Understanding the Functional Significance of the Labia Minora: A Scoping Review on Sexual 
Physiology 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 

 
 
 
 
 
 
 
 
 
 
 
 



Introduction 1 
The labia minora, a vital yet understudied part of female genital anatomy, are two inner folds of skin that 2 
extend outward from the vaginal and urethral openings, encompassing the vestibule. Part of the 3 
ectodermal-derived vulva, the labia minora stretch from the clitoris obliquely downward, laterally, and 4 
backward on either side of the vulvar vestibule, terminating between the base of the vestibule and the 5 
labia majora1. The posterior ends of the labia minora typically converge at the midline, connected by the 6 
frenulum. 7 
  8 
The labia minora have been postulated to play a role in the female sexual response (FSR), a complex 9 
interplay of physiological, psychological, and anatomical factors2–4. Specifically, the labia minora has 10 
been reported to have rich vascularization and a high concentration of nerve endings, which may 11 
contribute to vascular engorgement and heightened sensation and arousal, respectively, during sexual 12 
activity5,6. Yet empirical evidence to link these anatomical characteristics with FSR remains sparse. While 13 
research on the role of the vulvar vestibule7,8 and clitoris9,10 in FSR has made significant strides in recent 14 
years, the labia minora has yet to be comprehensively reviewed.  15 
  16 
Furthermore, individual variations in labial morphology have been widely established, highlighting the 17 
need for a nuanced approach to studying the role of the labia minora in sexual function11. While some 18 
women may experience heightened sexual pleasure due to specific anatomical characteristics of their 19 
labia minora, others may encounter challenges related to discomfort or dissatisfaction2. The interplay 20 
between anatomical variability and sexual function is complex and warrants investigation to provide 21 
evidence-based insights into clinical practice and sexual health education. 22 
  23 
In light of these considerations, this paper aims to identifiy and critically assess the existing literature on 24 
the sexual function of the labia minora, identify gaps in current knowledge, and propose directions for 25 
future research. By elucidating the physiological mechanisms and anatomical correlates of the labia 26 
minora in sexual function, this study seeks to contribute to a comprehensive understanding of female 27 
sexual health.  28 
 29 
Methods 30 
The objectives, inclusion criteria, and methods for this systematic review were specified in advance and 31 
documented in a protocol12. The Preferred Reporting Items for Systematic Reviews and Meta-analyses 32 
extension for Scoping Reviews (PRISMA-ScR)13 was used to guide the reporting in this study and 33 
standard methods were followed; checklists can be found in Supplementary Table 1. The protocol has 34 
been registered in PROSPERO (CRD42024519600) a priori. 35 
  36 
Search Strategy 37 
A comprehensive search of the literature was conducted in biomedical, public health, and social science 38 
databases, including PubMed, Web of Science, Scopus, Global Index Medicus, Science Direct, Google 39 
Scholar, Cochrane Library, and HINARI to identify relevant articles published from inception of database 40 
through to March 2024. The final searches were performed in all the databases on March 31, 2024. 41 
Databases were searched using a combination of controlled vocabulary and free text terms for labia minora 42 
and characteristics related to sexual function. Details of the full search strategies are listed in Supplementary 43 
Table 2.  44 
 45 
Evidence Screening 46 
The eligibility criteria for this scoping review were based on the PCC (Population, Concept, Context) 47 
framework, as recommended by the Joanna Briggs Institute (https://jbi.global/critical-appraisal-tools). 48 
Population: Studies involving cis females without congenital abnormalities of the vulva or ambiguous 49 
genitalia. Concept: Studies examining the gross and microscopic anatomy, innervation, vasculature, or 50 
sexual function of the labia minora. Context: Studies conducted across various settings, including clinical, 51 

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anatomical, and histological studies. No geographical restrictions were applied. Additional eligibility 52 
criteria included peer-reviewed articles, studies in English, and original research (quantitative, qualitative, 53 
or mixed methods). Studies were excluded if they were preprints, conference abstracts, narrative or 54 
literature reviews, case reports, studies not available in English, and those with an unclear methodology or 55 
focus on populations outside the defined eligibility criteria. 56 
These criteria were developed to ensure the inclusion of relevant and high-quality studies while maintaining 57 
consistency and replicability. 58 
  59 
The Rayyan Software (https://new.rayyan.ai/) was used to aid in the screening process. Duplicate 60 
publications were immediately excluded. The screening process was conducted in two phases: 1) title and 61 
abstract screening, where two independent reviewers screened all titles and abstracts retrieved from the 62 
database searches to assess their relevance based on the eligibility criteria, and 2) full-text screening where 63 
relevant abstracts were reviewed in full-text format to confirm eligibility. Full-text articles that did not meet 64 
the inclusion criteria were excluded, with reasons for exclusion documented. Conflicts at either stage were 65 
resolved through discussion and, if necessary, adjudication by a third reviewer. 66 
  67 
Data Extraction 68 
Three independent reviewers extracted variables from the full texts of included studies. A full list of 69 
variables extracted can be found in Supplementary Table 3. Data were entered into a 'data charting form' 70 
using Google Forms, which captured general information about the study characteristics, population 71 
demographics,  intervention, outcomes, and study design.  72 
 73 
Assessment of risk of bias 74 
Manuscripts were assessed for the quality of evidence using the Oxford Centre for Evidence-Based 75 
Medicine (OCEBM) Levels of Evidence (https://www.cebm.ox.ac.uk/resources/levels-of-evidence/ocebm-76 
levels-of-evidence). This scale grades manuscripts from 1 (highest) to 5 (lowest) based on their study 77 
design. Studies were also assessed using the JBI Critical Appraisal Checklist (https://jbi.global/critical-78 
appraisal-tools). Given the scope of this review, which included studies with diverse methodologies, the 79 
combined use of these tools offered a more comprehensive evaluation of evidence quality. The OCEBM 80 
Levels of Evidence provided a hierarchical framework for categorizing studies based on design, while the 81 
JBI checklist ensured a detailed critique of each study’s methodological rigor. Together, these tools allowed 82 
for a robust and multidimensional assessment of the included literature, supporting the validity and 83 
reliability of the review findings. 84 
                                               85 
Data Analysis 86 
The data analysis focused on systematically organizing and descriptively summarizing the characteristics 87 
and findings of the identified studies to provide a comprehensive overview of the current state of knowledge 88 
on the labia minora and its role in sexual function. We conducted a quantitative, qualitative, and formal 89 
narrative synthesis of the extracted data. Study methodologies, populations, and key outcomes were 90 
tabulated to highlight trends and contextualize findings within the broader research landscape of female 91 
sexual health. A thematic analysis was conducted to identify key patterns across studies, such as anatomical, 92 
vascular, and functional aspects, while also mapping evidence to highlight areas of concentration and 93 
research gaps, including limited exploration of hormonal influences and androgen receptors. Furthermore, 94 
it emphasized the descriptive mapping of evidence and thematic insights. While a risk-of-bias assessment 95 
was performed to enhance rigor, the primary aim was to identify gaps in the literature and provide direction 96 
for future research and clinical practice. By mapping the evidence and summarizing trends, this analysis 97 
contextualizes the findings and underscores areas where further exploration is needed to advance the 98 
understanding of the labia minora within female sexual health. 99 
 100 
Results 101 
Study Selection 102 

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The literature search identified 480 entries, which represents 345 unique articles after duplicates were 103 
removed. After abstract screening, 60 articles were included for the full-text review, where 27 articles 104 
matched the inclusion criteria and were included in this review. The PRISMA Flow diagram is illustrated 105 
in Figure 1. All the selected articles were published between 1975 and 2024, described and evaluated the 106 
labia minora. Study characteristics are presented in Supplementary Table 3.  107 
 108 
Figure 1. PRISMA flowchart. Additional information on screening methodology can be found in the 109 
supplementary material. 110 
 111 
The included studies span a wide range of years, encompassing diverse methodologies and designs to 112 
investigate the anatomy, physiology, and clinical implications of the labia minora. Majority of studies 113 
(n=11) utilized a cross-sectional design (Figure 2A). Data collection methods varied, with the majority of 114 
studies utilizing direct clinical measurements (n=22), followed by surveys or questionnaires (n=12), 115 
imaging techniques such as MRI and ultrasound (n=8), immunohistochemistry (n=4), and observational 116 
approaches (n=3) (Figure 2B). Among the surveys used, the Female Sexual Function Index (FSFI) was the 117 
most frequently employed (n=6 studies), followed by the McCoy Female Sexuality Questionnaire (MFSQ) 118 
(n=5) and the Beck Depression Inventory (BDI) (n=5). These varied approaches reflect the 119 
multidimensional nature of research on the labia minora, addressing both anatomical and psychosocial 120 
factors. 121 
 122 
The studies were conducted across multiple countries, with the largest number originating in the United 123 
States (n=9), followed by Italy (n=6), Spain (n=5), and Turkey and Germany (n=3 each). Other contributing 124 
countries included Canada, China, France, Egypt, the Netherlands, Sweden, and Czechoslovakia, 125 
highlighting the international scope of research in this field (Figure 3B). Sample sizes varied widely, with 126 
some studies focusing on small cohorts of cadaveric specimens or post-surgical tissues, while others 127 
included larger cohorts of live participants. Of the included studies, 17 focused on participants within 128 
reproductive age (15–50 years), while 9 included subjects outside this age range (Figure 3C). Additionally, 129 
11 studies specifically included menopausal participants, providing valuable insights into the hormonal and 130 
life-stage-related changes in labial morphology and function (Figure 3D).  131 
 132 
Overall, the risk of bias assessment using the Oxford tool revealed that study quality was mixed, with 133 
variability in methodological rigor across studies. While some studies demonstrated strong methodological 134 
approaches with robust data collection techniques, others had limitations related to sample size, 135 
measurement consistency, and reporting transparency. This heterogeneity in study quality underscores the 136 
need for standardized methodologies in future research on the labia minora. 137 
 138 
Figure 2. Study Design of included studies (A) and type of data collection (B). 139 
 140 
Figure 3. Studies by region. (A) Continent of origin and (B) country of origin. Study population in 141 
reproductive years (C) and menopausal status (D). 142 
 143 
 144 
Risk of bias of included studies 145 
Although risk of bias assessment is not mandatory for a scoping review, we included it to enhance the rigor 146 
of our analysis by evaluating the credibility of study outcomes. Of the included studies, 37% (10) were 147 
Level 2, 4% (1) were Level 3, 56% (15) were Level 4, and 4% (1) were Level 5. Evidence quality, assessed 148 
using the JBI Critical Appraisal Tool, was generally good, with over 90% of studies scoring “yes” in three 149 
or more domains. 56% (15) of studies received a “high” overall appraisal, 41% (11) were rated as 150 
“moderate,” and 4% (1) as “low.” Detailed quality assessments are provided in Supplementary Table 4. 151 
  152 
Synthesis of results 153 



The main outcomes fell into four themes: anatomy, vascularization, innervation, and sexual function 154 
(Figure 4) 155 
 156 
Figure 4. Summary and take-home messages of thematic areas identified. 157 
 158 
 159 
Anatomy  160 
Seven articles investigated the anatomy of the labia minora. Two studies used cadaveric specimens14,15 161 
and five studies examined live subjects16–20 with the goal of furthering understanding the anatomy of the 162 
labia minora. 163 
 164 
Gross Anatomy 165 
Ginger et al. described the gross anatomy of the labia minora using cadaveric specimens, characterizing 166 
the labia minora as folds of tissue situated between the introitus and the labia majora. These folds extend 167 
laterally from the interlabial sulcus to the introitus medially. The study defines the superior aspect of the 168 
labia minora as inserting on the ventral aspect of the clitoral glans or frenulum, with the inferior tip 169 
inserting at the inferior aspect of the vaginal introitus. The labia minora is clearly demarcated from the 170 
labia majora by the absence of adipose tissue in the labia minora, in contrast to the abundant adipose 171 
tissue found in the labia majora6,14. It has been hypothesized that the labia minora function to shield the 172 
vestibule from mechanical irritation, dryness, and infections21,22. This protective role is attributed to the 173 
fact that the vestibule is derived from endodermal tissue, which is more susceptible to these issues, 174 
compared to the ectodermally derived labia minora, which possess relatively greater structural resilience. 175 
Several studies have explored the asymmetry of the labia minora. For instance, Cao et al. 202115 used 176 
cadaveric specimens and discarded labial tissue to report that 67% of their study population exhibited 177 
asymmetry. Conversely, Kaya et al. 201818 found that 31.5% of the 89 participants had asymmetry, while 178 
68.5% had symmetric labia minora. Cao et al. 202115 based their findings on cadaveric specimens and 179 
discarded tissue samples whereas Kaya et al. 201818 collected measurements from live participants. The 180 
use of cadavers and surgically removed tissues can impact measurement accuracy, as tissue shrinkage and 181 
size changes can occur post-mortem and after the cessation of perfusion. Additionally, these studies did 182 
not clarify whether peri or postmenopausal patients were included, which could be significant, as 183 
vulvovaginal atrophy due to estrogen loss in this population may influence labial size23. The inconsistency 184 
in asymmetry findings across studies underscores the need for further research to determine the 185 
prevalence of labial asymmetry accurately. The Kaya et al. 201818 study had limitations, including the 186 
exclusion of three patients with asymmetric labial diameters who did not meet inclusion criteria. 187 
Additionally, only six patients in this study had a labium minus width of 40 mm or more, potentially due 188 
to the study population's composition, which primarily consisted of patients seeking interventions for 189 
non-cosmetic gynecological reasons. This may have led to an underestimation of the prevalence of labial 190 
asymmetry in the general population. 191 
 192 
Labia Minora Width 193 
The width of the labia minora has been assessed using various methods, including digital calipers16, 2D 194 
US imaging 19,20, and 2D MRI imaging17. Studies have reported significant variability in labial width, 195 
influenced by factors such as age, hormonal status, and individual anatomical differences23,24. For 196 
instance, Cao et al. 202115 reported mean labial widths of 20.94 ± 6.50mm (left) and 20.11 ± 5.92mm 197 
(right) in cadaveric specimens, but the lack of age stratification limited the interpretation of how these 198 
dimensions change across life stages (Table 1). This omission is significant given the known changes in 199 
labial anatomy during puberty and the regression that occurs during and after menopause23,24. In contrast, 200 
Suh et al. 200417 observed age-related differences, with premenopausal women having wider labia (11 ± 2 201 
mm) compared to postmenopausal women (9 ± 2 mm), consistent with vulvovaginal atrophy due to 202 
decreased estrogen levels. These findings align with the well-documented trend of vulvovaginal atrophy 203 
and a decrease in tissue size following menopause23.  204 

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 205 
Kaya et al. 201818 conducted a study measuring labia minora width bilaterally, dividing the labia into 206 
three sections based on the Banwell classification25 and utilized the Mokatef classification26 to categorize 207 
labial protrusion (Table 1). Notably, there is a large range and variation in the natural size of the labia 208 
minora that has been reported in the literature, and it has also been observed that the size of the labia can 209 
change over time11,27. The fact that the patient population in the study analyzed were majority multiparous 210 
and study design lacked stratification by participant weight could introduce confounding variables. Such 211 
studies emphasize the need for broader investigations to better characterize labial anatomy and its natural 212 
variations. A more detailed exploration of labial asymmetry, which is commonly observed, is also 213 
warranted. Many women present with asymmetrical labia, yet societal and cultural norms often label 214 
these differences as "abnormal," contributing to misconceptions about female genital anatomy. Future 215 
research should seek to clarify the range of labia minora width in order to demedicalize non-pathological 216 
labia and educate the public on diverse genital appearance.  217 
 218 
The concept of labial asymmetry, while physiologically normal and widely prevalent, has not been 219 
adequately addressed in clinical or public discussions; many women are unaware of the wide variability 220 
in normal anatomical structures. This lack of awareness can contribute to psychological distress, as 221 
women may feel pressured to conform to unrealistic ideals of genital appearance. Such distress can 222 
negatively impact sexual self-esteem and overall sexual health. Vulvar psychology, particularly as it 223 
relates to perceptions of "normalcy," plays a critical role in shaping sexual self-esteem and may in part 224 
contribute to an increase in demand for labiaplasty. While labiaplasty can alleviate discomfort caused by 225 
hypertrophic labia during physical activities or intercourse, it is often sought to achieve an idealized 226 
appearance. A detailed discussion of the motivations for labiaplasty, its outcomes, and its potential impact 227 
on sexual self-esteem is essential. Clinicians must adopt a patient-centered approach when addressing 228 
concerns about labial appearance, emphasizing the natural diversity of genital anatomy and dispelling 229 
harmful stereotypes. Public health education campaigns can play a critical role in normalizing labial 230 
variability and promoting body positivity. 231 
 232 
Interestingly, several intrinsic factors have been reported to affect the width of the labia minora. Battaglia 233 
et al. 201219 observed that labia minora thickness varied across the menstrual cycle, with measurements 234 
taken during the follicular phase being significantly smaller than during the periovulatory phase. This 235 
finding suggests a positive correlation between estradiol levels, which peak around the periovulatory 236 
phase, and labia minora thickness. Estradiol's effect on labial thickness may be explained by its 237 
enhancement of  nitric oxide (NO) production through increasing expression and activity of endothelial 238 
nitric oxide synthase (NOS)28. NO subsequently raises cGMP levels and allows calcium influx into the 239 
vascular labia minora, causing vasodilation and resulting in labial engorgement17. However, studies have 240 
observed a significant decrease in labia minora thickness after three months of treatment with a 241 
combination oral contraceptive pill (OCP) containing 30mg ethinylestradiol and 3mg drospirenone29. 242 
While estriol is associated with increased labia minora thickness, the exogenous administration of 243 
combination estrogen and progestin, like drospirenone in OCPs, has the opposite effect. OCP-induced 244 
hypoestrogenism is well-documented30–32, and linked to an increased resistance of the posterior labial 245 
artery, contributing to reduced labial thickness20. Furthermore, OCPs are known to lower androgen levels, 246 
which may further reduce labial thickness, though the role of androgens in labia minora morphology 247 
remains unclear33,34. Further research is needed to elucidate androgen influence on the anatomy and 248 
physiology of the labia minora.  249 
 250 
One study investigated labia minora width in regards to the FSR, where labia minora width was measured 251 
before and after arousal induced by an erotic film17. They found that labia minora width increased 252 
significantly in both pre- and postmenopausal women, as well as MRI signal enhancement. However, it is 253 
important to consider that the study used only psychogenic stimuli (an erotic film) to induce arousal, 254 

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which may have affected the degree or capacity of arousal achieved by participants, potentially 255 
influencing the results. 256 
 257 
Microanatomy Histological Characterization  258 
Five studies investigated the microanatomy of the labia minora tissue through histological 259 
characterization5,6,14,35,36 (Table 2). From cadaveric and discarded surgical tissue samples, the labia minora 260 
is consistently described as being lined by stratified squamous epithelium with papillary protrusions, and 261 
melanocytes distributed throughout the basal layer of the epithelium5,15. The epidermis of the labia minora 262 
comprises four layers: the basal layer, spinous layer, granular layer, stratum corneum, and a superficial 263 
cornified layer. Beneath this, the dermis was reported to have a papillary structure with fine collagen, 264 
reticular, and elastic fibers, and a deeper reticular layer with collagen and elastic fibers5. Sebaceous 265 
glands and eccrine sweat glands were also identified, with openings to the skin's surface through 266 
sebaceous glands. In postmenopausal women, the labia minora epithelium was found to be more thinly 267 
keratinized6. The labia minora were also noted to have an abundance of elastin fibers and a lack of 268 
smooth muscle, thought to be related to the labia minora's function in engorgement during sexual 269 
arousal6,14.  270 

Martin-Alguacil et al. 200835 conducted immunohistochemical (IHC) staining to investigate estrogen 271 
receptor (ER) expression in the labia minora. They found ER-α staining on cell membranes of fibroblasts 272 
as well as basal and suprabasal epidermal cells in the superficial labia minora, and ER-α nuclear staining 273 
in the stroma localized superiorly near the clitoris35. ER-β staining was more concentrated in the basal 274 
epidermal and apocrine glandular epithelial cell membranes (Table 2). Clinical implications of these 275 
findings are demonstrated through a case report of a 29-month-old girl from Italy who presented with 276 
labial adhesions which were resolved with topical estriol37. Although the precise pathophysiology of 277 
labial adhesions remains unclear, they are thought to develop due to the low endogenous estrogen in 278 
young girls, exacerbated by the thin and immature nature of the labia minora38. The patient's favorable 279 
response to estriol 0.05% cream underscores the presence of estrogen receptors in the labia minora and 280 
suggests a potential treatment approach for labial adhesions in young, prepubertal girls35. It is important to 281 
note that research on the presence of androgen receptors in the labia minora is scarce. Hodgins et al. 282 
199839 reports androgen receptors in the epidermis of labia minora, but further characterization and 283 
understanding of clincial implication is largely lacking. 284 

Vascularisation 285 
Blood Vessel Morphology 286 
Vascularization of the labia minora was investigated by five papers15,18,40–42. Collectively, these studies 287 
report four main arteries supplying the labia minora: a central dominant vessel along with two posterior 288 
arteries and one small anterior artery, all of which anastomose along the edge of the labia minora15,18,40–42. 289 
The origin of the blood supply involves the external and internal pudendal arteries in creating 290 
anastomoses15,18,42. The external pudendal artery is described as the communication between the posterior 291 
labial arteries, where two additional collateral arteries communicate between this posterior system and the 292 
internal pudendal artery on the anterolateral aspect of the labia minora42. Moreover, the external pudendal 293 
artery plays a role in the perfusion of the clitoris and communicates with the posterior system via the 294 
frenulum arteries, connecting blood supplies at the mucosal surface of the anterior part of the labia 295 
minora42. Additionally, the superficial pudendal artery was observed to supply both the skin of the labia 296 
minora and the foreskin of the clitoris15,18. Regarding the anatomic journey of the blood vessels through 297 
the labia minora, the dominant central artery is reported to project perpendicular to the long axis of the 298 
labia minora42. When the edge of the labia minora is reached, the artery continues coursing under the edge 299 
in a posterior to anterior direction, fading as the anterior part of the labia minora is reached18,42. The edge 300 
artery is characterized as the anastomosis between anterior and posterior arteries18. Lack of coloration of 301 
the most anterior part of the labia minora with latex injection suggests that the more anterior labia minora 302 
represents the least perfused part42. The two posterior arteries and the smallest anterior artery were 303 

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reported to have a perpendicular trajectory to the long axis of the labia minora42. Finally, the base artery is 304 
at the introitus indicating anastomosis with the internal pudendal artery18 (Figure 2).  305 
 306 
To investigate labia minora arterial morphology one study used cold light illumination to assess whether 307 
the central dominant labial artery coursed medially, superior, or posterior, as well as any differences 308 
between left and right labia minora18. The authors reported that in 93.3% (n=83) of all cases, regardless of 309 
whether the artery was medial, superior, or posterior, the artery was observed on the right labia minora18. 310 
The significance of having right-sided-dominant arteries is unclear, and further research should 311 
investigate whether there are any functional anatomical or clinical implications associated with right 312 
versus left-sided arterial prominence. One limitation of this study is that in using cold light illumination it 313 
is not possible to precisely distinguish between arteries and veins, introducing potentially biased results. 314 
A study performing contrast dye injection and rotational angiography on fresh cadavers investigated labia 315 
minora arteries emergence42. The authors reported that the central artery typically emerges around the 316 
midpoint of the labia minora, at about the 55th percentile of its length. The two posterior arteries emerge 317 
closer to the posterior end, at the 17th and 32nd percentiles 42. Lastly, the small anterior artery is located 318 
towards the anterior end, at the 76th percentile of the labia minora's length42. 319 
 320 
 321 
Figure 5. Vascular Morphology of the Labia Minora. 1: Branch of external pudendal, 2: Superficial 322 
pudendal, 3: Edge artery, 4: Anterior artery, 5: Central dominant artery, 6: Posterior artery, 7: Base artery, 323 
8: Branch of internal pudendal. 324 
 325 
 326 
Microanatomy and Histology of Vasculature 327 
Microanatomy investigation of the labia minora has provided insight into its vasculature characteristics. 328 
Authors consistently report that the labia minora contains vascular tissue immediately deep to the 329 
epithelium, and is composed of vessels embedded in fibrous tissue rather than smooth muscle6,14. The 330 
tissue contains variably-shaped vascular spaces, which are postulated to accommodate volumes of blood 331 
during arousal14, supported by MRI studies6. These findings were consistent regardless of menopausal 332 
status6. Moreover, PDE4 markers were reported in vascular labia minora tissue, with significant PDE4 333 
expression observed in the arterioles of the subepithelial layer and PDE5 expression in the vascular 334 
smooth muscle43(Table 2). PDE4 has been shown to contribute to endothelial and epithelial barrier 335 
stability44. In contrast, PDE5 in vascular smooth muscle degrades cGMP, allowing vasorelaxation; in 336 
penile arteries during male erection inhibition of PDE5 allows cGMP to accumulate and activate a 337 
cascade of downstream phosphorylation and dilation of blood vessels45. However, whether the roles of 338 
PDE4 and PDE5 in the vasculature of the labia minora function similarly to their roles in the penis is 339 
unclear. Further research is needed to clarify their specific functions and significance in labia minora 340 
physiology. 341 
 342 
The vasculature of the venous system has received far less attention than the arterial network. Venous 343 
distribution has been described as having similar anastomotic branching in the same direction as 344 
arteries15. Additionally, deep veins from Kobelt’s plexus are reported to penetrate the tunica albuginea of 345 
the clitoral cavernosa, traversing the angle of the clitoris between the glans and the corporal bodies, 346 
meeting the lamina propria of the anterior vestibule36. Kobelt’s plexus and the surrounding stroma form 347 
the pars intermedia, a key structure in the sexually responsive nonerectile tissues of the labia minora, 348 
coordinating differential drainage following sexual arousal and engorgement36,46. Future research should 349 
investigate the FSR as it relates to venous drainage during arousal and orgasm, compared to basal 350 
conditions.  351 
 352 
Clinical Implications  353 

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Three articles in our review emphasize the critical importance of accurately identifying vascular 354 
morphology when planning surgical procedures involving the labia. Kaya et al. 201818 stratified patients 355 
based on the upper, middle, or lower position of the central artery in the labia minora, finding a 356 
significantly higher percentage of the central vessel in labia with an upper morphology compared to those 357 
with a lower morphology18. This highlights the need to consider the extent of central vasculature 358 
disruption during surgery. For example, labiaplasties, which are often performed using a wedge resection 359 
technique, require a choice between anterior, posterior, or central wedge approaches47. In labia with a 360 
lower morphology, the central vessel is located lower, with the posterior vessel branching from it18. A 361 
posterior wedge resection in these cases can severely disrupt blood flow by cutting the main artery. 362 
Conversely, in labia with a middle morphology, the posterior vessel is positioned higher, increasing the 363 
risk of cutting the central vessel during a central wedge resection. These findings underscore the 364 
importance of tailoring surgical techniques to each patient’s specific vascular map to optimize outcomes 365 
and minimize bleeding risks during labiaplasties. In addition to wedge resection, another labiaplasty 366 
technique is de-epithelialization. It was first proposed by Choi et al. 200048 that a wedge excision 367 
sacrifices major vessels which may result in dehiscence, and that a de-epithelization technique solves this 368 
problem48. However, Choi assumed that with de-epithelization, the labial vessels are preserved. The more 369 
recent findings of Georgiou et al. 201542 reported that the arteries of the labia minora run just under the 370 
mucosa of the skin and not in the central core of the labia minora, such that even de-epithelialization may 371 
interrupt these vessels. Having this model in mind, labiaplasty techniques should be discussed in terms of 372 
arterial flow preservation. It is crucial to understand the implications of surgical interventions and the 373 
potentially life-altering complications that can arise if individualized vascular morphology is not 374 
considered.  375 
 376 
Innervation  377 
Critical to understanding the functional and clinical importance of the labia minora is comprehensive 378 
knowledge of its innervation. Of the 26 papers we included, 14 focused on the innervation of the labia 379 
minora. Among these, five analyzed cadaveric specimens14,15,42,49,50, seven examined surgical 380 
specimens5,15,40,50–53, and five examined live human subjects40,41,54–56. Various methods were used to 381 
evaluate neuroanatomy: six papers employed immunohistochemistry5,15,35,49,52,53, three used gross 382 
anatomical observation and measurements14,40,51, one utilized radiologic imaging42, one conducted nerve 383 
conduction studies56, two performed sensory testing54,55, and three performed qualitative assessments of 384 
sensation40,41,57. 385 
 386 
Gross anatomy 387 
A cadaveric study using computed tomography with contrast suggested that the neuroanatomy of the labia 388 
minora originates from the pudendal nerve42. Though the sample size was small (n=9), the anatomy found 389 
was consistent in all cases observed. Two studies found that once neural branching occurs in the labia 390 
minora, the network is largely concentrated to a central neural core extending the length of the labia 391 
minora and traveling alongside vascular structures14,15. Indeed, nerve count has been reported higher in 392 
the medial region than the lateral region15, with higher overall nerve and nerve bundle density in the 393 
superior middle region of the labia minora40,49.  394 
 395 
Nerve Endings 396 
In the labia minora, sensory nerve endings are reported to include free nerve endings, arborizations, 397 
spray-like endings, clew-like nerve endings, and Pacinian-like corpuscles50. A collective hypothesis from 398 
three independent studies has emerged that labia minora central core nerves are predominantly clew-like 399 
formed by one or more thick branching myelinated afferent axons with large nucleated Schwann cells and 400 
small nerve fibers toward the edges14,15,50. The average length of clew-like endings was reported to be 401 
256μm with an average width of 199μm, where thickness and variation in nerve endings were 402 
independent of age50. Free nerve endings, identified via Cajal-type silver staining, were found to pass 403 
through the dermis and terminate in the stratum granulosum, basale, and spinosum of the epidermis5. 404 

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Nerve density was reported to be most concentrated at the subepithelial plexus as well as at basal and 405 
spinous layers of the exterior epithelium5. Interestingly, in a study examining the sensory nerve endings in 406 
hypertrophic labia minora, the rate of occurrence of genital corpuscles was significantly higher (28.43%) 407 
in hypertrophic labia, compared to control (10.2%), which the authors suggest to be indicative that 408 
hypertrophy may be related to an underlying growth factor that induces nerve growth51.  409 

 410 
Histological Molecular Characterization 411 
Immunostainng of the labia minora has consistently reported peripheral Pacinian-like corpuscle of the 412 
labia minora5,15,50,53. The corpuscle itself, initially elucidated by Mason's trichrome, demonstrated an axon 413 
surrounded by an inner core with 5HTT and neuropeptide Y (NPY), outer core with positive PGP 9.5, 414 
5HTT, 5HT1A, neuron specific enolase (NSE), and ERα, and an external capsule with PGP 9.5, neuronal 415 
nitric oxide (nNOS), and ERα positive staining53 (Table 3). PGP 9.5, NPY, and NSE are all nerve-specific 416 
markers, while 5HTs are serotonin receptors, and nNOS is a vasodilator and mediator of synaptic 417 
plasticity. Evidently, neuroprotection, neurodegeneration, and neurovascular interplay of the labia minora 418 
appear to be serotonin, estrogen, and nitric oxide mediated. Interestingly, nNOS and S-100, a neural 419 
marker, stain more intensely and widespread at the introital border versus the exterior border of the labia 420 
minora5,35. Subsidiary innervation in the stroma was positive to VIP and NPY53 (Table 3). NPY is a 421 
pleiotropic peptide involved in vasoconstriction and inflammation58,59. Various dermatologic pathologies 422 
are partially explained by genetic variations in NPY and modulated by inflammatory stress60. VIP also 423 
acts as an immunoregulator61.Variations in the genetic disposition of these peptides may have a role in 424 
labia minora function such as immunomodulated dermatose pathologies, highlighting the need for further 425 
investigation to improve clinical diagnosis and outcomes.  426 
 427 
Consolidation of Sexual Function Evidence of the Labia Minora 428 
Integral to the fundamental understanding of the labia minora is a thorough understanding of their role in 429 
sexual function. Despite this importance, this review identified limited literature focused on defining their 430 
sexual function; of the 28 papers included in this study, ten examined sexual function. Among these, nine 431 
used questionnaires: four studies used the Female Sexual Function Index (FSFI)16,40,41,54, three studies 432 
used the McCoy Female Sexuality Questionnaire (MFSQ)20,29,62, one study used both FSFI and MFSQ63, 433 
and one study used the Index of Female Sexual Function55. While most studies used a questionnaire to 434 
evaluate sexual function, few focused on the sexual function of the labia minora, and instead examined 435 
the relationship between lifestyle or comorbidities (pregnancy, diabetes, alcohol, smoking, oral 436 
contraception) on sexual function. Six papers posited connections to the possible roles of the labia minora 437 
in sexual function based on original physiological evidence16,20,53,62–64.  438 
 439 
The finding of abundant clew-like and pancianin-like corpuscles to the labia minora suggests their role as 440 
sensory organs crucial to female sexual arousal53. Pacinian corpuscles are well-known for their role in 441 
sensory perception and rapid response to pressure, and similar corpuscles have been identified in the 442 
clitoris, the primary organ involved in sexual arousal65,66. The finding that these labia minora corpuscles 443 
contain ERs, indicates that hormonal fluctuations—such as those occurring during the menstrual cycle, 444 
pregnancy, or menopause—could influence their function, potentially altering the labia minora's ability to 445 
become aroused, engorge with blood, and participate in the FSR53.  446 
 447 
Two studies analyzed the pulsatility index (PI) of the labial artery in association with sexual function20,63. 448 
The PI is a non-invasive method of assessing vascular resistance with Doppler ultrasonography67. One 449 
study found that as the PI of the posterior labial artery decreased, the labia minora thickness increased, 450 
indicating that lower resistance in the labial artery allows for easier engorgement, leading to the observed 451 
increase in labial thickness63. Further, as the labia minora became thicker, so too did the patient-reported 452 
frequency of intercourse, purported to be due to increased arousal of the genital tissues63. A different 453 
study examining smoking and sexual function via Doppler histogram analysis of labia minora 454 
vascularization, reported that the labia minora PI progressively increased from non-smokers to current 455 

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heavy smokers (p≤0.01)20. As a high PI is associated with increased vessel resistance and thereby 456 
decreased engorgement function, it was concluded that current heavy smokers may experience a 457 
decreased FSR due to impeded vascularity, likely attributed to atherosclerosis of labial arteries from 458 
carcinogens20. Taken together, these findings indicate a link between vascular responsiveness in the labia 459 
minora and sexual function, suggesting that PI may be a useful tool in assessing the FSR of the labia 460 
minora.  461 
 462 
A cohort study involving two groups watching a neutral and erotic film in different orders examined labia 463 
temperature changes to explore the sexual function of the labia minora.54. The study found that 464 
participants who watched the neutral film first experienced a significantly higher increase in labia 465 
temperature during the erotic film compared to those who watched the erotic film first54. This suggests 466 
that initial exposure to neutral stimuli may maximize sexual response, possibly due to increased comfort 467 
in the testing environment or a lack of baseline sensory testing. The study also indicated that the labia 468 
minora plays a role in sexual arousal, as the observed temperature increase correlates with increased 469 
blood flow54. However, the study's focus on pain response rather than pleasure may have skewed the 470 
results, and further research is needed to clarify the link between labia minora temperature, blood flow, 471 
and sexual function. 472 
 473 
One study used the modified Clark oxygen electrode to examine the difference in labia minora arterial 474 
blood flow between basal, self-stimulation, and orgasm, utilizing pO2 levels64. This study reported that 475 
from baseline levels (18.3 ± 3.7mmHg), upon initiation of sexual self-stimulation, there was a significant 476 
increase in oxygen tension in the labia minora which peaked (47.3 ± 4.mmHg) immediately after orgasm 477 
began64. Once the orgasm ended, there was a decrease in oxygen tension in the labia minora, but post-478 
orgasm oxygen tension in the labia minora remained higher than at baseline levels for 20-30 minutes64. 479 
Given the substantial changes in pO2 in the labia minora before and after orgasm, these findings suggest a 480 
role of pO2 in the labia minora and sexual function. Namely, it is possible to infer that the labia minora 481 
could support an increase in blood flow and engorgement function in the FSR. Further investigation is 482 
needed to understand how the changes in vasculature of the labia minora contribute to orgasm. 483 
 484 
Overall, most of the data examining the sexual function of the labia minora focused on blood flow, and 485 
other ways that the labia minora may impact sexual function have been largely ignored. Additional 486 
studies are needed to explore the possibility of changes in labia minora function, sensitivty, and 487 
innervation attributed to pacinian-like corpuscles with serotonin and ER receptors. Furthermore, research 488 
related to altered hormonal state should be investigated, and the presence of androgen receptors in should 489 
be investigated. Additionally, the order of blood flow between the labia and clitoris, and the relationship 490 
between the two needs to be better understood. It is unclear whether blood flows sequentially or in 491 
parallel, or if blood flow from the labia facilitates blood flow to the clitoris and vice versa. 492 
 493 
Labia Minora Over a Lifetime 494 
The labia minora undergo significant changes throughout a woman's life, starting as almost absent in the 495 
prepubertal stage, growing in size during puberty, and eventually resorbing during menopause24. This 496 
pattern of growth and regression has not been extensively studied, leaving a gap in our understanding of 497 
its physiological and developmental significance. Notably, the development of the median raphe in males, 498 
which forms early in fetal life, suggests a possible role of androgens in the development of the labia 499 
minora, given that the labia minora is the female homologue to the median raphe69,70. This hypothesis is 500 
further supported by observations in patients with congenital adrenal hyperplasia (CAH), who may offer 501 
valuable insights into the androgenic influences on labia minora development and function71–73. These 502 
observations underscore the need for further research to explore the hormonal and developmental factors 503 
influencing the labia minora across different life stages. 504 
 505 
Limitations 506 

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The included studies in this review present several limitations that highlight the need for further research. 507 
Methodological variability, such as differences in study designs—ranging from cadaveric to live subject 508 
studies and imaging versus histological techniques—complicates cross-comparisons of findings. 509 
Population biases are evident, with many studies relying on small or non-representative samples, such as 510 
cadaveric tissues or patients undergoing surgery for unrelated reasons. The reliance on cadaveric 511 
specimens, in particular, introduces potential limitations, as post-mortem changes such as tissue 512 
shrinkage, loss of vascular perfusion, and alterations in tissue elasticity may not accurately reflect the 513 
functional anatomy observed in living individuals. These factors can lead to under- or overestimation of 514 
measurements, particularly in studies examining vascularization and innervation. Furthermore, few 515 
studies stratified results by age or menopausal status, limiting understanding of how labial anatomy and 516 
function evolve across different life stages. Notably, there is evidence that the anatomy of the labia 517 
minora varies significantly depending on age and hormonal status, with changes such as decreased tissue 518 
size and vascularization observed in postmenopausal individuals. These variations underscore the need 519 
for a more in-depth discussion of how life stage, hormonal environment, and sample type influence labial 520 
morphology and function.  521 
 522 
To address these gaps, future research should focus on comprehensive anatomical studies to establish 523 
population-based data on labial asymmetry, size variations, and normative ranges across ages and 524 
hormonal statuses. Investigating the relationship between androgen exposure and labial development, 525 
particularly in conditions like congenital adrenal hyperplasia (CAH), could offer valuable insights. 526 
Advanced imaging modalities, such as Doppler ultrasonography and angiography, could be employed to 527 
map arterial and venous systems under different physiological and hormonal conditions. These 528 
approaches would also help elucidate the interplay between labial and clitoral blood flow in sexual 529 
response. Understanding the functional roles of nerve endings and hormonal receptors, including 530 
estrogen, serotonin, and nitric oxide, in sensory function and arousal is equally crucial. Clinical 531 
correlations, such as the impact of labial morphology on sexual satisfaction and function, warrant 532 
exploration using validated tools like the Female Sexual Function Index (FSFI). Additionally, surgical 533 
guidelines must incorporate individualized vascular and neural maps to minimize complications during 534 
labiaplasty and other interventions, while non-surgical treatments for labial adhesions and atrophy should 535 
leverage hormonal and neurochemical insights. 536 
 537 
Finally, limitations inherent to the scoping review methodology must be acknowledged. Exclusion of 538 
non-English studies may have omitted relevant findings from other regions, and the omission of grey 539 
literature, preprints, and conference abstracts may have narrowed the scope of included evidence. 540 
Moreover, as a scoping review, the focus was on mapping evidence rather than conducting in-depth 541 
synthesis or quantitative meta-analysis, limiting insights into specific outcomes. Nonetheless, by 542 
addressing these limitations and pursuing interdisciplinary, targeted research, future studies can deepen 543 
understanding of the labia minora’s anatomy and function. This is particularly important for examining 544 
differences influenced by age, hormonal factors, and the type of specimen studied, improving clinical 545 
practices and advancing female sexual health. 546 
 547 
Conclusion 548 
In summary, the labia minora likely plays a critical, but poorly understood, role in FSR. Studies have 549 
brought attention to rich vascularization and innervation patterns of the tissue, and their potential 550 
involvement in FSR through engorgement and sensory functions. Despite these insights, significant 551 
knowledge gaps persist, particularly concerning whether the anatomy of blood vessels is dependent on an 552 
individual’s unique labial morphology (right vs left dominant, upper vs low prominence), the exact 553 
innervation pathways and locations of nerves, and the effect of androgens on the labia minora. This lack 554 
of knowledge impedes comprehension of these vital structures and hampers the ability to optimize 555 
procedures to minimize bleeding and prevent nerve damage. Additionally, the development of effective 556 
therapeutic interventions for vulvar-associated pathologies is compromised. Without a comprehensive 557 



understanding, clinicians and researchers lack the necessary insights to develop treatments that preserve 558 
the function and overall well-being of affected individuals. Future research should prioritize detailed 559 
anatomical and physiological studies to fully explore the labia minora's role in FSR. Gaining deeper 560 
insights into the labia minora will enhance our knowledge of female genital anatomy and sexual health, 561 
helping to prevent complications and improve the diagnosis and treatment of related disorders. 562 
 563 
 564 
 565 
 566 
 567 
 568 
 569 

Author Population 
Characteristics 

Pre-/Post 
Menopausal 

Method of 
Measurement 

Mean Width (mm) Significance 

Cao et al 
202115 

Cadavers (n=7): 47yo 
 
Discarded Labia Minora 
Tissue (n =18): 28.89 yo 

Postmenopausal  Not specified Right labium minora width: 20.11 ± 5.92 
 
Left labium minora width: 20.94 ± 6.50 
 

No hypothesis 
testing done 

Kaya et al. 
201818 

Patients who underwent 
any gynecological 
intervention excluding 
aesthetic genital surgery 
 
(n= 89) 
34.3 +/- 8.6 yo  

pre- and 
postmenopausal 

Not specified Right labium minus width:  
     0-20mm, 51.7%  
     20-40mm, 47.2%  
     >40mm, 1%  
  
Left labium minus width:  
     0-20mm, 16% 
     20-40mm, 41.6% 
     >40mm,4% 

p = 0.017 
 
 
 
 
p = 0.069 

Kaya et al. 
202016 

Healthy, non-pregnant, 
no OCP or IUD use 
 
(n=208) 
35.2 +/- 9.1 

premenopausal Digital stainless-
steel Vernier 
caliper 

Right labium minora width:  21.2 ± 8.6 
 
Left labium minora width: 22.0 ± 9.6  

No hypothesis 
testing done 

Suh et al 
200417 

Healthy Women 
 
Premenopausal (n=11): 
30.3 years  
 
Menopausal (n=8): 56.4 
years 

pre-and 
postmenopausal 

2D MRI Labia minora, Premenopausal: 
     Neutral: 11 ± 2 
     During arousal: 13 ± 2  
 
Labia minora, Menopausal: 
     Neutral: 9 ± 2  
     During arousal period: 10 ± 2 

p < 0.01 
 
 
 
p < 0.01  

 570 
Table 1. Summary of results from studies on labia minora width 571 
 572 
 573 
 574 
 575 
 576 
 577 
 578 
 579 
 580 
 581 
 582 

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 583 
 584 
 585 
 586 
 587 
 588 

Author Sample Method Marker Findings 

Schober et al 
201052 

Waste tissue strips from 
the surgical separation 
of the labial fusion of 
10 girls 2-9y/o  

Waste tissue strips from the surgical 
separation of the labial fusion of 10 2-
9y/o girls were taken. Tissue was stained 
with Masson’s and Hematoxolin and 
Eosin, fixed, frozen and cut into 30μm 
sections.  

H&E Labia minora are lined by Stratified squamous epithelium. 
Epidermis has the typical 4 layers (basal, spinous, granular, and 
stratum corneum). The dermis is differentiated into papillary and 
reticular, with the latter containing vascular and lymphatic plexus 
surrounded by collagen and elastic fibers. The papillary was 
composed of fine collagen, elastic, and reticular fibers. Connective 
tissue papillae from this layer sometimes projected into the 
epithelium.Labia minora has dense sebaceous glands and eccrine 
sweat glands that open onto the skin.  

Shih et al. 
201336 

9 cadaveric female 
vulvectomy specimens  

Samples were embalmed and buffered in 
formalin for processing. All vulvectomy 
specimens were serially sectioned and 
submitted in separate cassette blocks. 
Serial sections were then stained with 
H&E to examine general histologic 
features.  

H&E The pars intermedia is composed of predominantly collagen-rich 
stroma supporting the veins of Kobelt’s plexus, traveling 
longitudinally in the angle of the clitoris. Observed non-erectile 
specialized vascular tissue of the labia minora, which allows 
differential drainage following sexual arousal and engorgement to 
occur.  

Martin- 
Alguacil et 
al. 200835 
 
 

Waste tissue strips from 
the surgical separation 
of the labial fusion of 
10 girls 2-9y/o  

Labial tissue was fixed in 4% 
paraformaldehyde, buggered, frozen and 
cut into 30μm thick sections. The 
specimens were incubated with rabbit 
anti-ER alpha, rabbit anti-ERbeta, and 
rabbit anti-nNOS. The sections were then 
processed in rabbit IgG Vectastain ABC 
Kit.  

ERα  ERα present in the stroma of the labia minora near the clitoris and 
basal and suprabasal epidermal cells membrane in superficial labia 
minora  

ERβ  ERβ stained positively in the cell membrane basal and suprabasal 
epithelial cells as well as apocrine glandular epithelial cell 
membrane superficially. Lamina propria contained ERβ positive 
fibroblasts. 

nNOS nNOS was diffusely distributed and corresponded with nerve 
bundles and fibers in the stroma of the labia minora. 

Martin, 
Alguacil et 
al. 201153 

Waste tissue strips from 
the surgical separation 
of the labial fusion of 
10 girls 2-9y/o  

Labial tissue was fixed in 4% 
paraformaldehyde, buggered, frozen, and 
cut into 30μmthick sections. The 
specimens were incubated with rabbit 
anti-ERα, and rabbit anti-ERβ. The 
sections were then processed in rabbit 
IgG Vectastain ABC Kit 

ERα  ERα present in the outer core, external capsule, and stroma of the 
Pacinian-like corpuscle of the labia minora  

ERβ  ERβ stained positively in the stroma of the Pacinian-like corpuscle 
of the labia minora 

Uckert et al. 
2007 43 

Human labial tissue was 
obtained from 4 fresh 
female cadavers. 

Vibratome sections prepared from 
formaldehyde fixed tissue specimens, 
and incubated with primary antibodies 
against PDE isoenzymes. Sections were 
then incubated with fluorochrome 
(fluorescein isothiocyanate, Texas Red)-
labeled secondary antibodies. 
Visualization was commenced using a 
laser fluorescence microscope. 

PDE3 PDE3 was widespread in epithelial layer cells, epithelial sebaceous 
glands, and neuroendocrine labial epithelium cells  

PDE4 PDE4 was diffusely present but prominent in arterioles throughout 
the subepithelial layer as well as vascular smooth muscle and 
vascular endothelium 

PDE5 PDE5 was prominent in the vascular smooth muscle 

PDE11 PDE11 was mainly registered in epithelial glandular-like structures 

 589 
Table 2. Histological Characterization of Labia Minora Tissue and Vasculature. Abbreviations: H&E, 590 
Haematoxylin & Eosin; ERα, estrogen receptor-alpha; ERβ, estrogen receptor-beta; nNOS, neuronal 591 
nitric oxide; PDE3, phosphodiesterase 3; PDE4, phosphodiesterase 4; PDE5, phosphodiesterase 5; 592 
PDE11, phosphodiesterase 11. 593 
 594 

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 595 
 596 
 597 
 598 
  599 

Author Method Marker Findings 

Malinovsky 
et al. 197550 

Triangular resections of 5 surgical specimens and one 
cadaver was performed and divided into 3 parts, fixed 
immediately, and impregnated with silver nitrate. 
Evaluated 2,136 sensory nerve endings in total. 

Silver 
nitrate 

The labia minora consists of simple branched nerve endings, spray-like nerve 
endings, and most prominently, clew-like sensory nerve endings formed by one or 
more thick branching myelinated afferent axons with large nucleated Schwann 
cells and small nerve fibers toward the edges. They observed seven variations of 
the clew-like nerve endings, the most prominent being the Pacinian-like ‘genital 
corpuscle’ which contains a thick capsule. The average length of clew-like endings 
was reported to be 256μm with an average width of 199μm, independent of age.  

Cao et al. 
202115 

Surgical and cadaveric labia minora specimen were fixed 
in 10% formaldehyde, embedded in paraffin, sectioned, 
and processed. IHC performed using the S100 antibody 
to identify neurons.  

S-100  Abundant large myelinated sensory nerve endings in the central area of the labia 
minora and small, sparse, and dispersed nerve endings laterally. 

Kelishadi et 
al. 201649 

Four fresh tissue cadaver labia minora were analyzed. 
Each labia minora was divided into 6 anatomic areas and 
analyzed for the presence of nerve bundles using H&E 
and IHC for S100. Nerve density was analyzed under 
light microscopy, counted, and then expressed as 
percentage nerve density as well as number of bundles 
per square millimeter. 

S-100  Though there is a higher trend toward overall nerve density in the superior outer 
and superior middle regions of the labia minora compared to inferior regions, these 
differences are not statistically significant, suggesting that sensory innervation may 
be heterogeneous throughout the labia minora. 

Schober et 
al. 201052 

Waste tissue strips from the surgical separation of the 
labial fusion of 10 2-9y/o girls were taken. Tissue was 
stained, fixed, frozen and cut into 30μm sections. 
Specimens were incubated with rabbit anti-neuronal 
nNOS and rabbit anti S-100 dilution 1:400. Specimen 
was then processed with IgG Vectastain ABC kit. Some 
sections were stained with Bielschowsky silver stain.  

Bielschows
ky silver 
stain 

Thick nerve fibers were found in reticular and papillary dermis while thin nerve 
fibers were throughout the dermis and epidermis. Nerve density was reported to be 
most concentrated at the subepithelial plexus as well as at basal and spinous layers 
of the exterior epithelium. Free endings and arborizations were described with 
spray-like endings and seven types of clew or ball-like nerve endings as well as 
Pacinian corpuscles were described. Dense nerve fibers surround vascular and 
lymphatic plexuses.  

S-100 and 
nNOS 

S-100 and nNOSwas found more intensely and widespread at the introital border 
versus the exterior border as well as at the subepithelial plexus 

Martin, 
Alguacil et 
al. 201153 

Labial tissue samples were obtained following labial 
fusion. Immunocytochemistry against PGP 9.5, NSE, 
VIP, 5HTT, 5HT1A, NPY, nNOS, were performed. 

PGP 9.5, 
NSE, VIP, 
5HTT, 
5HT1A, 
NPY, and 
nNOS 

Pacinian-like corpuscle 
Inner core: 5HTT and NPY positive  
Outer core: PGP 9.5, 5HTT, 5HT1A, NSE 
External capsule: PGP 9.5, nNOS 
Stroma: VIP, NPY 

Schober et 
al. 20155 

The tissue was stained, fixed, frozen, and cut into 30μm  
sections. The specimens were stained by Cajal-type 
silver impregnation and by immunocytochemistry 
against protein gene product (PGP) 9.5 and neuron-
specific enolase (NSE).  

Cajal-type 
Silver 
staining 

Free nerve endings (FNE) found in the dermis were thin, mostly tortuous, 
branched or single processed, straight or bent. FNEs in epidermis terminated in the 
stratum granulosum; dense network of free endings was identified in the strata 
basale and spinosum.  Neither FNE in the dermis or epidermis had associated 
connective tissue or Schwann cells. Pacinian corpuscles, with a central structure 
surrounded by an encapsulated stroma, and central axon surrounded by an inner 
core, outer core, and external capsule, protruded into the epidermis from the 
dermis. There were non-capsulated or Meissner-like corpuscles were scattered in 
the dermal papillae and interdigitated with the epidermal ridges of the skin, 

PGP 9.5 Schwann-related cells, perineurial-related cells, and terminal axons of the non-
capsulated corpuscles in the dermis were positive for PGP 9.5. 

NSE Central axon and outer core of Pacinian corpuscles, as well as Schwann-related 
cells, perineurial-related cells, and terminal axons of the non-capsulated corpuscles 
in the dermis were positive for NSE 

 600 

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Table 3. Summary of results from studies on the innervation of the labia minora. Abbreviations: NSE, neuron-601 
specific enolase; PGP 9.5, protein gene product 9.5; VIP, vasoactive intestinal peptide; NPY, neuropeptide Y; 602 
nNOS, neuronal nitric oxide. 603 
 604 
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