Vu l v o d y n i a : N e w

Concepts and Review

o f t h e Li t e r a t u re
Vlada Groysman, MD

KEYWORDS
 Vulvodynia  Genital tract  Vulvar discomfort
 Multifactorial disorder

Vulvodynia is defined by the International Society disorder must be ruled out; patients must be prop-
for Study of Vulvovaginal Disease (ISSVD) as erly classified and also appropriate education and
“vulvar discomfort, most often described as psychological support/counseling must be admin-
burning pain without relevant visible findings or istered. As vulvodynia receives increased attention
a specific, clinically identifiable, neurologic by both the medical profession and the media,
disorder.”1 Patients with vulvodynia often describe more women are seeking care, information, and
it as chronic vulvar burning, stinging, irritation, guidance.
rawness, and, rarely, pruritis.2 It may be felt only
during sexual intercourse, experienced continu-
CAUSES
ally, or triggered by nonsexual activities such as
Infection and Vulvodynia
walking.3e6 Although believed in the past to be
an uncommon condition, vulvodynia is a major The causes of vulvodynia are unknown; however,
contributing cause for patient referral. Data from several hypothesis have been proposed to identify
a population-based study funded by the National causative factors. One of the most consistently re-
Institutes of Health found that 15.7% of women re- ported clinical findings associated with the onset
ported lower genital tract discomfort persisting 3 of vulvodynia is a history of frequent yeast infec-
months or longer.7 Recent population-based tions. A chronic subclinical yeast infection was
studies show estimates as high as 28%, with 1 believed to play a role in the development of symp-
study showing that 39% of women who suffer toms, but the use of antifungal medications has
from chronic vulvar pain fail to seek treatment.7 been shown to be inadequate for patients with
Frequency of vulvodynia is underestimated undocumented yeast infection.9e11 It is not clear
partially because of the belief of the medical whether the culprit is the yeast itself, the treat-
community that this problem is psychological ments undertaken that can sensitize the tissue,
and thus is not in their realm, and also because an underlying sensitivity present in the tissue, or
affected women are reluctant to discuss their simply the most common diagnosis made for
symptoms because of fear of neglect. Vulval pain unexplained symptoms. A recent study suggested
has been highlighted as a highly prevalent condi- that diverse urogenital infections such as yeast
tion that is associated with substantial disability.8 infection, urinary tract infection, trichomonas,
Although vulvodynia is a multifactorial pain and human papilloma virus (HPV) may precede
syndrome in which psychological, social, and the onset of vulvodynia, with multiple assaults
sexual function interact, it is a diagnosis of exclu- significantly compounding risk.12,13 However, this
sion, in which treatable causes such as derma- has not been a consistent finding within other
toses, infection, neoplasia, and neurologic studies, and prospective studies documenting
derm.theclinics.com

The author has financial relationships to disclose.

No funding support was provided for the purposes of this article.
Department of Dermatology, University of Alabama at Birmingham, EFH 414, 1530 3rd Avenue South,
Birmingham, AL 35294-0009, USA
E-mail address: [email protected]

Dermatol Clin 28 (2010) 681–696

doi:10.1016/j.det.2010.07.002
0733-8635/10/$ e see front matter Ó 2010 Published by Elsevier Inc.
682 Groysman

urogenital infections in association with vulvodynia to a pain disorder that is progressive and ongoing
are warranted. even with the avoidance of any further inter-
Although HPV was initially reported as a frequent course.8,28 The role of neuropathic pain in vulvody-
cause of vulvodynia, testing for HPV has shown that nia is supported by a documented response to
this virus is absent in most women with vulvar agents used to treat neuropathic pain. Immunohis-
pain.14e17 One recent study observed that the low tochemistry has shown altered density of nerve
rate of observed infection in women with vulvody- endings such as the vanilloid receptor VR1
nia, and the diversity of HPV types detected in the (TRPV1), which is expressed by nociceptors, and
patient population studied, suggest incidental virus is triggered by capsaicin, noxious heat, protons,
carriage rather than direct cause and effect.18,19 and chemicals produced during inflammation; as
well as increased number of intraepithelial free
Genetic Factors nerve endings, calcitonin-related gene peptide
(peptide found in nerve fibers), lowered tactile
Gerber and colleagues20 conducted studies on
and pain thresholds, nociceptor sensitization,
genetic predisposition and the onset of vulvody-
and overall peripheral nerve hyperplasia.30e34
nia. They found that more affected women were
Several studies report successful treatment of
homozygous for allele 2 in the interleukin-1b
localized vulvodynia with botulin toxin A.35e38
receptor antagonist and for allele 2 interleukin-1b
Moreover, increased blood flow and erythema in
gene than nonaffected women. Each of these
the posterior vestibular mucosa have been shown
alleles has been associated with prolonged inflam-
in vulvodynia via laser Doppler perfusion imaging
matory response. Susceptibility to vulvodynia
of the superficial blood flow in the vestibular
might be influenced by carriage of this polymor-
mucosa. Researchers postulated that such obser-
phism. They concluded that these findings
vation is the result of both neovascularization and
strongly imply that women with vulvodynia may
angiogenesis along with the release of neuropep-
be at increased risk for a proinflammatory immune
tides from C fibers in the skin, which produces
response to be triggered by a variety of stimuli and
an axon reflex causing vasodilatation and
may have difficulty in terminating an inflammatory
increased blood flow.39
event that involves interleukin-1b production. A
similar deficit in interleukin-1receptor antagonist
Pelvic Floor Abnormalities and Vulvodynia
production has been shown to contribute to
chronic inflammation in individuals with inflamma- Most women with vulvodynia exhibit pelvic floor
tory bowel disease. The investigators also stated abnormalities. Pelvic floor performance is signifi-
that some women have a genetic predisposition cantly lower in affected patients in terms of
to develop a chronic inflammatory response after contractile and resting ability and stability and effi-
an inciting event, such as a yeast infection. The ciency of contraction.40e44 Pelvic floor abnormality
prolonged inflammation could trigger other events may serve as causative or aggravating factors in
such as increased sensitivity in both genital and the development of vulvodynia. Rehabilitation of
nongenital areas of the body. It has been reported pelvic floor muscles via surface electromyography
that affected women have more somatic pain has been successful in reducing pain and
disorders and show increases in sensitivity to increasing sexual interest, pleasure, and activity.8
nongenital touch, pain, and temperature.21e23
Hormonal Influence
Vulvodynia as a Neuropathic Disorder
Hormones have a role in the genesis and continu-
Vulvodynia has features that are characteristic of ance of many pain syndromes. Some clinic-based
other chronic neuropathic pain conditions. These studies support an association between hormonal
features include the persistent and burning quality contraception and vulvodynia. The effect of oral
of the pain, the allodynia and hyperpathia, the contraceptives (OCs) on vulvar epithelium is
absence of physical findings on examination, largely unknown, however they may “alter the
lack of associated pathologic condition of the vaginal epithelium by promoting loss of a cyclic
tissues, and strong association with depression, pattern, low karyopyknotic index and the appear-
and are all reminiscent of other neuropathic ance of navicular cells with marked curling and
syndromes such as regional pain syndrome folding.”45,46 The presence of estrogen from OCs
(formerly reflex sympathetic dystrophy), and and the increased number of parabasal cells (a
pudendal neuralgia.8,24e29 The transition from the marker of atrophy), is unexpected. According to
nociceptive to neuropathic pain is key in vulvody- a recent study, women taking OCs have lower
nia because it underlies the shift from a pain mechanical pain thresholds in the vestibular region
disorder in which sexual intercourse elicits pain compared with controls.45 Other studies suggest
 Vulvodynia 683

that there is only a modest risk of OC use and vul- good assessment is essential to differentiate
vodynia, and that risk is confined to women whose between vulvar pain caused by an objective
exposure occurred before the age of 18 years. It is abnormality, and vulvodynia, in which pain is unas-
often difficult to assess whether OCs truly influ- sociated with abnormal clinical findings; to differ-
ence the risk of vulvodynia because OC prepara- entiate between the different subsets of
tions are variable. vulvodynia (localized, generalized, provoked,
However, hormone supplementation influences unprovoked, or overlapping) according to ISSVD
sensory discrimination and pain sensitivity. terminology (Box 1).1 A systematic assessment is
Estrogen is known to affect inflammatory neuro- essential in both early diagnosis and appropriate
peptides involved in chronic pain, in which the management of vulvodynia. Previous descriptions
lack of estrogen is associated with increased of vulvodynia have grouped patients according to
density of sympathetic, parasympathetic, and whether pain is provoked by coitus (vulvar vestibu-
sensory nerve fibers in the vulva, whereas acute litis syndrome) or generalized and neuropathic
or chronic estrogen administration may result in pain (dysesthetic vulvodynia). Recent terminology
a decrease in the total and sympathetic fiber debates have questioned whether the term vulvo-
numbers.45,46 Moreover, estrogen regulates dynia should be replaced by dysesthesia, and the
uterine sympathetic nerve remodeling through term vestibulitis avoided because there is no
actions on myometrium, ganglion, and interme- inflammation in vulvodynia. Definitions of pain
diary pituitary factors. Vaginal dysfunction during provocation, quality, duration, and distribution
menopause is generally assumed to occur vary. Terminology developed by the ISSVD recom-
because of diminished estrogen-mediated trophic mends standardization of the definition of vulvar
support of vaginal target cells. In addition, studies pain and the classification of vulvodynia into
show that increased sympathetic innervation may subtypes of generalized versus localized and
change vasoconstriction and promote vaginal provoked versus unprovoked.3,50e52 Generalized
dryness, whereas sensory axon proliferation may specifies involvement of the whole vulva, and
contribute to symptoms of pain, burning, and itch- localized specifies involvement of a portion of
ing associated with menopause and vulvody-
nia.47,48 Estrogen can therefore both lower the
pain threshold and be a potent mediator of periph- Box 1
eral nerve remodeling. ISSVD Terminology and Classification of Vulvar
Vulvodynia is a multifactorial disease. Although Pain (2003)
most clinicians find that depression and anxiety A) Vulvar Pain Related to a Specific Disorder53
are often associated with the disease and some-
times exacerbate it, studies do not support 1) Infectious (eg, candidiasis, herpes, etc)
a psychosexual dysfunction as a primary cause of 2) Inflammatory (eg, lichen planus, immuno-
vulvodynia. Data show that vulvodynia results in bullous disorders, etc)
a significant psychosocial effect and, compared 3) Neoplastic (eg, Paget’s disease, squamous
with dermatologic disorders conventionally re- cell carcinoma, etc)
garded as affecting well-being, patients with vulvo- 4) Neurologic (eg, herpes neuralgia, spinal
dynia experienced a more severe effect on quality nerve compression, etc)
of life.49 However, some experienced vulvologists
are certain that psychosexual dysfunction is the B) Vulvodynia
major causal factor.22 Also, conditions such as 1) Generalized
interstitial cystitis, headaches, fibromyalgia, and a) Provoked (sexual, nonsexual, or both)
irritable bowel syndrome are overrepresented in
women with vulvodynia, with depression com- b) Unprovoked
pounding, and at times worsening, the condition. c) Mixed (provoked and unprovoked)
Although clinical management should begin with 2) Localized (vestibulodynia, clitorodynia,
careful examination to rule out skin disease and hemivulvodynia, etc)
infection, overall psychosocial effects should also
a) Provoked (sexual, nonsexual, or both)
be addressed during treatment.
b) Unprovoked
c) Mixed (provoked and unprovoked)
Diagnosis
Data from Moyal-Barracco M, Lynch PJ. 2003 ISSVD
Getting the terminology terminology and classification of vulvodynia: a histor-
Assessment of a woman with possible vulvodynia ical perspective. J Reprod Med 2004;49:772e7.
includes both history and physical findings. A
684 Groysman

vulva, such as vestibule (vestivulodynia), clitoris visible on the vaginal walls, and there is vulvar
(clitorodynia), hemivulva (hemivulvodynia).53 erythema, rarely with pustules.8,53,54
Unprovoked implies discomfort that occurs spon- A routine vaginal culture is indicated for a patient
taneously, without a trigger, provoked asserts that with vulvar pain, because some patients exhibit
the discomfort is caused by physical contact, such a heavy growth of group B Streptococcus.
as intercourse, clothing pressure, tampon use, Although group B Streptococcus is usually an
cotton-tipped pressure or fingertip pressure.53 asymptomatic colonizer of vagina, many clinicians
The ISSVD has recommended elimination of the believe that it occasionally produces vulvar
term dysesthesia because it is an “unnecessary burning or irritation. These patients may benefit
modification of previous terminology.”53 from penicillin administration.59
Moreover, vulvodynia is a diagnosis of exclu- Skin diseases of the vulva or vagina can also
sion; it occurs in the absence of clinically identifi- cause pain. Such conditions as lichen planus are
able findings such as active or chronic infection a common cause of vulvar pain. Approximately
of the vulva, inflammation, neoplasia, spasmodic 50% of women with cutaneous lichen planus
pelvic musculature, trauma, or a neurologic have genital involvement. Erosive lichen planus is
disorder as evident in peripheral neuropathy, a distinct subtype of the disease, which manifests
pudendal neuralgia, herpes neuralgia, spinal nerve as vestibular, introitus, and vaginal erosions, re-
compression, and so forth.54e56 These can often sulting in inflammatory vaginal discharge even in
be ruled out on examination. Sphincter dysfunc- the absence of vulvar involvement. There is also
tion, weakness in the lower limbs, sensory contact bleeding and marked erythema of vaginal
changes such as anesthesia of the affected area, mucosa. Erosive lichen planus is a scarring
allodynia, and symmetric sensation of bilateral disease, therefore loss of the normal architecture
limbs should be assessed. of the vulva is common, and, in severe cases,
results in obliteration of the vaginal canal. Inflam-
Examination matory vaginitis may occasionally be caused by
A complete genitourinary physical examination is other erosive skin diseases, such as cicatricial
recommended in assessing a patient with vulvody- pemphigoid, pemphigus vulgaris, bullous pemphi-
nia. The examination should include visual inspec- goid, erythema multiforme, and fixed drug
tion of the external genitalia and labia for eruption.12,54,60e62 More common noninfectious
erythema, erosions, crusting, pallor, dryness and causes of vaginal inflammation include atrophic
ulceration, and hypopigmentation, and it should vaginitis and a clinical syndrome seen in premen-
include a speculum.57,58 A pediatric-sized spec- opausal women consisting of diffuse vaginal
ulum, and single-digit internal examination to eval- erythema and vaginal secretions that are micro-
uate pelvic floor muscle strength and tenderness is scopically purulent and exhibit increase in imma-
advised for patient comfort.8 A wet mount is often ture epithelial cells. Sobel63,64 named this
helpful in evaluation of vaginal secretions for yeast, syndrome desquamative inflammatory vaginitis.
pH, and white blood cells.2 Lichen sclerosis is another chronic inflammatory
Candida is usually the first working diagnosis disease with a predilection for the anogenital
that needs to be ruled out. Itching is a predominant region. It often presents with pruritis as the most
symptom in Candida albicans infection with frequent symptom, and clinical signs such as
secondary pain and rawness. Some organisms, pallor, atrophy, fissures, and foci of hyperkera-
such as Candida glabrata, Candida parapsilosis, tosis. Dyspareunia is a common complaint.
Candida krusei, and Saccharomyces cerevisae, Vulvar dermatitis may also present with symp-
can cause symptoms similar to vulvodynia such toms of dyspareunia; however, the main symptom
as burning, soreness, rawness, and irritation. is again pruritis. It has traditionally been classified
These organisms are difficult to detect and treat, into endogenous dermatitis, such as seborrheic
and they are often not responsive to initial anti- dermatitis, atopic dermatitis, and lichen simplex
fungal therapy. A fungal culture is imperative in chronicus, and exogenous dermatitis from irri-
diagnosis, because it is easy to miss these organ- tants and allergic contact dermatitis. However,
isms on microscopic analysis. In contrast with C there is often an overlap. Lichenification, excoria-
albicans, the organisms listed earlier do not tions, and, at times, fissures are evident on exam-
produce pseudohyphae or hyphae in the vagina, ination. Biopsy of a specific skin finding is
but form small, budding yeast. Isolation of a fungal necessary. Recent study reported that 61% of
organism does not ensure that the cause of the women who presented with chronic vulvar pain
symptoms has been identified, but the treatment had identifiable disease on biopsy. The remaining
could help in case the symptoms are related. On 39 % had nonspecific findings. The investigators
physical examination, creamy white curds are recommended performing biopsies in patients
 Vulvodynia 685

who present with vulvodynia symptoms even in Box 2

the absence of skin or mucosal changes. This Nonspecific activities for managing vulvodynia
recommendation has been debated in the litera-
ture.65 However, biopsy of a specific skin finding Validate symptoms, be supportive
is often best to avoid false positives, and evalua- Treat any objective abnormalities
tion by a trained dermatopathologist is Topical estrogens (estradiol vaginal cream [Es-
essential.25,66,67 trace] can be used intravaginally or topically)
(conjugated equine estrogen [Premarin])
Evaluation of Psychosocial Effects
Discontinue irritants (eg, excessive washing, irri-
Vulvodynia often significantly affects a woman’s tating lubricants, tight clothing, douching,
psychological health. Reports of psychosocial nonessential medications, sanitary pads, hair
stress are common in the literature and include dryers)
depression, altered body image, impaired social Apply lubrication during sexual activity (eg,
relationships, altered sexual function, and difficulty vegetable oil, Astroglide)
in physical activities and daily activities of life. An Apply lylocaine 2% jelly or 5% ointment for
overall decrease in quality of life is seen in women pain 20 minutes before sexual activity
with vulvodynia.8,68
Apply cold compresses (eg, crushed ice, frozen
As with other areas, conflicting studies exist
peas, gel pack)
regarding the psychosocial effect of vulvar
discomfort. The only consistent psychological Address and manage depression
effect in women with vulvodynia was difficulty Offer education (including written material) for
with sexual functioning. Although studies find both patient and partner
that affected women’s physiologic sexual arousal Refer patient for membership in National Vul-
is not impaired, because of fear of sexual inti- vodynia Association
macy from previous experiences with pain with Refer both patient and partner for sex therapy
intercourse, patients become fearful and thus and counseling to help cope with symptoms
sexual arousal is decreased. It is often necessary
to perform a psychosexual assessment or to
send patient and partner to be properly
evaluated.69,70 threatening disease. The self-management
program that the Robert Wood Johnson Medical
Treatment School-University of Medicine and Dentistry of
New Jersey used during a vulvodynia clinical trial
The management of vulvodynia includes nonspe- introduces empowerment through individual self-
cific supportive measures (Box 2) as well as management. It consists of 3 components,
specific therapies directed toward the treatment including a psychoeducation component that
of neuropathic pain, pelvic floor muscle dysfunc- involves understanding of exacerbating and allevi-
tion, and the psychosexual factors and sequelae ating factors, mental preparation and generalized
(Box 3). awareness of their condition, and the ability to
control factors affecting the condition. Learning
Education
to manage factors was empowering to patients.
Patients who have vulvodynia often endure The second component involved physically
multiple therapeutic modalities. First, it is essential training the pelvic floor through understanding
to properly diagnose and identify the pain pattern the physiology of pelvic pain and learning exer-
of vulvodynia. It is important to fully educate the cises to decrease the painful sensations. The third
patient and the partner and to fully explain both component of self-management is sexual prepara-
the condition and treatment options. Always intro- tion of both patient and partner, which consists of
duce the concept early in the treatment process learning other forms of sexual pleasure. The study
and warn that initial treatment is a trial of found these techniques to be highly effective
therapy.53,57,71e74 Validation of the patient’s because the woman empowers herself through
symptoms is invaluable in treatment. Many women taking control of the condition and her response
are convinced that their symptoms result from to the condition.8
a yeast infection or are fearful that their symptoms There are almost no scientific data on the effi-
signify a serious underlying medical illness or cacy of therapies for vulvodynia. Clinical trials are
future infertility. Patients need reassurance primarily limited to small, open series of patients,
regarding these concerns and that their symptoms and placebo-controlled studies are too small to
are not caused by a sexually transmitted or life- yield useful data. However, because vulvodynia
686 Groysman

Box 3 Vulvar Care and Topical Preparations

Standard therapy for vulvodynia A variety of general nonspecific measures are
Treat abnormal visible conditions such as infec- available to increase the comfort level of women
tions, dermatoses, and both malignant and with vulvodynia (see Box 2). All potential irritants
premalignant conditions should be eliminated, including the frequent appli-
Vulvar care measures; avoidance of irritants cation of medications, particularly creams that
contain alcohols and other irritating substances.
Topical medications Excessive washing of the vulvar region by patients
Lidocaine 5% jelly at introitus at bedtime is common, and many commercial lubricants (eg,
Nitroglycerine K-Y lubricating jelly [Ortho McNeil, Raritan, NJ,
USA]) may cause irritation. Astroglide (BioFilm,
Amitriptyline 2%, baclofen 2%
Vista, CA, USA) and vegetable oil are good alterna-
(ketofen 2%)
tives. Xylocaine (AstraZeneca, Wilmington, DE,
Capsaicin USA) 2% jelly (does not burn on application) and
Oral medications: 5% ointment (brief burning sensation on applica-
tion but is more potent) can help relieve the symp-
Antidepressant class
toms of burning in many women and, when
Tricyclic medications (150 mg/d) applied liberally 20 minutes before sexual activity,
Venlafaxine extended release (150 mg/d) may facilitate intercourse. Zolnoun and
Duloxetine (60 mg twice a day) colleagues79 trialed 5% lidocaine ointment in 61
patients with vulvodynia, and a significant increase
Anticonvulsant class in patients’ ability to have intercourse was noted
Gabapentin (3600 mg/d) (76% of women reported ability to have inter-
Pregabalin (300 twice a day) course, compared with 36% before
treatment).78e81 In this study, patients applied
Injections
the ointment on the cotton ball and placed it in
Triamcinolone 10 mg/mL, 0.2e0.4 mL into the vestibule overnight. Patients continued to
trigger point apply the preparation for 7 weeks, although
Botulinum toxin A injections some applied it for a longer period of time. Dan-
Intralesional interferon (IFN)-a (no longer ielsson and colleagues66 compared application
used) of topical lidocaine gel with biofeedback in 46
women and found improved sexual function in
Pelvic floor physical therapy
both groups at 12 months. Lidocaine application
Pelvic floor surface electromyography and does have side effects, so it is important to instruct
biofeedback patients that transient penile numbness may occur
Low-oxalate diet with calcium citrate supple- for sexual partners and that a remote chance of
mentation (controversial) lidocaine toxicity exists.57 A condom may
Cognitive-behavioral therapy (CBT), sexual decrease such side effects. Application of topical
counseling anesthetics may result in significant increase in
Surgery (for vestibulodynia only) localized exci- the degree of comfort during intercourse.72,78
sion/vestibulectomy/perineoplasty The application of cold compresses or ice to the
vulva may help relieve symptoms. Rinsing and
patting dry the vulva after urination may be helpful.
Use of hair dryers should be discouraged. Benzo-
caine is the anesthetic in Vagicaine (Clay-Park
has gained recognition as a common and treatable Laboratories Inc, Bronx, NY, USA) and Vagisil
entity, more studies are ongoing. A broad range of (Combe Inc, White Plains, NY, USA), but this may
possible management strategies exists, but the cause allergic contact dermatitis and should be
trial and error approach is necessary to find the avoided. Diphenhydramine (Benadryl; Warner
most effective treatment of a patient. The concern Wellcome, Morris Plains, NJ, USA), present in
is that few of the treatment strategies have been many topical anesthetics and anti-itch prepara-
confirmed in randomized controlled trials.75e77 tions, is also is a common sensitizer that should
However, therapies should not be disregarded be avoided.54
because of lack of randomized controlled clinical The topical immune response modifier imiqui-
trials, because this is a complicated and difficult- mod (Aldara, 3M Pharmaceuticals) has been sug-
to-treat condition. gested as a potential therapy because of its
 Vulvodynia 687

stimulation of the cellular immune system and therapy to treat generalized and localized vulvody-
induction of cytokines such as IFN-a. However, nia. Respondents were more likely to use TCAs,
this medication is a potential irritant and no clinical gabapentin, and psychiatric care, and less likely
studies on its use in vulvodynia have been pub- to use local anesthesia and vestibulectomy.86
lished. Topical and oral corticosteroids are not
useful for vulvar pain, except in the case of accom- Antidepressants
panying inflammatory skin disease such as lichen
Although most antidepressants do not confer
planus.
specific relief from neuropathic pain, several are
Some clinicians anecdotally describe improve-
useful in this regard: tricyclic medications, venla-
ment in premenopausal and noneestrogen-defi-
faxine, and duloxetine. Tricyclic medications,
cient women by avoidance of all painful stimuli,
particularly amitriptyline (Elavil, AstraZeneca) and
including intercourse, for 1 to 2 months, along
desipramine (Norpramin, Aventis Pharmaceuti-
with the application of estrogen creams to the
cals, Bridgewater, NJ, USA), improve pain
affected area. A study by Eva and colleagues82
substantially in most patients who can tolerate
showed decreased estrogen receptor expression
doses of 100 to 150 mg.8,54,87 Patients must be
in women with vulvar dysfunction; thus introduc-
counseled that, although these medications are
tion of estrogen, both vaginally and topically,
known primarily for their antidepressant effects,
may improve both vulvar and vaginal atrophy and
they are also being used for their beneficial effects
associated pain.
on neuropathic pain. Many information sheets
Steinberg and colleagues83 retrospectively eval-
provided by pharmacies currently list these medi-
uated the effects of capsaicin 0.025% applied
cations as commonly indicated for pain (although
daily for 12 weeks with preventative application
the pain indications are not approved by the US
of lidocaine. Although results showed a significant
Food and Drug Administration). Patients who
improvement of vulvar pain, the investigators did
believe they are receiving the medication to treat
not indicate a specific number of patients in
depression are likely to feel deceived and there-
whom the therapy was effective. Moreover, given
fore may not take their medication. With amitripty-
the prior application of lidocaine, it is impossible
line, patients should be started on half of a 10-mg
to isolate the effect of capsaicin. Murina and
tablet and the dose should be gradually increased
colleagues84 also studied the application of
to minimize potential adverse reactions until the
capsaicin cream preceded by an application of
total dose is 150 mg or until symptoms are
lidocaine, but did so with a prospective design,
controlled, whichever occurs first. Other side
a higher dosage, and a longer treatment duration.
effects include constipation, weight gain, urinary
Results indicated that 59% of participants re-
retention, tachycardia, blurred vision, and confu-
ported an improvement of their vestibular pain,
sion. Serious side effects include seizures, stroke,
but the symptoms recurred 2 weeks after capsa-
infarctions, agranulocytosis, and thrombocyto-
icin discontinuation. Despite the preventive appli-
penia.8 If unacceptable drowsiness or fatigue
cation of lidocaine, all participants indicated an
occurs, the dose can be decreased slightly and
intense burning sensation after capsaicin use.
the patient given a week to acclimate before trying
Care should be taken with the application of
again to increase the dose. If the patient continues
capsaicin because of its potential as a strong irri-
to experience drowsiness, desipramine, which is
tant.78 Topical nitroglycerin has been reported to
less sedating, can be substituted using the same
improve symptoms associated with vulvodynia,
dosing schedule (ie, target dose of 125e150 mg/d).2
but headache was a significant side effect of
However, desipramine is more likely to produce
treatment.85
anxiety and tremulousness compared with
amitriptyline, so, occasionally, patients might
Oral Medications
benefit from combination therapy with these 2
Pharmacologic therapies, both oral and topical, drugs to minimize these side effects while main-
are a mainstay of vulvodynia management. taining the beneficial effects. Other side effects
Specific first-line therapy for most patients with of tricyclic medications include dryness of the
either form of vulvodynia is standard therapy for mouth and eyes, constipation, increased appetite,
neuropathic pain. A survey of 167 providers who and, rarely, urinary retention. Reed and
treat vulvar pain was conducted in 2005. The colleagues88 showed that of 83 women taking
most commonly used treatment of vulvodynia a TCA at the first follow-up, 49 improved by
was tricyclic antidepressants (TCAs). There was more than 50%, compared with 30 of 79 not taking
no difference in the use of physical therapy, estro- a TCA at follow-up. They concluded that women
gens, injected or topical steroids, IFN, or laser prescribed TCAs in general were more likely to
688 Groysman

have pain improvement compared with those USA) have also been used to treat
women not taking these medications.54,88 vulvodynia.8,93,94,97
Other antidepressants have been used for pain Some women remain refractory to most
control. These selective serotonin and norepi- commonly used oral therapy. Recent study evalu-
nephrine reuptake inhibitors, such as venlafaxine ated the efficacy of a central nervous system
and duloxetine, have been used for women with agent, lamotrigine, which is an anticonvulsant
vulvodynia. These medications are often used with demonstrated benefits in both mood and
when a patient does not respond readily to the pain syndromes. Lamotrigine (Lamictal, Glaxo-
common tricyclics, and are often used in conjunc- SmithKline Pharmaceuticals, Durham, NC, USA)
tion with anticonvulsants. Venlafaxine is started at is an anticonvulsant and mood stabilizing agent
37.5 mg daily in the morning with an increase to that works by stabilizing the slow, inactivated
75 mg daily after 1 to 2 weeks. Medication can conformation for the type IIA neuronal sodium
be increased gradually to 150 mg daily. When channels, which prevents ongoing firing of action
stopping the medication, it is important to wean potentials in conditions of sustained neuronal
slowly. Duloxetine is begun at 20 to 30 mg each depolarization. A study of 31 patients who
day and titrated to as much as 60 mg twice completed the trial showed a clinically significant
a day. Because most selective serotonin reuptake response to treatment with lamotrigine as shown
inhibitors can theoretically inhibit the metabolism by decreased pain scores and improved mood
of tricyclics, monitoring tricyclic levels in these and anxiety symptoms. Subjects from the vulvo-
patients is prudent.54,58,89e91 dynia group had especially robust reductions on
all measures of pain at both the 8- and 12-week
visits.98
Anticonvulsants
For women who cannot tolerate adequate doses
Pelvic Floor Physical Therapy and Biofeedback
of tricyclic medications or who fail to improve, ga-
bapentin (Neurontin, Parke-Davis, Morris Plains, Although it was once a second-line treatment of
NJ, USA) may be considered. This medication is vulvodynia, pelvic floor therapy has become
effective in diabetic neuropathy and postherpetic a major therapy in the treatment of
neuralgia at doses of 3600 mg/d or less.92,93 Anec- vulvodynia.99e101 Physical therapy has been
dotally, many clinicians have reported beneficial shown to be efficacious in the treatment of vulvo-
effects of gabapentin in treating vulvodynia.94,95 dynia and, in this author’s opinion, is essential in
Overall, this anticonvulsant is better tolerated successful management of vulvodynia. Pelvic floor
and than tricyclic medications. However, it should physical therapy is widely available and effective.
be administered in divided doses 3 to 4 times It involves the assessment of the patient history
a day, it is more expensive than amitriptyline, and pelvic musculature, joints, and muscle
and it also has several side effects, including tension. The function of related structures, such
drowsiness, fatigue, dizziness, and ataxia. Serious as bowel and bladder, is assessed as well. Most
reactions include leucopenia. Similar to tricyclic therapists use a weekly session focused on exer-
medications, this drug can be administered at cise for the pelvic girdle and floor, soft tissue mobi-
low doses initially and gradually increased. Gaba- lization, and joint manipulation.89,99e101
pentin comes in 100-, 300-, 400-, 600-, and Physical therapy has the advantage of treating
800-mg tablets. It is started at 300 mg by mouth the associated abnormalities that may worsen
daily for 3 days, then 300 mg by mouth twice daily the symptoms of vulvodynia, such as joint pain, fi-
for 3 days, and then 300 mg by mouth 3 times daily. bromyalgia, and interstitial cystitis. A study per-
It can be increased gradually to 3600 mg. Do not formed by Hartman and colleagues72 sought to
exceed 1200 mg in a dose and, for elderly patients, identify current practice trends of physical thera-
do not exceed 2700 mg/d. If there is a partial pists in the United States. treating women with
response to tricyclics, they may be continued at localized, provoked vulvodynia. Assessment
lower doses, such as 10 to 20 mg, in combination modalities used by more than 70% included
with gabapentin, and the combination of the 2 detailed history; assessment of posture, tension
drugs may be better than either alone.96 in the pelvic floor, pelvic girdle, associated pelvic
A similar medication, pregabalin (Lyrica), can be structures, and bowel/bladder function; strength
used, titrating to as much as 150 mg twice a day. testing of abdominals and lower extremities; and
Side effects are similar to those of gabapentin. voiding diaries. Nearly 70% used exercise for the
Carbamazepine (Tegretol; Novartis Corporation pelvic girdle and pelvic floor; soft tissue mobiliza-
Pharmaceuticals) and Topiramate (Topamax, tion/myofascial release of the pelvic girdle,
Ortho Pharmaceutical Corporation, Raritan, NJ, pelvic floor, and associated structures; joint
 Vulvodynia 689

mobilization/manipulation; bowel/bladder retrain- pelvic floor relaxation with biofeedback and elec-
ing and help with contact irritants, dietary troanalgesia is safe and effective in improving
changes; and sexual function.72 An evaluation by vulvar pain and dyspareunia in women with vulvo-
a physical therapist may identify and help alleviate dynia.98 Another study in Italy assessed 40 women
dysfunctional aspects of the musculoskeletal with vulvodynia who underwent transcutaneous
system, such as the obturator internus and coccy- electrical nerve stimulation. Twice-weekly active
geus muscles, and the sacrospinous and sacrotu- TENS or sham treatments were delivered through
berous ligaments.67,100,101 Other areas that can be a vaginal probe via a calibrated dual channel
targeted by physical therapy include fascial YSY-EST device. Women of both groups under-
attachment and tissue tension levels of the went 20 treatment sessions. The study concluded
bladder and urethra, uterine mobility, and sacro- that marked improvement was shown in most
coccygeal mobility and positioning.101 Physical women compared with placebo.103 Moreover,
therapy treatment techniques include both internal recent literature on vulvodynia also mentions
and external soft tissue mobilization and myofas- a novel therapeutic approach to treatment of the
cial release.40,45,66,100 disease with noninvasive cortical stimulation.
A recent retrospective study reported the This may be effective in very resistant cases.104,105
response rate of 24 patients with either vulvar ves-
tibulitis syndrome or dysesthetic vulvodynia who
Intralesional Injections
were treated with pelvic floor rehabilitation by the
Glazer method and concomitant physical Clinically, botulinum toxin A blocks the cholinergic
therapy.99,101 Patients with vulvodynia are more innervation of the target tissue. Recently, it has
likely than asymptomatic women to exhibit been shown to be effective in women with vulvo-
increased resting pelvic floor muscle tension with dynia.106 Several studies have concluded that
fasciculation, but overall weakness.102 This profile conditions and symptoms that are caused by
probably predates symptoms and may predispose pelvic floor spasms, daily pelvic pain, and dyspar-
these women to the development of vulvodynia. eunia are most likely to be improved by botulinum
These abnormalities are too subtle to be identified toxin A. Limited data regarding use for provoked
during physical examination, but they can be iden- vestibulodynia indicate an improvement in pain
tified by surface electromyography (Glazer scores. A recent study in Korea examined 7
method). Biofeedback training helps patients learn women with pain on genitalia that could not be
exercises to strengthen weakened pelvic floor controlled with conventional pain managements.
muscles and to relax these muscles, with a resul- Between 20 and 40 U of botulinum toxin A were
tant reduction in pain. The Glazer method uses used in each injection. Injection sites were the
a small vaginal probe (about the size of a tampon) vestibule, levator ani muscle, or the perineal
with electrical sensors connected to a computer. body. Repeat injections were administered every
If pelvic floor abnormalities are identified by 2 weeks if the patient’s symptoms had not fully
surface electromyography, then retraining the subsided. In all patients, pain disappeared with
pelvic floor muscles with twice-daily exercises botulinum toxin A injections. Five patients needed
can be extremely beneficial. A home training to be injected twice; the other 2 patients needed
device can be attached to the vaginal probe so only 1 injection. The study did not observe compli-
the patient can monitor the effectiveness of her cations related to botulinum toxin A injections,
exercise regimen as a biofeedback procedure.35 such as pain, hemorrhage, infection, or muscle
The exercises must be performed regularly, and paralysis, but potential problems with botulinum
improvement is generally observed after several toxin A injection include toxin reactions, urinary
months. After 8 to 12 months, the exercises can and fecal incontinence, urinary retention, and
be discontinued and patients generally retain the secondary treatment failure caused by antibody
improvement in symptoms, although the profile production.21,107e109 In a case study by Romito
of high resting tension of pelvic floor muscles, and colleagues,110 the 2 participants reported
fasciculation, and weakness usually returns.99,102 complete pain relief within 2 to 7 days after the
A retrospective study in Italy assessed a total of injections, lasting for 5 to 6 months.111 Dykstra
145 women diagnosed with vulvodynia who were and Presthus106 conducted a study with 12
treated with weekly biofeedback and transcuta- patients who reported a significant reduction of
neous electroanalgesia (TENS), in association their pain for 8 to 14 weeks after the injection,
with functional electrical stimulation and home with a higher dosage leading to a longer-lasting
therapy with stretching exercises for the pelvic effect. Nevertheless, only 25% of patients re-
floor. An improvement of vulvar pain was seen in ported a significant improvement of their quality
75.8% of subjects. The study concluded that of life on follow-up. The optimum dose and
690 Groysman

injection technique of botulinum toxin has not treatment option for patients with vestibulodynia
been determined, which probably explains the because most experts believe that surgery should
different conclusions of these studies. be reserved for long-standing cases of severe
IFN-a has been reported to be beneficial, vulvar pain and after all other managements have
primarily when injected locally.112e115 It was yielded unsatisfactory results.55,118,125,126
initially advocated in vulvar vestibulitis, because Three approaches are often used in the surgical
there was an association with HPV and vulvar treatment of vulvodynia, including a local excision
pain. Recent studies have disputed that notion. (clinical identification and removal of extreme
However, a report of a focal depression in natural painful areas), total vestibulectomy (skin, mucous
killer lymph cell activity in patients with vulvodynia membrane, hymen, and adjacent tissue are
supports the use of IFN.115 The most common removed, along with vestibular glands and trans-
regimen consists of IFN-a 1 million units injected action of Bartholin ducts), and perineoplasty
3 times per week for 4 weeks circumferentially at (tissues of perineum removed ending just above
the periphery of the vestibule. In this procedure, the anal orifice), in which denervation of the vesti-
the vestibule is divided into 12 areas as in a clock bule (vestibuloplasty) has been shown to be in-
face; for example, a first injection could be given at effective.55,118,125e129 Many surgeons remove all
the 6:00 position, the second injection at the 7:00 areas of the vestibule, including areas that do not
position, and so on until the entire periphery has exhibit pain, because vestibulectomy failures
been injected once. Patients may experience flu- result in recurrences in remaining vestibule tissue.
like symptoms such as fever, malaise, and myal- About 85% of patients experience a cure or
gias; pretreatment with acetaminophen or remarkable improvement in their symptoms after
ibuprofen may minimize these symptoms.112e114 surgery.55,118,125e129 However, dehiscence, recur-
In addition, patients may experience significant rence of symptoms, or worsening of pain occa-
injection-site pain, which may be relieved by sionally occurs after vestibulectomy. Although
pretreatment of 20 to 30 minutes with a topical vestibulectomy was once the treatment of choice
anesthetic. Improvement 1 year after IFN-a therapy for vulvar vestibulitis syndrome, the scarcity of
is variable.112e114 experienced surgeons, the discomfort of the
Although topical steroids do not help patients procedure, the cost, and the success of less-
with vulvodynia, trigger point injections are useful, aggressive therapies have relegated this proce-
especially when a patient occasionally reports dure to second- or third-line therapy.
pain that is localized in origin. When one of these
trigger points is identified, 0.2 to 0.3 mL of
Laser Therapy
3 mg/mL triamcinolone acetonide injected into
the affected area may substantially improve pain Early reports of some forms of laser ablation
within 1 to 2 weeks.2,116 An additional injection described improvement in vulvodynia.130e135
4 to 6 months later occasionally resolves the pain However, worsening pain and recurrence are
permanently. Some investigators combine triam- common,24 and laser treatment is now contraindi-
cinolone acetonide 0.1% injections with bupiva- cated in women with vulvar pain. Laser ablation of
caine, with injections into a specific area or as the vulvar epithelium is an alternative to the vesti-
a pudendal block. Segal and colleagues117 exam- bulectomy, but laser therapy for vulvodynia
ined the effects of subcutaneous injections of remains a controversial issue. Reid and
betamethasone plus lidocaine administered at colleagues130 advocated the use of flashlamp-
1-week intervals in the vestibule. At follow-up, excited dye laser to selectively photocoagulate
the participant indicated a complete relief of her symptomatic subepithelial blood vessels in 168
pain and improvement in sexual intercourse. The women and the removal of painful Bartholin glands
efficacy of methylprednisolone injections plus lido- in 52 women not responsive or not suited to
caine were studied prospectively by Murina and flashlamp-excited dye laser photothermolysis.
colleagues.84 Results revealed that 32% of partic- The study showed statistically significant clinical
ipants had a complete remission of their pain improvement. Results of laser therapy for vulvody-
symptoms, and 36% of the patients showed nia compare similarly with vestibulectomy.
improvement. Complete response occurs in 62% versus
improvement in 92%.130 Ketoprofen-neodymiu-
m:yyttrium-aluminum-garnet (KTP-Nd:YAG) laser
Surgical Therapy
treatment has been used in the treatment of vulvo-
Another treatment option for patients with vulvar dynia, with a study examining patient response
vestibulitis syndrome is surgical excision of the after 2 years. Sixty-eight percent reported less
vestibule.18,31,118e124 It is commonly the last pain with sexual intercourse and 29% reported
 Vulvodynia 691

no change. The KTP-Nd:YAG laser and pulsed- to help the couple to discover alternative types of
dye laser offer the benefit of being absorbed by painless sexual activity.
vasculature and thus encouraging collagen Behavioral interventions for chronic pain empha-
remodeling.136 Because angiogenesis and in- size a self-management approach, deemed more
creased nerve density are characteristics of vulvo- effective than more conventional medical and reha-
dynia, the laser is used to disrupt this phenomenon bilitation therapies.145 CBT for vulvodynia can help
and to advance collagen remodeling without to decrease pain, reduce fear and anxiety associ-
changing the innate structure.136 CO2 laser ated with pain, and reestablish satisfying sexual
therapy for vulvodynia was not recommended in functioning.23,42,146,147 Kuile and colleagues148
a study of 3 cases of vulvodynia after CO2 laser evaluated the efficacy of therapy in a group format;
treatment of condylomata acuminata or bowenoid the investigators reported that participants had
papulosis of the female genital mucosa. Laser a significant reduction of vulvar pain, in addition
treatment was associated with a delay in healing to a significant improvement of sexual satisfaction
and chronic pain. and perceived pain control.149 Masheb and
colleagues150 tested the efficacy of CBT and
Dietary Modifications supportive psychotherapy (SPT) in women with vul-
vodynia. Participants had statistically significant
The theory that high urinary and tissue oxalate
decreases in pain severity, with 42% achieving clin-
levels cause pain in some patients has led to the
ical improvement; participants in CBT reported
use of a low-oxalate diet and mealtime calcium
greater treatment improvement and satisfaction
citrate supplementation. The addition of oral
than participants in SPT. Bergeron and
calcium citrate (Citracal), 2 tablets (200 mg and
colleagues151 conducted the only randomized
950 mg) orally 3 times a day, is used to neutralize
study that examined CBT. More specifically, partic-
oxalates in the urine.137 One theory is that oxalate
ipants were randomized either to CBT, biofeed-
may irritate the vestibulum and may be a contrib-
back, or vestibulectomy. The participants of the 3
uting cause to vulvodynia pain over a long
treatment groups reported noteworthy improve-
period.57,58 Other studies have indicated that
ments of their pain.83,151 The average pain reduc-
patients with vulvodynia do not have increased
tion was 47% to 70% for vestibulectomy, 19% to
oxalate levels, and that there is no correlation
35% for biofeedback, and 21% to 38% for CBT.
between oxalate levels and symptom improve-
Although vestibulectomy was shown to be appre-
ment, so most vulvologists do not find dietary
ciably more successful than the 2 other treatments
modification useful for vulvodynia.138e141
in terms of pain decline, the 3 treatments resulted in
equal levels of improvement. Moreover, the CBT
Counseling
group presented a significantly lower dropout rate
Vulvodynia is often devastating, affecting than the vestibulectomy group, and participants
a patient’s personal relationships and quality of were more content with their treatment than those
life. Depression is a common symptom and should who took part in biofeedback.
be addressed.28 Sargeant and O’Callaghan116 re-
ported that women with vulvar pain reported
significantly worse mental health-related quality SUMMARY
of live than women without vulvar pain. In their
study, illness perceptions played an important Vulvodynia is a multifactorial chronic pain disorder
role in the women’s mental health-related quality that is distressing to the patient and exigent to the
of life. The clinician should make it clear that coun- physician. Although the condition is common, it
seling and antidepressant therapy are recommen- remains little understood, so patients remain undi-
ded not to treat their pain, but because they can agnosed and untreated or undertreated for many
minimize the depression and disruption of years. Although multiple therapies exist in the
personal relationships.68,69,142 A referral to treatment of vulvodynia, few randomized
couples counseling is ideal and can help the controlled clinical trials have been performed.
patient and her partner cope with vulvodynia. Thus, treatment should be individualized and
Patients need to understand that referral to tailored to a patient’s diagnosis, symptoms, and
therapy does not meant that a patient’s condition psychosexual functioning. Patient education is
is imagined; therapy is just another tool in the also important and is facilitated by patient
treatment of vulvodynia. Sex therapy, couples brochures providing assurance that vulvodynia is
counseling, and psychotherapy can be important a real disease. In addition, joining the National Vul-
in proper management of patient.108,137,143,144 A vodynia Association (www.nva.org), a clearing-
therapist with expertise in sex therapy is preferred house for information and updates on vulvar
692 Groysman

pain, helps to inform patients and to alleviate the 16. Shafik A. Pudendal canal syndrome as a cause of
sense of isolation that patients may experience. vulvodynia and its treatment by pudendal nerve
decompression [abstract]. Eur J Obstet Gynecol
Reprod Biol 1998;80:215e20.
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