Sage Journals: Discover world-class research

Abstract

Vulvodynia, or chronic vulvar pain, is a common but poorly understood condition. Although its etiology is not well understood, it appears to be multifactorial. As such, treatment options are targeted to reduce singular symptoms in a piecemeal fashion. A number of randomized, controlled trials have been conducted and at least one paper on combination therapy has been published; however, further systematic research is needed in order to more fully inform clinical practice.

Keywords

antidepressant medication botox dyspareunia lidocaine pelvic floor physical therapy/biofeedback psychological treatments vestibulectomy vestibulitis vestibulodynia vulvodynia

Vulvodynia (chronic vulvar pain) affects 16% of women in the general population over a lifetime [1]. In many cases, the pain is mislabeled or undiagnosed, even following multiple physician visits [2]. Women are often told that no physical cause can be found for their pain, implying that their pain is the result of psychological problems or does not exist at all [3]. Not surprisingly, women with vulvodynia report decreased overall wellbeing and low quality of life [4].

Despite its high prevalence and negative ramifications, vulvodynia is still far from understood. Much remains unknown regarding the factors involved in the etiology and maintenance of this condition. In addition, the treatment literature presents numerous options that target singular symptoms, but it includes few methodologically sound investigations and even fewer controlled trials. Over the past 10 years, however, there has been an exponential increase in research examining vulvodynia, particularly localized provoked vulvodynia (LPV). Furthermore, the nomenclature and classification criteria of vulvodynia and its subtypes have evolved, and will continue to evolve over time given new knowledge.

Definitions & prevalence of vulvodynia

Vulvodynia, as defined by the International Society for the Study of Vulvovaginal Disease (ISSVD), refers to medically unexplained vulvar discomfort and pain [5]. The ISSVD classifies vulvodynia into two subtypes based on pain location. Generalized vulvodynia (GVD) is defined as pain affecting the entire vulvar region and occurs in 6–7% of women in the general population [1]. Pain that is restricted to a portion of the vulva is referred to as localized vulvodynia; for example, the pain may be restricted to areas such as the vestibule, clitoris (termed clitorodynia) or a portion of the vulva (termed hemivulvodynia).

Whether generalized or localized, the pain may occur in response to provocation (e.g., pressure to the affected area via sexual and/or nonsexual activities, such as tampon insertion) or it may be unprovoked (i.e., the pain occurs in the absence of an external trigger). Some women experience both provoked and unprovoked pain. Although provoked pain can occur in both sexual and nonsexual situations, painful intercourse (referred to as dyspareunia) is the most common symptom reported by women with LPV [6]. In a cross-sectional national survey, Laumann et al. found that 21% of young women (aged 18–29 years) reported experiencing painful intercourse during the past 12 months [7]. However, the prevalence estimates of dyspareunia have been found to vary according to the measures used, the minimum timeframe specified for the pain and whether sexual distress is assessed [8,9].

In addition, the cross-sectional nature of prevalence research does not allow for incidence and remission rates to be calculated [10]. Based on self-reported symptoms at follow-up, however, 1.8–5% of women may develop vulvodynia annually [10,11]. A number of women also experience symptom remission or recurrence, with one study finding that 11% of women presenting with vulvodynia reported being pain-free at 2-year follow-up [10]. Thus, the course of vulvodynia may fluctuate over time and heal spontaneously, although rigorous longitudinal studies are needed.

The most common subtype of vulvodynia is LPV, which has an estimated lifetime prevalence of 12% among premenopausal women [1]. LPV is often qualified according to the onset of the pain (primary/lifelong vs secondary/acquired). Women with primary LPV experience pain beginning with their first attempt at vaginal penetration; others have a period of pain-free vaginal penetration before the pain develops (secondary LPV).

Pathophysiology

The etiology of vulvodynia remains unclear, although it is believed to result from a multifactorial process [12]. A current problem is the lack of a distinct conceptual model for this condition. Most clinicians believe that the presence of vulvar pain is attributable to an underlying inflammatory process or a dysregulation of the peripheral nervous system and the CNS; this model is termed the ‘neuropathic pain hypothesi’ [13]. However, not all studies find evidence of inflammatory mediators and the cause of hyperinnervation is not known.

Alternatively, others believe that the presence of pain in the vulva is the result of a pre-existing psychosexual dysfunction and, thus, is psychosomatic in nature [14]. Although a lack of longitudinal studies prevents conclusions regarding cause and effect, the general consensus in the field is that the pain is triggered by a physical occurrence and, as time progresses and the pain continues, a vicious cycle develops. This cycle often includes physical (e.g., heightened pelvic floor muscle tension) and psychosocial (e.g., pain hypervigilance, anxiety and reduced sexual function) consequences, all of which serve to heighten pain intensity.

Very few studies have systematically investigated the etiology of GVD; however, LPV has been the subject of several etiological investigations. Many factors have been proposed, including infectious, inflammatory, embryological, genetic, hormonal and mechanical etiologies [15]. Changes in these systems can lead to pathophysiological changes in three interdependent systems: nervous system pain regulatory pathways, pelvic floor muscles, and the patient's psychosocial and sexual function [16].

Nervous system pain regulatory pathways

Recurrent vaginal candidiasis has been suggested to be a precursor to LPV [1,17]. A total of 5–8% of all fertile women suffer from repetitive episodes of vulvovaginal candidiasis [18]. One study has speculated that LPV may result from regionally elevated proinflammatory cytokine levels produced by vulvar vestibule-specific fibroblasts in women with candidiasis [19].

Several histopathological studies have reported signs of chronic vulval inflammation, specifically inflammation predominantly characterized by T lymphocytes, plasma cells and mast cells [20]. Recently, mast cells have been recognized for their modulating effect on the immune system and their contribution to LPV [21]. Mast cells are normally present in all tissues where they modulate the immune system. When inflammation occurs, they release granules containing angiogenic, proinflammatory and neutrophic factors, such as the enzyme heparanase [22]. Bornstein et al. found that heparanase is capable of degrading the vestibular stroma and epithelial basement membrane, thus permitting stromal proliferation and intraepithelial extension of nerve fibers (i.e., hyperinnervation) [21].

Hyperinnervation has been thought to cause the vestibular hyperesthesia distinctive of LPV. Several studies have documented increased intraepithelial innervation in skin biopsies obtained from women with LPV from vestibulectomy or by punch biopsies, and an increase in the number of C-afferent nociceptors on special histopathological staining (S-100) has also been demonstrated [21,23–25].

The role of inflammation in vulvodynia has also been supported by the findings of a genetic contribution caused by an increase in proinflammatory genetic variants of IL1RA and MC1R genes in women with LPV compared with healthy controls [26 –28].

In support of central involvement in vulvar pain, Pukall et al. have found evidence of altered central sensory processing in response to painful vestibular stimulation in women with LPV compared with nonaffected women [30]. These results indicate an augmentation of sensory processing in the brain, consistent with a recently published study by Schweinhardt et al., demonstrating that women with LPV have significantly more gray-matter density in pain modulatory and stress-related areas in the brain compared with nonaffected women. These findings indicate that morphological alterations in supraspinal pain modulatory circuitry occur in LPV, which may contribute to its symptoms [31].

Pelvic floor muscles

Studies have suggested that hypertonicity of the pelvic floor musculature may play a role in the maintenance of LPV [32,33]. In support of this suggestion, treatment studies have demonstrated various degrees of success in decreasing pain intensity secondary to reducing tension of the pelvic floor muscles using electromyographic (EMG) biofeedback or physical therapy [34 –38]. Interest in the utility of physical therapy for LPV has recently increased and attempts are being made to standardize this form of intervention [39].

Psychosocial & sexual function

Psychosocial aspects of vulvodynia have been investigated in numerous studies, with many contradictory results. Both controlled and uncontrolled investigations have demonstrated that the level of psychological distress among women with LPV is within the normal range [40 –42]. However, Gates and colleagues demonstrated that women with PVD report more psychological distress than controls on a standardized questionnaire [43], and a case–control study using the same validated measure revealed the same pattern of results [44].

The lifetime prevalence of depression among women with vulvodynia has been estimated to be 45% and, for two-thirds of patients, their first depressive episode appears to have preceded the pain [45]. Other authors report that twice as many patients as controls report previous depressive episodes [42,46], although some studies have found no differences in history of depression between women with vulvodynia and controls [4,47]. In addition, some studies have demonstrated that women with vulvar pain report more symptoms of anxiety than women in the control group [48,49].

Not surprisingly, sexual function is often adversely affected. Several controlled studies have demonstrated that women with LPV exhibit a significant deterioration in their sexual functioning, high levels of dissatisfaction with their sexual life and low levels of desire, arousal and orgasmic frequency [41,50–52]. Recently, a study examining primary and secondary LPV demonstrated that women with primary LPV had more heightened anxiety related to body exposure during sexual activity than women with secondary LPV [53].

Maintaining or establishing a partnership can be difficult for women with vulvodynia. Dyadic adjustment appears to influence the pain intensity of vulvodynia [54]; this pattern has also been demonstrated in patients with other chronic pain conditions [55,56]. One recently published study revealed that partner solicitousness and hostility were significantly associated with higher levels of pain during intercourse [57]. A second study found that higher levels of pain intensity predicted increased psychological distress in male partners [58]. These results imply that psychosexual treatment may need to include the partner to reduce pain and improve the sexual and couple relationship.

Other factors

In addition to the etiological factors mentioned above, many others have been proposed. Recently, much research has been conducted regarding the role of hormones and hormonal changes in women with vulvodynia. Results are conflicting; for example, some studies report an association between LPV and oral contraceptives [59,60], while others have found no such relationship [61]. However, this area of investigation has only recently been pursued rigorously and may hold important information, since one study has found that the use of oral contraceptives can lead to vulvar atrophy and lower mechanical thresholds as compared with women not taking oral contraceptives [62].

Another area of interest is that of comorbid conditions. Vulvodynia patients often report symptoms in the urethral and bladder regions in conjunction with their vulvar pain. Studies have explored the possible joint pathologies for vulvar pain and interstitial cystitis (e.g., see [63]) and have found parallel symptomatologies and chronic pain characteristics, without recognizable pathologies. One study by Arnold et al. suggested that LPV, GVD, urethral syndrome, clitorodynia and interstitial cystitis all share a common pathology and are symptomatic of pelvic floor muscle dysfunction [4]. Furthermore, vulvodynia has been associated with other chronic pain syndromes, such as fibromyalgia and irritable bowel syndrome [64].

How does one assess vulvodynia?

Medical history

Guidelines on vulvodynia that include suggestions for an adequate assessment and diagnostic work-up have been developed by the ISSVD [65] and American College of Obstetrics and Gynecology (ACOG) [66]. A distinction between LPV and GVD is mainly based on subjective reports and the result of the cotton-swab test. Some health professionals have also developed algorithms for the physical examination of women suspected of suffering from vulvodynia [65,67].

Vulvodynia is a diagnosis of exclusion (for information regarding differential diagnosis, please see [68 –70]). A medical history should identify the patient's past medical and surgical history, risk factors, previous treatments and sexual history. The diagnostic criteria for LPV are based on Friedrich's original criteria: first, severe pain on vestibular touch or attempted vaginal entry; second, tenderness to pressure within the vestibule (i.e., a positive cotton-swab test); and third, physical findings confined to vestibular erythema of various degrees [71]. Studies have not found erythema to be a reliable, useful diagnostic criterion; however, the cotton-swab test has been established as a reliable tool for diagnosing LPV [6,72].

In an attempt to find clinical and psychosexual predictors associated with the diagnosis of vulvodynia upon referral to a physician, some studies have retrospectively performed analyses of patient charts and pathology reports [73 –75]. Bowen et al. found that 61% of refractory vulvodynia patients in a tertiary vulvovaginal clinic had a clinically relevant dermatological condition [73]. The authors therefore recommended taking a vulvar biopsy with analysis by a dermatopathologist as standard practice in the early management of refractory vulvar pain patients. A simple decision-making tree was also proposed, aimed at identifying and treating the most common identifiable causes of vulvar pain: infections and dermatologic diseases. For this approach, a standard pelvic examination is recommended, including wet preparations, vulvar and vaginal cultures (if indicated), and a low threshold for a dermatopathologist-evaluated vulvar biopsy.

Two other retrospective studies examined predictors for the diagnosis of LPV based on the medical records of 250 Danish patients referred to a vulvar clinic and 50 Norwegian patients diagnosed with LPV in a vulvar clinic. The authors of the Danish study found that self-reported dyspareunia and stinging pain was strongly associated with vulvodynia [75]. Self-reported pruritus and a tendency toward fissures in the vulva were not associated with vulvodynia. The authors also questioned whether vulvar biopsies should be performed regularly when redness and pain is present, as only 12.5% of all the biopsies taken demonstrated histopathological signs of a clinically relevant skin disease. The remaining samples showed histopathological signs of chronic, nonspecific inflammation, for which there is no cure at present. The Norwegian study demonstrated that bacterial vaginosis is a statistically significant risk factor (odds ratio: 3.8) for LPV, which led the authors to recommend wet smears as part of routine patient evaluation [74]. Other authors agree with this procedure [76]. In addition, a review on the role of colposcopic examination of the vulva concluded that the use of the colposcope and acetic acid adds little to the examination and diagnosis of women with vulvar complaints [77].

Pain history

A systematic history of the patient's reported pain is important for differential diagnosis [70]. The duration and onset of the pain are important to inquire about; the onset will distinguish between a primary and a secondary condition. The pain site(s) may help the clinician exclude other potential conditions. Asking about eliciting factors can be of help not only in finding a treatable cause but also in helping the patient in her everyday life and avoid possible provocative factors. The characteristics of the pain (e.g., burning, stinging, irritating and raw sensations) may aid in diagnosis.

The patient may have tried different pain treatments, of which most have been ineffective, possibly owing to incorrect dosage or administration. In addition, ineffective treatments may be due to the lack of understanding of pain mechanisms, which do not allow for the most appropriate selection of effective treatments. Compliance is also often a substantial problem in chronic pain conditions, which should lead to a careful history of the length of treatment, dosage, side effects and reasons for ending a treatment. Lastly, it is important to obtain knowledge of the limitations that the pain condition may have on the patient's daily activities, sexual life and mood; this information needs to be taken into account when choosing an appropriate treatment.

The pain is most often described as burning, but it may have an irritating, sharp, stinging, and/or occasionally pruritic (itchy) quality. It may have arisen suddenly, with or without provocation, and may last for several days following coitus or a gynecological examination. In LPV, there is pain upon touching the circumference of the vestibular region. Typically, the most sensitive vestibular areas include the posterior portion of the vestibule (4 to 8 o'clock), just outside the hymeneal ring, but can also involve the areas around the Skene's ducts.

Women with GVD most often experience an unpleasant abnormal sensation over the entire vulvar area. The pain is usually spontaneous, although it can also result from provocation. GVD is believed to be entirely idiopathic, but in rare cases it may result from a dermatological condition or from pudendal nerve entrapment.

It is also important to inquire on the subject of other pain problems, as vulvodynia has been found to be comorbid with conditions such as interstitial cystitis/painful bladder syndrome and irritable bowel syndrome [64].

Physical assessment

In conjunction with the physical examination, an assessment of the pelvic floor should be carried out. Often, the pelvic floor muscles are suspected of contributing to the pain; thus, the pelvic floor should be examined manually and evaluated by EMG biofeedback and other tools when possible. Adding EMG biofeedback to the treatment program may provide the patient with objective information on the relevance and adequacy of pelvic floor training and can provide the clinician with objective assessment for tracking improvement during, and following, treatment [78,79].

Psychosocial & sexual assessment

A professional encountering a woman with vulvar pain should also assess her psychosocial and sexual health. Details on the sexual life of the patient, including any relevant previous and current sexual experiences, should be addressed. The information is best obtained with the patient sitting clothed and after obtaining permission to talk about the subject from the patient. Putting the patient at ease with such gestures will make her feel more comfortable and will probably enable her to speak more freely regarding sexual matters.

Management

Given that the effects of vulvodynia are often complex, an individualized treatment approach is needed. When choosing one or several appropriate treatment modalities, the decision should be based on the results of controlled studies. However, more research is needed to determine what variables predict a satisfactory outcome for the individual patient regarding pain, psychosocial adjustment and sexual function [80].

For decades, treatment decisions have been predominantly based on expert opinion and not on evidence from randomized, clinical trials (RCTs). However, in the last few years, RCTs have shown varying degrees of success for some topical treatments (lidocaine and capsaicin), surgery, cognitive behavior therapy (CBT) and pelvic floor physical therapy. This discussion will primarily focus on RCTs and non-RCTs for LPV, since the literature on treatment for GVD is sparse and does not yet include any RCTs. It is important to note, however, that treatments for GVD and LPV often remain the same, with the exception of surgery. Treatment for LPV can be divided into four categories: medical, surgical, behavioral/cognitive–behavioral and alternative. See Table 1 for a summary of the studies cited below.

Table 1.

Summary of treatment outcome studies presented in the management section.

Treatment	Study	Study characteristics: sample size design	Outcomes	Ref.
Medical Rx (topical/local injections)
Botulinum toxin A (Botox)	Brown et al. (2006)	Two women with LPV received 20 and 40 U of Botox, respectively	One patient reported modest reduction in intercourse pain	[81]*
		Outcomes assessed 12 weeks post-Rx	Both patients demonstrated improvements in pelvic floor muscle function
			No significant changes in vestibular pain sensitivity
	Dykstra & Presthus (2006)	19 women with LPV (seven received 35 U; 12 received 50 U of Botox)	Significant decrease in pain ratings within both groups	[82]*
			Significant improvement in medication use and quality of life
			Duration of effect: 35 U group = 8 weeks; 50 U group = 14 weeks
	Petersen et al. (2009)	64 women with LPV received 20 U of Botox or placebo	Significant decrease in pain ratings within groups, but not between groups (i.e., placebo as successful as Botox injections)	[84]*
		Outcomes assessed 3, 6, 9 and 12 months post-Rx	No significant improvement in sexual function, quality of life or depression following Rx
	Yoon et al. (2007)	Seven women with intractable genital pain received 20 U Botox at multiple genital sites Five women received 40 U after another 2 weeks	All improved at 11-month follow-up	[83]*
Lidocaine	Danielsson et al. (2006)	46 women with LPV randomized to receive EMG biofeedback or topical lidocaine Rx over 4 months	Nine women dropped out during Rx	[36]¶
		Follow-up 6 and 12 months post-Rx	Both groups showed significant improvements in vestibular pain thresholds, quality of life and sexual function at 12-month follow-up
			No significant differences found between the Rx groups at follow-up
	Rapkin et al. (2008)	27 women with LPV (six also experienced unprovoked vestibular pain), for whom previous medical/surgical Rx had been unsuccessful	Significant improvements post-Rx in: vestibular pain sensitivity; self-reported pain ratings, McGill Pain Questionnaire pain ratings; improvements on the Female Sexual Functioning Index (pain and arousal subscales)	[86]*§
		All women received five Rx sessions with caudal epidural, pudendal nerve block and vestibular injections of local anesthetic agents Follow-up occurred 8–12 weeks post-Rx
	Zolnoun et al. (2003)	61 women with LPV applied 5% lidocaine ointment nightly	There were significant improvements pre- to post-Rx in the ability to have intercourse and intercourse-related pain scores	[85]§
		Pain ratings were measured daily and post-Rx Mean Rx length = 7 weeks
Topical gabapentin	Boardman et al. (2008)	51 women with vulvodynia (37% [19/51] diagnosed with GVD; 63% [32/51] diagnosed with LPV) treated with 2–6% gabapentin	Pain ratings reduced by 50% in both women with GVD and LPV	[87]
			Increased sexual function in women with LPV
Medical Rx (systemic medications)
TCAs	Reed et al. (2006)	209 out of 271 women diagnosed with vulvodynia were treated with TCAs Follow-up of 60% (162/271) of women initially diagnosed with vulvodynia	Women prescribed a TCA were more likely to report over 50% improvement in pain, compared with women not taking such medications at follow-up 59% of TCA group (n = 49/83) improved, versus 38% (n = 30/79) of women not taking TCAs at follow-up	[88]‡
Gabapentin	Harris et al. (2007)	152 women with unprovoked GVD treated with gabapentin, who were followed-up for 30 months or more	64% (n = 98) reported resolution of at least 80% of their symptoms	[89]‡
			26% (n = 40) reported side effects (e.g., fatigue), with 11% (n = 17) discontinuing Rx owing to side effects
Surgical Rx
	Bergeron et al.	78 women with LPV randomly assigned to EMG biofeedback (12 weeks), group cognitive behavioral therapy (12 weeks) or vestibulectomy Rx	All groups reported significant pain reduction on pain measures post-Rx and at follow-up (only study completers included in analyses)	[95,96]
		Outcomes assessed post-Rx, with 6-month and 2.5-year post-Rx follow-up (n = 51)	Vestibulectomy was significantly more successful than the other two Rxs; however, seven women assigned to the group did not undergo the surgery
			All groups reported significant improvement in psychosexual function at 6-month follow-up At 2.5-year follow-up, treatment gains maintained, with women reporting less pain compared with 6-month follow-up
	Bohm-Starke & Rylander (2008)	67 women with LPV who underwent vestibulectomy; follow-up minimum of 12 months following Rx	56% of women with secondary LPV and 17% of women with primary LPV reported complete or major improvement	[94]‡
			79% reported improved psychological function Significant improvement in reported quality of life and intercourse pain
	Eva et al. (2008)	110 women with LPV who underwent vestibulectomy; follow-up at 2 months and 1 year following Rx	Pain scores continuously improved throughout follow-up	[93]‡
			Mean patient satisfaction = eight out of ten 83% reported they would recommend the procedure as an effective Rx for LPV
Psychosexual & behavioral Rx
	Backman et al. (2008)	24 women with LPV underwent combined physical and psychosexual therapy	79% (19/24) reported total or great improvement Significant increase in intercourse frequency Significant decrease in intercourse pain	[34]§
		Outcomes assessed minimum 6 months post-Rx
		Mean Rx length = 15 and 12 weeks, respectively
	Bergeron et al.	See above	See above	[95,96]¶
	Masheb et al. (2009)	50 women with vulvodynia underwent 10 weeks of CBT or SPT	Significant decrease in pain severity and improvement in sexual function post-Rx 42% (n = 21) achieved clinical improvement Rx effects maintained at 1 year follow-up CBT group reported significantly greater improvement, satisfaction and credibility, compared with the SPT group	[97]¶
		Outcomes assessed post-Rx and at 1 year follow-up (n = 47)
	ter Kuile et al. (2006)	76 women with LPV underwent CBT Follow-up 12 weeks post-Rx	Participants reported significant reductions in dyspareunia and significant improvements in sexual satisfaction and perceived pain were found from pre- to post-Rx	[98]§
Alternative Rx
TENS	Murina et al. (2008)	40 women with LPV underwent Rx twice weekly (TENS or sham Rx), over 20 Rx sessions	TENS group demonstrated significant improvements in:	[99]¶
		Outcomes measured post-Rx and at 3 months follow-up	Pain ratings and scores on the McGill Pain Questionnaire (short-form);
			Scores on the Marinoff Scale for dyspareunia Scores on the Female Sexual Functioning Index Improvements maintained at follow-up There was no improvement in any outcome measures in the placebo group
Pulsed laser therapy	Leclair et al. (2007)	41 women with LPV who had undergone laser Rx were contacted for a follow-up survey (final n = 37)	68% (24 patients) reported decreased pain during intercourse; 29% (11 patients) reported no change in pain; one patient reported increased pain following Rx	[100]‡
			60% (21 patients) reported increases in sexual satisfaction
			35% had undergone surgery post-laser therapy
Acupuncture	Powell & Wojnarowska (1999)	12 women with vulvodynia attended weekly acupuncture sessions over 5 weeks	42% (five patients) reported significant or total improvement; 33% (four patients) reported some improvement; 25% (three patients) reported no improvement	[102]*
Hypnosis	Pukall et al. (2007)	Eight women with LPV underwent six hypnotherapy sessions	Significant decreases in gynecological examination pain and intercourse pain, as well as on some measures of noncoital vulvar pain	[103]*
		Follow-up conducted 1 and 6 months post-Rx	No significant improvement in vestibular pain thresholds and no changes in psychosocial measures post-Rx
			Improvement in overall sexual function
Transcranial direct electrical stimulation	Cecilio et al. (2008)	Case study: GVD pain presentation; ten daily sessions of transcranial direct electrical stimulation over 2 weeks	Pain relief beginning 4 weeks post-Rx; improvement peaked 8 weeks post-Rx	[101]
			Improvement in mood reported

The above table contains a summary of the treatment studies included in the management section of the paper; however, for a comprehensive review please see Landry et al. [80].

Pilot study

‡

Retrospective study

Prospective study

Randomized controlled trial.

CBT: Cognitive-behavioral therapy; EMG: Electromyographic; GVD: Generalized vulvodynia; LPV: Localized provoked vestibulodynia; Rx: Treatment

SPT: Supportive psychotherapy; TCA: Tricyclic antidepressants; TENS: Transcutaneous electrical nerve stimulation; U: Units.

Medical treatment options

Several medical therapies, consisting of topical or intralesionally administered drugs and oral drugs, have been evaluated in predominantly open trials.

Topical/local injections

The effect of locally active drugs, such as fluconazole, cromolyn cream, capsaicin cream and intralesional β-interferon, have not been proven successful, yet RCT studies are still warranted. Other topical and injectable treatments, such as Botulinum toxin A (Botox®, Allergen, Irvine, CA, USA), lidocaine and topical gabapentin, have recently been investigated.

Botox is hypothesized to reduce the hypertonicity of the pelvic floor muscles and peripheral neuropathy, thus leading to less pain and improved sexual function. It has recently been tested in pilot studies and has shown promising results [81 –83]; however, these studies suffer from serious methodological flaws (e.g., small sample sizes, heterogeneous vulvar pain groups and short follow-up assessments), which limit any recommendation. Furthermore, the results of the first-ever RCT of Botox raise questions regarding the utility of this treatment [84]. This randomized, placebo-controlled, double-blinded study found that injections of 25 units (U) in the vestibular epithelium and the underlying introital muscles of women with LPV produced significant pain reduction within both the Botox and placebo groups at 6-month follow-up. In addition, pain reduction, sexual functioning and quality of life were not more significantly improved in the Botox versus placebo group. Further studies of this kind are needed in order to establish the efficacy of Botox for vulvodynia.

Two RCTs on the effect of lidocaine (topical or injectable) for LPV have demonstrated significant results. Lidocaine 5% ointment has been demonstrated to be effective as an overnight treatment by Zolnoun et al.; it reduced dyspareunia by 50% [85]. Lidocaine 5% ointment has also recently been proven effective in a prospective randomized study, when used topically multiple times daily, in comparison with EMG biofeedback. No differences in outcome between the two treatments were observed and the authors concluded that the two treatments may potentially be more efficacious if combined [36]. Furthermore, treatment with multilevel local lidocaine neural blockades, consisting of caudal epidural, pudendal and vulvar vestibular injections has recently been tested in a pilot study and demonstrated significant improvement in pain thresholds (41%) and tolerance (51%) [86].

Topical gabapentin has been tested in a retrospective study. Results indicated that pain ratings were reduced by 50% in both women with generalized and localized vulvodynia; furthermore, it was shown to increase sexual function among women with LPV. The drug, however, may not be available as an ointment in some countries [87].

Systemic medications

Systemic pharmacologic therapy for vulvodynia consists mostly of tricyclic antidepressant medications, such as amitriptyline, imipramine, nortriptyline and desipramine, selective serotonin reuptake inhibitors, serotonin–norepinephrine reuptake inhibitors, and anticonvulsants. Systemic medical treatments are often mentioned as second-line therapy after improving vulvar hygiene, despite the lack of evidence for this step-wise approach. The few studies investigating the effect of systemic medical treatment are nonrandomized and have many methodological limitations, limiting their potential for recommendations in guidelines. A recent retrospective study by Reed et al. demonstrated that women with vulvodynia who were treated with tricyclic antidepressant medications demonstrated reductions of more than 50% in their pain ratings [88].

Antiepileptic drugs (e.g., gabapentin or pregabalin) have also been demonstrated to result in some positive effects. For example, one retrospective study indicated that 64% of women with GVD reported a reduction of at least 80% in subjective complaints (primarily burning pain in the vulva, dyspareunia and vulvar irritation) following 30 months of treatment with gabapentin [89].

A common problem for all systemic medications is their side-effect profile. Despite the lower dosages for pain than what is required for the treatment for depression, antidepressant medications may negatively impact a patient's quality of life, daily activities and sexual function. RCTs are needed to clarify the correct dosage, the effectiveness and the long-term implications on the predominantly young population affected by vulvodynia.

Surgical treatment

Surgical treatment for vestibulodynia has evolved greatly over the past 25 years since Woodruff and Parmley initially described perineoplasty for vestibulodynia [90]. The most utilized method today is the modified vestibulectomy [91]. This procedure typically consists of the excision of the hymeneal ring from the 3 to 9 o'clock position and of the superficial vestibular mucosa in the vestibulum to Hart's line. Approximately 2–3 cm of the posterior vaginal mucosa is then undermined and advanced to cover the area of excised tissue. Prospective studies have documented the positive effect of the procedure [92]. A retrospective study by Eva et al. found that vestibulectomy is an effective long-term treatment for women with LPV with high levels of patient satisfaction, low complication rates and lower pain scores from pre- to post-treatment (1-year follow-up) [93]. Another study by Bohm-Starke et al. demonstrated that complete or major improvement was reported by 56% of women with secondary LPV and 17% of women with primary LPV [94]. The authors concluded that the monitoring of surgical outcome should include questions on pain relief and psychosexual wellbeing.

Bergeron et al. published the results from the first randomized treatment outcome study of vestibulectomy, EMG biofeedback and CBT in 2001 [95]. The study focused on women with LPV and results demonstrated that long-term treatment gains associated with vestibulectomy, biofeedback and CBT are maintained at 2.5 years [96]. This study has demonstrated that women continue to benefit from the positive effect of such treatments over time. However, the authors concluded that patients who have an avoidant attitude towards sex should not be offered vestibulectomy as a first-line treatment; furthermore, they advise that sex therapy be introduced prior to and postsurgical treatment, since sexual function did not improve proportionally to pain reduction.

Psychosexual & behavioral treatment

The complexity of the clinical features of chronic pain in the vulva often affects psychosexual health, leading to or exacerbating symptoms of anxiety, somatization, depression and sexual dysfunction. In addition, the pelvic floor muscles may become more tense. To address these aspects, a multidisciplinary approach is often needed, which has been increasingly acknowledged in the literature [65]. Since the publication of the first randomized treatment outcome study in 2001 [95], one other controlled study and two prospective studies examining psychosexual treatment for women with LPV have been published, with promising results [34,97,98].

In a 2001 study by Bergeron et al., results demonstrated that participants in all three treatment groups (EMG biofeedback, CBT and surgery) reported statistically significant reductions on pain measures at post-treatment and at 6-month follow-up [95]. Although vestibulectomy was demonstrated to be more effective with regard to pain reduction than the other two treatments, many participants dropped out of the surgery-treatment arm. All three groups demonstrated equally significant improvement in psychosexual functioning. A 2.5-year follow-up demonstrated that post-treatment gains were maintained [96]. In 2006, ter Kuile et al. published their results from a prospective open trial of CBT (n = 76) for LPV lasting 12 weeks. Participants reported significant reductions in dyspareunia, and significant improvements in sexual satisfaction and perceived pain were found from pre- to post-treatment [98].

To standardize and evaluate a program of combined physical and psychosexual therapy, a Swedish research group undertook an open trial, prospective study on 24 women with LPV. The women took part in sessions with a psychosexual counselor and were taught exercises for mucosal desensitization and re-establishment of pelvic floor function by a midwife. Results indicated that 79% (19 out of 24) of participants reported symptom remission or great improvement. Intercourse frequency was significantly increased and coital pain was significantly reduced from pre- to post-treatment [34].

Masheb et al. compared the efficacy of CBT and supportive psychotherapy. Results demonstrated that while both treatments lead to improvements, CBT participants experienced a greater improvement in pain severity and overall sexual functioning than supportive psychotherapy participants. These improvements were maintained at 1-year follow-up [97].

Alternative treatments

Despite the many treatment avenues available to women with LPV, none have been demonstrated to be effective for all women. Therefore, researchers continue to seek new treatments for LPV. Some seek to modulate the peripheral nervous system; for example, one new approach is transcutaneous electrical nerve stimulation (TENS). An RCT of TENS has reported that it is a simple, effective and safe treatment [99]. Despite a short follow-up period of 3 months, this study demonstrated that the TENS group improved with respect to pain intensity and sexual function as compared with the control group. A longer follow-up period is called for to estimate the efficacy of TENS, which is known to be effective in other chronic pain conditions, mainly owing to the ‘gate control theory of pain’ mechanism and hypothesized release of endogenous opioids by stimulation of afferent and motor fibers.

A second approach has been to test whether pulsed laser therapy, as an alternative to vestibulectomy, can reduce sexual pain and function related to LPV. Leclair et al. performed a retrospective investigation among 37 women and found that 24 of the respondents reported less pain with sexual intercourse [100]. Despite the lack of a control group, laser therapy may be an attractive alternative to women who do not respond to medical treatment or who wish to avoid the more invasive surgery.

Pilot studies have tested the effect of acupuncture, hypnosis and transcranial direct current stimulation [101 –103]; however, results from controlled studies need to be published before recommendations can be made.

Combined treatments: the multimodal approach

For many years, recommendations for the management of vulvodynia have been based on isolated medical, surgical, physical, cognitive–behavioral and alternative therapies. A multimodal approach is increasingly being recommended despite very few studies on any combination of therapies. In addition, the question of how to prioritize the line of treatments remains unanswered. Some initial data, however, can help with this question. Backman et al. evaluated and standardized a combined physical and psychosexual therapy for women with LPV [34]. The authors established a combined program consisting of sessions with a psychosexual counselor in which issues related to sexual functioning, psychological adjustments and stress were discussed. Exercises for mucosal desensitization and re-establishment of pelvic floor function were furthermore established and supervised by a midwife. Results were positive, illustrating the importance of adopting a multimodal approach.

Executive summary

Vulvodynia

Vulvodynia, or chronic vulvar pain, is a prevalent condition, affecting 16% of women in the general population.

Despite its high prevalence and negative ramifications, much remains unknown regarding the factors involved in the etiology and maintenance of vulvodynia.

Few methodologically sound treatment investigations and even fewer controlled trials exist in the literature.

Definitions and prevalence of vulvodynia

Vulvodynia can be either generalized or localized.

Different subtypes of vulvodynia exist, the most common of which is localized, provoked vestibulodynia (LPV).

Pathophysiology

The etiology of vulvodynia remains unclear, although it is believed to result from a multifactorial process.

The general consensus in the field is that the pain is triggered by a physical occurrence; as time progresses and the pain continues, a vicious cycle develops that involves both physical and psychosocial factors.

Pathophysiological changes in at least three interdependent systems (nervous system pain regulatory pathways, pelvic floor muscles, and the patient's psychosocial and sexual function) may play a role in vulvodynia.

Assessment of vulvodynia

Vulvodynia is a diagnosis of exclusion.

A thorough assessment of vulvodynia includes a medical history, pain history, physical assessment and questions pertaining to psychosocial wellbeing and sexual function.

The pelvic floor musculature should also be examined with appropriate methods.

Management

When choosing one or several appropriate treatment modalities, the decision should be based on the results of controlled studies and not on expert opinion.

Therapeutic options include medical, surgical, behavioral/cognitive–behavioral and alternative therapies.

Few randomized, controlled trials exist and few studies examine combination therapy. However, the field is growing and movements towards more rigorous treatment approaches are occurring.

Conclusion

The absence of a clear pathology should not lead one to conclude that a purely psychological explanation exists for the pain.

A thorough clinical examination, recognition of the emotional repercussions and knowledge of the treatment options available can lead to the appropriate multimodal treatment for the patient.

Treatment expectations should be realistic.

Future perspective

An integrated classification system that includes an assessment of the multiple factors potentially involved in vulvodynia should be developed in an attempt to lead to individualized and multimodal treatment plans.

As more studies examine a multimodal approach to the treatment of vulvodynia, healthcare professionals will have to communicate more frequently and work together more closely. Currently, referrals for each form of treatment (e.g., psychotherapy and physical therapy) tend to be made independently, with waiting lists of varying lengths depending on the health professional. Thus, if treatment gains are maximized through treatment combinations, changes in the structure of vulvodynia patient care will be necessary.

Conclusion

The absence of a clear pathology should not lead one to conclude that a purely psychological explanation exists for the pain, especially since all diagnoses of vulvodynia and its subtypes are diagnoses of exclusion. A thorough clinical examination, recognition of the emotional and sexual repercussions, and knowledge of the treatment options available can lead to the appropriate multimodal treatment for the patient. The patient and clinician should work together to determine the treatment avenue, and expectations should be realistic. A quick cure will not be likely in most cases, even if a treatment has proven to be effective in research. Patience will be needed: pain reduction and psychosexual improvement may take weeks, months or years. Unfortunately, vulvodynia and its subtypes remain a challenge for clinicians to manage, and it continues to have negative consequences for women's overall health.

Future perspective

An integrated classification system that includes an assessment of the multiple factors potentially involved in vulvodynia (e.g., inflammation, pelvic floor dysfunction and psychosexual variables) should be developed in an attempt to lead to individualized and multimodal treatment plans. Although one paper includes some of this information as a guideline [15], it has not been empirically tested. Predictors of who will be likely to benefit most from which treatment(s) would aid clinicians and patients alike.

Footnotes

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

References

Papers of special note have been highlighted as:

of interest

of considerable interest

Harlow

Wise

Stewart

: Prevalence and predictors of chronic lower genital tract discomfort. Am. J. Obstet. Gynecol. 185, 545–550 (2001).

First epidemiological study of chronic vulvar pain.

Harlow

Stewart

: A population-based assessment of chronic unexplained vulvar pain: have we underestimated the prevalence of vulvodynia? J. Am. Med. Womens Assoc. 58, 82–88 (2003).

Pukall

Payne

Kao

Khalifé

Binik

: Dyspareunia. In: Handbook of Sexual Dysfunction. Balon

Segraves

(Eds). Taylor & Francis, NY, USA 249–272 (2005).

Arnold

Bachmann

Rosen

Kelly

Rhoads

: Vulvodynia: characteristics and associations with comorbidities and quality of life. Obstet. Gynecol. 107, 617–624 (2006).

Moyal-Barracco

Lynch

: 2003 ISSVD terminology and classification of vulvodynia: A historical perspective. J. Reprod. Med. 49, 772–777 (2004).

10.

Summary of the history of the terminology of vulvodynia and the most recent classification and terminology.

11.

Bergeron

Binik

Khalifé

Pagidas

Glazer

: Vulvar vestibulitis syndrome: reliability of diagnosis and evaluation of current diagnostic criteria. Obstet. Gynecol. 98, 45–51 (2001).

12.

Laumann

Paik

Rosen

: Sexual dysfunction in the United States: prevalence and predictors. JAMA 281, 537–544 (1999).

13.

Hayes

Bennett

Fairley

Dennerstein

: What can prevalence studies tell us about female sexual difficulty and dysfunction? J. Sex. Med. 3, 589–595 (2006).

14.

Hayes

Dennerstein

Bennett

Fairley

: What is the ‘true’ prevalence of female sexual dysfunctions and does the way we assess these conditions have an impact? J. Sex. Med. 5, 777–787 (2008).

15.

Reed

Haefner

Sen

Gorenflo

: Vulvodynia incidence and remission rates among adult women: a 2-year follow-up study. Obstet. Gynecol. 112, 231–237 (2008).

16.

Sutton

Bachmann

Arnold

Rhoads

Rosen

: Assessment of vulvodynia symptoms in a sample of U.S. women: a follow-up national incidence survey. J. Womens Health (Larchmt) 17, 1285–1292 (2008).

17.

Schultz

Weijmar W

Basson

Binik

: Women's sexual pain and its management. J. Sex. Med. 2, 301–316 (2005).

18.

Lynch

: Vulvodynia as a somatoform disorder. J. Reprod. Med. 53, 390–396 (2008).

19.

Mascherpa

Bogliatto

Lynch

Micheletti

Benedetto

: Vulvodynia as a possible somatization disorder. More than just an opinion. J. Reprod. Med. 52, 107–110 (2007).

20.

Goldstein

Pukall

: Provoked vestibulodynia. In: Female Sexual Pain Disorders: Evaluation and Management. Goldstein

Pukall

Goldstein

(Eds). Wiley-Blackwell, Oxford, England, 43–48 (2009).

21.

Zolnoun

Hartmann

Lamvu

: A conceptual model for the pathophysiology of vulvar vestibulitis syndrome. Obstet. Gynecol. Surv. 61, 395–401 (2006).

22.

First paper to present a unified conceptual model of vulvodynia that encompasses multiple levels of pathophysiology.

23.

Sarma

Foxman

Bayirli

Haefner

Sobel

: Epidemiology of vulvar vestibulitis syndrome: an exploratory case–control study. Sex. Transm. Infect. 75, 320–326 (1999).

24.

Ehrstrom

Rylander

: Glucose in vaginal secretions before and after oral glucose tolerance testing in women with and without recurrent vulvovaginal candidiasis. Obstet. Gynecol. 108, 1432–1437 (2006).

25.

Foster

Piekarz

Murant

: Enhanced synthesis of proinflammatory cytokines by vulvar vestibular fibroblasts: implications for vulvar vestibulitis. Am. J. Obstet. Gynecol. 196, 346 E1–E348 (2007).

26.

Chadha

Gianotten

Drogendijk

: Histopathologic features of vulvar vestibulitis. Int. J. Gynecol. Pathol. 17, 7–11 (1998).

27.

Bornstein

Cohen

Zarfati

Sela

Ophir

: Involvement of heparanase in the pathogenesis of localized vulvodynia. Int. J. Gynecol. Pathol. 27, 136–141 (2008).

28.

Galli

: New concepts about the mast cell. N. Engl. J. Med. 328, 257–265 (1993).

29.

Bohm-Starke

Hilliges

Falconer

Rylander

: Increased intraepithelial innervation in women with vulvar vestibulitis syndrome. Gynecol. Obstet. Invest. 46, 256–260 (1998).

30.

Halperin

Zehavi

Vaknin

Ben-Ami

Pansky

Schneider

: The major histopathology characteristics in the vulvar vestibulitis syndrome. Gynecol. Obstet. Invest. 59, 75–79 (2005).

31.

Weström

Willén

: Vestibular nerve fiber proliferation in vulvar vestibulitis syndrome. Obstet. Gynecol. 91, 572–576 (1998).

32.

Foster

Sazenski

Stodgell

: Impact of genetic variation in interleukin-1 receptor antagonist and melanocortin-1 receptor genes on vulvar vestibulitis syndrome. J. Reprod. Med. 49, 503–509 (2004).

33.

Gerber

Bongiovanni

Ledger

Witkin

: Interleukin-1β gene polymorphism in women with vulvar vestibulitis syndrome. Eur. J. Obstet. Gynecol. Reprod. Biol. 107, 74–77 (2003).

34.

Jeremias

Ledger

Witkin

: Interleukin 1 receptor antagonist gene polymorphism in women with vulvar vestibulitis. Am. J. Obstet. Gynecol. 182, 283–285 (2000).

35.

Fenton

: Limbic associated pelvic pain: a hypothesis to explain the diagnostic relationships and features of patients with chronic pelvic pain. Med. Hypotheses 69, 282–286 (2007).

36.

Pukall

Strigo

Binik

: Neural correlates of painful genital touch in women with vulvar vestibulitis syndrome. Pain 115, 118–127 (2005).

37.

First brain imaging study of vulvodynia.

38.

Schweinhardt

Kuchinad

Pukall

Bushnell

: Increased gray matter density in young women with chronic vulvar pain. Pain 140, 411–419 (2008).

39.

Reissing

Binik

Khalifé

Cohen

Amsel

: Vaginal spasm, pain, and behavior: an empirical investigation of the diagnosis of vaginismus. Arch. Sex. Beh. 33, 5–17 (2004).

40.

Reissing

Brown

Lord

Binik

Khalifé

: Pelvic floor muscle functioning in women with vulvar vestibulitis syndrome. J. Psychosom. Obstet. Gynaecol. 26, 107–113 (2005).

41.

Backman

Widenbrant

Bohm-Starke

Dahlof

: Combined physical and psychosexual therapy for provoked vestibulodynia – an evaluation of a multidisciplinary treatment model. J. Sex. Res. 45, 378–385 (2008).

42.

First published paper on a combination therapy for vestibulodynia.

43.

Bergeron

Brown

Lord

: Physical therapy for vulvar vestibulitis syndrome: a retrospective study. J. Sex Marital Ther. 28, 183–192 (2002).

44.

Danielsson

Torstensson

Brodda-Jansen

Bohm-Starke

: EMG biofeedback versus topical lidocaine gel: a randomized study for the treatment of women with vulvar vestibulitis. Acta Obstet. Gynecol. Scand. 85, 1360–1367 (2006).

45.

Glazer

Rodke

Swencionis

Hertz

Young

: Treatment of vulvar vestibulitis syndrome with electromyographic biofeedback of pelvic floor musculature. J. Reprod. Med. 40, 283–290 (1995).

46.

Goldfinger

Pukall

Gentilcore-Saulnier

McLean

Chamberlain

: A prospective study of the effectiveness of pelvic floor physical therapy: pain and psychosexual outcomes in provoked vestibulodynia. J. Sex. Med. (2009) (In press).

47.

First study to prospectively examine pelvic floor physical therapy in women with vestibulodynia.

48.

Hartmann

Strauhal

Nelson

: Treatment of women in the United States with localized, provoked vulvodynia: practice survey of women's health physical therapists. J. Reprod. Med. 52, 48–52 (2007).

49.

Brotto

Basson

Gehring

: Psychological profiles among women with vulvar vestibulitis syndrome: a chart review. J. Psychosom. Obstet. Gynaecol. 24, 195–203 (2003).

50.

Danielsson

Sjoberg

Wikman

: Vulvar vestibulitis: medical, psychosexual and psychosocial aspects, a case–control study. Acta Obstet. Gynecol. Scand. 79, 872–878 (2000).

51.

Reed

Haefner

Punch

: Psychosocial and sexual functioning in women with vulvodynia and chronic pelvic pain. A comparative evaluation. J. Reprod. Med. 45, 624–632 (2000).

52.

Gates

Galask

: Psychological and sexual functioning in women with vulvar vestibulitis. J. Psychosom. Obstet. Gynaecol. 22, 221–228 (2001).

53.

Wylie

Hallam-Jones

Harrington

: Psychological difficulties within a group of patients with vulvodynia. J. Psychosom. Obstet. Gynaecol. 25, 257–265 (2004).

54.

Masheb

Wang

Lozano

Kerns

: Prevalence and correlates of depression in treatment-seeking women with vulvodynia. J. Obstet. Gynaecol. 25, 786–791 (2005).

55.

Arnold

Bachmann

Rosen

Rhoads

: Assessment of vulvodynia symptoms in a sample of US women: a prevalence survey with a nested case control study. Am. J. Obstet. Gynecol. 196, 128 E1–E6 (2007).

56.

Aikens

Reed

Gorenflo

Haefner

: Depressive symptoms among women with vulvar dysesthesia. Am. J. Obstet. Gynecol. 189, 462–466 (2003).

57.

Granot

Lavee

: Psychological factors associated with perception of experimental pain in vulvar vestibulitis syndrome. J. Sex Marital Ther. 31, 285–302 (2005).

58.

Pukall

Baron

Amsel

Khalifé

Binik

: Tender point examination in women with vulvar vestibulitis syndrome. Clin. J. Pain 22, 601–609 (2006).

59.

Brauer

Laan

ter Kuile

: Sexual arousal in women with superficial dyspareunia. Arch. Sex. Beh. 35, 191–200 (2006).

60.

Hallam-Jones

Wylie

Osborne-Cribb

Harrington

Walters

: Sexual difficulties within a group of patients with vulvodynia. Sex. Rel. Ther. 16, 113–126 (2001).

61.

Payne

Binik

Pukall

: Effects of sexual arousal on genital and non-genital sensation: a comparison of women with vulvar vestibulitis syndrome and healthy controls. Arch. Sex. Beh. 36, 289–300 (2007).

62.

Sutton

Pukall

Chamberlain

: Pain, psychosocial, sexual, and psychophysical characteristics of women with primary vs. secondary provoked vestibulodynia. J. Sex. Med. 6, 205–214 (2009).

63.

Meana

Binik

Khalifé

Cohen

: Biopsychosocial profile of women with dyspareunia. Obstet. Gynecol. 90, 583–589 (1997).

64.

Flor

Turk

Scholz

: Impact of chronic pain on the spouse: marital, emotional and physical consequences. J. Psychosom. Res. 31, 63–71 (1987).

65.

Kerns

Haythornthwaite

Southwick

Giller

Jr : The role of marital interaction in chronic pain and depressive symptom severity. J. Psychosom. Res. 34, 401–408 (1990).

66.

Desrosiers

Bergeron

Meana

: Psychosexual characteristics of vestibulodynia couples: partner solicitousness and hostility are associated with pain. J. Sex. Med. 5, 418–427 (2008).

67.

Jodoin

Bergeron

Khalifé

: Male partners of women with provoked vestibulodynia: attributions for pain and their implications for dyadic adjustment, sexual satisfaction, and psychological distress. J. Sex. Med. 5, 2862–2870 (2008).

68.

Bazin

Bouchard

Brisson

: Vulvar vestibulitis syndrome: an exploratory case–control study. Obstet. Gynecol. 83, 47–50 (1994).

69.

Bouchard

Brisson

Fortier

Morin

Blanchette

: Use of oral contraceptive pills and vulvar vestibulitis: a case–control study. Am. J. Epidemiol. 156, 254–261 (2002).

70.

Harlow

Vitonis

Stewart

: Influence of oral contraceptive use on the risk of adult-onset vulvodynia. J. Reprod. Med. 53, 102–110 (2008).

71.

Bohm-Starke

Johannesson

Hilliges

Rylander

Torebjork

: Decreased mechanical pain threshold in the vestibular mucosa of women using oral contraceptives: a contributing factor in vulvar vestibulitis? J. Reprod. Med. 49, 888–892 (2004).

72.

Stewart

Berger

: Parallel pathologies? Vulvar vestibulitis and interstitial cystitis. J. Reprod. Med. 42, 131–134 (1997).

73.

Pukall

Binik

: Vulvodynia. In: Functional Pain Syndromes: Presentation and Pathophysiology. Mayer

Bushnell

(Eds). IASP Press, Washington, DC, USA, 71–84 (2009).

74.

Haefner

Collins

Davis

: The vulvodynia guideline. J. Low. Genit. Tract. Dis. 9, 40–51 (2005).

75.

ACOG Committee on Gynecologic Practice: ACOG current opinion: number 345, October 2006: vulvodynia. Obstet. Gynecol. 108, 1049–1052 (2006).

76.

Stewart

: Developments in vulvovaginal care. Curr. Opin. Obstet. Gynecol. 14, 483–488 (2002).

77.

Dennerstein

Scurry

Brenan

Allen

Marin

: The Vulva & Vaginal Manual. Gynederm Publishing, Victoria, Australia (2005).

78.

Heller

Wallach

: Vulvar Disease: A Clinicopathological Approach. Informa Healthcare, NY, USA (2007).

79.

Kaufman

Faro

Brown

: Benign Diseases of the Vulva (5th edition). Mosby, Philadelphia, PA, USA (2005).

80.

Friedrich

: Vulvar vestibulitis syndrome. J. Reprod. Med. 32, 110–114 (1987).

81.

Masheb

Lozano

Richman

Minkin

Kerns

: On the reliability and validity of physician ratings for vulvodynia and the discriminant validity of its subtypes. Pain Med. 5, 349–358 (2004).

82.

Bowen

Vester

Marsden

: The role of vulvar skin biopsy in the evaluation of chronic vulvar pain. Am. J. Obstet. Gynecol. 199, 467 E1–E6 (2008).

83.

Edgardh

Abdelnoor

: Vulvar vestibulitis and risk factors: a population-based case–control study in Oslo. Acta Derm. Venereol. 87, 350–354 (2007).

84.

Petersen

Kristensen

Lundvall

Giraldi

: Which diagnostic procedures are relevant for women who may have vulvodynia? A retrospective study. J. Reprod. Med. (2009) (In press).

85.

Goldstein

Pukall

Goldstein

: Vulvovaginitis. In: Female Sexual Pain Disorders: Evaluation and Management. Wiley-Blackwell, Oxford, UK, 95–104 (2006).

86.

Micheletti

Bogliatto

Lynch

: Vulvoscopy: review of a diagnostic approach requiring clarification. J. Reprod. Med. 53, 179–182 (2008).

87.

Abbott

: The use of botulinum toxin in the pelvic floor for women with chronic pelvic pain – a new answer to old problems? J. Minim. Invasive Gynecol. 16(2), 130–135 (2008).

88.

Jantos

: Vulvodynia: a psychophysiological profile based on electromyographic assessment. Appl. Psychophysiol. Biofeedback 33, 29–38 (2008).

89.

Landry

Bergeron

Dupuis

Desrochers

: The treatment of provoked vestibulodynia: a critical review. Clin. J. Pain 24, 155–171 (2008).

90.

Brown

Glazer

Vogt

Menkes

Bachmann

: Subjective and objective outcomes of botulinum toxin type A treatment in vestibulodynia: pilot data. J. Reprod. Med. 51, 635–641 (2006).

91.

Dykstra

Presthus

: Botulinum toxin type A for the treatment of provoked vestibulodynia: an open-label, pilot study. J. Reprod. Med. 51, 467–470 (2006).

92.

Yoon

Chung

Shim

: Botulinum toxin A for the management of vulvodynia. Int. J. Impot. Res. 19, 84–87 (2007).

93.

Petersen

Giraldi

Lundvall

Kristensen

: Botulinum toxin A – a novel treatment for provoked vestibulodynia? Results from a randomized, placebo controlled, double blinded study. J. Sex. Med. (2009) (In press).

94.

First-ever randomized, controlled trial of Botox® for the treatment of vestibulodynia.

95.

Zolnoun

Hartmann

Steege

: Overnight 5% lidocaine ointment for treatment of vulvar vestibulitis. Obstet. Gynecol. 102, 84–87 (2003).

96.

Rapkin

McDonald

Morgan

: Multilevel local anesthetic nerve blockade for the treatment of vulvar vestibulitis syndrome. Am. J. Obstet. Gynecol. 198, 41 e1–e5 (2008).

97.

Boardman

Cooper

Blais

Raker

: Topical gabapentin in the treatment of localized and generalized vulvodynia. Obstet. Gynecol. 112, 579–585 (2008).

98.

Reed

Caron

Gorenflo

Haefner

: Treatment of vulvodynia with tricyclic antidepressants: efficacy and associated factors. J. Low. Genit. Tract. Dis. 10, 245–251 (2006).

99.

Harris

Horowitz

Borgida

: Evaluation of gabapentin in the treatment of generalized vulvodynia, unprovoked. J. Reprod. Med. 52, 103–106 (2007).

100.

Woodruff

Parmley

: Infection of the minor vestibular gland. Obstet. Gynecol. 62, 609–612 (1983).

101.

Goldstein

: Surgery for vulvar vestibulitis syndrome. J. Sex. Med. 3, 559–562 (2006).

102.

Kehoe

Luesley

: Vulvar vestibulitis treated by modified vestibulectomy. Int. J. Gynaecol. Obstet. 64, 147–152 (1999).

103.

Eva

Narain

Orakwue

Luesley

: Is modified vestibulectomy for localized provoked vulvodynia an effective long-term treatment? A follow-up study. J. Reprod. Med. 53, 435–440 (2008).

104.

Bohm-Starke

Rylander

: Surgery for localized, provoked vestibulodynia: a long-term follow-up study. J. Reprod. Med. 53, 83–89 (2008).

105.

Bergeron

Binik

Khalifé

: A randomized comparison of group cognitive – behavioral therapy, surface electromyographic biofeedback, and vestibulectomy in the treatment of dyspareunia resulting from vulvar vestibulitis. Pain 91, 297–306 (2001).

106.

First-ever published randomized treatment outcome study for vestibulodynia.

107.

Bergeron

Khalifé

Glazer

Binik

: Surgical and behavioral treatments for vestibulodynia: two-and-one-half year follow-up and predictors of outcome. Obstet. Gynecol. 111, 159–166 (2008).

108.

Report of the 2.5-year follow-up of the first-ever published randomized treatment outcome study for vestibulodynia.

109.

Masheb

Kerns

Lozano

Minkin

Richman

: A randomized clinical trial for women with vulvodynia: cognitive-behavioral therapy vs. supportive psychotherapy. Pain 141, 31–40 (2009).

110.

First-ever randomized trial examining psychotherapy for vestibulodynia.

111.

ter Kuile

Weijenborg

: A cognitive-behavioral group program for women with vulvar vestibulitis syndrome (VVS): factors associated with treatment success. J. Sex Marital Ther. 32, 199–213 (2006).

112.

Murina

Bianco

Radici

Felice

Di Martino

Nicolini

: Transcutaneous electrical nerve stimulation to treat vestibulodynia: a randomised controlled trial. BJOG 115, 1165–1170 (2008).

113.

Leclair

Goetsch

Lee

Jensen

: KTP-nd:YAG laser therapy for the treatment of vestibulodynia: a follow-up study. J. Reprod. Med. 52, 53–58 (2007).

114.

Cecilio

Zaghi

Cecilio

Correa

Fregni

: Exploring a novel therapeutic approach with noninvasive cortical stimulation for vulvodynia. Am. J. Obstet. Gynecol. 199, E6–E7 (2008).

115.

Powell

Wojnarowska

: Acupuncture for vulvodynia. J. R. Soc. Med. 92, 579–581 (1999).

116.

Pukall

Kandyba

Amsel

Khalifé

Binik

: Effectiveness of hypnosis for the treatment of vulvar vestibulitis syndrome: a preliminary investigation. J. Sex. Med. 4, 417–425 (2007).

Current Perspectives in Vulvodynia

Abstract

Keywords

Definitions & prevalence of vulvodynia

Pathophysiology

Nervous system pain regulatory pathways

Pelvic floor muscles

Psychosocial & sexual function

Other factors

How does one assess vulvodynia?

Medical history

Pain history

Physical assessment

Psychosocial & sexual assessment

Management

Medical treatment options

Topical/local injections

Systemic medications

Surgical treatment

Psychosexual & behavioral treatment

Alternative treatments

Combined treatments: the multimodal approach

Conclusion

Future perspective

Footnotes

References