PERSPECTIVES

OPINION are often, contentiously, considered to be

anatomically and functionally different
Beyond the Gspot: clitourethrovaginal from each other, which further complicates
attempts to define the anatomical basis
complex anatomy in female orgasm of CAO and VAO. This article discusses
these provocative issues and provides evi-
Emmanuele A.Jannini, Odile Buisson and Alberto Rubio-Casillas dence supporting the novel paradigm of
the clitourethrovaginal (CUV) complex,
Abstract | The search for the legendary, highly erogenous vaginal region, the Grfenberg which might increase understanding of the
spot (G-spot), has produced important data, substantially improving understanding of multifaceted sexual responses in women. In
the complex anatomy and physiology of sexual responses in women. Modern imaging addition, we aim to analyse whether pelvic
techniques have enabled visualization of dynamic interactions of female genitals floor surgery could affect the function of
during self-sexual stimulation or coitus. Although no single structure consistent with the proposed CUV complex and, therefore,
a distinct Gspot has been identified, the vagina is not a passive organ but a highly sexual function.
dynamic structure with an active role in sexual arousal and intercourse. Theanatomical
relationships and dynamic interactions between the clitoris, urethra, and anterior The vaginal wall and orgasm
vaginal wall have led to the concept of a clitourethrovaginal (CUV) complex, defining Upon publication of the book The G spot
a variable, multifaceted morphofunctional area that, when properly stimulated during and other discoveries about human sexu-
ality in 1982,3 many scientists began the
penetration, could induce orgasmic responses. Knowledge of the anatomy and
search for a specific, discrete organ or a
physiology of the CUV complex might help to avoid damage to its neural, muscular,
site within the anterior vaginal wall (AVW)
andvascular components during urological and gynaecological surgical procedures.
with a high nerve density that could explain
Jannini, E. A. etal. Nat. Rev. Urol. 11, 531538 (2014); published online 12 August 2014; the increased sensitivity reported by many
doi:10.1038/nrurol.2014.193 women in this region. This suggest ion
was in contrast to the classic anatomical
Introduction and in the absence of direct stimulation and gynaecological literature, wherein the
As a relatively well-defined and exact of the external clitoris: 2 we proposed to human vagina is described as poorly inner-
field of biomedicine, gross anatomy rarely name this type the vaginally activated vated, with little chance of being itself an
provides opportunities for controversial orgasm(VAO). erotogenic structure.4,5 Nevertheless, the
disagreements over hypotheses; however, The anatomical structures that might existence of such an erog enous zone in
the anatomy of the organs, tissues, and provoke VAOs rather than CAOs have thevagina remains a subject of debate,
structures involved in the subjective orgas- not been completely and unequivocally andthe results of the relatively few anato
mic experience in women seems to be an described, probably representing a unique mical studies that havesought to address
exception. For experts in sexual medicine case of remaining major uncertainty this issue to date have addedto this con-
and specifically andrologists, urologists, regarding human gross anatomy. In fact, troversy rather than providing clarity. In
gynaecologists, and urogynaecologists several issues relating to this gap in our an immunohistochemical study,6 in which
with a necessary interest in female orgasmic anatomical knowledge remain contro biopsy samples from various regions
function as well as the related clinical and versial. First, the functional relationship of the normal human vaginal mucosa
surgical aspects, the current nomenclature between the clit oris and the vagina is were labelled with an antibody target-
and, consequently, the taxonomy, represent still debated. Second, disagreements over ing a general neuronal marker (PGP9.5),
important areas of contention. Whereas a whether the vagina is sufficiently inner- differences in innervation were found
single male type of orgasm is classically vated to provide pleasure, or is poorly sen- (Table1). Interestingly, biopsy tissues
recognized, at least two distinct varieties of sitive to facilitate the processes of labour from the anterio r wall of the vagina
orgasms are described in women.1 The first and birth, have not been resolved. Third, were generally more densely innervated
type of female orgasm is obtained through whether the Grfenberg spot (G-spot; than samples from the posterior wall. 6
the direct stimulation of the external cli ahypothetical, discrete, highly erogenous Furthermore, distal areas ofthe vaginal
toris, without any kind of internal stimu- region of the vagina) is a discrete entity, wall had a greater numberof nerve bres
lation. Herein, we refer to this orgasm as a complex structure, or a gynaecological than proximal regions.6 Song etal.7 con-
the clitorally activated orgasm (CAO). myth created for journalistic purposes, or firmed these findings in a microdissection
The second form of orgasm is described as with the aim of supporting surgical aesthe and immunohistochemical study, and also
that obtained during vaginal penetration tic manipulations of the female genitals, found that the distal AVW is markedly
remains unclear. Finally, whereas the thicker than the proximal AVW. Together,
Competing interests functional anatomy of men is, rightly or these studies support the existence of
The authors declare no competing interests. wrongly, considered to be constant, women locoregional differences in theability of the

NATURE REVIEWS | UROLOGY VOLUME 11 | SEPTEMBER 2014 | 531

2014 Macmillan Publishers Limited. All rights reserved
PERSPECTIVES
Table 1 | Evidence for and against locoregional differences in innervation of the human vagina
Finding
Evidence in favour
More nerves are present in the distal than
in the proximal vagina
More nerves are present in the distal than
inthe proximal vagina, and the distal AVW is
signicantly thicker than the proximal AVW
ICC are present in the smooth muscle
ofthe vagina
Evidence against
No differences in the nerve density in the
distal with respect to the proximal vagina.
All women from this study had prolapse
Abbreviations: AVW, anterior vaginal wall; ckit, mast/stem cell growth factor receptor Kit; ICC, interstitial cells of Cajal;
PGP9.5, ubiquitin carboxyl-terminal hydrolase isozyme L1.
vaginal tissues to triggerthe erotic stimuli
and, therefore, seem to be consistent with
the possible presence of a Gspot. On the
other hand, another immunohistochemical
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 Gspot, 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,
532 | SEPTEMBER 2014 | VOLUME 11  www.nature.com/nrurol
Method
Immunohistochemistry with an
antiserum against the general neuronal
marker PGP9.5
Microdissection and
immunohistochemical study
of the human vagina
Immunohistochemical investigation
using the specic ICC marker ckit (2007)15
Immunohistochemistry with the
antibody against the general neuronal
marker protein S100
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
postul ated 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
2014 Macmillan Publishers Limited. All rights reserved
were suggested to function in the vaginal
pacemaker that generates the electrical
Study
waves and that signals smooth muscle
to contract.15 On the basis of these find-
Hilliges etal. ings, it has also been hypothesized that the
(1995)6 vaginal pacemaker might increase sexual
arousal during coitus, and might repre-
Song etal. sent the Gspot.14 However, the proximal
(2009)7
posterior positioning of this pacemaker
is not in keeping with traditional think-
Shafik etal.
ing regarding the location of the Gspot,
or the proposed role of the CUV complex
inorgasm.
Pauls etal. On the basis of these findings, one can
(2006)8
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
theGspot.14
The complex CUV relationships
Our knowledge of clitoral anatomy has
evolved over time. In 1998, OConnell and
colleagues16 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
 PERSPECTIVES

of sexual stimulation,18 potentially bring-

a b Posterior Anterior
ing the clitoral structures in closer prox-
imity to the vagina. The same relationship Clitoral
with the clitoral bulbs applies to the female raphe Bladder
urethra. 17 In addition, the biochemical Clitoral
machinery mediating peripheral excitatory cavernous
body
signalling is expressed in tissues surround-
ing the distal regions of both the vagina and Pubic bone
the urethra. This machinery includes blood Vagina
vessels (corpora cavernosa) lined by cells
rich in phosphodiesterase type 5 (PDE5),11 Urethra
Clitoral
nerves characterized by nitric oxide syn- bulb Clitoral bulb Clitoral
thase (NOS) expression, 12 and exocrine cavernous body
Urethra
glands (female prostate glands) capable Vagina
Clitoral glans Clitoral
of producing the prostate specific antigen raphe
(PSA), which are found at sites along and
around the urethra in some women. 1921 Figure 1 | Clitourethrovaginal (CUV) complex and its relationship to female anatomy.
These observations further support a a|Representative echographic image of the CUV complex in a healthy nulliparous woman,
pivotal role of the vagina, in conjunction showing the double arch made of the two cavernous bodies and two bulbs. Between the vagina
with the surrounding urethral and clitoral 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
tissues (the proposed CUV complex), in
from John Wiley and Sons Buisson,O. & Jannini, E. A. J. Sex. Med. 10, 27342740 (2013).
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
unanimously identified as the Gspot.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 Gspot 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 func-
tional unit being activated by vaginal pene-
tration 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 definition that more accu-
rately and scientifically describes the true
nature of the Gspot. 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 visualization of the anatomy in
live individuals, which offers the oppor-
tunity to obtain unique insights into such
changes, which are not attainable using
classic dissection studies in cadavers. MRI
has been used to obtain a multiplanar rep-
resentation of clitoral anatomy invivo,
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 clitoral
bulbs also partially encircle the vagina
(Figure1). 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
ultrasonography 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 anteriorlydownward.27

NATURE REVIEWS | UROLOGY VOLUME 11 | SEPTEMBER 2014 | 533

2014 Macmillan Publishers Limited. All rights reserved
PERSPECTIVES
COITUS Anterior
Clitoral Clitoral
cavernous cavernous
body body
19.50 mm 19.50 mm
Vagina
8.14 mm
Clitoral bulb Clitoral bulb
7.91 mm
Penile
dorsal vein
Penile corpus
cavernosum Penile corpus
cavernosum
Corpus
spongiosum
Vagina Vagina
Posterior
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).
Importantly, both MRI and ultrasono through hypervascularization of erectile
graphy can be used to assess the modifi- tissue.29 These phenomena probably affect
cations of the genitalia that occur during all the components of the CUV complex,
coitus. In 1999, Schultz etal.28 used MRI and such modification and dilatation of the
to examine a couple having intercourse, CUV complex might increase its coaptation
and obtained some of the first images with the erect penis during coitus, which
that directly demonstrated how a curved, is in turn reinforced through intensifica-
bow-like, erect penis stretches the CUV tion of the pressure effects described. This
complex and applies pressure that stimu- mechanism could explain how the CUV
lates the clitoris, which is gently squeezed complex would function to increase sexual
between the AVW and the pubic symphy- arousal, possibly leading to VAO.
sis.10 In 2010, sonography of genitals during Imaging methods that provide additional
coitus (Figure2) was used to describe, for physiological data are vital to understand-
the first time, the specif ic modifications ing the sexual function of the genitals in
and displacement of the clitoris under women. Relevant techniques that can be
penile thrusting.10 Similar to the MRI find- used to assess the dynamic local changes
ings, ultrasonography revealed that penile in blood flow during sexual stimulation
thrusting exerts pressure on the AVW, include duplex Doppler ultrasonography
which causes movement of the entire CUV using flowmetric measurements, 30 cli
complex against the pubic symphisis.10 The toral photoplethysmography,31 and vaginal
AVW was seen to be pushed against the photoplethysmography of vaginal pulse
root of the clitoris, which was stretched in amplitude, 32 although photoplethysmo
an ascending direction and the component graphy is not yet well validated in this
parts were widened, and the Kobelt venous setting and needs to be improved.
plexus seemed to be repeatedly compressed
by the penis.10 In an earlier study that used Functional anatomy of orgasms
Doppler ultrasonography, pressure applied The ability of men to achieve orgasm
on the distal part of the vagina was shown usually accompanied by ejaculation
to increase blood flow in the clitoral arter- through the same general mechanism upon
ies, which enhanced the size of the clitoris different types of stimulation has been well
534 | SEPTEMBER 2014 | VOLUME 11  www.nature.com/nrurol
2014 Macmillan Publishers Limited. All rights reserved
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
stimul ation, 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 revolution tended
to deny the machist vaginal penetration
and to emphasize the feminist clitoral
stimulation is well known. 37 Neverthe
less, the proportion of women who have
experienced VAO, according to subjective
experiences reported in population studies,
is estimated to be 6083%. 1,38 Moreover,
several studies have provided evidence
that direct mechanical 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 Gspot), the concept of
the CUV complex could explain how sexual
pleasure from vaginal penetration, leading
to orgasm, could result from indirect
stimulation of the inner clitoris, in line with
the hypothesis of Masters and Johnson, as
well as from the direct activation of the
structures 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 clitoral
stimulation have been reported to be
sharp, bursting, short-lasting, superficial,
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-l asting. 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 involve-
ment of different nerves receiving sensory
activity from each of these regions. The
clitoris 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 stimul ation, only the pudendal
nerve is directly stimulated, this could,
at least partially, explain pe rception
differences 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 volunt ary 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 theurethrovaginal
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 noncontrast 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
NATURE REVIEWS | UROLOGY VOLUME 11 | SEPTEMBER 2014 | 535
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 clitoris 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 stimulation 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 veloc ity 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
perineal contractions (whether reex or
voluntary) generated a descending move-
ment of the clitoral cavern ous bodies,
together with an anterior movement of
the raphe that pushed the glans anteriorly
anddownward 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 vasomotor 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 clitoral
compon ents and the vagina, andcould
contrib ute to sexual pleasureand 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
2014 Macmillan Publishers Limited. All rights reserved
PERSPECTIVES
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 Gspot that, if sufficiently
stimulated, could result in VAO. However,
individual sexual preferences are prob-
ably also important in determining sexual
arousal: some women prefer clitoral stimu-
lation over vaginal penetration to achieve
orgasm and viceversa, and variation in the
subjective representation of sensory infor-
mation from the genitals between women
might result from differences in central per-
ception and processing. 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
experienced without partners being pres
ent, although some women reported self-
stimulation as more physically pleasurable
than sex with a male partner, even when the
latter provides sufficient sexual arousal to
generate an orgasm.47
Implications for surgery
Considering the possible existence of a
Gspot or the role of the proposed CUV
complex in sexual arousal and orgasm,
gynaecol ogical 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]
questionn aire). 49 Similarly, a study that
used a quality-of-life questionnaire with
sexual domains (the electronic personal
assessment qu estionnairepelvic floor)
revealed that vaginal surgery for prolapse
generally improved sexual function, but
PERSPECTIVES
also reported that the improvement was
greater after anterior repair than posterior
repair.49 These findings have been consid-
ered to support the case against the exis-
tence of a distinct anatomical region in
the anterior vagina that is responsible for
sexual pl easure 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 neurovascular factors, including
the vaginal pacemaker, containing inter-
stitial cells of Cajal, which was reported
as being localized to the posterior wall of
the vagina. 14,15,50,51 Damage to this pace-
maker incurred during posterior 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, satisfaction, 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 possibly 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
536 | SEPTEMBER 2014 | VOLUME 11  www.nature.com/nrurol
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 transobturator 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 enhancement
in sexual function after hysterectomy has
been reported.58 Areview of the current lit-
erature found that sexual function gener
ally improves after benign gynaecological
surgery, including hysterectomy, bilateral
salpingo-oophorectomy, tubal ligation,
anti-incontinence surgery, and pelvic organ
prolapse reconstruction. 57 Aconflicting
report notes that a corresponding enhance-
ment of sexual function is not consistently
seen after surgical correction of the pre-
existing urological problem, and that
deterioration in sexual function can occur
after surgery.52 Komisaruk etal.59 proposed
that discrepancies in the effects of surgery,
specifically hysterectomy, on sexual func-
tion might be explained by differences
in the reported outcomes depending on
the preferred mode of genital stimula-
tion among the women surveyed. These
researchers noted that the lack of data on
this aspect was a glaring omission from
the available literature.59 They hypothesized
that no deleterious effect of hysterectomy
on sexual response would be expected if
the patient preferred clitoral stimulation,
but if vaginal and/or cervicalstimula-
tion was preferred,sexualarousal, and
possibly reported sexual function, might
be compromised by the effect of surgery
2014 Macmillan Publishers Limited. All rights reserved
on the sensitivity of these organs. 59 This
possibility 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.
Another factor that could hinderdetec
tion of possible negative effects of gynae
cological surgery is the duration of the
postoperative follow-up period. Moststud
ies 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 perfectly reflects
the complexity of female sexual anatomy
and physiology. Women are able to experi
ence 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 understand-
ing that human sexuality represents a
complex interaction of biopsychosexual,61
cognitive-a ffective, 62 neurophysiologi-
cal, and biochemical mechanisms, 63 the
idea that women might have the capacity
to compensate for anatomical damage to
their genital tissues through enhancement
of other sensory and erotic areas, and/or
by deriving increased pleasure from emo-
tions and fantasy, seems plausible.64 Such
complexity highlights the difficulties in
defining the mechanism of sexual arousal
and orgasm in women, not only after uro-
logical or gynaecological surgery, but also
among healthy women who are each indivi
dual, with wide-ranging physiological and
psychologicalcharacteristics.

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 geni
tal stimulationclitoral or vaginalto
provide objective information on whether
this has an influence on sexual func-
tionaftersurgery. 59 A longer follow-up
period after surgery is also recommended,
together with the use of indices that exam
ine sexual domains, particularly those relat-
ing to arousal and orgasm, in appropriate
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,
78951SaintGermain-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
1. Jannini, E.A. etal. Female orgasm(s): one, two,
several. J. Sex. Med. 9, 956965 (2012).
2. Jannini, E.A., Gravina, G.L., Buisson, O.
&Foldes, P. A letter to the editor on the article
by Burri etal. J. Sex. Med. 7, 22892292;
author reply 22922284 (2010).
3. Ladas, A.K., Whipple, B. & Perry, J.D.
TheGspot and other discoveries about human
sexuality (Holt, Reinehart & Winston, 1982).
4. Kinsey A.C., Pomeroy W.B., Martin C.E.
&Gebhard, P.H. Sexual behaviour in the human
female (W.B. Saunders, 1953).
NATURE REVIEWS | UROLOGY VOLUME 11 | SEPTEMBER 2014 | 537
5. Masters, W.H. & Johnson V.E. Human sexual
response (Little Brown, 1966).
6. Hilliges, M., Falconer, C., Ekman-Ordeberg, G.
&Johansson, O. Innervation of the human
vaginal mucosa as revealed by PGP 9.5
immunohistochemistry. Acta Anat. (Basel) 153,
119126 (1995).
7. Song, Y.B., Hwang, K., Kim, D.J. & Han, S.H.
Innervation of vagina: microdissection and
immunohistochemical study. J. Sex Marital Ther.
35, 144153 (2009).
8. Pauls, R. etal. A prospective study examining
the anatomic distribution of nerve density
inthe human vagina. J. Sex. Med. 3, 979987
(2006).
9. Buisson, O. & Jannini, E.A. Pilot echographic
study of the differences in clitoral involvement
following clitoral or vaginal sexual stimulation.
J. Sex. Med. 10, 27342740 (2013).
10. Buisson, O., Foldes, P., Jannini, E.A. &
Mimoun,S. Coitus as revealed by ultrasound
inone volunteer couple. J. Sex. Med. 7,
27502754 (2010).
11. DAmati, G. etal. Type 5 phosphodiesterase
expression in the human vagina. Urology 60,
191195 (2002).
12. DAmati, G. etal. Functional anatomy of the
human vagina. J. Endocrinol. Invest. 26, 9296
(2003).
13. Jannini, E.A., dAmati, G. & Lenzi, A. in
Womens sexual function and dysfunction: study,
diagnosis and treatment (eds Goldstein, I.,
Meston, C., Davis, S. & Traish, A.) 125133
(Taylor & Francis, 2006).
14. Shak, A., El-Sibai, O., Shak, A.A., Ahmed, I.
&Mostafa, R.M. The electrovaginogram: study
of the vaginal electric activity and its role in the
sexual act and disorders. Arch. Gynecol. Obstet.
269, 282286 (2004).
15. Shafik, A., Shafik, A.A., Sibai, O.E. &
Shafik,I.A. Identification of a vaginal
pacemaker: an immunohistochemical and
morphometric study. J. Obstet. Gynaecol. 27,
485488 (2007).
16. OConnell, H.E., Hutson, J.M., Anderson, C.R.
& Plenter, R.J. Anatomical relationship
between urethra and clitoris. J. Urol. 159,
18921897 (1998).
17. OConnell, H.E., Eizenberg, N., Rahman, M.
&Cleeve, J. The anatomy of the distal vagina:
towards unity. J. Sex. Med. 5, 18831891
(2008).
18. Yang, C.C., Cold, C.J., Yilmaz, U. &
Maravilla,K.R. Sexually responsive vascular
tissue of the vulva. BJU Int. 97, 766772 (2006).
19. Zaviacic, M. & Ablin, R.J. The female prostate.
J. Natl Cancer Inst. 90, 713714 (1998).
20. Zaviacic, M. & Ablin, R.J. The female prostate
and prostate-specific antigen.
Immunohistochemical localization, implications
of this prostate marker in women and reasons
for using the term prostate in the human
female. Histol. Histopathol. 15, 131142
(2000).
21. Zaviacic, M. etal. Immunohistochemical
localization of human protein 1 in the female
prostate (Skenes gland) and the male
prostate. Histochem. J. 29, 219227 (1997).
22. Grafenberg, E. The role of the urethra in female
orgasm. Int. J. Sexol. 3, 145148 (1950).
23. OConnell, H.E., Sanjeevan, K.V. &
Hutson,J.M. Anatomy of the clitoris. J. Urol.
174, 11891195 (2005).
24. Maravilla, K.R. etal. Noncontrast dynamic
magnetic resonance imaging for quantitative
assessment of female sexual arousal. J. Urol.
173, 162166 (2005).
2014 Macmillan Publishers Limited. All rights reserved
PERSPECTIVES
25. Suh, D.D., Yang, C.C., Cao, Y., Garland, P.A.
&Maravilla, K.R. Magnetic resonance imaging
anatomy of the female genitalia in
premenopausal and postmenopausal women.
J. Urol. 170, 138144 (2003).
26. Buisson, O., Foldes, P. & Paniel, B.J.
Sonography of the clitoris. J. Sex. Med. 5,
413417 (2008).
27. Foldes, P. & Buisson, O. The clitoral complex:
adynamic sonographic study. J. Sex. Med. 6,
12231231 (2009).
28. Schultz, W.W., van Andel, P., Sabelis, I.
&Mooyaart, E. Magnetic resonance imaging
ofmale and female genitals during coitus and
female sexual arousal. BMJ 319, 15961600
(1999).
29. Lavoisier, P., Aloui, R., Schmidt, M.H. &
Watrelot,A. Clitoral blood flow increases
following vaginal pressure stimulation.
Arch.Sex. Behav. 24, 3745 (1995).
30. Kukkonen, T.M. etal. Convergent and
discriminant validity of clitoral color Doppler
ultrasonography as a measure of female sexual
arousal. J. Sex Marital Ther. 32, 281287
(2006).
31. Gerritsen, J. etal. The clitoral
photoplethysmograph: a new way of assessing
genital arousal in women. J. Sex. Med. 6,
16781687 (2009).
32. Meston, C.M., Rellini, A.H. & McCall, K.
Thesensitivity of continuous laboratory
measures of physiological and subjective
sexual arousal for diagnosing women with
sexual arousal disorder. J. Sex. Med. 7,
938950 (2010).
33. Jannini, E.A., Simonelli, C. & Lenzi, A.
Disorders of ejaculation. J. Endocrinol. Invest.
25, 10061019 (2002).
34. Singer, J. & Singer, I. Types of female orgasm.
J.Sex Res. 8, 255267 (1972).
35. Meston, C.M., Levin, R.J., Sipski, M.L.,
Hull,E.M. & Heiman, J.R. Womens orgasm.
Annu. Rev. Sex Res. 15, 173257 (2004).
36. Jannini, E.A. etal. Whos afraid of the Gspot?
J. Sex. Med. 7, 2534 (2010).
37. Millet, K. Sexual politics (Doubleday, 1969).
38. Lloyd, E.A. The case of the female orgasm: bias
in the science of evolution (Harvard University
Press, 2005).
39. Whipple, B., Gerdes, C. & Komisaruk, B.R.
Sexual response to self-stimulation in women
with complete spinal cord injury. J. Sex Res. 33,
231240 (1996).
40. Komisaruk, B.R., Gerdes, C.A. & Whipple, B.
Complete spinal cord injury does not block
perceptual responses to genital self-
stimulation in women. Arch. Neurol. 54,
15131520 (1997).
41. Komisaruk, B.R. etal. Brain activation during
vaginocervical self-stimulation and orgasm
inwomen with complete spinal cord injury:
fMRIevidence of mediation by the vagus
nerves. Brain Res. 1024, 7788 (2004).
42. Komisaruk, B.R., Beyer-Flores, C. & Whipple, B.
The science of orgasm (Johns Hopkins
University Press, 2006).
43. Gravina, G.L. etal. Measurement of the
thickness of the urethrovaginal space in
women with or without vaginal orgasm. J. Sex.
Med. 5, 610618 (2008).
44. Battaglia, C. etal. 3D volumetric and vascular
analysis of the urethrovaginal space in young
women with or without vaginal orgasm. J. Sex.
Med. 7, 14451453 (2010).
45. Oakley, S.H. etal. Clitoral size and location
inrelation to sexual function using pelvic MRI.
J.Sex. Med. 11, 10131022 (2014).
PERSPECTIVES
46. Rees, M.A., OConnell, H.E., Plenter, R.J.
&Hutson, J.M. The suspensory ligament of
theclitoris: connective tissue supports of the
erectile tissues of the female urogenital region.
Clin. Anat. 13, 397403 (2000).
47. King, R., Belsky, J., Mah, K. & Binik, Y. Are there
different types of female orgasm? Arch. Sex.
Behav. 40, 865875 (2011).
48. Laan, E., Rellini, A.H. & Barnes, T. Standard
operating procedures for female orgasmic
disorder: consensus of the International
Society for Sexual Medicine. J. Sex. Med. 10,
7482 (2013).
49. Fayyad, A.M. etal. Symptomatic and quality
oflife outcomes after site-specic fascial
reattachment for pelvic organ prolapse repair.
Int. Urogynecol. J. Pelvic Floor Dysfunct. 19,
191197 (2008).
50. Dua, A., Jha, S., Farkas, A. & Radley, S.
Theeffect of prolapse repair on sexual function
in women. J. Sex. Med. 9, 14591465 (2012).
51. Brandner, S., Monga, A., Mueller, M.D.,
Herrmann, G. & Kuhn, A. Sexual function after
rectocoele repair. J. Sex. Med. 8, 583588
(2011).
52. Pauls, R.N. & Karram, M.M. Sexual function
following anti-incontinence surgery.
MinervaUrol. Nefrol. 60, 113122 (2008).
538 | SEPTEMBER 2014 | VOLUME 11  www.nature.com/nrurol
53. Lau, H.H., Su, T.H., Su, C.H., Lee, M.Y. &
Sun,F.J. Short-term impact of tension-free
vaginal tape obturator procedure on sexual
function in women with stress urinary
incontinence. J. Sex. Med. 7, 15781584
(2010).
54. Achtari, C. etal. Anatomical study of the
obturator foramen and dorsal nerve of the
clitoris and their relationship to minimally
invasive slings. Int. Urogynecol. J. Pelvic Floor
Dysfunct. 17, 330334 (2006).
55. Goldstein, I. & Berman, J.R. Vasculogenic
female sexual dysfunction: vaginal
engorgement and clitoral erectile insufciency
syndromes. Int. J. Impot. Res. 10 (Suppl. 2),
8490 (1998).
56. Caruso, S. etal. Clitoral blood flow changes
after surgery for stress urinary incontinence:
pilot study on TVT versus TOT procedures.
Urology 70, 554557 (2007).
57. Pauls, R.N. Impact of gynecological surgery
onfemale sexual function. Int. J. Impot. Res. 22,
105114 (2010).
58. Mokate, T., Wright, C. & Mander, T.
Hysterectomy and sexual function. J. Br.
Menopause Soc. 12, 153157 (2006).
59. Komisaruk, B.R., Frangos, E. & Whipple, B.
Hysterectomy improves sexual response?
2014 Macmillan Publishers Limited. All rights reserved
Addressing a crucial omission in the literature.
J. Minim. Invasive Gynecol. 18, 288295
(2011).
60. Feldner, P.C. Jr etal. Sexual function after
anterior vaginal wall prolapse surgery.
Clinics(Sao Paulo) 67, 871875 (2012).
61. Leiblum, S.R. Redefining female sexual
response. Contemp. Ob. Gyn. 45, 120126
(2000).
62. Basson, R. Human sex-response cycles. J. Sex
Marital Ther. 27, 3343 (2001).
63. Levine, S.B. The nature of sexual desire:
aclinicians perspective. Arch. Sex. Behav. 32,
279285 (2003).
64. Berg, R.C. & Denison, E. Does female genital
mutilation/cutting (FGM/C) affect womens
sexual functioning? A systematic review of the
sexual consequences of FGM/C. Sex. Res. Soc.
Policy 9, 4156 (2011).
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.