietal regions, most notably in the posterior
parietal cortex and the supplementary motor area
[66]. Given that these regions are important for
making a mental representation of another per-
son’s actions [76], differential activity in these
regions as a function of gender may reflect behav-
ioral gender differences related to perspective
taking and empathy [77]. By contrast, women’s
brain responses during orgasm did not differ sig-
nificantly from the male counterpart [66]. This
suggests that men and women use different cere-
bral strategies to reach orgasm.
Factors Influencing Brain Patterns During Sexual
Stimuli in Women. Sexual Orientation. Neuro-
anatomical gender differences have been found in
large parts of the brain [78], but most notably in the
amygdala, hippocampus, and PFC [79–81]. These
regions are important for memory and learning,
executive function, and emotion, and, together
with sexual dimorphism of basic structures like the
J Sex Med 2010;7:2637–2660
2644
Table 2 Comparison of major brain sites in women during orgasm and clitoral ↓ and deactivation ↑ activation
stimulation (Courtesy Georgiadis JR)
Orgasm vs. rest
Parietal lobe
↑ Primary somatosensory cortex (SI) (genital)
Frontal lobe
↑ Primary motor cortex (pelvic floor)
↓ Ventromedial prefrontal cortex
Temporal lobe
↓ Inferior temporal gyrus
↓ Middle temporal gyrus
↓ Fusiform gyrus
↓ Temporal pole
Occipital lobe
↓ Lingual gyrus
Limbic system
↑ Posterior insula
↓ Amygdala
Cerebellum
↑ Deep cerebellar nuclei
↑ Anterior vermis
↑ Cerebellar hemisphere
hypothalamus, might explain why women behave
differently from men.
In this context, PET studies have shown the
putative role of the hypothalamus in sexual orien-
tation in humans [82–84]. More specifically, het-
erosexual women activated the ventromedial
hypothalamus and POA when smelling an
androgen-like substance such as pheromones,
whereas heterosexual men smelling an estrogen-
like odor activated the dorsomedial and paraven-
tricular nucleus [85]. Lesbian women, in contrast,
showed partial congruence with heterosexual men
in the dorsomedial and paraventricular hypothala-
mus [86]. Similar congruent activity has been
found between homosexual men and heterosexual
women in the POA and ventromedial hypothala-
mus [87], suggesting a coupling between hypotha-
lamic function and sexual preference, irrespective
of gender.
Savic et al. [88] recently demonstrated that indi-
viduals who prefer male sexual partners have sym-
metrical cerebral volumes, whereas those who
prefer female sexual partners possess a rightward
cerebral asymmetry. Moreover, sexual preference
determined the functional connectivity patterns of
the amygdala, a putative part of the emotional and
memory system. Heterosexual women (and homo-
sexual men) showed more widespread connections
from the left than from the right amygdala,
whereas the opposite was the case for homosexual
women (and heterosexual men) [88].
J Sex Med 2010;7:2637–2660
Salonia et al.
Orgasm vs. clitoris stimulation
Parietal lobe
↓ Secondary somatosensory cortex (SII)
↓ Superior parietal lobule
↓ Precuneus
Frontal lobe
↑ Primary motor cortex (pelvic floor)
↓ Lateral orbitofrontal cortex
↓ Ventromedial prefrontal cortex
↓ Dorsomedial prefrontal cortex
Temporal lobe
↓ Inferior temporal gyrus
↓ Middle temporal gyrus
↓ Fusiform gyrus
↓ Temporal pole
Limbic system
↑ Posterior insula
Cerebellum
↑ Deep cerebellar nuclei
↑ Anterior vermis
↑ Cerebellar hemisphere
Hormonal Milieu. Hormonal fluctuations during
the menstrual cycle influence mood, cognition,
memory, and arousal [89,90] along with sexual
interest [91]. During the follicular phase, for
instance, when performing a cognitive task involv-
ing male faces, heterosexual women showed less
metabolic effort in the right lateral OFC and the
caudal anterior cingulate cortex, as compared with
the luteal phase. Because task performance
remained unchanged, the authors proposed that
most efficient neural processing of sexually salient
stimuli occurs when pregnancy is possible [92].
Hormonal influences have been studied using
fMRI and have been shown to correlate with mea-
surable changes of brain activation responses with
general (nonsexual) arousal. Gizewski et al. [93]
demonstrated that VSS induced more brain
responses in women during their midluteal phase
than during their menses. The increase in activa-
tion was most apparent in the anterior cingulate,
left insula and orbitofrontal cortices [93]. Simi-
larly, Goldstein et al. [89] found a significantly
greater magnitude of BOLD signal changes
during the early follicular phase—most notably in
the amygdala, hypothalamus, hippocampus, OFC,
anterior cingulate gyrus (ACG), and brain stem,
a network of regions implicated in the stress
response—as compared with the late follicular
phase (midcycle or ovulatory phase). Arousal cor-
related positively with brain activity in amygdala,
OFC, and ACG during late follicular but not in
Psychophysiology of Women’s Sexual Arousal and Orgasm
early follicular phase, suggesting less cortical
control of amygdala during early follicular phase,
when arousal was increased. This study was the
first to suggest that estrogens, which are elevated
during the early follicular phase, may attenuate
arousal in women via cortical–subcortical control
within hypothalamic–pituitary–adrenal circuitry.
A further example of the influence of the hor-
monal milieu toward the functional brain activa-
tion comes from the finding that premenopausal
women have greater global brain signal than
menopausal women, in response to VSS [94,95].
HSDD. Arnow et al. [42] conducted fMRI studies
in a group of women with HSDD as compared with
a control group of sexually healthy women. The
study found significantly greater subjective arousal
response in the group without SD; likewise, many
areas of brain activation were found to be correlated
with sexual arousal in both groups, but only a
limited number of brain regions showed significant
differences of activation between groups, when
comparing erotic minus control video stimulus.
There was increased activation in the HSDD group
compared with controls in the medial frontal gyrus
[Brodmann area (BA) #10], the right inferior
frontal gyrus (BA #47), and the putamen on both
sides. The entorhinal cortex on both sides was the
only area that displayed reduced activation. The
authors concluded that the increase in activation in
the medial frontal and the right inferior frontal gyri
suggested that the HSDD group was directing
more of their attention to self-evaluation of their
responses which may have been distracting and
interfered with the normal sexual arousal response
[42]. Even more interestingly, this study also com-
pared simultaneous VPP with the fMRI and found
no between-group differences in VPP–fMRI cor-
related activation, nor was VPP correlated with
subjective arousal response [96].
Central Neuroimaging and Women’s Sexual Func-
tioning: The Take-Home Message. There is a recent
growing interest in using neuroimaging tech-
niques to explore and understand the cerebral cor-
relates underlying the sexual response. Several
innovative techniques have been developed as
powerful tools which are capable of providing a
great deal of information on brain activity in
response to sexual stimuli. However, there are
many limitations and potential pitfalls that must be
considered when planning a study using these
tools or even when reading a literature report
describing results of a functional brain imaging
2645
study. Appendix 1 lists a number of recommenda-
tions for performing or evaluating (female) sexo-
logical brain activation studies.
Genital Anatomy and Physiology of Women’s
Sexual Function
Functional Anatomy. The female genitalia can be
subdivided into the internal genitalia (vagina,
cervix, uterus, fallopian tubes, and the ovaries) and
external genitalia (vulva), including mons pubis,
clitoris, the labia majora and minora, which are the
structures surrounding the urogenital cleft [97].
This article summarizes a number of findings con-
cerning the structures involved directly in the
physiology of the sexual response.
1. Mons pubis is the hair-covered area over the
pubic bone and forms the anterosuperior limit
of the urogenital cleft and ends posteriorly at
the anterior margin of the perineal body [43].
2. Labia majora are the two prominent, fatty
lateral boundaries of the urogenital cleft. Ante-
riorly, they meet creating the anterior commis-
sura in front of the glans of the clitoris,
posteriorly forming the posterior commissura.
Each labium has external pigmented hairy,
slightly wrinkled skin and, internally, a smooth
surface lined with multiple sebaceous glands.
3. Labia minora are the two highly innervated
smaller medial boundaries of the vulva, which
anteriorly split into two layers forming the cli-
toral prepuce and the clitoral frenulum. They
consist of elastic skin and contain erectile tissue
but have no subcutaneous fat and have an
appearance ranging from smooth surfaced to
extensively corrugated [43,98,99].
4. The clitoris is a triplanar complex of erectile
tissue, comprising a midline shaft of some 2 cm
long and 1–2 cm wide dividing internally into a
pair of crura some 5–9 cm in length [100–103].
The erectile tissue consists of trabecular
smooth muscle and collagen connective tissue
encircled by a thin fibrous capsule surrounded
by large nerve trunks [100,104]. Externally, the
shaft is covered by the prepuce and is capped by
a glans some 2 cm in length and 3 cm wide
[101–103,105]. Linked into the structure are
two vestibular bulbs on either side of the
vaginal introitus closely applied the urethra,
which when vasocongested might support the
vaginal wall during the coital thrusting.
5. The vulvar vestibule includes the vulvar area
comprised between the inferior part of the cli-
toris, the medial part of the labia minora and
the fourchette [106,107].
J Sex Med 2010;7:2637–2660
2646
6. Periurethral glans. Although controversies exist
[108,109], the term “periurethral glans” delin-
eates a triangular part of the vaginal vestibule
surrounding the urinary meatus, extending
from below the clitoral glans to the vaginal
introitus and laterally to the beginnings of the
labia minorae. During coitus, the thrusting of
the penis causes the area to be pushed into and
then dragged out of the vagina. As the area is an
innervated mucous membrane, this induced
movement will create pleasurable erotic stimu-
lation. The area, its mobility and density of
innervation could be the answer as to why a
subgroup of women can have orgasms from
simple penile coital thrusting alone (so-called
“vaginal orgasms”) [108].
7. Vagina. In the unaroused condition, the vagina
is a “virtual” space, with its anterior and poste-
rior walls collapsed and resting together,
without any actual adherence since the walls are
covered with a thin film of fluid. The cross-
section is similar to either a “H” or “W,” while
the longitudinal axis is like a greatly stretched
out “S” (length range 6–12 cm). Its entrance
(introitus) is usually gated by the labia minora,
while its back culminates in a cul-de-sac, the
anterior wall of which is penetrated by the
cervix of the uterus usually at right angles to
the vaginal longitudinal axis [43,110]. The
layered structure of the vagina consists of
the luminal stratified squamous epithelium, a
lamina propria layer containing connective
tissue, blood vessels, nerves and receptors, col-
lagen, elastin fibers, and, finally, a layer of
smooth muscle [108,111–113]. The organ is set
in the pelvis surrounded by powerful striated
pelvic musculature, while at the introitus, two
superficial striated muscles, the ischiocaverno-
sus and bulbocavernosus, can contract around
the penis during orgasmic arousal [114].
External Genital—Arterial Supply. Women’s geni-
talia have a rich arterial blood supply [43,97]. The
labia are supplied from the inferior perineal and
posterior labial branches of the internal pudendal
artery as well as from superficial branches of the
femoral artery. The clitoris is supplied by the ilio-
hypogastric pudendal arterial bed, through the
common clitoral artery, which gives off the clitoral
cavernosal arteries and the dorsal clitoral artery.
The proximal (middle) part of the vagina is sup-
plied by the vaginal branches of the uterine artery
and the hypogastric artery. The distal part of the
J Sex Med 2010;7:2637–2660
Salonia et al.
vagina is supplied by the middle hemorrhoidal and
clitoral arteries.
Peripheral Neurophysiology. The female genitalia
are richly innervated; the anatomic structures
involved in the female genital sexual response are
innervated by both autonomic and somatic nerves
[101,110,111,115–119]. The uterine nerves arise
from the inferior hypogastric plexus formed by the
union of the hypogastric nerves (sympathetic T10-
L1) and the splanchnic fibers (parasympathetic
S2-S4). At the cervix arrive both sympathetic and
parasympathetic nerves form the paracervical
ganglia. The pudendal nerve (S2-S4) reaches the
perineum through Alcock’s canal and provides
sensory and motor innervation to the genitalia.
Sensory stimuli relevant to sexual function are
conveyed by afferent pathways consisting of
pudendal, pelvic and hypogastric nerves, and the
lumbosacral sympathetic chain. They relay infor-
mation to the dorsal horn, medial central and
lateral grey matter of the lumbosacral spinal cord,
and the vagal afferent fibers convey sensory infor-
mation from the genital apparatus to the nucleus
tractus solitarius [120]. A great variety of
neurotransmitters/mediators and receptor types
have been demonstrated in nerves in the female
genitals in both animal and human studies
[112,121].
Physiology of Peripheral Arousal
During sexual stimulation, the FSA response is
elicited by sensory stimulation as well as central
nervous activation resulting in increased blood
flow to the genitals. This culminates in a series of
vasocongestive as well as neuromuscular events
leading to physiological changes [119,120,122].
Studies by Yang et al. [123]—correlating in vivo
MR imaging of genitalia together with gross and
histologic examinations of cadaveric specimens—
have demonstrated six vascular compartments,
comprising the external female genitalia, the clito-
ris, clitoral bulbs, labia minora, urethra, and
vestibule/vagina. These compartments are com-
posed of erectile (namely, the clitoris and the cli-
toral bulbs) as well as nonerectile tissues with
erectile tissue demonstrating the greatest volume
change with engorgement during sexual arousal
[100,120–124].
External Genitalia—Labia. During sexual arousal,
the labia become engorged with blood increasing
in size by as much as two- to threefold [1,125] and
their sensitivity to touch is enhanced. Because they
Psychophysiology of Women’s Sexual Arousal and Orgasm
are the gateway into the vagina, painless initiation
of coitus by penile thrusting requires their lubri-
cation [126,127].
External Genitalia—Clitoris. Under basal condi-
tions, the blood vessels in the clitoris have a high
tone (through sympathetic activity) and are mainly
closed [128], but show evidence of vasomotion
[129], the random opening and closing depending
on local tissue needs. The neural innervation is
through vipergic nerves releasing vasoactive intes-
tinal peptide (VIP) which dilates the arterial
supply [108,130], and nitric oxide (NO), which
promotes relaxation of the smooth muscle of the
cavernous sinuses [131–139]. During sexual
arousal, the central reduction of sympathetic tone
and the release of the two vasodilator neurotrans-
mitters create an increase in the blood flow to the
clitoris relaxing the trabecular smooth muscles,
thus promoting clitoral vasocongestion along with
increased width of the clitoris during arousal
[120,122,124,140]. Since there is no subalbugineal
layer between its tunica and the erectile tissue, the
clitoris only becomes swollen or tumescent and
not rigid even when fully filled [141].
Internal Genitalia—Urethra. The female urethra is
only 4 cm long. Its wall has venous sinuses that are
filled with blood; in the lining of the urethra are
triangular-shaped paracrine cells that are thought
to have mechanoreceptor properties and contain
serotonin (5-hydroxytryptamine). Serotonin is
known to power the sensitivity of nerve endings
[142,143]. Stretching of the urethra usually occurs
during coitus [144] or during digital stimulation of
the anterior wall and this may well activate these
mechanoreceptor cells to release serotonin, thus
sensitizing the nerve endings in the urethra, even-
tually creating pleasurable sensations [144], and
converting a urinary structure into a sexual one
[142].
Internal Genitalia—Vaginal Microcirculation in the
Basal and Aroused Conditions. The vaginal micro-
circulation is extensively innervated by adrenergic,
cholinergic, and vipergic nerves together with
neuropeptides like substance P (a sensory trans-
mitter), neuropeptide Y (a vasonconstrictor), cal-
citonin gene-related peptide (a possible sensory
transmitter and a peptide influencing capillary per-
meability) and NO [111,117,142–146]. The exact
functions of the various innervations have yet to be
ascertained [147].
Like other microcirculations, during quies-
cence, vaginal capillaries are closed due to contrac-
2647
tion of the precapillary sphincters; the surface pO2
of the vagina wall is thus basally at a low, hypoxic
level [148]. When the local area around one of these
becomes hypoxic, the released metabolites (pCO2,
lactic acid, K+, adenosine triphosphate [ATP]) cause
precapillary sphincter relaxation and the supplied
capillaries to open up washing away the metabolites
and refreshing the local area with oxygen and nutri-
ents. This intermittency of the microcirculation is
known as “vasomotion” [149]; the degree of vaginal
vasomotion is a sensitive and useful index of genital
arousal. Thus, during basal conditions, a high vaso-
motor tone of the arterial supply through central
sympathetic activation and a high level of vasomo-
tion keep the blood flow to the vagina at minimal
levels. Recently, slow oscillations in vaginal blood
flow have been also described both in rats and
humans as a marker of sexual arousal [150–152],
although they appear independent of vaginal vaso-
congestion. The slow oscillations in vaginal blood
flow have been correlated with subjective physi-
ological arousal in healthy human volunteers, but
display diminished responsiveness in women with
female sexual arousal disorder (FSAD) [151].
At the beginning of sexual arousal, the blood
supply to the vagina is minimal due to the high
sympathetic vasomotor tone and vasomotion.
Then, usually within seconds of an acceptable or
consensual sexual stimulus, the central sympa-
thetic tone is reduced and the arterial supply is
enhanced through the action of released neuronal
VIP and some NO via the sacral anterior nerve
root [153]; vasomotion thus decreases as more
opened capillaries are recruited [149]. Fairly
rapidly, the recruitment of the capillaries becomes
maximal, the vagina becomes fully vasocongested
(along with the labia and clitoris), and vasomotion
is absent. The woman will subjectively perceive
that her pelvis feels “full and congested’ creating
the desire (so-called reactive desire) to dissipate
the congestion by the induction of an orgasm.
Internal Genitalia—The Aroused Vagina and the
Formation of Vaginal Lubrication. Within the sexu-
ally aroused vagina, the capillaries of the microcir-
culation are filled with blood and the increased
hydrostatic pressure inside them forces out a
plasma transudate (ultrafiltrate) into the interstitial
space around the blood vessels. Continued forma-
tion of this neurogenic transudate fills up the
interstitial space and then passes through and
between the cells of vaginal epithelium to leak
onto the surface wall of the vagina as the vaginal
lubrication. The final fluid is a modified plasma
J Sex Med 2010;7:2637–2660
2648
filtrate because the cells of the vagina can transfer
Na+ ions vectorially from the lumen back into the
blood [154] and add K+ ions by secretion and the
cell shedding [153,155]. The ionic concentrations
of these ions are much different to those in the
plasma, vaginal basal fluid having a higher K+ and
a lower Na+ than plasma throughout the menstrual
cycle [155]. In contrast, the arousal lubrication
fluid has a much higher Na+ concentration than
the basal fluid approaching that of plasma [113].
On cessation of the sexual arousal, the vaginal Na+
together with osmotically drawn fluid is trans-
ferred back into the blood, thus resetting the
vagina to the basal “just moist” condition
[143,156]. In the rat vagina, water channel pro-
teins called “aquaporins” (AQPs) have been
recently localized, which seem to facilitate the
transport of water and other small molecules like
glycerol, eventually playing a role in the fluid
movements of vaginal lubrication [157]. Prelimi-
nary unpublished evidences suggested that AQPs
distribution in premenopausal human vagina was
similar to that described in the female rat [158].
Any possible role of these water channels in human
vaginal lubrication has yet to be determined.
Internal Genitalia—The Anterior Vaginal Wall and
Its Putative Erotic Structures. The anterior vaginal
wall, when stimulated by deep pressure, is known
to generate a more sexually pleasurable feeling
than either of the lateral or posterior vaginal walls.
Closely associated with this wall, are (i) the
urethra; (ii) the so-called “G-Spot” (a “controver-
sial” site on the anterior wall of the vagina that
when stimulated by deep pressure becomes
swollen and/or enlarged protruding into the
vaginal lumen and which has been reported to be
highly effective in causing orgasm in women when
stimulated) [159,160]; and (iii) Halban’s fascia (the
fascial-filled space between the bladder and the
anterior wall of the vagina that has been suggested
to elicit highly pleasurable sensations that can lead
to orgasm when adequately pressure stimulated)
[161,162]. Recently, Gravina et al. [163] reported
the results of a controversial ultrasonographic
study showing that sexually healthy women with a
thicker urethrovaginal space were more likely to
experience vaginal orgasm.
Internal Genitalia—The Cervix and the Uterus. De-
spite many studies, the role of both the cervix and
the uterus in sexual arousal has not been definitely
settled [142,164]. In this context, it has been
reported that the uterus contracts during high
levels of sexual excitement and at orgasm [1,142].
J Sex Med 2010;7:2637–2660
Salonia et al.
Nipple/Breast Stimulation. While genital stimula-
tion is very effective in creating FSA, the stimula-
tion of the female nipple/breast can significantly
enhance sexual arousal, but very few studies are
available. Interestingly, a recent psychometric
study showed that stimulation of women’s nipples/
breasts caused or enhanced their sexual arousal in
the vast majority of the sample, while roughly 80%
of the women agreed that when sexually aroused,
stimulation of the nipples further increased their
arousal [165].
Peripheral Physiology of Orgasm
Several changes occur in the striated pelvic
muscles, the smooth muscle of the uterus and
vagina and circulation of the genitalia at orgasm
[166].
Striated Pelvic Muscle Changes. Classical accounts
subdivide pelvis muscles into the superficial
muscles (namely, the urogenital diaphragm,
including the ischiocavernosus, the bulbocaverno-
sus, and the deep and transverse perineii) and the
deep muscles, often described as the “pelvic dia-
phragm,” consisting of the coccygeus (ischiococ-
cygeus) and the levator ani [167].
Pelvic muscles have both afferent (sensory) and
efferent (motor) innervation, which belongs to the
pudendal nerve pathway [168]. This pathway is
responsible for the generation of the rhythmic
contractions of these muscles which eventually
occur in most women at and during orgasm. The
actual number of the contractions varies with the
duration and intensity of the orgasm [1,169] and
their frequency, strength and pleasurable power all
decrease after the first few. While in the male, the
purpose of the involuntary rhythmic contractions
of the pelvic muscles at orgasm is clearly to force-
fully ejaculate during the expulsion phase, their
role at orgasm in the female is less attributable. In
this context, five possible functions have been sug-
gested, including (i) to eject glandular secretions
from the urethra (viz female ejaculation, which is
reported only by a small group of women as ure-
thral ejection at orgasm); (ii) to create sexual plea-
surable feelings; (iii) to restore the vasocongested
pelvic tissues to their basal state [149]; (iv) to
stimulate the male to ejaculate (as by creating
increased pressure on the thrusting penis, the
sexually excited male is pushed over his threshold
of ejaculatory containment and delivers his semen
into the vagina); and (v) to end sexual arousal, since
women are multiorgasmic, and a single orgasm—
with the concomitant contractions—does not nec-
essarily end their sexual arousal. Interestingly,
Psychophysiology of Women’s Sexual Arousal and Orgasm 2649

while Masters and Johnson [1] and, subsequently, effect, while Masters and Johnson [1] proposed
Levin [170] described the pelvic contractions as an that they were expulsive and not involved in “up-
intrinsic and indispensable part of the orgasmic sucking” material from the vagina. Unfortunately,
process, others (namely Kinsey et al. [171,172] and remarkably few measurements of this uterine
Bohlen et al. [169]) regarded them as not occur- activity during orgasm have been recorded and
ring at orgasm. published so far [1,129,177].
Overall, hypoactivity of the muscles (low tone)
Cervix. It has been described that a minimal dila-
leads to poor sexual function and lack of pleasure
tation occurs at the level of cervix os immediately
during coitus and orgasm; in contrast, hyperactiv-
after orgasm, lasting for 20–30 minutes [1], with
ity (high tone) may be pathophysiologically linked
the potential purpose of facilitating spermatozoal
to the sexual pain disorders called dyspareunia
transport through the endocervical canal.
(namely either coital or noncoital pain) and
Although the mechanism for this dilatation has
vaginismus [168,173].
never been investigated, the cervix’s second-
Vagina. The vagina is a compliant organ and is set highest concentration of VIP in the genital tract
in a surround of powerful pelvic striated muscula- makes possible that its relaxant action on the
ture. Its innervation by vipergic nerves suggests sparse smooth muscle present could be involved.
that the muscle will become relaxed during arousal
Rectal Sphincter and Pressure. The rectal sphincter
and coitus probably to avoid occluding its blood
contracts at orgasm, especially in younger women
vessels. At orgasm, the contractions of the striated
[1], mirroring the contractions of the vagina
muscles will impinge on the vagina causing passive
[169,178,179]. RP changes during orgasm have
increases in its intraluminal pressure. How much
been analyzed by calculating the spectral power in
the vaginal smooth muscle contributes per se to
various frequency bands [180], with the finding of
the activity is uncertain as no study has measured
peculiar alpha band (8–13 Hz) modifications
the vaginal smooth muscle and the striated at the
which may be identified in roughly 90% of the
same time during orgasm. Gillan and Brindley
orgasms induced in normal women by clitoral
[174] recorded what was presumably the electrical
masturbation undertaken by their partners.
activity of the vaginal smooth muscle showing a
continuous electrical activity, which was increased
by clitoral vibration and then replaced with inter- Translational Science: What is the Role of Sexual
mittent activity associated with the orgasmic con- Arousal and Orgasm in Females?
tractions. Later, Shafik et al. [175] showed a slow
Sexual arousal in women serves both procreation/
wave pattern with intermittent action potentials
reproduction and recreation/pleasure. In this
recorded in women who were not sexually
context, the changes that occur in the female geni-
aroused. These action potentials were concomi-
tals and genital tract can be divided into those that
tant with increased intraluminal vaginal pressure
serve procreation, those that serve recreation, and
and represent the spontaneous vaginal motility
those that serve both procreation and recreation
[156]. The function of these basal contractions
[129,181].
were assumed to be for clearing the vagina of cel-
lular debris, secretions, and blood and possibly as Vaginal Changes Induced by Arousal that
maintenance to activate vaginal blood flow during Facilitate Procreation
sexual quiescence.
The sexually unaroused vagina has the function of
Attempts to relate aspects of the physical nature
being the passage for the discharge of the menses
of the vaginal contractions to the pleasure felt
and as the birth canal. All that these demand is a
during their activity have not been successful.
basal, just moist, lubricated, and expandable vagina.
Indeed, while Masters and Johnson [1] reported
For painless penile penetration and coital thrust-
that the stronger the orgasm, the greater was the
ing, a much higher level of lubrication is necessary;
number of contractions experienced, recordings of
this is thus obtained during sexual arousal by the
the intraluminal vaginal pressure during orgasm
agency of the neural release of the vasodilators
have not shown any linkage between the orgasmic
transmitters VIP and NO. These dilate the arterial
contractions and the intensity of pleasure [176].
supply to the vagina and the enhanced blood flow
Uterus. Controversies exist concerning the con- and together with the central reduction of sympa-
tractile activity of the uterus at orgasm. Kinsey thetic tone open closed capillaries creating genital
et al. [172] regarded them as having a sucking vasocongestion [149]. This eventually leads to an

J Sex Med 2010;7:2637–2660

2650
increased formation of interstitial fluid that fills up
the interstitial space and percolates between and
through the vaginal epithelial cells, to finally reside
on the surface of the vaginal wall as a thin, lubrica-
tive film [1,113,153,156,182].
The sexually induced increase in vaginal blood
flow and lubrication creates a vaginal lumen that is
much more oxygenated than in the hypoxic basal
state and the neurogenic transudate partially neu-
tralizes the acidity of the basal vaginal fluid [183].
The increased oxygenation facilitates the produc-
tion of usable energy by the spermatozoa. Like-
wise, the partial neutralization of the vaginal
acidity by the transudate [183] reduces the delete-
rious effect of the basal low vaginal pH on sperm
function. Thus, sexual arousal creates a more
favorable and receptive vaginal milieu for sperm
function and survival.
Does Orgasm Have any Essential Role to Play in
Female Reproductive Mechanisms?
The Uterine “Upsuck Hypothesis”
The possible role(s) of orgasm and their impor-
tance in the female have always been disputed.
Motions CON. Recently, Lloyd [184], having criti-
cally examined some 26 papers on the topic, con-
cluded that there was little or no real evidence to
show that orgasm was important for reproduction.
This would be supported by the finding that
numerous women have become pregnant without
an orgasm and that artificial insemination creates
pregnancies without orgasm. Likewise, as female
orgasm created by penile thrusting alone is far
from a universal feature among women [185]
natural selection has clearly not favored those who
could orgasm easily from such stimulation indicat-
ing that it could not be an essential for the repro-
duction of our species.
Motions PRO. The other school of thought has
proposed that the uterine contractions observed at
orgasm (supposedly thought to be induced by oxy-
tocin release at orgasm) create a uterine “upsuck”
and hasten the transport of the sperm, but mostly
single-based case studies have been reported to
support this hypothesis [177,186–189].
Sperm Transport in the Unaroused and Aroused
Female Genital Tract
A few early reports proposed that orgasmic uterine
contractions may have a proactive role on sperm
transport in the female reproductive tract facilitat-
ing and speeding up their movement through the
J Sex Med 2010;7:2637–2660
Salonia et al.
cervix into the uterus and fallopian tube [129]. In
contrast, a fast transport of spermatozoa in the
female tract has been showed in the sexually
unstimulated woman [189,190] due to the contrac-
tions of the uterine archimyometrium (stratum
subvasculare) [191] which create the rapid, passive
uptake of the spermatozoa and direct them into
the fallopian tube on the side of the ovulating
ovary rather than into the contralateral tube.
The “Tenting” of the Cervicouterine Complex—A
Mechanism to Delay Sperm Transport
In the basal unaroused state, the vagina is a poten-
tial space with the cervix close to or touching its
posterior wall. Sexual arousal causes the release of
VIP from vipergic nerves innervating the vagina,
which relaxes its smooth muscle during the initia-
tion of coital thrusting. Sexual arousal then pro-
motes the contraction of the pelvic levator ani
muscle, followed by the smooth muscle in the con-
nective tissue septa attached to the uterus. These
contractions lift the cervicouterine complex away
from the posterior wall and up into the “false”
pelvis. The back cul-de-sac of the vagina (fornix)
becomes ballooned out creating a receptacle for
the ejaculate to come. This lifting of the cervix
and ballooning of the vagina—originally named
“vaginal tenting” by Masters and Johnson
[1]—seems a mechanism of great importance to
the reproductive process, since it would remove
the os cervix from the path of the ejaculate, even-
tually reducing the possibility of rapid sperm entry
into the uterus and delaying the transport of sper-
matozoa into the cervical canal. This delay is pur-
poseful as freshly ejaculated spermatozoa in semen
in the vagina are barely motile, trapped in a gel
formed by coagulation of semen protein, and are
incompetent to fertilize the ovum. Therefore, they
have to be reprogrammed into a fertilizing state
(called capacitation) and liberated from the trap-
ping gel. It is now known that the process of acti-
vating sperm to become capable of fertilization
requires the delay imposed on sperm transport by
vaginal tenting, in order to allow a variety of
mechanisms involved in the activation [129,192–
194]. Rapid transport without the spermatozoa
undergoing these changes delivers incompetent
spermatozoa unable to fertilize.
Interactions between Physiological and
Psychological States of Women’s
Sexual Response
A clear interaction between physiology and psy-
chology in the sexual response has been suggested
Psychophysiology of Women’s Sexual Arousal and Orgasm
for human beings, with recently growing evidence
that a gender difference in this interaction exists.
Among women, there is a lower degree of cor-
respondence between the physiological and psy-
chological states of sexual response, termed
concordance, compared to that observed among
men. Similarly, low agreement has also been
observed between physiological responses and
psychological traits, namely sexual orientation,
particularly among heterosexual women, a phe-
nomenon termed nonspecificity. The potential for
low concordance and nonspecificity of sexual
response are examples of the relative indepen-
dence between physiological, psychological, and
behavioral aspects of women’s sexuality.
Concordance of Women’s Sexual Arousal
Psychological and physiological processes charac-
terize the human sexual response. Sexual arousal is
an emotional state [195] and, similar to other emo-
tions, it possesses distinct antecedents (e.g., sexual
stimuli) and patterns of expression (e.g., psycho-
logical, physiological, behavioral) serving to regu-
late behaviors fundamental to sexual reproduction
[196].
The degree to which the female’s experience of
sexual arousal corresponds with her physiological
response (concordance) is a matter of great interest,
since subjective (or self-reported) experience and
genital measures of sexual arousal do not always
agree. The most frequently cited moderator of
concordance is gender, such that men show signifi-
cantly greater concordance than women [197]. In
this context, however, agreement between actual
genital arousal and self-reported arousal in women
is not zero; a recent meta-analysis by Chivers et al.
[197] indeed showed that that physiological sexual
response is positively related to subjective experi-
ence of and awareness of genital sexual arousal in
women. Moreover, women’s experience of sexual
arousal is not primarily related to experience of
physiological responding and is mediated by addi-
tional cognitive and emotional mechanisms [197].
It is not clear how much appraisal of subjective
sexual arousal is influenced by perception of
genital responding, or vice versa, but these mea-
sures are highly positively correlated in women
[198].
Therefore, there is a difference between expe-
riencing sexual arousal and perceiving physical
changes. Concordance between perception of
genital response and actual genital sexual arousal is
an index of interoceptive awareness, which means the
psychological capacity to perceive internal physi-
2651
ological changes. The tendency for women to
demonstrate low sexual interoceptive awareness
may result from the information women use to
appraise their emotional state of sexual arousal;
women attend more to external, situational cues
when appraising their emotional states than men
do [199]. The greater reliance on external infor-
mation suggests that women’s experience of sexual
arousal is more influenced by their attitudes,
beliefs, and values regarding sexuality, as well as
immediate contextual factors such as sexual stimu-
lus properties and their appraisals of these proper-
ties [200]. Women’s concordance estimates can
vary widely such that some women’s reports of
sexual arousal are unrelated or even negatively
related to genital responses, whereas other women
show large and positive correlations between self-
reported sexual arousal and genital vasocongestion
[201].
Concordance and the Pathophysiology of Female
Sexual Response
Cognitive models suggest that concordant sexual
response is a desirable, or even a necessary, state
for satisfactory sexual functioning [202]. The
potential for concordance to vary with sexual func-
tioning has been demonstrated in studies of sexu-
ally dysfunctional women [197,203,204]. Studies
comparing the concordance of sexual responses of
sexually functional and dysfunctional women have
yielded mixed results, reporting either greater
concordance [213,205–219] or negative concor-
dance [210–212], or even no group differences
[213]. Among sexually functional women, concor-
dance may be related to better sexual functioning,
such that women who show greater concordance
also report greater frequency of orgasm during
penile–vaginal intercourse, but not during other
sexual behaviors [214,215]. Similarly, significantly
positive concordance estimates have been obtained
for frequently orgasmic women [216].
Nonspecificity of Women’s Sexual Arousal
The relationship between the psychological and
physiological sexual response, and psychological
traits, like sexual orientation, also shows marked
discordance in women. Gender differences have
been observed in the relationship between self-
reported sexual attractions (toward males or
females) and patterns of genital and self-reported
sexual arousal to female and male sexual stimuli;
men’s sexual arousal patterns are very strongly
associated with their self-reported sexual orienta-
tion, whereas women’s are not [217–223].
J Sex Med 2010;7:2637–2660
2652
Women’s genital arousal responses are less related
to their sexual preferences; although a woman
might report psychological (attraction, thoughts,
self-reported sexual arousal) and behavioral pref-
erences for women or men, her genital responses
are not higher to sexual images of her preferred
gender. Women report increased sexual arousal to
both preferred and nonpreferred sexual stimuli
[222,224–226], which suggests that their cognitive
and affective responses to sexual stimuli are not
dependent upon their sexual preferences, such as
sexual orientation.
Contrary to data on peripheral genital respond-
ing, both heterosexual and lesbian women’s brain
responses showed specificity in brain areas associ-
ated with processing of visual stimuli and motiva-
tion, that is, greater response to stimuli matching a
woman’s sexual orientation [18,227]. Hypotha-
lamic response, however, did not show category-
specific response for either group. Similar to the
pattern of genital responses [222], specificity in
amygdala function was found for lesbian women
only; heterosexual women showed nonspecific
amygdalar responses. The general pattern of
results from these different lines of research dem-
onstrates that specificity and nonspecificity of
peripheral sexual responses are mirrored in central
aspects of sexual functioning in women.
Nonspecificity of Sexual Arousal and Women’s
Sexual Orientation
Research on the specificity of women’s sexual
arousal converges with current models of female
sexual orientation that emphasize flexibility in
women’s sexual attractions and sexual identities.
Flexibility refers to a pattern of intraindividual vari-
ability in sexual preferences, attitudes, and behav-
iors [200]. With respect to sexual orientation and
identity, women are more likely than men to expe-
rience and express same-gender attractions and
less likely to engage in exclusively heterosexual or
homosexual sexual behaviors [171,172,200,228–
230], and women’s sexual identities show less tem-
poral stability than men’s [231–236]. Diamond has
suggested that the processes underlying romantic
and affectionate bonding are not intrinsically gen-
dered toward females or males, and that romantic
and affectionate feelings have the capacity to
kindle sexual desire, particularly among women
[237]. Therefore, a woman’s sexual desire for
another woman may emerge from a close emo-
tional relationship instead of from sexual attrac-
tion to and arousal by women. Self-reported data
on the development of female sexual orientation
J Sex Med 2010;7:2637–2660
Salonia et al.
support this proposition; women report that social
and emotional factors are more salient than sexual
arousal to the development of their sexual interests
in either the same gender [234,235] or opposite
gender [238]. Nonspecific sexual responding may
increase the potential for flexibility in women’s
sexuality because patterns of sexual arousal do not
constrain women’s sexual behavior, feelings, or
identity.
Nonspecific Sexual Response and Inferences about
Women’s Sexual Interests and Desire
The potency of stimuli depicting any sexual activ-
ity to evoke genital response, regardless of the
actors portrayed or context of the sexual activity
[222], is also highlighted in studies where women
show physiological sexual responses to other
clearly nonpreferred sexual stimuli, such as films of
nonhuman sexual activity [221,222] and sexual
threat stimuli [219,225,239–241].
Overall, current research suggests that little can
be inferred about a woman’s sexual orientation or
motivation from her genital responses alone. Some
have proposed that physiological sexual response
in women is an automatic reflex that is elicited by
sexual stimuli before conscious appraisal of a
sexual stimulus as being sexually arousing or pre-
ferred [242–244]. Genital response precedes sub-
jective sexual arousal [245], is evident within
seconds of the onset of a sexual stimulus [246], and
can occur in the absence of subjective experience
of sexual arousal [221]. Primary sexual cues, such
as sexual activity [222], may initiate reflexive vaso-
congestion, leading to vaginal lubrication, and
preparing the genitals for possible sexual activity.
In this context, reports of women’s genital
response and orgasm during sexual assault and
research showing that women experience genital
responses to sexual threat stimuli suggest that
genital response under conditions of nonconsen-
sual sexual stimuli may be typical in women [247].
For this reason, inferences regarding a woman’s
sexual desire and relative sexual attractions based
solely on her genital responding would very likely
be inaccurate.
Conclusions
Physiology is the cornerstone of women’s sexual
functioning. A comprehensive understanding of
the anatomical, neurobiological, and psychological
mechanisms underlying sexual function and
response is therefore of paramount importance.
New findings concerning the biopsychological
Psychophysiology of Women’s Sexual Arousal and Orgasm
paradigm, which considers aspects of sexual differ-
entiation of the brain, brain functioning, transla-
tional science, and psychophysiology may provide
the foundation for understanding pathophysiology
in a clinical setting in the future. Many matters still
have to be solved. Research in sexual medicine can
still move forward!
Acknowledgment
We are grateful to Dr. Helen O’Connell for her com-
ments on the manuscript.
Corresponding Author: Andrea Salonia, MD,
Department of Urology, Universita’ Vita Salute San
Raffaele, Via Olgettina 60, 20132 Milan, Italy. Tel:
00390226437286; Fax: 00390226437298; E-mail:
saloniaandrea@yahoo.com
Conflict of Interest: None.
Statement of Authorship
Category 1
(a) Conception and Design
Andrea Salonia; Annamaria Giraldi; Meredith L.
Chivers; Janniko R. Georgiadis; Roy Levin;
Kenneth R. Maravilla; Margaret M. McCarthy
(b) Acquisition of Data
Andrea Salonia; Annamaria Giraldi; Meredith L.
Chivers; Janniko R. Georgiadis; Roy Levin;
Kenneth R. Maravilla; Margaret M. McCarthy
(c) Analysis and Interpretation of Data
Andrea Salonia; Annamaria Giraldi; Meredith L.
Chivers; Janniko R. Georgiadis
Category 2
(a) Drafting the Article
Andrea Salonia; Annamaria Giraldi; Meredith L.
Chivers; Janniko R. Georgiadis; Roy Levin;
Kenneth R. Maravilla; Margaret M. McCarthy
(b) Revising It for Intellectual Content
Andrea Salonia; Annamaria Giraldi; Meredith L.
Chivers; Janniko R. Georgiadis; Roy Levin;
Kenneth R. Maravilla; Margaret M. McCarthy
Category 3
(a) Final Approval of the Completed Article
Andrea Salonia; Annamaria Giraldi; Meredith L.
Chivers; Janniko R. Georgiadis; Roy Levin;
Kenneth R. Maravilla; Margaret M. McCarthy
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Appendix 1: Recommendations for Performing or
Evaluating (Female) Sexological Brain Activation
Studies
Use the Appropriate Technique
• [15O]-H2O PET is less sensitive to head motion than other
techniques, but has relatively poor spatial and temporal resolu-
tion. PET-signal is not stable over time because of radioactive
decay and a single bolus infusion of isotope.
• BOLD fMRI offers good spatial and temporal resolution with
exquisite sensitivity for detecting areas of brain activation, but is
not sensitive to mental and emotional states that develop over
minutes. BOLD scanning loses sensitivity with stimuli > 1
minute. BOLD signal is unreliable in air-tissue transition zones
because of magnetic susceptibility effects that cause rapid decay
of T2*.
Multi-subject Experiments are the Rule
• In a single subject the level of activation is small and there are
many sites of brain activation. Multi-subject studies will show
which sites have high reproducibility and are likely to be con-
nected to the (sexual) task, thus enhancing the power of the
study. A typical multi-subject (BOLD) fMRI study comprises
10–20 subjects. For multi-group studies, 15 subjects per group
are usually necessary. The number of subjects needed to yield
an expected effect size may be calculated using the freely avail-
able tool G-power (http://www.psycho.uni-duesseldorf.de/aap/
projects/gpower/).
Subject Cohort(s)
• Subjects should be matched as closely as possible on gender,
sexual orientation, menstrual cycle phase, age, handedness, etc.
to reduce statistical noise in the data. If not possible remember
to collect information on heterogenicity.
Careful Attention to Experiment Design is Essential
Visual Sexual Stimulation
• Have good arguments for choosing videos versus still pictures. If
video is used with BOLD fMRI, the duration of each video
block should be as short as possible (ideally < 1 minute). Mode
and duration of the stimuli will bias the activation pattern.
• Validate the effectiveness of the chosen stimuli (and the para-
digm) outside the scanner in a separate group of subjects. Like-
wise, appropriate control stimuli should be chosen for a selected
(sexual) activation task, since inappropriate, neutral or mildly
pleasant control stimuli may result in considerable non-specific
activation.
• Check to determine whether subjects were attentive to the
stimuli.
J Sex Med 2010;7:2637–2660
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Sexual Arousal Assessment
• Many tools are available to assess perceived level of sexual
arousal that may be used during scanning or at end of scan (i.e.,
perceived level of arousal questionnaire). For fMRI and objec-
tive sexual arousal (e.g., vaginal photopletysmography), make
sure that devices you want to use are MR-compatible (are not
paramagnetic).
Sexual Consummation
• Decide the type of genital stimulation to use. The selected
stimulus should induce as little head motion as possible.
Limit Head Motion
• Major Limitation of fMRI technique. A priori limits for head
motion should be set and images that exceed these limits should
J Sex Med 2010;7:2637–2660
Salonia et al.
be removed from dataset. Motion correction software should be
used to align remaining images within dataset. If task-induced
head motion correlates with the model (such as for sexual con-
summation study), these procedures can become problematic
since such correlated motion may remove “true” task-related
activity or introduce “false activations”.
Analysis Strategies
• Parametric: Most widely used. Assumes brain activity correlates
with pre-defined model and/or behavioral parameters.
• Non parametric: May be used to find brain activation patterns
uncorrelated with a model or behavioral parameters that were
nevertheless important during the experiment. Is used particu-
lary to find sites where activation sites/patterns are correlated
with each other (network) rather than with the model.