NATURE REVIEWS | UROLOGY ADVANCE ONLINE PUBLICATION | 1

Introduction
As a relatively well-defined and exact
field of biomedicine, gross anatomy rarely
provides opportunities for controversial
disagreements over hypotheses; however,
the anatomy of the organs, tissues, and
structures involved in the subjective orgas-
mic experience in women seems to be an
exception. For experts in sexual medicine
and specifically andrologists, urologists,
gynaecologists, and urogynaecologists
with a necessary interest in female orgasmic
function as well as the related clinical and
surgical aspects, the current nomenclature
and, consequently, the taxonomy, represent
important areas of contention. Whereas a
single male type of orgasm is classically
recognized, at least two distinct varieties of
orgasms are described in women.
1
The first
type of female orgasm is obtained through
the direct stimulation of the external cli-
toris, without any kind of internal stimu-
lation. Herein, we refer to this orgasm as
the clitorally activated orgasm (CAO).
The second form of orgasm is described as
that obtained during vaginal penetration
and in the absence of direct stimulation
of the external clitoris:
2
we proposed to
name this type the vaginally activated
orgasm(VAO).
The anatomical structures that might
provoke VAOs rather than CAOs have
not been completely and unequivocally
described, probably representing a unique
case of remaining major uncertainty
regarding human gross anatomy. In fact,
several issues relating to this gap in our
anatomical knowledge remain contro-
versial. First, the functional relationship
between the cli toris and the vagina is
still debated. Second, disagreements over
whether the vagina is sufficiently inner-
vated to provide pleasure, or is poorly sen-
sitive to facilitate the processes of labour
and birth, have not been resolved. Third,
whether the Grfenberg spot (G-spot;
ahypothetical, discrete, highly erogenous
region of the vagina) is a discrete entity,
a complex structure, or a gynaecological
myth created for journalistic purposes, or
with the aim of supporting surgical aesthe-
tic manipulations of the female genitals,
remains unclear. Finally, whereas the
functional anatomy of men is, rightly or
wrongly, considered to be constant, women
are often, contentiously, considered to be
anatomically and functionally different
from each other, which further complicates
attempts to define the anatomical basis
of CAO and VAO. This article discusses
these provocative issues and provides evi-
dence supporting the novel paradigm of
the clito urethrovaginal (CUV) complex,
which might increase understanding of the
multi faceted sexual responses in women. In
addition, we aim to analyse whether pelvic
floor surgery could affect the function of
the proposed CUV complex and, therefore,
sexual function.
The vaginal wall and orgasm
Upon publication of the book The G spot
and other discoveries about human sexu-
ality in 1982,
3
many scientists began the
search for a specific, discrete organ or a
site within the anterior vaginal wall (AVW)
with a high nerve density that could explain
the increased sensitivity reported by many
women in this region. This sugges tion
was in contrast to the classic anato mical
and gynaecological literature, wherein the
human vagina is described as poorly inner-
vated, with little chance of being itself an
erotogenic structure.
4,5
Nevertheless, the
existence of such an ero genous zone in
the vagina remains a subject of debate,
andthe results of the relatively few anato-
mical studies that havesought to address
this issue to date have addedto this con-
troversy rather than providing clarity. In
an immuno histochemical study,
6
in which
biopsy samples from various regions
of the normal human vaginal mucosa
were labelled with an antibody target-
ing a general neuronal marker (PGP9.5),
differences in innervation were found
(Table 1). Interestingly, biopsy tissues
from the anteri or wall of the vagina
were generally more densely innervated
than samples from the posterior wall.
6

Furthermore, distal areas ofthe vaginal
wall had a greater numberof nerve bres
than proximal regions.
6
Song etal.
7
con-
firmed these findings in a micro dissection
and immunohisto chemical study, and also
found that the distal AVW is markedly
thicker than the proximal AVW. Together,
these studies support the existence of
locoregional differences in theability of the
vaginal tissues to triggerthe erotic stimuli
and, therefore, seem to be consistent with
OPINION
Beyond the G-spot: clitourethrovaginal
complex anatomy in female orgasm
Emmanuele A.Jannini, Odile Buisson and Alberto Rubio-Casillas
Abstract | The search for the legendary, highly erogenous vaginal region, the Grfenberg
spot (G-spot), has produced important data, substantially improving understanding of
the complex anatomy and physiology of sexual responses in women. Modern imaging
techniques have enabled visualization of dynamic interactions of female genitals
during self-sexual stimulation or coitus. Although no single structure consistent with
a distinct G-spot has been identified, the vagina is not a passive organ but a highly
dynamic structure with an active role in sexual arousal and intercourse. Theanatomical
relationships and dynamic interactions between the clitoris, urethra, and anterior
vaginal wall have led to the concept of a clitourethrovaginal (CUV) complex, defining
a variable, multifaceted morphofunctional area that, when properly stimulated during
penetration, could induce orgasmic responses. Knowledge of the anatomy and
physiology of the CUV complex might help to avoid damage to its neural, muscular,
andvascular components during urological and gynaecological surgical procedures.
Jannini, E. A. etal. Nat. Rev. Urol. advance online publication 12 August 2014; doi:10.1038/nrurol.2014.193
Competing interests
The authors declare no competing interests.
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the possible presence of a G-spot. On the
other hand, another immuno histochemical
study of biopsy specimens that examined
the distribution of a different neuronal
marker (protein S100) reported that no
vaginal location had an increased nerve
density, with the vaginal nerves found to be
located regularly throughout the anterior
and posterior wall of the vagina, includ-
ing apex and cervix, as well as proximally
and distally within each wall.
8
However,
although discrepancies regarding the
locoregional variation in innervation of
the vagina clearly exist in anatomical lit-
erature (Table1), the idea that the vagina
is a poorly innervated organ is no longer
tenable, and so, independently of the exis-
tence of the G-spot, the stimulation of
abundant nerves in the AVW might have
a key role in VAO.
A possibly more important scientific
question is whether any evidence supports
a relationship between an area of higher
nerve density in the vaginamost probably
located in the distal region of the anterior
walland the potential to achieve VAO.
Conclusive data demonstrating such a
relationship have not been reported to date.
Nonetheless, the association of particular
regions of the vagina with an increased
likelihood of VAO might be inferred by the
findings of invivo ultrasonography studies
of the female genitals during self-sexual
stimulation or coitus. Such studies have
demonstrated that when the AVW is stimu-
lated, the pressure exerted is transmitted
to the urethra and the surrounding erec-
tile tissues, including the clitoral bulbs.
9,10

Thus, interactions between these elements,
forming the CUV complex, could explain
the pleasurable sensations that lead to VAO,
rather than any distinct region of increased
innervation. However, other factors might
explain the controversy regarding the exis-
tence of a specific erotogenic region of the
vagina. For example, anatomical and clini-
cal findings have indicated that large dif-
ferences in vaginal anatomy are observed
between women.
1113
Other findings further suggest that
the vagina is to be considered a contrac-
tile organ, having important roles during
sexual intercourse,
14
rather than a passive
canal. In particular, the vagina was shown
to exhibit electrical activity in the form of
slow waves with a regular rhythm and more
random action potentials, and the action
potentials were associated with eleva-
ted vaginal pressure that was assumed to
reflect increased muscle contraction.
14

Importantly, distention of the vagina, using
an inated condom to simulate penetration
by an erect penis, produced an increase in
the frequency of the electrical impulses
and vaginal pressure.
14
Thus, it has been
postu lated that penile thrusting during
coitus stimulates a vaginal pacemaker,
which was localized to the proximal vagina
rather than the supposedly more highly
innervated distal vaginabased on the
caudad spread of the electrical waves dis-
covered using regional anaesthetization of
the vaginal wall.
14
Interestingly, subsequent
research by the same group demonstrated
the presence of interstitial cells of Cajal,
which are involved in the stimulation of
smooth muscle contraction, in the vaginal
wall (Table1).
15
The highest concentration
of these cells was observed in a proximal
posterior region of the vagina and so they
were suggested to function in the vaginal
pacemaker that generates the electrical
waves and that signals smooth muscle
to contract.
15
On the basis of these find-
ings, it has also been hypothesized that the
vaginal pacemaker might increase sexual
arousal during coitus, and might repre-
sent the G-spot.
14
However, the proximal
posteri or positioning of this pacemaker
is not in keeping with traditional think-
ing regarding the location of the G-spot,
or the p roposed role of the CUV complex
inorgasm.
On the basis of these findings, one can
conclude that the vaginal wall might have at
least two active roles that could contribute
to VAO. First, the transmission of pressure
changes caused by penetration to the eroto-
genic components of the CUV complex.
Second, the production of electrical signals
has been hypothesized to regulate smooth
muscle contractions during coitus. This
vaginal pacemaker might increase sexual
arousal during coitus, and has been con-
sidered as a possible representation of
theG-spot.
14
The complex CUV relationships
Our knowledge of clitoral anatomy has
evolved over time. In 1998, OConnell and
colleagues
16
demonstrated that the distal
vaginal wall, the urethra, and surrounding
erectile tissue were closely situated within
the perineum, caudal superficial to the
pubic arch. Detailed dissections revealed
that the spongy tissues that closely flank
the distal regions of vagina and urethra to
variable degreesreferred to at the time as
bulbs of the vestibulewere in fact related
most closely to the clitoris. The research-
ers therefore recommended that these
structures be termed the bulbs of the cli-
toris.
16
In addition, OConnell etal.
17
noted
that the distal vagina is a structure that
is so interrelated with the clitoris that it is
a matter of some debate whether the two
are truly separate structures, and coined
the term clitoral complex to reflect this
concept.
17
Indeed, although the distal
vagina and the urethra are not erectile
tissues, these structures are intimately
related to the bulbs and cavernous bodies
of the clitoris (Figure1). The three struc-
tures share vasculature and nerve supply,
and respond as a unit during sexual stimu-
lation.
17
Unlike the thick capsule that
encloses the clitoral body, the bulbs of the
clitoris are surrounded by a considerably
more delicate membrane that might permit
greater expansion of the bulbs as a result of
sexual stimulation,
18
potentially bringing
the clitoral structures in closer proximity
Table 1 | Evidence for and against locoregional differences in innervation of the human vagina
Finding Method Study
Evidence in favour
More nerves are present in the distal than
in the proximal vagina
Immunohistochemistry with an
antiserum against the general neuronal
marker PGP9.5
Hilliges etal.
(1995)
6
More nerves are present in the distal than
inthe proximal vagina, and the distal AVW is
signifcantly thicker than the proximal AVW
Microdissection and
immunohistochemical study
of the human vagina
Song etal.
(2009)
7
ICC are present in the smooth muscle
ofthe vagina
Immunohistochemical investigation
using the specifc ICC marker c-kit
Shafk etal.
(2007)
15
Evidence against
No differences in the nerve density in the
distal with respect to the proximal vagina.
All women from this study had prolapse
Immunohistochemistry with the
antibody against the general neuronal
marker protein S100
Pauls etal.
(2006)
8
Abbreviations: AVW, anterior vaginal wall; c-kit, mast/stem cell growth factor receptor Kit; ICC, interstitial cells of Cajal;
PGP9.5, ubiquitin carboxyl-terminal hydrolase isozyme L1.
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to the vagina. The same relationship with
the clitoral bulbs applies to the female
urethra.
17
In addition, the biochemical
machinery mediating peripheral excitatory
signal ling is expressed in tissues surround-
ing the distal regions of both the vagina and
the urethra. This machinery includes blood
vessels (corpora cavernosa) lined by cells
rich in phosphodiesterase type 5 (PDE5),
11

nerves characterized by nitric oxide syn-
thase (NOS) expression,
12
and exocrine
glands (female prostate glands) capable
of producing the prostate specific antigen
(PSA), which are found at sites along and
around the urethra in some women.
1921

These observations further support a
pivotal role of the vagina, in conjunction
with the surrounding urethral and clitoral
tissues (the proposed CUV complex), in
sexual arousal and VAO.
The proposed CUV complex
In studies describing the histology of
female vaginal tissues, no single anatomi-
cal structure within the AVW has been
unani mously identified as the G-spot.
7,8,1013

However, the available evidence is not
incompatible with the original findings
of the eponym Ernst Grfenberg, who
reported that the female urethra and the
AVW were erotogenic structures in some
women,
22
which formed the foundation for
the G-spot paradigm.
3
Indeed, being so rich
in nerves, blood vessels, muscles,
16,17
and
exocrine glands,
12,1921
as well as express-
ing the biochemical machinery of human
excitation, such as NOS and PDE5,
11,12
this
anatomical region cannot be considered
irrelevant to female excitation.
On the basis of the anatomical relation-
ships and the dynamic interaction between
the clitoris, urethra, and the AVW evi-
denced through ultrasound imaging during
coitus (Figure2),
10
Jannini etal.
2
concluded
that the clitoris and vagina could be seen
as an anatomical and functional unit being
activated by vaginal penetration during
intercourse. To additionally recognize the
probable involvement of the urethraand
the female prostate in this anatomical
and functional unit, we have proposed a
change in the nomenclature.
2
Specifically,
we named this anatomical region, which we
envisage to be key to triggering the VAO,
the CUV complex (Figure1)a defini-
tion that more accurately and scientifically
describes the true nature of the G-spot. In
fact, the dynamic changes observed in the
CUV complex and associated blood vessels
and muscles during sexual stimulation or
orgasm suggest that sexual pleasure cannot
be attributed to a single organ, providing
a rationale for the replacement of an old
term (G-spot) and unproved concept that
is deeply rooted in our society. This change
in terminology could help medical doctors,
gynaecologists, urogynaecologists, experts
in sexual medicine, and the general public
to understand that the erotogenic anatomy
associated with VAO extends beyond a
single sensitive area of tissue in the AVW.
Imaging female sexual arousal
In general, anatomical changes accom-
pany changes in the functional status of
organs and tissues, and such changes are
particularly important over the course of
sexual stimulation and orgasm. Modern
imaging techniques enable objective
dynamic visual ization of the anatomy in
live indivi duals, which offers the oppor-
tunity to obtain unique insights into such
changes, which are not attainable using
classic dissec tion studies in cadavers. MRI
has been used to obtain a multiplanar rep-
resentation of clitoral anatomy in vivo,
which revealed that the bulbs and caver-
nous bodies forming the erectile root of
the clitoris closely flank, and are extensively
related to, the urethra, and that the cli toral
bulbs also partially encircle the vagina
(Figure 1).
23
In addition, MRI permits
visualization of the changes that occur in
the genitalia during sexual arousal, and can
be used to quantitatively analyse various
biological parameters before, during,
and after sexual arousal. Assessments of
clitoral volume and the relative regional
blood volume seem to be the most reliable
arousal indicators,
24
and further explain
the theory of the CUV complex, which
should be considered a dynamic and func-
tional entity rather than a static anatomical
region. During sexual arousal, changes in
the female genitalia are particularly evident
in the clitoris, especially the body and the
crura (cavernous bodies), and MRI has
shown that the size of the clitoral bulbs
increases, together with a slight increase in
the signal raised by the minor and major
labia, suggesting greater blood flow to
theseareas.
25
Ultrasonography is another investiga-
tional imaging modality that is relevant
to studies of the external clitoris and
CUV complex. The technique is simple to
perform, nonintrusive, and closely repli-
cates the findings of MRIat consider-
ably lower cost.
26
Another advantage of
ultra sonography is that examination of the
genital anatomy is possible during volun-
tary perineal contraction. Such examina-
tions have demonstrated that the clitoris
is not an inert organ: in fact, the vault of
the clitoris descends, the clitoral body and
glans angle, the angle of the double vault
the double arch comprising the bulbs
and cavernous bodies (Figure1)becomes
more acute (towards the vagina), and
movement of the perineal raphe pushes the
glans a nteriorlydownward.
27
Importantly, both MRI and ultrasono-
graphy can be used to assess the modifi-
cations of the genitalia that occur during
a b
Clitoral
raphe
Clitoral
cavernous
body
Clitoral
bulb
Vagina
Urethra
Clitoral glans Clitoral
raphe
Clitoral bulb
Vagina
Bladder
Pubic bone
Clitoral
cavernous body
Anterior Posterior
Urethra
Figure 1 | Clitourethrovaginal (CUV) complex and its relationship to female anatomy.
a|Representative echographic image of the CUV complex in a healthy nulliparous woman,
showing the double arch made of the two cavernous bodies and two bulbs. Between the vagina
and the double arch, the urethra is visualized. b | Ultrasonographic 3D reconstruction of the CUV
complex, revealing the close relationship between the vagina and clitoris. Permission obtained
from John Wiley and Sons Buisson,O. & Jannini, E. A. J. Sex. Med. 10, 27342740 (2013).
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coitus. In 1999, Schultz etal.
28
used MRI
to examine a couple having intercourse,
and obtained some of the first images
that directly demonstrated how a curved,
bow-like, erect penis stretches the CUV
complex and applies pressure that stimu-
lates the clitoris, which is gently squeezed
between the AVW and the pubic symphy-
sis.
10
In 2010, sono graphy of genitals during
coitus (Figure2) was used to describe, for
the first time, the speci fic modifications
and displacement of the clitoris under
penile thrusting.
10
Similar to the MRI find-
ings, ultrasonography revealed that penile
thrusting exerts pressure on the AVW,
which causes movement of the entire CUV
complex against the pubic symphisis.
10
The
AVW was seen to be pushed against the
root of the clitoris, which was stretched in
an ascending direction and the component
parts were widened, and the Kobelt venous
plexus seemed to be repeatedly compressed
by the penis.
10
In an earlier study that used
Doppler ultrasonography, pressure applied
on the distal part of the vagina was shown
to increase blood flow in the clitoral arter-
ies, which enhanced the size of the clitoris
through hypervascularization of erectile
tissue.
29
These phenomena probably affect
all the components of the CUV complex,
and such modification and dilatation of the
CUV complex might increase its coaptation
with the erect penis during coitus, which
is in turn reinforced through intensifica-
tion of the pressure effects described. This
mechanism could explain how the CUV
complex would function to increase sexual
arousal, possibly leading to VAO.
Imaging methods that provide additional
physiological data are vital to understand-
ing the sexual function of the genitals in
women. Relevant techniques that can be
used to assess the dynamic local changes
in blood flow during sexual stimulation
include duplex Doppler ultrasonography
using flowmetric measurements,
30
clito-
ral photoplethysmography,
31
and vaginal
photo plethysmography of vaginal pulse
amplitude,
32
although photoplethysmo-
graphy is not yet well validated in this
setting and needs to be improved.
Functional anatomy of orgasms
The ability of men to achieve orgasm
usually accompanied by ejaculation
through the same general mechanism upon
different types of stimulation has been well
described.
33
However, in women, the pres-
ence of different types of orgasm, each with
differences in the inducing stimuli and/or
underlying mechanisms, has been variously
claimed as fact, treated as a hypothesis, or
even strongly denied.
1
Unfortunately, not
all of these positions are evidence-based.
Although the classic opinion of Masters
and Johnson,
5
that all female orgasms
are mediated by direct or indirect clitoral
stimu lation, is not supported by robust
data, that the CAO is the easiest and com-
monest way for a healthy woman to reach
climax is almost universally accepted.
34,35

The existence of the VAO, based on the
opinion or experiences of a number of
women, has often been rejected, largely for
political rather than scientic reasons.
36

The fact that the feminist revolu tion tended
to deny the machist vaginal penetration
and to emphasize the feminist clitoral
stimulation is well known.
37
Nevertheless,
the proportion of women who have
experi enced VAO, according to subjective
e xperiences reported in population studies,
is estimated to be 6083%.
1,38
Moreover,
several studies have provided evidence
that direct mechani cal stimulation of the
vagina or cervix, in the absence of direct
clitoral stimulation, can generate orgasms
in women.
3942
Assuming that these reports
are accurate, the evidence, therefore, sug-
gests that the VAO is a reality.
2
In the
absence of a defined hypersensitive region
of the vagina (the G-spot), the concept of
the CUV complex could explain how sexual
pleasure from vaginal penetration, leading
to orgasm, could result from indirect
stimu lation of the inner clitoris, in line with
the hypothesis of Masters and Johnson, as
well as from the direct activation of the
s tructures composing the CUVcomplex.
9,10
Importantly, we do not currently know
the exact percentages of women who are
unable to describe their own orgasm(s),
who have knowledge of only the CAO,
or who are able to experience VAO. How-
ever, individuals from the latter group often
describe substantial differences between
types of orgasmic experience. For example,
orgasms attained through direct cli toral
stimulation have been reported to be
sharp, bursting, short-lasting, super ficial,
and more localized, being confined only
to the pubic area.
41,42
By contrast, the VAO
has been described as more diffuse, whole
body radiating, psychologically more
satisfying, and longer- lasting.
41,42
These
descriptions suggest that anatomophysio-
logical differences exist between CAO and
VAO. The difference in sensory quality of
stimulating the clitoris, vagina, or cervix is
probably attributable to the involvement
Clitoral
cavernous
body
Clitoral bulb
Vagina
Vagina
Anterior
Posterior
COITUS
Penile
dorsal vein
Clitoral
cavernous
body
Clitoral bulb
Corpus
spongiosum
Penile corpus
cavernosum
Penile corpus
cavernosum
Vagina
19.50mm 19.50mm
7.91 mm
8.14mm
Figure 2 | Ultrasonographic coronal plane image taken at the top of the vulva during coitus in
ahealthy nulliparous woman. The image obtained during vaginal penetration shows the close
proximity of components of the clitourethrovaginal (CUV) complex, specifically the clitoral bulbs
and cavernous bodies, and the vaginal wall. Dynamic echography demonstrated that the CUV
complex is stretched and stimulated by the penis during coitus. This observation suggests that
such stimulation of the CUV complex could contribute to the attainment of vaginally activated
orgasms. Permission obtained from John Wiley and Sons Buisson, O. et al. J. Sex. Med. 7,
27502754 (2010).
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NATURE REVIEWS | UROLOGY ADVANCE ONLINE PUBLICATION | 5
of different nerves receiving sensory
activity from each of these regions. The
cli toris is innervated mainly by the puden-
dal nerve, the vagina primarily by the
pelvicnerve, and the cervix by the hypo-
gastric, pelvic, and vagus nerves.
42
If several
neural pathways are activated during CUV
complex stimulation (the pelvic, hypo-
gastric, and vagus nerves), whereas during
clitoral stimu lation, only the pudendal
nerve is directly stimulated, this could,
at least partial ly, explain p erception
d ifferences between CAO and VAO.
The anatomy of the CUV complex
cannot be understood if separated from
its function.
12
The functional anatomy of
thefemale orgasm is a concept based onthe
macroanatomy of the CUV complex and
evidence that movements of the compo-
nent structures change when sexually
stimulated during vaginal penetration
and during volun tary or reex perineal
contractions.
10,27,28
Gravina etal.
43
demon-
strated that women who report VAO have a
larger distance between the urethra and the
vaginal mucosa than women who report no
experience of VAO, suggesting a bigger and
possibly more active CUV. This finding was
confirmed by other researchers, who found
that VAO was associated not only with a
thicker but also with a longerurethrovagi-
nal septum.
44
Although theurethrovagi nal
septum is to be considered an approximate
representation of thesize of the CUV, the
distance between the external clitoris and
the vagina could also influence the ability
to experience orgasm. A cross-sectional
study
45
obtained detailed clitoral measure-
ments using non contrast MRI of the pelvis
to assess whether differences were evident
in women with anorgasmia compared
withwomen with normal orgasmic func-
tion. The findings of this study indicated
that closer proximity of the clitoral glans
to the vagina might be critical for enhanced
sexual sensation, assessed using sexual
health questionnaires.
45
A greater dis-
tance of the clitoris from the vagina and a
smaller clitoral glans were noted in women
with anorgasmia, suggesting that clitoral
size and location could be key influences
on sexual function, specically orgasm.
45

These findings might be compatible with
the importance of the CUV complex to
VAO, in that factors that would increase
the interactions during coitus (larger cli-
toral tissues and closer proximity between
the components ofthe complex) seem to
be associated with theability to attain this
type of orgasm.
In an ultrasonographic examination of
the stimulated clitoris during either direct
stimulation of the external cli toris or vagi-
nal penetration,
9
the components of the cli-
toris (glans, raphe, and bodies) moved in a
manner dependent on the type of stimu-
lation. Under digital external stimu lation of
the glans and the raphe without voluntary
perineal contraction, the clitoral cavernous
bodies were almost inert, and movement
of the root of the clitoris did not seem to
be involved in sexual arousal.
9
Moreover,
the Kobelt venous plexus did not seem to
be involved during external sexual stimula-
tion, as colour Doppler signal assessment
revealed that the velo city of blood ow
in these veins was not enhanced.
9
During
vaginal distension due to tampon penetra-
tion, genital reexes were triggered, leading
to contraction of the bulbocavernosus and
ischiocavernosus pelvic muscles. These
peri neal contractions (whether reex or
volun tary) generated a descending move-
ment of the clitoral caver nous bodies,
together with an anterior movement of
the raphe that pushed the glans anteriorly
and downward subsequent to penetra-
tion and thrusting, such that the root of
the clitoris came closer to the distal AVW,
enhancing the contact between the vaginal
wall andthe richly innervated clitoris.
9

These vaso motor changes are also known
to result in the well-documented increase
in clitoral vasocongestion, and enhanced
clitoral volume during sexual arousal,
18
and
this activity in erectile tissues might fur-
ther increase the proximity of the cli toral
compo nents and the vagina, and could
contri bute to sexual pleasure and VAO
during coitus. In addition to the poten-
tially important role for engorgement of
the vascular erectile components of the
CUV complex during sexual arousal,
46

these tissues were found to be located
supercially below the mucosal layer of
the vagina in a cadaveric autopsy study, so
tactile contact near the clitoral bulbs from
inside the vagina, just above the urethra,
might have a considerable effect on female
sexual arousal andorgasm.
46
Vaginal sexual stimulation elicits more
complex anatomofunctional interactions
between elements of the CUV complex
than those observed during external cli-
toral stimulation. Indeed, the functional
unit of the clitoris and vagina identied in
cadavers by OConnell etal.,
16,17
seems to
be active only during vaginal stimulation,
whereas evidence suggests that external
stimulation exclusively activates the glans
clitoris. These functional findings support
the hypothesis that more than one type of
female orgasm exists, and that CAO and
VAO are not only psychologically, but also
functionally distinct.
9
Together, these data
suggest that the CUV complex has a critical
role in sexual arousal during penetration,
and support the hypothesis that functional
interplay between the active components of
this complex heightens stimulation of the
highly innervated clitoris. These findings
could explain why the distal anterior wall
of the vagina was postulated to harbour
a hypersensatory G-spot that, if suffi-
ciently stimulated, could result in VAO.
However, individual sexual preferences
are probably also important in determin-
ing sexual arousal: some women prefer
clitoral stimulation over vaginal penetra-
tion to achieve orgasm and viceversa, and
variation in the subjective representation
of sensory information from the genitals
between women might result from dif-
ferences in central perception and pro-
cessing. Such influences are exemplified
by the finding that, on average, orgasms
achieved by women with the aid of their
partners scored higher in terms of pleasure
and sensation than orgasms experi enced
without partners being present, although
some women reported self- stimulation as
more physically pleasurable than sex with
a male partner, even when the latter pro-
vides sufficient sexual arousal to generate
an orgasm.
47
Implications for surgery
Considering the possible existence of a
G-spot or the role of the proposed CUV
complex in sexual arousal and orgasm,
gynaeco logical or urological interven-
tions, and particularly surgeries involv-
ing the AVW, might have adverse effects
on sexual function.
48
However, evidence
to the contrary has been reported when
sexual function has been evaluated in
women who have undergone such surger-
ies. For example, a marked improvement
in sexual function was demonstrated after
the repair of AVW prolapse, according
to a questionnaire focused on this condi-
tion (the Prolapse Quality of Life [P-QOL]
question naire).
49
Similarly, a study that
used a quality-of-life questionnaire with
sexual domains (the electronic personal
assessment q uestionnairepelvic floor)
revealed that vaginal surgery for prolapse
generally improved sexual function, but
also reported that the improvement was
greater after anterior repair than posterior
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repair.
49
These findings have been consid-
ered to support the case against the exis-
tence of a distinct anatomical region in
the anteri or vagina that is responsible for
sexual p leasure and orgasm.
36
However,
since human sexual function encompasses
multiple domains that are involved in deter-
mining overall sexual function, it might
be that vaginal surgery, although associ-
ated with increased sexual function scores
overall, could still have negative effects on
arousal and orgasm, particularly the ability
to achieve VAO. During coitus, both the
distal vagina and the proximal vagina are
active, and a posterior repair in conjunc-
tion with an anterior repair can cause
dyspareunia.
50
Normal functioning of the
vagina seems to be dependent on anatomi-
cal and neuro vascular factors, including
the vaginal pacemaker, containing inter-
stitial cells of Cajal, which was reported
as being localized to the pos terior wall of
the vagina.
14,15,50,51
Damage to this pace-
maker incurred during pos terior vaginal
repair might negatively affectvaginal con-
tractility and could explain the negative
effect of such surgery on sexual function.
50

Interestingly, a study of sexual function
in 68 women at 6months after posterior
vaginal repair of pelvic organ prolapse that
used a questionnaire focused specifically on
sexual domains (the female sexual function
index [FSFI]), revealed a marked improve-
ment in sexual desire, satis faction, and pain
domains, but not those on arousal, lubrica-
tion, and orgasm.
51
This finding indicates
that, although general sexual function can
improve after posterior vaginal surgery,
specific domains related to arousal and
orgasm might notimprove.
Studies have also provided evidence
that surgical treatment of incontinence
can be associated with deterioration of
some sexual domains. For example, trans-
obturator tape procedures can affect the
orgasm domain of sexual function in some
women,
52
possi bly as the tape is passed via
the obturator foramen through the dorsal
nerve of the clitoris.
53,54
During this pro-
cedure, vaginal dissection could dimin-
ish sexual function because of scarring
and reduced elasticity of the vaginal wall,
resulting in a reduced blood supply to the
erectile tissues of theclitoris.
55
Arousal involves the blood flow to the
clitoris, and adequate engorgement might
be particularly important for function-
ing of the postulated CUV complex. In
a study that assessed clitoral blood flow
using Doppler ultrasonography before and
6months after surgery for urinary inconti-
nence, clitoral blood flow was reduced
after tension-free vaginal tape procedures,
but not trans obturator tape procedures.
56

The change in clitoral blood flow might
be a result of the fact that the tension-free
vaginal tape is passed via the retropubic
space in close proximity to clitoral tissue,
whereas the transobturator tape is placed
through the obturator membrane, poten-
tially avoiding this area. Changes in inner-
vation and blood flow in the clitoris would
be expected to influence the interactions
of CUV complex components and might
affect the capacity for VAO.
Abnormal uterine bleeding, endometri-
osis, and ovarian or uterine pathology are
known to decrease sexual activity, prob-
ably primarily as these conditions cause
pain during coitus.
57
Urinary inconti-
nence and pelvic organ prolapse can
affect sexual function through a variety of
means, including embarrassment result-
ing from urinary leakage during inter-
course, coexisting depression, discomfort,
and body image issues.
57
Surgery for such
conditions would be expected to improve
overall sexual function, and enhance-
ment in sexual function after hysterec-
tomy has been reported.
58
A review of
the current literature found that sexual
function gener ally improves after benign
gynaecological surgery, including hyster-
ectomy, bilateral salpingo-oophorectomy,
tubal ligation, anti-incontinence surgery,
and pelvic organ prolapse reconstruc-
tion.
57
Aconflicting report notes that a
corresponding enhancement of sexual
function is not consistently seen after sur-
gical correction of the pre-existing uro-
logical problem, and that deterior ation in
sexual function can occur after surgery.
52

Komisaruk etal.
59
proposed that discrep-
ancies in the effects of surgery, specific-
ally hysterectomy, on sexual function
might be explained by differences in the
reported outcomes depending on the pre-
ferred mode of genital stimulation among
the women surveyed. These researchers
noted that the lack of data on this aspect
was a glaring omission from the avail-
able literature.
59
They hypoth esized that
no deleter ious effect of hysterectomy on
sexual response would be expected if the
patient preferred clitoral stimulation,
but if vaginal and/or cervical stimula-
tion was preferred, sexual arousal, and
possibly reported sexual function, might
be compromised by the effect of surgery
on the sensitivity of these organs.
59
This
possi bility exemplifies the requirement for
well-designed scientific protocols that use
appropriate instruments and outcomes,
and that must include both control and
experimental groups. Most studies to date
have only compared the sexual function
of women before and after the surgical
pro cedure, and have not compared scores
(baseline or postsurgery) with a control
group of healthy women. Conclusions
regarding the positive effect of gynaeco-
logic surgery on sexual function based
on data from women with disorders that
could have substantially impaired base-
line sexual function and satisfaction are
not completely valid. That an unhealthy
woman reports improved sexual function
after surgery, once factors such as pain,
bleeding, and inflammation are alleviated,
is notunexpected.
Anot her factor t hat coul d hi nder
detection of possible negative effects of
gynaeco logical surgery is the duration of
the postoperative follow-up period. Most
studies evaluate changes in sexual function
within a short timeframe after surgery, and
a longer follow-up period might identify
changes in sexual function.
60
On the other
hand, it might be that partial damage to
tissues and nerves of the CUV complex
upon gynaecological surgery does not
negatively affect overall sexual function.
In his work Metaphysica, Aristotle
wrote that The whole is more than the
sum of its parts. This famous phrase per-
fectly reflects the complexity of female
sexual anatomy and physiology. Women
are able to experience sexual pleasure or
achieve orgasm through stimulation of
different genital and nongenital areas,
and some women have been reported to
achieve orgasms by imagery alone.
42
With
the understanding that human sexual-
ity represents a complex interaction of
biopsychosexual,
61
cognitive- affective,
62

neurophysi ol ogi cal , and bi ochemi -
cal mechanisms,
63
the idea that women
might have the capacity to compensate
for anato mical damage to their genital
tissues through enhancement of other
sensory and erotic areas, and/or by deriv-
ing increased pleasure from emotions and
fantasy, seems plausible.
64
Such complexity
highlights the difficulties in defining the
mechanism of sexual arousal and orgasm
in women, not only after urological or
gynaecological surgery, but also among
healthy women who are each individual,
with wide-ranging p hysiological and
psychologicalcharacteristics.
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NATURE REVIEWS | UROLOGY ADVANCE ONLINE PUBLICATION | 7
Conclusions
Modern imaging tools have revealed
complex dynamic interactions of female
genitals during self-stimulation and during
coitus. The dynamic changes observed in
the proposed CUV complex and associ-
ated blood vessels and muscles during
sexual stimulation or orgasm suggest
thatsexual pleasure cannot be attributed
to a single organ, providing a rationale for
the replacement of an old term (G-spot)
and unproved concept that is deeply rooted
in our society. Appropriate stimulation of
the CUV complex could induce orgasmic
responses, but not necessarily in all women,
as considerable anatomical variability
existsinthisregion.
No definitive consensus has been reached
regarding the effects of gynaecological
surgery on female sexual function. This
issue remains highly controversial and
deserves to be carefully studied. Possibly
owing to methodological biases in studies
to date, impairment in sexual function has
not been detected. Future studies should
investigate the preferred source of genital
stimulationclitoral or vaginalto pro-
vide objective information on whether
this has an influence on sexual func-
tion after surgery.
59
A longer follow-up
period aftersur gery is also recommended,
together with the use of indices that
examine sexual domains, particularly those
relating to arousal and orgasm, in appro-
priate detail. In the absence of firm data
relating to the effect of surgery on sexual
function, selecting surgical procedures
that would be expected to have a minimal
impact on the function of the CUV complex
should beconsidered.
Department of Systems Medicine, Tor Vergata
University of Rome, Via Montpellier 1,
00133Rome, Italy (E.A.J.). Centre
dchographie, 20 rue du Dr Timsit,
78951Saint-Germain-en-Laye, France (O.B.).
Laboratorio de Biologa, Escuela Preparatoria
Regional de Autln, Universidad de
Guadalajara, Jalisco, Mexico (A.R.-C.).
Correspondence to: E.A.J.
emmanuele.jannini@uniroma2.it
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Acknowledgements
Figure 1b is a modification of an original image
created by Laurent Buffo.
Author contributions
All authors made substantial contributions to
eachstage of the preparation of this manuscript
forsubmission.
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