Alessandra Graziottin1, 2 and Filippo Murina3
(1)
Center of Gynecology and Medical Sexology, H. San Raffaele Resnati, Milan, Italy
(2)
Graziottin Foundation for the cure and care of pain in women, Italy
(3)
Department of Vulvar Disease V. Buzzi Hospital Obstetrics and Gynecological Clinic, University of Milan, Milan, Italy
Abstract
This is difficult to achieve with vulvodynia in view of the heterogeneity of factors involved in the etiology of the disorder. Indeed, vulvodynia may be a final result of or common pathway for several pathological processes, such that any one management strategy may not be adequate for all women complaining of vulvar pain.
Treatment for any medical disorder should be directed at the underlying mechanisms or pathophysiological processes involved.
This is difficult to achieve with vulvodynia in view of the heterogeneity of factors involved in the etiology of the disorder. Indeed, vulvodynia may be a final result of or common pathway for several pathological processes, such that any one management strategy may not be adequate for all women complaining of vulvar pain.
Many women with vulvodynia experience loss of hope, which can lead to psychological, and emotional issues. Treatment should be holistic and focus not only on the primary site of pain but on its subsequent impact on the patient’s lifestyle and sexual functioning.
A lead clinician should triage patients and consider referral to other healthcare professionals who are experienced in the management of vulvodynia, e.g. Urologist, Physiotherapist, Gastroenterologist, Clinical Psychologist, and pain-management teams.
It is recommended that the patient be asked about the types and outcomes of treatment she may have already used. It is important to bear these in mind, but the clinician should remember that not all treatments are delivered in the same fashion by all providers, and that not all patients adhere to treatment regimens as recommended.
Multimodal and multidisciplinary interventions should be part of a treatment strategy for patients with vulvodynia. Multimodal interventions constitute the use of more than one type of therapy for the care of patients with chronic pain. Multidisciplinary interventions are multimodality approaches in the context of a treatment program that includes more than one discipline. The literature indicates that the use of multidisciplinary treatment programs compared with conventional treatment programs is effective in reducing the intensity of pain reported by patients.
Box 1
The aims of therapy for vulvodynia
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• Optimize pain control, recognizing that a pain-free state may not be achievable |
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• Enhance functional abilities, and physical and psychologic well-being |
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• Enhance the quality-of-life of patients |
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• Minimize adverse outcomes |
Treatment guidelines recommend a standard treatment algorithm for all women with vulvodynia, but we believe that a more personalized guided approach is needed, constructed using ‘end points’ that reflect differences within patients with vestibulodynia or generalized vulvodynia. The proposal is derived from a cluster analysis of patients that explored whether subgroups exist among women with vulvodynia with respect to pain-related and personality variables.
Box 2
End-points for vulvodynia therapy
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• Reduction of triggers and irritating stimuli |
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• Peripheral nociceptive blockade |
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• Central inhibition |
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• Limit associated pelvic floor dysfunction |
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• Limit psychosexual dysfunctions of the syndrome |
Reduction of Triggers and Irritating Stimuli
We recommend that the patient initially be encouraged to follow general advice for minimizing vulvar irritation. This is the first level of treatment that each physician must recommend to any patient with vulvodynia.
Box 3
Vulvar care measures to minimize vulvar irritation
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• Avoid vulvar irritants (perfumes, dyes, shampoos, detergents) and douching |
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• Using adequate lubrication for intercourse |
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• Wear all-white cotton underwear |
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• Wear loose-fitting pants or skirts; do not wear pantyhose |
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• Use dermatologically/gynecologically approved intimate detergents |
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• Use soft, white, unscented toilet paper |
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• Avoid getting shampoo on the vulvar area |
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• Do not use bubble bath, feminine hygiene products, or perfumed creams or soaps |
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• Urinate before the bladder is full |
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• Prevent constipation by adding fiber to your diet and drinking at least 8 glasses of water daily |
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• Use 100% cotton menstrual pads and tampons |
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• Use a water-soluble lubricant during sexual activity |
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• Apply ice, or a frozen blue gel pack (lunchbox size), wrapped in a single layer of towel to relieve burning after intercourse |
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• Urinate (to prevent infection) and rinse vulva with cool water after sexual intercourse |
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• Avoid exercises that puts direct pressure on the vulva such as bicycle riding and horseback riding |
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• Limit intense exercise that create a lot of friction in the vulvar area (try lower intensity exercises such as walking) |
Adapted from ‘Self-Help Tips for Vulvar Skin Care’, National Vulvodynia Association (http://www.nva.org/Self_Help_Tips.html)
Topical agents in general should be avoided in order to avoid the problem of irritation and exacerbation of symptoms. Skin reactions to topical medications are not uncommon, and it is often the base that the cream or gel is to blame rather the active ingredient.
Topical lidocaine gels or ointments can be used in women with provoked vestibulodynia making penetrative sex possible. It is generally advised that the gel or ointment is applied 15–20 minutes prior to sex, and patients should to be warned of the possibility of irritation.
In a study in a group of patients with vulvodynia (mainly provoked pain), 5% lidocaine ointment was applied liberally to the affected area at night, and then a cotton wool ball soaked in 5% lidocaine was inserted into the vestibule and left overnight. At follow-up there was an improvement from 36% to 76% of women reporting the ability to have intercourse.
Some reactions are associated with topical anesthetics such as stinging, erythema and edema. Benzocaine, an anesthetic frequently found in overthe- counter topical preparation, should be avoided due to its frequent association with allergic contact dermatitis. It is also important to warn patients of the potential affects on the partner, such as penile numbness (male partners may prefer to wear condoms). Partners should also be advised to avoid oral contact.
Lidocaine can burn when applied, but can be mixed with a little vaseline (the use of vaseline can reduce the lidocaine burning effect). If the patient cannot tolerate this, consider 2.5% lubricant jelly.
Topical compound of estradiol applied to the vestibule can be helpful in women with a pale and thin vestibular surface. Recurrent yeast should be considered as a triggering factor (see Chapter 6). In this case, long term maintenance therapy with a suppressive prophylactic regimen may be required. Weekly treatment with fluconazole (150 or 200 mg) for 1–2 months has been shown to be effective in preventing symptomatic vulvovaginal candidiasis, and use of an individualized, decreasing regimen can lead to efficient prevention of recurrence in the long term.
How To Reduce Pain in Vulvodynia
Peripheral Nociceptive Blockade and Central Inhibition
Transcutaneous electrical nerve stimulation (TENS) is a technique that provides neuromodulation via an electrical stimulus. It was originally developed in the early 1970s as a screening technique for the selection of women with chronic pain most likely to achieve satisfactory pain relief by implant of an electrical stimulator. The management of chronic pain such as in chronic neuropathies, postherpetic neuralgia and trigeminal neuralgia by TENS is supported by a large number of clinical trials. It has been demonstrated that TENS is of significant benefit in the management of vestibulodynia, but it is essential to use appropriate and validated stimulation parameters.
TENS treatment can be self-administered in the privacy of a woman’s home after a short period of supervision, using an inexpensive device. Our experience with a large series of provoked vestibulodynia patients (480 women) showed that there is a positive response after 10 to 15 sessions (symptom reduction >50%) which tends to peak after 25 to 35 sessions. A 65–75% response rate to TENS for provoked vestibulodynia has been reported.
Box 4
The use of TENS in the treatment of vestibulodynia
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Potential mechanisms for its effectiveness include: |
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‘Pain gate control’, that is, blocking the information travelling along the nociceptive fibers through stimulation of the large diameter afferent Ab fibers |
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‘Extrasegmental action’, based on the release of endogenous opioids by stimulation of small diameter afferent and motor fibers |
Stimulation is delivered via a vaginal probe 20 mm in diameter and 110 mm in length, with two gold metallic transversal rings as electrodes. It should be inserted into the vagina up to 20 mm.
The nociceptive system is best suited to the new situation through a gradual increasing of day numbers between TENS sessions.
Oral Agents
A survey of clinicians has indicated that oral medications are more likely to be used for the treatment of generalized vulvodynia than for provoked vestibulodynia.
Trycyclic antidepressant (TCAs) are an appropriate pharmacological management option in the treatment of vulvodynia, in particular for unprovoked and generalized pain. Originally used to treat depression, this class of medication is now commonly prescribed to treat chronic pain. Amitriptyline is the most commonly used TCA for this indication. Amitriptyline should be started at a low dose, with slow titration until either the patient responds or has unacceptable side effects. Furthermore it cannot be abruptly stopped and needs to be tapered according to the side effects. Side effects in some patients might influence compliance with treatment to a level that can cause withdrawal.
Side effects of TCA treatment should be discussed with the patient. Common side effects are: fatigue, dry mouth, weight gain, constipation; occasionally, cardiac and arrhythmic effects can occur, so TCAs should be used with caution in the elderly.
A 47% complete response rate to TCAs for unprovoked vulvar pain has been reported.
Box 5
Trycyclic antidepressant (TCAs)
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Amitriptyline is the most widely used TCA in vulvodynia patients |
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Start with a low dosage and slowly increase—10 mg tab |
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Increase in steps of 5 mg, as tolerated, every 3–7 days up to 125–150 mg |
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The average dosage is 60 mg daily |
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Dose should be taken at approximately at 1–2 hours before bedtime to help counteract morning sedation and fatigue |
Serotonin-norepinephrine reuptake inhibitors (SNRIs, such as venlafaxine and duloxetine) have proven to be effective in neuropathic pain, but have not been well studied in vulvar pain. The best results for pain are achieved with daily doses of venlafaxine 225 mg and duloxetine 60 mg.
The strength of the pain-relieving action of SNRIs is lower than that of tricyclic antidepressants, with a combined NNT (number-needed-to-treat) value in painful neuropathies of about 5 for the two SNRIs and 2.3 for tricyclic antidepressants. Indeed, for this very reason, the European Federation of Neurological Societies guidelines recommend SNRIs as second- line treatment.
Other drugs that can be used in vulvodynia patients are gabapentin and pregabalin. Gabapentin is an antiepileptic medication that is now indicated for the treatment of chronic pain. Although pregabalin has a mechanistically similar action to gabapentin and shares similar advantages, such as a lack of pharmacokinetic interactions with other medications or enzyme induction, there are several differences between the two drugs.
Unlike gabapentin, pregabalin exhibits linear pharmacokinetics after oral administration, with low intersubject variability. This provides a more predictable dose-response relationship, because plasma concentrations increase linearly with increasing dose. Gabapentin requires disproportionately larger dosage increases to achieve increases in plasma concentrations. The large doses required for some patients receiving gabapentin could worsen dose-dependent adverse effects, such as dizziness and somnolence. The linear pharmacokinetics of pregabalin impart a better-defined effective dosage range and may provide the basis for the efficacy of either fixed- or flexible-dosage regimens.
Despite these preclinical data, it is unclear if pregabalin has a clinical advantage over gabapentin, as the two drugs have not been compared in clinical trials. It has been reported that 64% of women with generalized vulvodynia had resolution of least 80% of their symptoms. Although no specific studies in vulvodynia have yet been conducted, one case report indicated that pregabalin is successful in managing the pain of generalized vulvodynia.
Box 6
Gabapentin and Pregabalin
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Gabapentin can be started at 100 mg and then slowly increased to bid, then tidgabapentin is slowly increased by 100 mg at each dose. The maximum recommended dose is 3200 mg daily |
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Pregabalin can be started at 25 mg twice daily and may be increased to 75 mg daily within two weeks based on efficacy and tolerability |
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Adverse effects : dizziness (8–43%); somnolence (6–30%), weight gain (5–20%), peripheral edema (3–19%) and diplopia (2–13%) |
Amytriptiline drop formulation allows an easy, slow titration (1 drop = 2 mg).
Combination therapy should preferably use drugs with complementary mechanisms.
The synergistic interactions between antidepressants and gabapentin/pregabalin, for example, are not only logical but also encouraged by a reduction of side effects by the use of lower doses.
Trigger Point Injection
The use of injectable therapy in the management of vestibulodynia can be useful, in selected patients, the main objective being the inactivation of the trigger point, thereby reducing pain. The therapy should be used in combination with other approaches as a complementary treatment or like treatment of a residual disease.
Various combinations of drugs have been suggested, but we currently think that only two regimens should be used: corticosteroid plus anesthetics and botulinum toxin (see section on pelvic floor dysfunction) (Table 8.1).
Table 8.1
Trigger point injection
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Corticosteroid plus anesthetics |
Botulinum toxin |
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Methylprednisolone and lidocaine |
Botulinum toxin type A |
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Rationale: |
Rationale: |
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- Corticosteroid act via inflammatory/cytokine alterations (decreased numbers of mast cells degranulated) |
- Inhibition of pelvic floor hypertonicity: injection into the pelvic floor muscles |
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- Anesthetic agents act by blocking sodium channels and can be effectively used for pain modulation at low doses that do not block complete nerve impulse propagation |
- Direct anti-nociceptive effect: injection in painful area of vestibular epithelium |
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Characteristics of patients eligible for therapy: |
Characteristics of patients eligible for therapy: |
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- Patients with dyspareunia (provoked pain) |
- Patients with dyspareunia (provoked pain) |
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- Pain only with sub urethral localization and very localized (two or three sites) |
- Patients with associated pelvic floor dysfunction |
Pudendal Nerve Block
The use of pudendal nerve block (Fig. 8.1) for treating pudendal neuralgia is a technique widely used by neurologists and anesthesiologists. Patients with pudendal neuralgia tend to describe neuropathic pain symptoms in the nerve’s distribution. We think that there is not a substantial difference between generalized vulvodynia and pudendal neuralgia, so that pudendal nerve block can be a possible therapy in patients with generalized vulvodynia (Table 8.2).
Fig. 8.1
a The palpating finger is used to locate the ischial spine and sacrospinous ligament per vaginam. The needle is inserted through the vaginal wall, is directed towards the spine and then passed through the sacrospinous ligament. As soon as the needle has passed through the ligament, a loss of resistance is felt. b The perineal approach to pudendal nerve block
Table 8.2
Pudendal neuralgia versus generalized vulvodynia
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Pudendal neuralgia |
Generalized vulvodynia |
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Mean age of presentation |
Sixth decade of life |
Postmenopausal women |
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Definition |
Pain involving the sensory distribution of pudendal nerve |
Symptoms anywhere within the distribution of the pudendal nerve |
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Presentation |
Pain is generally constant and it may be exacerbated with sitting and diminished by standing |
Symptoms are unprovoked and worsen with provocation, although the pain pattern is highly individualized |
The most widely used protocol is local anesthetic and sometimes corticosteroid injection performed at three levels, two at the ischial spine level and one at Alcock’s canal. There is no consensus on the maximum number of nerve blocks that should be given, and despite it was reported a response rate about 60% the long-term response effects are unknown. Various pudendal nerve block approaches have been described via different routes: transvaginal, transperineal and transgluteal. The main problem associated with these approaches is the risk for the patient, as this is a blind technique in a vascularized region close to the bowel and bladder. However, the approach can be guided by different imaging technique utilizing fluoroscopy or computed tomography.
Surgery
Surgical excision of the vestibule may be considered in patients with local provoked vulvodynia (vestibulodynia) after other non-surgical measures have been tried. The procedure that yields the best result is modified vestibulectomy in which a horseshoe-shaped area of the vestibule and inner labial fold is excised, followed by advancement of the posterior vaginal wall (Fig. 8.2).
Fig. 8.2 a-d
The procedure consists of an excision of a U-shaped area of the posterior vestibule up to the inner aspect of the labia minora and the lower portion of the hymenal ring, according to the marking. The thinnest possible tissue section was removed and sent for pathological examination. The vaginal epithelium was pulled out and attached to the skin of the perineum, replacing the excised area by interrupted dissolving sutures and the retain hymen is used as a flap
Surgical success rates range from 40% to 100%, with success defined as much improved or completely cured. Factors that limit direct comparison are differences in numbers of patients, presence of associated comorbidities such as painful bladder syndrome, other medical treatment at the time of surgery, the technique used, definition of success, and length of follow-up. Nevertheless, the 70% average success rate for surgery makes it a therapeutic approach to consider for this debilitating condition. First and foremost, however, patient selection is crucial. In addition, adequate counseling and support should be given to the patient both pre- and postoperatively.
Box 7
Surgical therapy for vulvodynia
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Predictors of surgical failure: |
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• Diffuse and unprovoked vulvar pain, urinary symptoms, and muscle hypertonicity |
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Predictors for a successful outcome: |
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• Provoked vestibular pain (dyspareunia), fewer sites of pain, relatively young age |
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Complications of surgery: |
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• Short-term: bleeding, infection, hematoma and partial wound separation |
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• Long-term: Bartholin duct cyst (2–6%), enhanced vestibular tenderness (5%) |
Action Towards Associated Pelvic Floor Dysfunction
There are many beneficial measures to help relax the pelvic floor muscles. Physical therapy is effective in lowering pelvic floor hypertonus and a variety of techniques, including pelvic floor exercises, external and internal soft tissue self-massage, trigger point pressure, biofeedback and use of vaginal trainers, can be used. Often patients have no awareness of their pelvic floor and instructing them to ‘check’ their pelvic floor tension throughout the day is helpful in their understanding of the the importance of keeping the pelvic floor relaxed. Biofeedback techniques are key to attaining this target.
With a vaginal probe, levator ani activity can be monitored by the patient and her therapist, and with careful coaching the patient can be taught how to contract and then relax her pelvic floor using various protocols. Generally the goal is to teach muscle awareness and relaxation.
Typically sessions last 20 to 30 minutes and a success rate in the 60–80% has been reported.
Manual therapy techniques are especially important for patients with myofascial pain disorders and include myofascial release, trigger point release, soft tissue mobilization, and massage. These internal techniques can be complemented by the patient being educated in the use of vaginal dilators for self massage.
Sexual partners should also be educated in these techniques in order to encourage and provide further supportive therapy at home. The presence of the dilator provides propioception to the musculature during exercise, augmenting improved pelvic floor contraction and relaxation. Vaginal dilatation can also diminish the anxiety associated with penetration as the woman has complete control of vaginal entry.
Botulinum neurotoxin (BoNT): The primary mode of action of BoNT is chemodenervation of muscle via blockade of presynaptic acetylcholine release at the neuromuscular junction, with subsequent paralysis. In therapeutic use, BoNT has also demonstrated effectiveness in the treatment of pelvic pain disorders characterized by functional abnormalities of muscle tension and relaxation, such as vaginismus. BoNT can be injected into the bulbospongiosus and pubococcygeus muscles. The majority of studies of BoNT in vulvar pain syndrome are targeted at pelvic floor spasm or inhibition of muscle spasticity. These trials represent some optimistic preliminary data that warrants further research in order to standardize dosing and optimize the number of injections.
Box 8
Pelvic floor rehabilitation
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• EMG Biofeedback |
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• Myofascial release: manual therapy technique that use light stretch to restore myofascial mobility and muscle length |
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• Myofascial trigger points release. Manual therapies used to eliminate trigger points include skin rolling, strumming and stripping of the affected muscle fibers |
Typically, pelvic floor dysfunction must be treated as part of a multimodal treatment plan and a physical therapist with experience in vulvodynia needs to be involved in the interdisciplinary treatment of the disease.
Action Towards Psychosexual Ramification of the Syndrome
Vulvar pain has physical, psychological and relationship aspects. Patients with localized and generalized vulvar pain need varying degrees of sexual counseling and emotional support.
Sexual dysfunction as predisposing/precipitating/maintaining factors contributing to vulvodynia should be investigated, including physical or sexual abuse, or adverse life experiences (e.g., parental divorce, pregnancy termination, difficult childbirth). Because living with chronic genital pain often has psychosexual consequences, some women may benefit from adjunct counseling or sex therapy. Cognitive-behavioral therapy is a useful psychological approach to reduce vulvar pain and improve sexual function.
It is important to keep in mind that decreasing dyspareunia does not necessarily lead to a restoration of sexual function, especially in women with long-term vulvodynia. In these cases sex therapy, couples counseling, psychotherapy, or a combination is often very helpful.
Case Studies
Case Study: “Julie”
· A 31-year-old, nulliparous woman;
· comfortable with intercourse until 3 years ago when she was treated for a severe bladder infection. Antibiotics precipitated a yeast infection, for which she was also treated;
· she complains of dyspareunia, with stinging and burning pain in the vestibule during and after intercourse;
· she has had increasing pain with intercourse, to the point that she has had to stop having sex.
Fig. 8.3
Physical findings of the patient
Case Study: “Sally”
· 53-year-old female;
· complains of chronic pain in the vulvar region of 4 years’ duration;
· the pain first began as discomfort in the vulvar region of moderate intensity, accompanied by painful burning and stinging sensations;
· pain was initially intermittent in nature, lasting for about 2 days per episode;
· the patient received hormone treatment and corticosteroids without any improvement of symptoms;
· one year after the start of vaginal discomfort, the pain became constant and diffuse in nature and was now characterized as a constant burning sensation with increased sensitivity to tactile stimuli;
· the patient rated the pain as 7 out of 10 in intensity on the visual analogue scale (VAS) for pain and was now unable to wear tight-fitting underwear;
· there was moderate improvement with analgesic drugs, and the patient described light relief of symptoms when lying down (VAS:3).
Fig. 8.4
Gynecologic examination, including vulvoscopy, revealed no abnormalities
