Expert Commentary

As we discussed in the first installment of this three-part series in the September issue of OBG Management, the causes of vulvar pain are many, and the diagnosis of this common complaint can be difficult. Once the diagnosis of vulvodynia has been made, however, the challenge shifts to finding an effective treatment. Here, our expert panel discusses the many options available, the data (or lack of it) behind each therapy, and what to do in refractory cases.

In Part 3 of this series, in the November issue, the focus will be vestibulodynia.

The lower vagina and vulva are richly supplied with peripheral nerves and are, therefore, sensitive to pain, particularly the region of the hymeneal ring. Although the pudendal nerve (arrow) courses through the area, it is an uncommon source of vulvar pain.

Management of vulvar pain begins with simple measures

Dr. Lonky: How do you approach treatment of vulvar pain syndromes?

Dr. Haefner: I often advise the patient to begin with simple measures. For example, I recommend that she wear cotton underwear during the day, but no underwear at night. If she perspires with exercise, wicking underwear may be helpful. I also counsel the patient to avoid vulvar irritants, douches, and the application of soap of any kind to the vulva. Cool gel packs are sometimes helpful.

When it comes to intercourse, I recommend adequate lubrication using any of a number of effective products, such as olive oil, vitamin E oil, Replens, Slippery Stuff, Astroglide, KY Liquid, and others.

There is an extensive list of lubricants at http://www.med.umich.edu/sexualhealth/resources/guide.htm

Topical agents might offer relief—but so might placebo

Dr. Lonky: What is the role of topical medications, including anesthetics, for treating vulvar pain syndromes?

Dr. Edwards: I don’t find topical medications to be particularly useful in the treatment of vulvodynia, except for lidocaine 2% jelly, or lidocaine 5% ointment, which tends to burn with application—but I never start a patient on only one medication, so judging the effectiveness of a topical therapy is difficult in that context. Good studies of topical medications in the treatment of vulvar pain syndromes are lacking, other than the recent report on amitriptyline and baclofen.¹

Dr. Haefner: For minor degrees of pain, consider lidocaine 5% ointment.

Lidocaine/prilocaine (eutectic mixture of local anesthesia or LMX) may be used but can be irritating.

Doxepin 5% cream can be applied to skin daily, gradually increasing the number of daily applications to as many as four.

Topical amitriptyline 2% with baclofen 2% in a water washable base has also been used for point tenderness (squirt 0.5 cc from a syringe onto the finger and apply it to the affected area three times a day).¹

Dr. Gunter: Topical estrogen is prescribed by many providers, but we lack studies supporting its efficacy, except for reversing hypoestrogenic changes in postmenopausal women. Some providers use a high-dose, compounded topical estrogen with lidocaine for vestibulodynia. Certainly, local hypoestrogenic changes should be reversed in postmenopausal women before a diagnosis of vulvodynia or vestibulodynia is given.

As for other topical therapies, they are widely used. Some women report improvement with application of plain petrolatum.² Response rates of 33% to 46% after use of a topical placebo for vestibulodynia are well described in the literature.^3,4

Topical analgesics are used frequently, either sporadically (during pain flares) or regularly (daily application). One method of application for localized vestibulodynia involves liberally coating a cotton ball with lidocaine 5% and then applying it to the vestibule overnight (for at least 8 hours of exposure). In this study, after 7 weeks, 76% of women were able to be sexually active, compared with 36% before the start of treatment. However, a randomized, placebo-controlled trial that included lidocaine 5% cream in one arm identified only a 20% reduction in pain for women who had localized vestibulodynia—although, in this trial, the lidocaine was massaged into the vestibule four times daily.⁵ In this study, interestingly enough, topical lidocaine was less effective than topical placebo, which produced a 33% response rate.³

Lidocaine gel has also been used, although some women report more local irritation with gel than with ointment.

Dr. Lonky: Do we have any data on topical application of other drugs?

Dr. Gunter: Compounded adjuvant medications have been evaluated. In a retrospective study of topical gabapentin in a Lipoderm base, women who had generalized or localized vulvodynia applied a dose of 2%, 4%, or 6% three times daily. Of these women, 80% experienced a reduction of at least 50% in the pain score. In addition, 67% of patients who had localized vestibular pain were able to resume intercourse.⁶

A retrospective review of 38 women who used 2% amitriptyline and 2% baclofen in a Lipoderm cream for localized vestibular pain found that 53% experienced an improvement in symptoms of at least 60%, but there was no change in the frequency of sexual intercourse.¹

Do tricyclic antidepressants ease chronic pain?

Dr. Lonky: Let’s talk, for a moment, about the use of oral tricyclic antidepressants in the treatment of vulvar pain syndromes. What do we know?

Dr. Haefner: Tricyclic antidepressants are a common treatment for vulvar pain. This group of drugs (including amitriptyline [Elavil], nortriptyline [Pamelor], and desipramine [Norpramin]) has been used to treat many idiopathic chronic pain conditions. Published and presented reports indicate that these drugs elicit about a 60% response rate for various pain conditions. A trial by the National Institutes of Health (NIH) is under way, analyzing the use of antidepressants in women who have vulvar pain.

Although treatment with tricyclic antidepressants has generally been reserved for women who have generalized vulvodynia, recent reports have found these medications to be helpful in the treatment of vestibular pain as well. The mechanism of action is thought to be related to inhibition of the reuptake of transmitters—specifically, norepinephrine and serotonin. However, the mechanism of action may be more closely related to anticholinergic effects. Tricyclics affect sodium channels and the N-methyl-d-aspartate (NMDA) receptor.

If you choose to prescribe one of these medications, consider emphasizing to the patient its effect on the sensation of pain rather than its effect on depression.

Dr. Lonky: Are there any types of patients who should not take a tricyclic?

Dr. Haefner: Yes. A patient should not take a tricyclic if she is pregnant, breastfeeding, or planning to conceive. These medicines also add to the effects of alcohol and other central nervous system depressants.

Dr. Lonky: What dosage is recommended?

Dr. Haefner: The dosage for pain control varies, depending on the age of the patient and the particular agent used. Amitriptyline is often used as a first-line medication. I start the patient on 10 to 25 mg nightly and increase that amount by 10 to 25 mg weekly, not to exceed 150 mg daily. A sample regimen might be 10 mg at bedtime for 1 week. If symptoms persist, increase the dose to 20 mg at bedtime for another week, and so on. Once a dose is established that provides relief, the patient should continue to take that amount nightly. Advise the patient not to discontinue the drug abruptly. Rather, it should be weaned.

In patients who are 60 years or older, I give a starting dose of 5 to 10 mg and increase it by 10 mg weekly.

In all age groups, it is important to advise patients to avoid consuming more than one alcoholic beverage daily while taking this medication. And in reproductive-age women, contraception is critical.

Dr. Edwards: I call these drugs tricyclic medications rather than antidepressants. They are extremely useful in managing the neuropathic component of vulvar pain. Despite a recent, apparently well-conducted study showing a lack of benefit, my 25 years of personal clinical experience with tricyclics convince me that I should wait for follow-up studies before abandoning this therapy.³

The pain literature reports that higher doses than previously reported of tricyclic medications are needed for optimal management of neuropathic pain. Doses from 100 to 150 mg are often required for substantial improvement, and a major design flaw in many studies of the effect of tricyclic medications on vulvodynia is the use of an insufficient dose.

Because of their low cost and their effectiveness, tricyclic medications are my first-line therapy for women who do not suffer severe constipation or dry eyes. The effect on depression is a useful side effect, I find.

Dr. Gunter: Although adjuvant medications, such as antidepressants and anticonvulsants, are considered by more than 80% of practitioners to be effective for vulvodynia, it is important to understand that only one randomized, double-blind, placebo-controlled prospective study has evaluated this approach, and that study found a placebo response rate of 33%.^3,7

Randomized studies indicate that low-dose amitriptyline (10–20 mg) and desipramine (150 mg) are ineffective for provoked vestibulodynia.^3,8 Cohort and retrospective studies with higher doses of amitriptyline (40 to 60 mg/day) indicate that improvement in pain scores of 50% or more can be achieved for 47% to 59% of women who have localized provoked vestibulodynia and generalized unprovoked vulvodynia.^9-11

Tricyclic antidepressants and anticonvulsants should be prescribed with caution for patients 65 years and older because they increase the risk of falls.

I give nortriptyline as a first-line agent to women who have both provoked and unprovoked pain. In general, it has fewer anticholinergic side effects than amitriptyline and is generic—it also is taken once daily. For women who have unprovoked pain, I use gabapentin as a second-line agent.

Dr. Lonky: Are any other antidepressants useful in the treatment of vulvar pain?

Dr. Haefner: I sometimes give duloxetine [Cymbalta], starting with an oral daily dose of 30 mg for 1 week. If symptoms persist, I increase the daily dose to a total of 60 mg. (If the patient is depressed, I have her take 30 mg twice daily; if she isn’t depressed, I have her take the full dose of 60 mg in the morning.) I also occasionally utilize venlafaxine [Effexor XR] for pain control, starting with an oral morning dose of 37.5 mg. This dose can be increased to 75 mg/day.

Dr. Edwards: Literature on venlafaxine for neuropathic pain suggests maximal effects at doses of 150 to 225 mg of the extended release formulation, which is often well tolerated. I start patients on 37.5 mg and increase weekly until I reach the 150-mg threshold.¹²

Are anticonvulsants effective pain relievers?

Dr. Lonky: How effective are oral anticonvulsants such as gabapentin [Neurontin]?

Dr. Haefner: Gabapentin has been used to treat chronic pain conditions. The drug is available in 100-mg, 300-mg, 400-mg, 600-mg, and 800-mg tablets. It is typically initiated at an oral dose of 300 mg daily for 3 days. The dosage is then increased to 300 mg twice daily for 3 days and, finally, to 300 mg three times daily. If necessary, it can gradually be increased to a total of 3,600 mg daily (usually divided into three doses). No more than 1,200 mg should be administered in a single dose. Side effects include somnolence, mental changes, dizziness, and weight gain.

Dr. Edwards: After tricyclic medications, I find gabapentin to be the most beneficial and easily tolerated agent. I give it to patients who have contraindications to tricyclics and who lack a strong component of depression.

Dr. Gunter: Retrospective reviews have found gabapentin to produce improvement of 80% or more in pain scores for 64% to 82% of women who have generalized unprovoked vulvodynia. And a small open-label, prospective trial of lamotrigine [Lamictal] found that it produced statistically significant improvement for generalized vulvodynia.^13-15

Dr. Lonky: What do you know about the use of the anticonvulsants pregabalin [Lyrica] and topiramate [Topamax] to treat vulvar pain syndromes?

Dr. Gunter: Pregabalin was reported to reduce symptoms by 80% for generalized, unprovoked vulvodynia in one case report.¹⁶

Dr. Edwards: I find that pregabalin is less well tolerated (and more expensive) than gabapentin, so it is one of the last agents I prescribe. I reported a small, uncontrolled series of patients who were treated with pregabalin. Of those who tolerated the drug, two thirds of the women improved by approximately 62%, as judged by a visual analog scale.

Dr. Haefner: Pregabalin is a relatively new addition to the armamentarium. I give 50 mg orally for 4 days to start. If symptoms persist, I increase the dose to 50 mg twice a day for 4 days. If symptoms still persist, I up the dose again to 50 mg three times daily and gradually increase it to 100 mg three times daily, if necessary. Some reports describe a dose as high as 300 mg twice daily (maximum).

As for topiramate, I have been using it much more frequently for vulvodynia and noticing many fewer side effects than with gabapentin.

Does capsaicin interrupt the pain circuit?

Dr. Lonky: Capsaicin has been mentioned in the literature as a therapy for vulvar pain. Is it effective? How does it work?

Dr. Haefner: Capsaicin activates A-delta sensory neurons and unmyelinated C fibers. It is a vanillyl amide that evokes the sensation of burning pain. It has been proposed as a means of desensitization, which occurs as an acute reaction mediated by neuropeptides (including substance P).¹⁷ Steinberg and colleagues found that topical capsaicin significantly decreased pain with intercourse.¹⁷ Patients applied capsaicin 0.025% cream for 20 minutes daily for 12 weeks.

In a study by Murina and colleagues, 33 women were treated with topical capsaicin 0.05%. The capsaicin cream was applied to the vulva twice daily for 30 days, then once daily for 30 days, then twice weekly for 4 months. In this study, however, the response to treatment was only partial.¹⁸

Dr. Edwards: I have never had a patient willing to try capsaicin after I describe the therapy to them.

Dr. Gunter: Two studies have evaluated daily applications of capsaicin in concentrations of 0.025% and 0.05%—one of them the study by Murina and colleagues that Dr. Haefner mentioned.^2,18 The initial release of substance P causes significant burning on application, so pretreatment with local anesthetic to help the patient tolerate the capsaicin is recommended, which could potentially confound the results. In one study, daily pain scores, as well as pain with intercourse, improved significantly for 59% of participants, but no patient experienced complete resolution of symptoms—and within 2 weeks after capsaicin was discontinued, symptoms returned.^2,18 I have had only one patient in 15 years of practice who was willing to try capsaicin and who could get past the initial burning.

Another application for botulinum toxin type A?

Dr. Lonky: Is botulinum toxin type A [Botox] at all effective?

Dr. Haefner: Botulinum toxin type A has been utilized to treat provoked vestibulodynia as well as vaginismus and was beneficial.^19-23 It blocks the cholinergic innervation of the target tissue. The therapeutic dose ranges from 20 IU to 300 IU.²⁴

A placebo-controlled trial found that injection of 20 IU of botulinum toxin into the vestibule of women with vestibulodynia did not reduce pain, improve sexual functioning, or impact the quality of life, compared with placebo.²⁵ However, this study utilized a lower dose of botulinum toxin than was used in many of the other studies.

Dr. Edwards: I have only used botulinum toxin type A in a low dose. I injected 6 IU of botulinum toxin A into the periphery of the vestibule at 3, 6, 9, and 12 o’clock in six patients, and half improved modestly. I am not prepared to use electromyography (EMG) localization in my office, but from anecdotal reports, as well as several small series and placebo-controlled trials, I would conclude that some patients improve. Those who have hypertonic pelvic floor muscles are likely to be the best candidates for this treatment.

Because the agent relieves pain only modestly, and because it is not covered by insurance for this application, I refer the patient to a gynecologist in my area who administers the drug under EMG localization.

Dr. Gunter: Given the well-documented effect on muscle spasticity, as well as studies that suggest they are also anti-nociceptive agents, botulinum toxins are certainly an attractive concept for vulvodynia. A small case series and a case report indicated significant improvement with vestibular injections of 20 to 40 U of botulinum toxin. However, a randomized, placebo-controlled, double-blind study indicated no significant improvement for women with localized vestibular pain.^25-27

I discuss botulinum toxin A with my patients. I explain that my clinical experience does differ from results published in the literature. I find that many women with vestibulodynia opt to try an injection before proceeding to vestibulectomy.

When combined with pelvic floor physical therapy, botulinum toxins are highly effective at treating muscle spasm and can be very useful for women who have a component to their pain of vaginismus or high-tone pelvic floor dysfunction.

How useful are steroids and nerve blocks?

Dr. Lonky: Is there a role for local injections of glucocorticoids or serial nerve blocks?

Dr. Edwards: The occasional patient with very localized pain (trigger point) responds fairly well in my office to intralesional corticosteroids. I have not used or seen reports describing administration of intralesional corticosteroids into a larger area, although two practitioners have told me informally that it is useful in their hands.

As a dermatologist, I cannot perform blocks. I have referred patients to gyn and pain clinics for this purpose, but neither venue has been willing to administer the blocks.

Dr. Haefner: Patients who present with small, localized areas of pain may benefit from local injections. In small areas—for example, a painful spot 1 cm in diameter—triamcinolone acetonide in combination with bupivacaine may be helpful. It is important to use a small dose of steroid in a small area, however, because tissue erosion or ulceration can occur with too high a dose of steroid in the skin. For large areas, as much as 40 mg of triamcinolone acetonide may be utilized in a single monthly dose. Generally, the dose is repeated monthly, if necessary, as many as three or four times.

For large areas, bupivacaine 0.25% is utilized, and for small areas, bupivacaine 0.5% is injected into the vulva along with the steroid. The steroid should be drawn into the syringe first (because the vial can be used at a later time), followed by bupivacaine, which is a single-dose vial.

Pudendal nerve blocks using bupivacaine have been helpful in some patients—particularly those who have unilateral pain.

Dr. Gunter: Local injections with a variety of agents for localized, provoked vestibulodynia have been described, including steroids, botulinum toxins, and interferon. It is important to interpret these studies with caution, however, as placebo response rates with injection therapy are significant.²⁵

A retrospective review of submucous injections of methylprednisolone and lidocaine found that 68% of women had a complete or marked response, and two case reports describe success with betamethasone.^26,28-30 I offer steroid injections to women who have vestibulodynia before proceeding to vestibulectomy; I find that about 50% get at least partial relief. As Dr. Haefner indicated from her own experience, my success seems best with steroid injections in the vestibule when the painful area is smaller.

Using injectable steroids and botulinum toxins, I estimate that I can prevent 33% to 40% of vestibulectomies. Although this may not be better than the placebo response rate and certainly represents biased patient selection (patients are not required to try local injection before vestibulectomy for vestibulodynia), those who are successful are uniformly happy for trying it, and those for whom it did not work are not unhappy that they “gave it a try,” as these women are all motivated to avoid surgery, if possible.

Pudendal nerve blocks with triamcinolone are also described for women who have generalized unprovoked vulvodynia due to suspected pudendal neuralgia. Ganglion impar blocks—steroid injection around the terminal branch of the sympathetic chain in the presacral space—have also been performed with good results for generalized vulvodynia. I have had good success with pudendal nerve blocks for unilateral pain that is suspected to be pudendal in origin and also with ganglion impar blocks for women with generalized vulvodynia, especially postmenopausal women. I perform all of my own nerve blocks (FIGURE).

Ganglion impar block
Ganglion impar blocks—steroid injection around the terminal branch of the sympathetic chain in the presacral space—may provide relief from generalized vulvodynia in some women.

Does physical therapy play a role in easing vulvar pain?

Dr. Lonky: What is the role of physical therapy and pelvic floor muscle rehabilitation?

Dr. Gunter: All women who have high-tone pelvic floor dysfunction should be referred to a physical therapist. Many women who lack muscle spasm but experience vulvar pain can still benefit from physical therapy, as gentle stretching and vibration therapy can sometimes be helpful. A physical therapist can also perform biofeedback.

Dr. Edwards: Physical therapy is crucial. It is my first-line therapy overall, with adjunctive oral medication for neuropathic pain. Besides addressing pelvic floor abnormalities, physical therapy can serve as desensitization therapy and psychological support.

Dr. Haefner: Physical therapy has been successful in the treatment of a number of disorders, including migraine and tension headaches, asthma, and anxiety disorders. It is also used in the treatment of vulvar pain. Physical therapists who have experience in vulvar pain may be extremely helpful, particularly if there is concomitant vaginismus—which isn’t uncommon in this population.

For vulvodynia, techniques include internal (vaginal and rectal) and external soft-tissue mobilization and myofascial release; trigger-point pressure; visceral, urogenital, and joint manipulation; electrical stimulation; therapeutic exercises; active pelvic floor retraining; biofeedback; bladder and bowel retraining; and therapeutic ultrasound.

Biofeedback may be used to assist in developing self-regulation strategies for confronting and reducing pain. Patients who have vestibular pain in general have an increased resting tone and a decreased contraction tone. With the aid of an electronic measurement and amplification system or biofeedback machine, an individual can view a display of numbers on a meter, or colored lights, to assess nerve and muscle tension. In this way, she may be able to develop voluntary control over the biological systems involved in pain, discomfort, and disease.

The duration of physical therapy overall and the frequency of visits varies from person to person. Success rates in the range of 60% to 80% have been reported.

How should we respond when medical treatment fails?

Dr. Lonky: What is the proper approach to the patient who has recalcitrant vulvar pain who fails all medical treatments and is not a candidate for vestibulectomy because her pain is outside the vestibule?

Dr. Edwards: The pain clinic. Actually, in a perfect world, the role of the gynecologist or dermatologist would be to give the patient a diagnosis, after which a pain clinic would offer treatment.

All patients should receive counseling. And clinicians who lack expertise should refer the patient to a vulvodynia specialist.

Dr. Haefner: This type of patient may benefit from physical therapy. Bupivacaine steroid injections could also be considered. A sacral nerve stimulator should be considered if the other measures fail to provide adequate relief.

I agree that counseling is extremely helpful in the patient who has vulvodynia. Sexual counseling, with tips on positions for intercourse, lubricants, and control of uncomfortable situations, is of utmost importance.

Dr. Gunter: I offer oral medications and nerve blocks (typically, ganglion impar blocks), and many patients do well.

I also highly recommend advanced programs for mind-body techniques.

Patients who fail all therapies may be candidates for a nerve stimulator, depending on psychiatric comorbidities and response to selective diagnostic nerve blocks.

What’s in the pipeline?

Dr. Lonky: What therapies for vulvar pain are on the horizon?

Dr. Edwards: I believe that cognitive behavioral therapy, sex therapy, and couple counseling will play a larger role in the management of vulvar pain.

Dr. Gunter: Any therapy used in other pain conditions will probably eventually find its way to the management of vulvodynia.

Some investigators believe that Tarlov cysts play a role in vulvar pain and recommend that all women undergo sacral spine and nerve-root magnetic resonance imaging. The problem is that many asymptomatic women have Tarlov cysts, and the surgery to remove them is not at all risk-free. I strongly believe that more research is needed before we can suggest that Tarlov cysts be removed.

Dr. Haefner: Transcutaneous electrical stimulation and biofeedback have been used successfully in the treatment of vulvodynia.³¹ Some patients benefit from spinal cord stimulators, such as the sacral nerve stimulator, for pain control. Sacral nerve modulation (SNM) works primarily by modulation of the nerve signals to and from the pelvic floor muscles, bladder, and rectum. It applies low-amplitude electrical stimulation to the third sacral nerve via electrodes in a tined lead passing through the S3 foramen, which contains afferent sensory, efferent autonomic motor, and voluntary somatic nerves. Other studies have utilized a different spinal cord level. More studies are needed to demonstrate the full effect of SNM on vulvodynia.

A comprehensive review of the various treatments for vulvodynia can be found in the Journal of Lower Genital Tract Disease.²

Dr. Lonky: Thanks again for your expertise. We’ll focus on provoked vestibulodynia in the final installment of this series on vulvar pain, in the November 2011 issue of OBG Management.

Vulvar pain therapies mentioned in this discussion

We want to hear from you! Tell us what you think.

As we discussed in the first installment of this three-part series in the September issue of OBG Management, the causes of vulvar pain are many, and the diagnosis of this common complaint can be difficult. Once the diagnosis of vulvodynia has been made, however, the challenge shifts to finding an effective treatment. Here, our expert panel discusses the many options available, the data (or lack of it) behind each therapy, and what to do in refractory cases.

In Part 3 of this series, in the November issue, the focus will be vestibulodynia.

The lower vagina and vulva are richly supplied with peripheral nerves and are, therefore, sensitive to pain, particularly the region of the hymeneal ring. Although the pudendal nerve (arrow) courses through the area, it is an uncommon source of vulvar pain.

Management of vulvar pain begins with simple measures

Dr. Lonky: How do you approach treatment of vulvar pain syndromes?

Dr. Haefner: I often advise the patient to begin with simple measures. For example, I recommend that she wear cotton underwear during the day, but no underwear at night. If she perspires with exercise, wicking underwear may be helpful. I also counsel the patient to avoid vulvar irritants, douches, and the application of soap of any kind to the vulva. Cool gel packs are sometimes helpful.

When it comes to intercourse, I recommend adequate lubrication using any of a number of effective products, such as olive oil, vitamin E oil, Replens, Slippery Stuff, Astroglide, KY Liquid, and others.

There is an extensive list of lubricants at http://www.med.umich.edu/sexualhealth/resources/guide.htm

Topical agents might offer relief—but so might placebo

Dr. Lonky: What is the role of topical medications, including anesthetics, for treating vulvar pain syndromes?

Dr. Edwards: I don’t find topical medications to be particularly useful in the treatment of vulvodynia, except for lidocaine 2% jelly, or lidocaine 5% ointment, which tends to burn with application—but I never start a patient on only one medication, so judging the effectiveness of a topical therapy is difficult in that context. Good studies of topical medications in the treatment of vulvar pain syndromes are lacking, other than the recent report on amitriptyline and baclofen.¹

Dr. Haefner: For minor degrees of pain, consider lidocaine 5% ointment.

Lidocaine/prilocaine (eutectic mixture of local anesthesia or LMX) may be used but can be irritating.

Doxepin 5% cream can be applied to skin daily, gradually increasing the number of daily applications to as many as four.

Topical amitriptyline 2% with baclofen 2% in a water washable base has also been used for point tenderness (squirt 0.5 cc from a syringe onto the finger and apply it to the affected area three times a day).¹

Dr. Gunter: Topical estrogen is prescribed by many providers, but we lack studies supporting its efficacy, except for reversing hypoestrogenic changes in postmenopausal women. Some providers use a high-dose, compounded topical estrogen with lidocaine for vestibulodynia. Certainly, local hypoestrogenic changes should be reversed in postmenopausal women before a diagnosis of vulvodynia or vestibulodynia is given.

As for other topical therapies, they are widely used. Some women report improvement with application of plain petrolatum.² Response rates of 33% to 46% after use of a topical placebo for vestibulodynia are well described in the literature.^3,4

Topical analgesics are used frequently, either sporadically (during pain flares) or regularly (daily application). One method of application for localized vestibulodynia involves liberally coating a cotton ball with lidocaine 5% and then applying it to the vestibule overnight (for at least 8 hours of exposure). In this study, after 7 weeks, 76% of women were able to be sexually active, compared with 36% before the start of treatment. However, a randomized, placebo-controlled trial that included lidocaine 5% cream in one arm identified only a 20% reduction in pain for women who had localized vestibulodynia—although, in this trial, the lidocaine was massaged into the vestibule four times daily.⁵ In this study, interestingly enough, topical lidocaine was less effective than topical placebo, which produced a 33% response rate.³

Lidocaine gel has also been used, although some women report more local irritation with gel than with ointment.

Dr. Lonky: Do we have any data on topical application of other drugs?

Dr. Gunter: Compounded adjuvant medications have been evaluated. In a retrospective study of topical gabapentin in a Lipoderm base, women who had generalized or localized vulvodynia applied a dose of 2%, 4%, or 6% three times daily. Of these women, 80% experienced a reduction of at least 50% in the pain score. In addition, 67% of patients who had localized vestibular pain were able to resume intercourse.⁶

A retrospective review of 38 women who used 2% amitriptyline and 2% baclofen in a Lipoderm cream for localized vestibular pain found that 53% experienced an improvement in symptoms of at least 60%, but there was no change in the frequency of sexual intercourse.¹

Do tricyclic antidepressants ease chronic pain?

Dr. Lonky: Let’s talk, for a moment, about the use of oral tricyclic antidepressants in the treatment of vulvar pain syndromes. What do we know?

Dr. Haefner: Tricyclic antidepressants are a common treatment for vulvar pain. This group of drugs (including amitriptyline [Elavil], nortriptyline [Pamelor], and desipramine [Norpramin]) has been used to treat many idiopathic chronic pain conditions. Published and presented reports indicate that these drugs elicit about a 60% response rate for various pain conditions. A trial by the National Institutes of Health (NIH) is under way, analyzing the use of antidepressants in women who have vulvar pain.

Although treatment with tricyclic antidepressants has generally been reserved for women who have generalized vulvodynia, recent reports have found these medications to be helpful in the treatment of vestibular pain as well. The mechanism of action is thought to be related to inhibition of the reuptake of transmitters—specifically, norepinephrine and serotonin. However, the mechanism of action may be more closely related to anticholinergic effects. Tricyclics affect sodium channels and the N-methyl-d-aspartate (NMDA) receptor.

If you choose to prescribe one of these medications, consider emphasizing to the patient its effect on the sensation of pain rather than its effect on depression.

Dr. Lonky: Are there any types of patients who should not take a tricyclic?

Dr. Haefner: Yes. A patient should not take a tricyclic if she is pregnant, breastfeeding, or planning to conceive. These medicines also add to the effects of alcohol and other central nervous system depressants.

Dr. Lonky: What dosage is recommended?

Dr. Haefner: The dosage for pain control varies, depending on the age of the patient and the particular agent used. Amitriptyline is often used as a first-line medication. I start the patient on 10 to 25 mg nightly and increase that amount by 10 to 25 mg weekly, not to exceed 150 mg daily. A sample regimen might be 10 mg at bedtime for 1 week. If symptoms persist, increase the dose to 20 mg at bedtime for another week, and so on. Once a dose is established that provides relief, the patient should continue to take that amount nightly. Advise the patient not to discontinue the drug abruptly. Rather, it should be weaned.

In patients who are 60 years or older, I give a starting dose of 5 to 10 mg and increase it by 10 mg weekly.

In all age groups, it is important to advise patients to avoid consuming more than one alcoholic beverage daily while taking this medication. And in reproductive-age women, contraception is critical.

Dr. Edwards: I call these drugs tricyclic medications rather than antidepressants. They are extremely useful in managing the neuropathic component of vulvar pain. Despite a recent, apparently well-conducted study showing a lack of benefit, my 25 years of personal clinical experience with tricyclics convince me that I should wait for follow-up studies before abandoning this therapy.³

The pain literature reports that higher doses than previously reported of tricyclic medications are needed for optimal management of neuropathic pain. Doses from 100 to 150 mg are often required for substantial improvement, and a major design flaw in many studies of the effect of tricyclic medications on vulvodynia is the use of an insufficient dose.

Because of their low cost and their effectiveness, tricyclic medications are my first-line therapy for women who do not suffer severe constipation or dry eyes. The effect on depression is a useful side effect, I find.

Dr. Gunter: Although adjuvant medications, such as antidepressants and anticonvulsants, are considered by more than 80% of practitioners to be effective for vulvodynia, it is important to understand that only one randomized, double-blind, placebo-controlled prospective study has evaluated this approach, and that study found a placebo response rate of 33%.^3,7

Randomized studies indicate that low-dose amitriptyline (10–20 mg) and desipramine (150 mg) are ineffective for provoked vestibulodynia.^3,8 Cohort and retrospective studies with higher doses of amitriptyline (40 to 60 mg/day) indicate that improvement in pain scores of 50% or more can be achieved for 47% to 59% of women who have localized provoked vestibulodynia and generalized unprovoked vulvodynia.^9-11

Tricyclic antidepressants and anticonvulsants should be prescribed with caution for patients 65 years and older because they increase the risk of falls.

I give nortriptyline as a first-line agent to women who have both provoked and unprovoked pain. In general, it has fewer anticholinergic side effects than amitriptyline and is generic—it also is taken once daily. For women who have unprovoked pain, I use gabapentin as a second-line agent.

Dr. Lonky: Are any other antidepressants useful in the treatment of vulvar pain?

Dr. Haefner: I sometimes give duloxetine [Cymbalta], starting with an oral daily dose of 30 mg for 1 week. If symptoms persist, I increase the daily dose to a total of 60 mg. (If the patient is depressed, I have her take 30 mg twice daily; if she isn’t depressed, I have her take the full dose of 60 mg in the morning.) I also occasionally utilize venlafaxine [Effexor XR] for pain control, starting with an oral morning dose of 37.5 mg. This dose can be increased to 75 mg/day.

Dr. Edwards: Literature on venlafaxine for neuropathic pain suggests maximal effects at doses of 150 to 225 mg of the extended release formulation, which is often well tolerated. I start patients on 37.5 mg and increase weekly until I reach the 150-mg threshold.¹²

Are anticonvulsants effective pain relievers?

Dr. Lonky: How effective are oral anticonvulsants such as gabapentin [Neurontin]?

Dr. Haefner: Gabapentin has been used to treat chronic pain conditions. The drug is available in 100-mg, 300-mg, 400-mg, 600-mg, and 800-mg tablets. It is typically initiated at an oral dose of 300 mg daily for 3 days. The dosage is then increased to 300 mg twice daily for 3 days and, finally, to 300 mg three times daily. If necessary, it can gradually be increased to a total of 3,600 mg daily (usually divided into three doses). No more than 1,200 mg should be administered in a single dose. Side effects include somnolence, mental changes, dizziness, and weight gain.

Dr. Edwards: After tricyclic medications, I find gabapentin to be the most beneficial and easily tolerated agent. I give it to patients who have contraindications to tricyclics and who lack a strong component of depression.

Dr. Gunter: Retrospective reviews have found gabapentin to produce improvement of 80% or more in pain scores for 64% to 82% of women who have generalized unprovoked vulvodynia. And a small open-label, prospective trial of lamotrigine [Lamictal] found that it produced statistically significant improvement for generalized vulvodynia.^13-15

Dr. Lonky: What do you know about the use of the anticonvulsants pregabalin [Lyrica] and topiramate [Topamax] to treat vulvar pain syndromes?

Dr. Gunter: Pregabalin was reported to reduce symptoms by 80% for generalized, unprovoked vulvodynia in one case report.¹⁶

Dr. Edwards: I find that pregabalin is less well tolerated (and more expensive) than gabapentin, so it is one of the last agents I prescribe. I reported a small, uncontrolled series of patients who were treated with pregabalin. Of those who tolerated the drug, two thirds of the women improved by approximately 62%, as judged by a visual analog scale.

Dr. Haefner: Pregabalin is a relatively new addition to the armamentarium. I give 50 mg orally for 4 days to start. If symptoms persist, I increase the dose to 50 mg twice a day for 4 days. If symptoms still persist, I up the dose again to 50 mg three times daily and gradually increase it to 100 mg three times daily, if necessary. Some reports describe a dose as high as 300 mg twice daily (maximum).

As for topiramate, I have been using it much more frequently for vulvodynia and noticing many fewer side effects than with gabapentin.

Does capsaicin interrupt the pain circuit?

Dr. Lonky: Capsaicin has been mentioned in the literature as a therapy for vulvar pain. Is it effective? How does it work?

Dr. Haefner: Capsaicin activates A-delta sensory neurons and unmyelinated C fibers. It is a vanillyl amide that evokes the sensation of burning pain. It has been proposed as a means of desensitization, which occurs as an acute reaction mediated by neuropeptides (including substance P).¹⁷ Steinberg and colleagues found that topical capsaicin significantly decreased pain with intercourse.¹⁷ Patients applied capsaicin 0.025% cream for 20 minutes daily for 12 weeks.

In a study by Murina and colleagues, 33 women were treated with topical capsaicin 0.05%. The capsaicin cream was applied to the vulva twice daily for 30 days, then once daily for 30 days, then twice weekly for 4 months. In this study, however, the response to treatment was only partial.¹⁸

Dr. Edwards: I have never had a patient willing to try capsaicin after I describe the therapy to them.

Dr. Gunter: Two studies have evaluated daily applications of capsaicin in concentrations of 0.025% and 0.05%—one of them the study by Murina and colleagues that Dr. Haefner mentioned.^2,18 The initial release of substance P causes significant burning on application, so pretreatment with local anesthetic to help the patient tolerate the capsaicin is recommended, which could potentially confound the results. In one study, daily pain scores, as well as pain with intercourse, improved significantly for 59% of participants, but no patient experienced complete resolution of symptoms—and within 2 weeks after capsaicin was discontinued, symptoms returned.^2,18 I have had only one patient in 15 years of practice who was willing to try capsaicin and who could get past the initial burning.

Another application for botulinum toxin type A?

Dr. Lonky: Is botulinum toxin type A [Botox] at all effective?

Dr. Haefner: Botulinum toxin type A has been utilized to treat provoked vestibulodynia as well as vaginismus and was beneficial.^19-23 It blocks the cholinergic innervation of the target tissue. The therapeutic dose ranges from 20 IU to 300 IU.²⁴

A placebo-controlled trial found that injection of 20 IU of botulinum toxin into the vestibule of women with vestibulodynia did not reduce pain, improve sexual functioning, or impact the quality of life, compared with placebo.²⁵ However, this study utilized a lower dose of botulinum toxin than was used in many of the other studies.

Dr. Edwards: I have only used botulinum toxin type A in a low dose. I injected 6 IU of botulinum toxin A into the periphery of the vestibule at 3, 6, 9, and 12 o’clock in six patients, and half improved modestly. I am not prepared to use electromyography (EMG) localization in my office, but from anecdotal reports, as well as several small series and placebo-controlled trials, I would conclude that some patients improve. Those who have hypertonic pelvic floor muscles are likely to be the best candidates for this treatment.

Because the agent relieves pain only modestly, and because it is not covered by insurance for this application, I refer the patient to a gynecologist in my area who administers the drug under EMG localization.

Dr. Gunter: Given the well-documented effect on muscle spasticity, as well as studies that suggest they are also anti-nociceptive agents, botulinum toxins are certainly an attractive concept for vulvodynia. A small case series and a case report indicated significant improvement with vestibular injections of 20 to 40 U of botulinum toxin. However, a randomized, placebo-controlled, double-blind study indicated no significant improvement for women with localized vestibular pain.^25-27

I discuss botulinum toxin A with my patients. I explain that my clinical experience does differ from results published in the literature. I find that many women with vestibulodynia opt to try an injection before proceeding to vestibulectomy.

When combined with pelvic floor physical therapy, botulinum toxins are highly effective at treating muscle spasm and can be very useful for women who have a component to their pain of vaginismus or high-tone pelvic floor dysfunction.

How useful are steroids and nerve blocks?

Dr. Lonky: Is there a role for local injections of glucocorticoids or serial nerve blocks?

Dr. Edwards: The occasional patient with very localized pain (trigger point) responds fairly well in my office to intralesional corticosteroids. I have not used or seen reports describing administration of intralesional corticosteroids into a larger area, although two practitioners have told me informally that it is useful in their hands.

As a dermatologist, I cannot perform blocks. I have referred patients to gyn and pain clinics for this purpose, but neither venue has been willing to administer the blocks.

Dr. Haefner: Patients who present with small, localized areas of pain may benefit from local injections. In small areas—for example, a painful spot 1 cm in diameter—triamcinolone acetonide in combination with bupivacaine may be helpful. It is important to use a small dose of steroid in a small area, however, because tissue erosion or ulceration can occur with too high a dose of steroid in the skin. For large areas, as much as 40 mg of triamcinolone acetonide may be utilized in a single monthly dose. Generally, the dose is repeated monthly, if necessary, as many as three or four times.

For large areas, bupivacaine 0.25% is utilized, and for small areas, bupivacaine 0.5% is injected into the vulva along with the steroid. The steroid should be drawn into the syringe first (because the vial can be used at a later time), followed by bupivacaine, which is a single-dose vial.

Pudendal nerve blocks using bupivacaine have been helpful in some patients—particularly those who have unilateral pain.

Dr. Gunter: Local injections with a variety of agents for localized, provoked vestibulodynia have been described, including steroids, botulinum toxins, and interferon. It is important to interpret these studies with caution, however, as placebo response rates with injection therapy are significant.²⁵

A retrospective review of submucous injections of methylprednisolone and lidocaine found that 68% of women had a complete or marked response, and two case reports describe success with betamethasone.^26,28-30 I offer steroid injections to women who have vestibulodynia before proceeding to vestibulectomy; I find that about 50% get at least partial relief. As Dr. Haefner indicated from her own experience, my success seems best with steroid injections in the vestibule when the painful area is smaller.

Using injectable steroids and botulinum toxins, I estimate that I can prevent 33% to 40% of vestibulectomies. Although this may not be better than the placebo response rate and certainly represents biased patient selection (patients are not required to try local injection before vestibulectomy for vestibulodynia), those who are successful are uniformly happy for trying it, and those for whom it did not work are not unhappy that they “gave it a try,” as these women are all motivated to avoid surgery, if possible.

Pudendal nerve blocks with triamcinolone are also described for women who have generalized unprovoked vulvodynia due to suspected pudendal neuralgia. Ganglion impar blocks—steroid injection around the terminal branch of the sympathetic chain in the presacral space—have also been performed with good results for generalized vulvodynia. I have had good success with pudendal nerve blocks for unilateral pain that is suspected to be pudendal in origin and also with ganglion impar blocks for women with generalized vulvodynia, especially postmenopausal women. I perform all of my own nerve blocks (FIGURE).

Ganglion impar block
Ganglion impar blocks—steroid injection around the terminal branch of the sympathetic chain in the presacral space—may provide relief from generalized vulvodynia in some women.

Does physical therapy play a role in easing vulvar pain?

Dr. Lonky: What is the role of physical therapy and pelvic floor muscle rehabilitation?

Dr. Gunter: All women who have high-tone pelvic floor dysfunction should be referred to a physical therapist. Many women who lack muscle spasm but experience vulvar pain can still benefit from physical therapy, as gentle stretching and vibration therapy can sometimes be helpful. A physical therapist can also perform biofeedback.

Dr. Edwards: Physical therapy is crucial. It is my first-line therapy overall, with adjunctive oral medication for neuropathic pain. Besides addressing pelvic floor abnormalities, physical therapy can serve as desensitization therapy and psychological support.

Dr. Haefner: Physical therapy has been successful in the treatment of a number of disorders, including migraine and tension headaches, asthma, and anxiety disorders. It is also used in the treatment of vulvar pain. Physical therapists who have experience in vulvar pain may be extremely helpful, particularly if there is concomitant vaginismus—which isn’t uncommon in this population.

For vulvodynia, techniques include internal (vaginal and rectal) and external soft-tissue mobilization and myofascial release; trigger-point pressure; visceral, urogenital, and joint manipulation; electrical stimulation; therapeutic exercises; active pelvic floor retraining; biofeedback; bladder and bowel retraining; and therapeutic ultrasound.

Biofeedback may be used to assist in developing self-regulation strategies for confronting and reducing pain. Patients who have vestibular pain in general have an increased resting tone and a decreased contraction tone. With the aid of an electronic measurement and amplification system or biofeedback machine, an individual can view a display of numbers on a meter, or colored lights, to assess nerve and muscle tension. In this way, she may be able to develop voluntary control over the biological systems involved in pain, discomfort, and disease.

The duration of physical therapy overall and the frequency of visits varies from person to person. Success rates in the range of 60% to 80% have been reported.

How should we respond when medical treatment fails?

Dr. Lonky: What is the proper approach to the patient who has recalcitrant vulvar pain who fails all medical treatments and is not a candidate for vestibulectomy because her pain is outside the vestibule?

Dr. Edwards: The pain clinic. Actually, in a perfect world, the role of the gynecologist or dermatologist would be to give the patient a diagnosis, after which a pain clinic would offer treatment.

All patients should receive counseling. And clinicians who lack expertise should refer the patient to a vulvodynia specialist.

Dr. Haefner: This type of patient may benefit from physical therapy. Bupivacaine steroid injections could also be considered. A sacral nerve stimulator should be considered if the other measures fail to provide adequate relief.

I agree that counseling is extremely helpful in the patient who has vulvodynia. Sexual counseling, with tips on positions for intercourse, lubricants, and control of uncomfortable situations, is of utmost importance.

Dr. Gunter: I offer oral medications and nerve blocks (typically, ganglion impar blocks), and many patients do well.

I also highly recommend advanced programs for mind-body techniques.

Patients who fail all therapies may be candidates for a nerve stimulator, depending on psychiatric comorbidities and response to selective diagnostic nerve blocks.

What’s in the pipeline?

Dr. Lonky: What therapies for vulvar pain are on the horizon?

Dr. Edwards: I believe that cognitive behavioral therapy, sex therapy, and couple counseling will play a larger role in the management of vulvar pain.

Dr. Gunter: Any therapy used in other pain conditions will probably eventually find its way to the management of vulvodynia.

Some investigators believe that Tarlov cysts play a role in vulvar pain and recommend that all women undergo sacral spine and nerve-root magnetic resonance imaging. The problem is that many asymptomatic women have Tarlov cysts, and the surgery to remove them is not at all risk-free. I strongly believe that more research is needed before we can suggest that Tarlov cysts be removed.

Dr. Haefner: Transcutaneous electrical stimulation and biofeedback have been used successfully in the treatment of vulvodynia.³¹ Some patients benefit from spinal cord stimulators, such as the sacral nerve stimulator, for pain control. Sacral nerve modulation (SNM) works primarily by modulation of the nerve signals to and from the pelvic floor muscles, bladder, and rectum. It applies low-amplitude electrical stimulation to the third sacral nerve via electrodes in a tined lead passing through the S3 foramen, which contains afferent sensory, efferent autonomic motor, and voluntary somatic nerves. Other studies have utilized a different spinal cord level. More studies are needed to demonstrate the full effect of SNM on vulvodynia.

A comprehensive review of the various treatments for vulvodynia can be found in the Journal of Lower Genital Tract Disease.²

Dr. Lonky: Thanks again for your expertise. We’ll focus on provoked vestibulodynia in the final installment of this series on vulvar pain, in the November 2011 issue of OBG Management.

Vulvar pain therapies mentioned in this discussion

We want to hear from you! Tell us what you think.

As we discussed in the first installment of this three-part series in the September issue of OBG Management, the causes of vulvar pain are many, and the diagnosis of this common complaint can be difficult. Once the diagnosis of vulvodynia has been made, however, the challenge shifts to finding an effective treatment. Here, our expert panel discusses the many options available, the data (or lack of it) behind each therapy, and what to do in refractory cases.

In Part 3 of this series, in the November issue, the focus will be vestibulodynia.

The lower vagina and vulva are richly supplied with peripheral nerves and are, therefore, sensitive to pain, particularly the region of the hymeneal ring. Although the pudendal nerve (arrow) courses through the area, it is an uncommon source of vulvar pain.

Management of vulvar pain begins with simple measures

Dr. Lonky: How do you approach treatment of vulvar pain syndromes?

Dr. Haefner: I often advise the patient to begin with simple measures. For example, I recommend that she wear cotton underwear during the day, but no underwear at night. If she perspires with exercise, wicking underwear may be helpful. I also counsel the patient to avoid vulvar irritants, douches, and the application of soap of any kind to the vulva. Cool gel packs are sometimes helpful.

When it comes to intercourse, I recommend adequate lubrication using any of a number of effective products, such as olive oil, vitamin E oil, Replens, Slippery Stuff, Astroglide, KY Liquid, and others.

There is an extensive list of lubricants at http://www.med.umich.edu/sexualhealth/resources/guide.htm

Topical agents might offer relief—but so might placebo

Dr. Lonky: What is the role of topical medications, including anesthetics, for treating vulvar pain syndromes?

Dr. Edwards: I don’t find topical medications to be particularly useful in the treatment of vulvodynia, except for lidocaine 2% jelly, or lidocaine 5% ointment, which tends to burn with application—but I never start a patient on only one medication, so judging the effectiveness of a topical therapy is difficult in that context. Good studies of topical medications in the treatment of vulvar pain syndromes are lacking, other than the recent report on amitriptyline and baclofen.¹

Dr. Haefner: For minor degrees of pain, consider lidocaine 5% ointment.

Lidocaine/prilocaine (eutectic mixture of local anesthesia or LMX) may be used but can be irritating.

Doxepin 5% cream can be applied to skin daily, gradually increasing the number of daily applications to as many as four.

Topical amitriptyline 2% with baclofen 2% in a water washable base has also been used for point tenderness (squirt 0.5 cc from a syringe onto the finger and apply it to the affected area three times a day).¹

Dr. Gunter: Topical estrogen is prescribed by many providers, but we lack studies supporting its efficacy, except for reversing hypoestrogenic changes in postmenopausal women. Some providers use a high-dose, compounded topical estrogen with lidocaine for vestibulodynia. Certainly, local hypoestrogenic changes should be reversed in postmenopausal women before a diagnosis of vulvodynia or vestibulodynia is given.

As for other topical therapies, they are widely used. Some women report improvement with application of plain petrolatum.² Response rates of 33% to 46% after use of a topical placebo for vestibulodynia are well described in the literature.^3,4

Topical analgesics are used frequently, either sporadically (during pain flares) or regularly (daily application). One method of application for localized vestibulodynia involves liberally coating a cotton ball with lidocaine 5% and then applying it to the vestibule overnight (for at least 8 hours of exposure). In this study, after 7 weeks, 76% of women were able to be sexually active, compared with 36% before the start of treatment. However, a randomized, placebo-controlled trial that included lidocaine 5% cream in one arm identified only a 20% reduction in pain for women who had localized vestibulodynia—although, in this trial, the lidocaine was massaged into the vestibule four times daily.⁵ In this study, interestingly enough, topical lidocaine was less effective than topical placebo, which produced a 33% response rate.³

Lidocaine gel has also been used, although some women report more local irritation with gel than with ointment.

Dr. Lonky: Do we have any data on topical application of other drugs?

Dr. Gunter: Compounded adjuvant medications have been evaluated. In a retrospective study of topical gabapentin in a Lipoderm base, women who had generalized or localized vulvodynia applied a dose of 2%, 4%, or 6% three times daily. Of these women, 80% experienced a reduction of at least 50% in the pain score. In addition, 67% of patients who had localized vestibular pain were able to resume intercourse.⁶

A retrospective review of 38 women who used 2% amitriptyline and 2% baclofen in a Lipoderm cream for localized vestibular pain found that 53% experienced an improvement in symptoms of at least 60%, but there was no change in the frequency of sexual intercourse.¹

Do tricyclic antidepressants ease chronic pain?

Dr. Lonky: Let’s talk, for a moment, about the use of oral tricyclic antidepressants in the treatment of vulvar pain syndromes. What do we know?

Dr. Haefner: Tricyclic antidepressants are a common treatment for vulvar pain. This group of drugs (including amitriptyline [Elavil], nortriptyline [Pamelor], and desipramine [Norpramin]) has been used to treat many idiopathic chronic pain conditions. Published and presented reports indicate that these drugs elicit about a 60% response rate for various pain conditions. A trial by the National Institutes of Health (NIH) is under way, analyzing the use of antidepressants in women who have vulvar pain.

Although treatment with tricyclic antidepressants has generally been reserved for women who have generalized vulvodynia, recent reports have found these medications to be helpful in the treatment of vestibular pain as well. The mechanism of action is thought to be related to inhibition of the reuptake of transmitters—specifically, norepinephrine and serotonin. However, the mechanism of action may be more closely related to anticholinergic effects. Tricyclics affect sodium channels and the N-methyl-d-aspartate (NMDA) receptor.

If you choose to prescribe one of these medications, consider emphasizing to the patient its effect on the sensation of pain rather than its effect on depression.

Dr. Lonky: Are there any types of patients who should not take a tricyclic?

Dr. Haefner: Yes. A patient should not take a tricyclic if she is pregnant, breastfeeding, or planning to conceive. These medicines also add to the effects of alcohol and other central nervous system depressants.

Dr. Lonky: What dosage is recommended?

Dr. Haefner: The dosage for pain control varies, depending on the age of the patient and the particular agent used. Amitriptyline is often used as a first-line medication. I start the patient on 10 to 25 mg nightly and increase that amount by 10 to 25 mg weekly, not to exceed 150 mg daily. A sample regimen might be 10 mg at bedtime for 1 week. If symptoms persist, increase the dose to 20 mg at bedtime for another week, and so on. Once a dose is established that provides relief, the patient should continue to take that amount nightly. Advise the patient not to discontinue the drug abruptly. Rather, it should be weaned.

In patients who are 60 years or older, I give a starting dose of 5 to 10 mg and increase it by 10 mg weekly.

In all age groups, it is important to advise patients to avoid consuming more than one alcoholic beverage daily while taking this medication. And in reproductive-age women, contraception is critical.

Dr. Edwards: I call these drugs tricyclic medications rather than antidepressants. They are extremely useful in managing the neuropathic component of vulvar pain. Despite a recent, apparently well-conducted study showing a lack of benefit, my 25 years of personal clinical experience with tricyclics convince me that I should wait for follow-up studies before abandoning this therapy.³

The pain literature reports that higher doses than previously reported of tricyclic medications are needed for optimal management of neuropathic pain. Doses from 100 to 150 mg are often required for substantial improvement, and a major design flaw in many studies of the effect of tricyclic medications on vulvodynia is the use of an insufficient dose.

Because of their low cost and their effectiveness, tricyclic medications are my first-line therapy for women who do not suffer severe constipation or dry eyes. The effect on depression is a useful side effect, I find.

Dr. Gunter: Although adjuvant medications, such as antidepressants and anticonvulsants, are considered by more than 80% of practitioners to be effective for vulvodynia, it is important to understand that only one randomized, double-blind, placebo-controlled prospective study has evaluated this approach, and that study found a placebo response rate of 33%.^3,7

Randomized studies indicate that low-dose amitriptyline (10–20 mg) and desipramine (150 mg) are ineffective for provoked vestibulodynia.^3,8 Cohort and retrospective studies with higher doses of amitriptyline (40 to 60 mg/day) indicate that improvement in pain scores of 50% or more can be achieved for 47% to 59% of women who have localized provoked vestibulodynia and generalized unprovoked vulvodynia.^9-11

Tricyclic antidepressants and anticonvulsants should be prescribed with caution for patients 65 years and older because they increase the risk of falls.

I give nortriptyline as a first-line agent to women who have both provoked and unprovoked pain. In general, it has fewer anticholinergic side effects than amitriptyline and is generic—it also is taken once daily. For women who have unprovoked pain, I use gabapentin as a second-line agent.

Dr. Lonky: Are any other antidepressants useful in the treatment of vulvar pain?

Dr. Haefner: I sometimes give duloxetine [Cymbalta], starting with an oral daily dose of 30 mg for 1 week. If symptoms persist, I increase the daily dose to a total of 60 mg. (If the patient is depressed, I have her take 30 mg twice daily; if she isn’t depressed, I have her take the full dose of 60 mg in the morning.) I also occasionally utilize venlafaxine [Effexor XR] for pain control, starting with an oral morning dose of 37.5 mg. This dose can be increased to 75 mg/day.

Dr. Edwards: Literature on venlafaxine for neuropathic pain suggests maximal effects at doses of 150 to 225 mg of the extended release formulation, which is often well tolerated. I start patients on 37.5 mg and increase weekly until I reach the 150-mg threshold.¹²

Are anticonvulsants effective pain relievers?

Dr. Lonky: How effective are oral anticonvulsants such as gabapentin [Neurontin]?

Dr. Haefner: Gabapentin has been used to treat chronic pain conditions. The drug is available in 100-mg, 300-mg, 400-mg, 600-mg, and 800-mg tablets. It is typically initiated at an oral dose of 300 mg daily for 3 days. The dosage is then increased to 300 mg twice daily for 3 days and, finally, to 300 mg three times daily. If necessary, it can gradually be increased to a total of 3,600 mg daily (usually divided into three doses). No more than 1,200 mg should be administered in a single dose. Side effects include somnolence, mental changes, dizziness, and weight gain.

Dr. Edwards: After tricyclic medications, I find gabapentin to be the most beneficial and easily tolerated agent. I give it to patients who have contraindications to tricyclics and who lack a strong component of depression.

Dr. Gunter: Retrospective reviews have found gabapentin to produce improvement of 80% or more in pain scores for 64% to 82% of women who have generalized unprovoked vulvodynia. And a small open-label, prospective trial of lamotrigine [Lamictal] found that it produced statistically significant improvement for generalized vulvodynia.^13-15

Dr. Lonky: What do you know about the use of the anticonvulsants pregabalin [Lyrica] and topiramate [Topamax] to treat vulvar pain syndromes?

Dr. Gunter: Pregabalin was reported to reduce symptoms by 80% for generalized, unprovoked vulvodynia in one case report.¹⁶

Dr. Edwards: I find that pregabalin is less well tolerated (and more expensive) than gabapentin, so it is one of the last agents I prescribe. I reported a small, uncontrolled series of patients who were treated with pregabalin. Of those who tolerated the drug, two thirds of the women improved by approximately 62%, as judged by a visual analog scale.

Dr. Haefner: Pregabalin is a relatively new addition to the armamentarium. I give 50 mg orally for 4 days to start. If symptoms persist, I increase the dose to 50 mg twice a day for 4 days. If symptoms still persist, I up the dose again to 50 mg three times daily and gradually increase it to 100 mg three times daily, if necessary. Some reports describe a dose as high as 300 mg twice daily (maximum).

As for topiramate, I have been using it much more frequently for vulvodynia and noticing many fewer side effects than with gabapentin.

Does capsaicin interrupt the pain circuit?

Dr. Lonky: Capsaicin has been mentioned in the literature as a therapy for vulvar pain. Is it effective? How does it work?

Dr. Haefner: Capsaicin activates A-delta sensory neurons and unmyelinated C fibers. It is a vanillyl amide that evokes the sensation of burning pain. It has been proposed as a means of desensitization, which occurs as an acute reaction mediated by neuropeptides (including substance P).¹⁷ Steinberg and colleagues found that topical capsaicin significantly decreased pain with intercourse.¹⁷ Patients applied capsaicin 0.025% cream for 20 minutes daily for 12 weeks.

In a study by Murina and colleagues, 33 women were treated with topical capsaicin 0.05%. The capsaicin cream was applied to the vulva twice daily for 30 days, then once daily for 30 days, then twice weekly for 4 months. In this study, however, the response to treatment was only partial.¹⁸

Dr. Edwards: I have never had a patient willing to try capsaicin after I describe the therapy to them.

Dr. Gunter: Two studies have evaluated daily applications of capsaicin in concentrations of 0.025% and 0.05%—one of them the study by Murina and colleagues that Dr. Haefner mentioned.^2,18 The initial release of substance P causes significant burning on application, so pretreatment with local anesthetic to help the patient tolerate the capsaicin is recommended, which could potentially confound the results. In one study, daily pain scores, as well as pain with intercourse, improved significantly for 59% of participants, but no patient experienced complete resolution of symptoms—and within 2 weeks after capsaicin was discontinued, symptoms returned.^2,18 I have had only one patient in 15 years of practice who was willing to try capsaicin and who could get past the initial burning.

Another application for botulinum toxin type A?

Dr. Lonky: Is botulinum toxin type A [Botox] at all effective?

Dr. Haefner: Botulinum toxin type A has been utilized to treat provoked vestibulodynia as well as vaginismus and was beneficial.^19-23 It blocks the cholinergic innervation of the target tissue. The therapeutic dose ranges from 20 IU to 300 IU.²⁴

A placebo-controlled trial found that injection of 20 IU of botulinum toxin into the vestibule of women with vestibulodynia did not reduce pain, improve sexual functioning, or impact the quality of life, compared with placebo.²⁵ However, this study utilized a lower dose of botulinum toxin than was used in many of the other studies.

Dr. Edwards: I have only used botulinum toxin type A in a low dose. I injected 6 IU of botulinum toxin A into the periphery of the vestibule at 3, 6, 9, and 12 o’clock in six patients, and half improved modestly. I am not prepared to use electromyography (EMG) localization in my office, but from anecdotal reports, as well as several small series and placebo-controlled trials, I would conclude that some patients improve. Those who have hypertonic pelvic floor muscles are likely to be the best candidates for this treatment.

Because the agent relieves pain only modestly, and because it is not covered by insurance for this application, I refer the patient to a gynecologist in my area who administers the drug under EMG localization.

Dr. Gunter: Given the well-documented effect on muscle spasticity, as well as studies that suggest they are also anti-nociceptive agents, botulinum toxins are certainly an attractive concept for vulvodynia. A small case series and a case report indicated significant improvement with vestibular injections of 20 to 40 U of botulinum toxin. However, a randomized, placebo-controlled, double-blind study indicated no significant improvement for women with localized vestibular pain.^25-27

I discuss botulinum toxin A with my patients. I explain that my clinical experience does differ from results published in the literature. I find that many women with vestibulodynia opt to try an injection before proceeding to vestibulectomy.

When combined with pelvic floor physical therapy, botulinum toxins are highly effective at treating muscle spasm and can be very useful for women who have a component to their pain of vaginismus or high-tone pelvic floor dysfunction.

How useful are steroids and nerve blocks?

Dr. Lonky: Is there a role for local injections of glucocorticoids or serial nerve blocks?

Dr. Edwards: The occasional patient with very localized pain (trigger point) responds fairly well in my office to intralesional corticosteroids. I have not used or seen reports describing administration of intralesional corticosteroids into a larger area, although two practitioners have told me informally that it is useful in their hands.

As a dermatologist, I cannot perform blocks. I have referred patients to gyn and pain clinics for this purpose, but neither venue has been willing to administer the blocks.

Dr. Haefner: Patients who present with small, localized areas of pain may benefit from local injections. In small areas—for example, a painful spot 1 cm in diameter—triamcinolone acetonide in combination with bupivacaine may be helpful. It is important to use a small dose of steroid in a small area, however, because tissue erosion or ulceration can occur with too high a dose of steroid in the skin. For large areas, as much as 40 mg of triamcinolone acetonide may be utilized in a single monthly dose. Generally, the dose is repeated monthly, if necessary, as many as three or four times.

For large areas, bupivacaine 0.25% is utilized, and for small areas, bupivacaine 0.5% is injected into the vulva along with the steroid. The steroid should be drawn into the syringe first (because the vial can be used at a later time), followed by bupivacaine, which is a single-dose vial.

Pudendal nerve blocks using bupivacaine have been helpful in some patients—particularly those who have unilateral pain.

Dr. Gunter: Local injections with a variety of agents for localized, provoked vestibulodynia have been described, including steroids, botulinum toxins, and interferon. It is important to interpret these studies with caution, however, as placebo response rates with injection therapy are significant.²⁵

A retrospective review of submucous injections of methylprednisolone and lidocaine found that 68% of women had a complete or marked response, and two case reports describe success with betamethasone.^26,28-30 I offer steroid injections to women who have vestibulodynia before proceeding to vestibulectomy; I find that about 50% get at least partial relief. As Dr. Haefner indicated from her own experience, my success seems best with steroid injections in the vestibule when the painful area is smaller.

Using injectable steroids and botulinum toxins, I estimate that I can prevent 33% to 40% of vestibulectomies. Although this may not be better than the placebo response rate and certainly represents biased patient selection (patients are not required to try local injection before vestibulectomy for vestibulodynia), those who are successful are uniformly happy for trying it, and those for whom it did not work are not unhappy that they “gave it a try,” as these women are all motivated to avoid surgery, if possible.

Pudendal nerve blocks with triamcinolone are also described for women who have generalized unprovoked vulvodynia due to suspected pudendal neuralgia. Ganglion impar blocks—steroid injection around the terminal branch of the sympathetic chain in the presacral space—have also been performed with good results for generalized vulvodynia. I have had good success with pudendal nerve blocks for unilateral pain that is suspected to be pudendal in origin and also with ganglion impar blocks for women with generalized vulvodynia, especially postmenopausal women. I perform all of my own nerve blocks (FIGURE).

Ganglion impar block
Ganglion impar blocks—steroid injection around the terminal branch of the sympathetic chain in the presacral space—may provide relief from generalized vulvodynia in some women.

Does physical therapy play a role in easing vulvar pain?

Dr. Lonky: What is the role of physical therapy and pelvic floor muscle rehabilitation?

Dr. Gunter: All women who have high-tone pelvic floor dysfunction should be referred to a physical therapist. Many women who lack muscle spasm but experience vulvar pain can still benefit from physical therapy, as gentle stretching and vibration therapy can sometimes be helpful. A physical therapist can also perform biofeedback.

Dr. Edwards: Physical therapy is crucial. It is my first-line therapy overall, with adjunctive oral medication for neuropathic pain. Besides addressing pelvic floor abnormalities, physical therapy can serve as desensitization therapy and psychological support.

Dr. Haefner: Physical therapy has been successful in the treatment of a number of disorders, including migraine and tension headaches, asthma, and anxiety disorders. It is also used in the treatment of vulvar pain. Physical therapists who have experience in vulvar pain may be extremely helpful, particularly if there is concomitant vaginismus—which isn’t uncommon in this population.

For vulvodynia, techniques include internal (vaginal and rectal) and external soft-tissue mobilization and myofascial release; trigger-point pressure; visceral, urogenital, and joint manipulation; electrical stimulation; therapeutic exercises; active pelvic floor retraining; biofeedback; bladder and bowel retraining; and therapeutic ultrasound.

Biofeedback may be used to assist in developing self-regulation strategies for confronting and reducing pain. Patients who have vestibular pain in general have an increased resting tone and a decreased contraction tone. With the aid of an electronic measurement and amplification system or biofeedback machine, an individual can view a display of numbers on a meter, or colored lights, to assess nerve and muscle tension. In this way, she may be able to develop voluntary control over the biological systems involved in pain, discomfort, and disease.

The duration of physical therapy overall and the frequency of visits varies from person to person. Success rates in the range of 60% to 80% have been reported.

How should we respond when medical treatment fails?

Dr. Lonky: What is the proper approach to the patient who has recalcitrant vulvar pain who fails all medical treatments and is not a candidate for vestibulectomy because her pain is outside the vestibule?

Dr. Edwards: The pain clinic. Actually, in a perfect world, the role of the gynecologist or dermatologist would be to give the patient a diagnosis, after which a pain clinic would offer treatment.

All patients should receive counseling. And clinicians who lack expertise should refer the patient to a vulvodynia specialist.

Dr. Haefner: This type of patient may benefit from physical therapy. Bupivacaine steroid injections could also be considered. A sacral nerve stimulator should be considered if the other measures fail to provide adequate relief.

I agree that counseling is extremely helpful in the patient who has vulvodynia. Sexual counseling, with tips on positions for intercourse, lubricants, and control of uncomfortable situations, is of utmost importance.

Dr. Gunter: I offer oral medications and nerve blocks (typically, ganglion impar blocks), and many patients do well.

I also highly recommend advanced programs for mind-body techniques.

Patients who fail all therapies may be candidates for a nerve stimulator, depending on psychiatric comorbidities and response to selective diagnostic nerve blocks.

What’s in the pipeline?

Dr. Lonky: What therapies for vulvar pain are on the horizon?

Dr. Edwards: I believe that cognitive behavioral therapy, sex therapy, and couple counseling will play a larger role in the management of vulvar pain.

Dr. Gunter: Any therapy used in other pain conditions will probably eventually find its way to the management of vulvodynia.

Some investigators believe that Tarlov cysts play a role in vulvar pain and recommend that all women undergo sacral spine and nerve-root magnetic resonance imaging. The problem is that many asymptomatic women have Tarlov cysts, and the surgery to remove them is not at all risk-free. I strongly believe that more research is needed before we can suggest that Tarlov cysts be removed.

Dr. Haefner: Transcutaneous electrical stimulation and biofeedback have been used successfully in the treatment of vulvodynia.³¹ Some patients benefit from spinal cord stimulators, such as the sacral nerve stimulator, for pain control. Sacral nerve modulation (SNM) works primarily by modulation of the nerve signals to and from the pelvic floor muscles, bladder, and rectum. It applies low-amplitude electrical stimulation to the third sacral nerve via electrodes in a tined lead passing through the S3 foramen, which contains afferent sensory, efferent autonomic motor, and voluntary somatic nerves. Other studies have utilized a different spinal cord level. More studies are needed to demonstrate the full effect of SNM on vulvodynia.

A comprehensive review of the various treatments for vulvodynia can be found in the Journal of Lower Genital Tract Disease.²

Dr. Lonky: Thanks again for your expertise. We’ll focus on provoked vestibulodynia in the final installment of this series on vulvar pain, in the November 2011 issue of OBG Management.

Vulvar pain therapies mentioned in this discussion

We want to hear from you! Tell us what you think.

A woman’s lifetime risk of surgery for pelvic organ prolapse is approximately 7%; more than 300,000 prolapse surgeries are performed annually in the United States alone.¹ Of the women who undergo surgery, an estimated 13% will require re-operation within 5 years, and as many as 29% will undergo another surgery for genital prolapse or a related condition at some point during their life.²

In the hope of improving the effectiveness and durability of vaginal prolapse repairs, many pelvic reconstructive surgeons have turned to reinforcement with synthetic mesh. However, because of concern about a higher risk of complications relative to other approaches, the use of transvaginal mesh for prolapse repair has come under increased scrutiny by the FDA. At this time, almost one quarter of all prolapse repairs involve placement of transvaginal mesh.³

Details of the trial

Withagen and colleagues enrolled 194 women from 13 Dutch medical centers. All women had recurrent pelvic organ prolapse and were randomized to either trocar-guided transvaginal mesh repair (Prolift) or conventional vaginal prolapse repair without mesh (i.e., native-tissue repair).

As in several other trials evaluating transvaginal mesh for anterior vaginal prolapse, the investigators found that it led to improved anatomic outcomes, compared with native-tissue repair, but at the expense of a higher complication rate. In this study, women in the mesh group experienced a cumulative rate of vaginal mesh exposure of 16.9% by 12 months and had a higher rate of hematoma and greater voiding dysfunction in the immediate postoperative period.

The most clinically relevant outcome to patients who have prolapse is resolution of their symptom of vaginal bulging; this symptom improved similarly in both treatment groups.⁴

Strengths and weakness of the study

This study has a number of strengths:

• an excellent rate of follow-up (98%)
• a large number of study sites
• use of multiple validated outcome measures.

The principal weakness is the use of strict anatomic criteria as the primary outcome measure. In the general population, 40% of asymptomatic women who present for annual gynecologic examination have vaginal support of Stage 2 or higher and would have been considered failures by this definition.⁵ Prolapse beyond the hymen appears to be a more clinically relevant threshold for defining anatomic success.

FDA gets involved

In July 2011, the FDA issued a safety update on the use of transvaginal mesh for prolapse repair. Its principal findings:

• Serious adverse events are not rare
• Transvaginally placed mesh in prolapse repair does not conclusively improve clinical outcomes over traditional non-mesh repair.³

The FDA noted that patients who undergo prolapse repair with mesh are subject to a unique set of complications, including erosion and mesh contraction, which can be life-altering and, in some women, may require multiple surgeries to correct.

Given the safety concerns regarding transvaginal mesh, the FDA is considering changing the regulatory process for the introduction of new transvaginal mesh devices.

We want to hear from you!  Tell us what you think.

A woman’s lifetime risk of surgery for pelvic organ prolapse is approximately 7%; more than 300,000 prolapse surgeries are performed annually in the United States alone.¹ Of the women who undergo surgery, an estimated 13% will require re-operation within 5 years, and as many as 29% will undergo another surgery for genital prolapse or a related condition at some point during their life.²

In the hope of improving the effectiveness and durability of vaginal prolapse repairs, many pelvic reconstructive surgeons have turned to reinforcement with synthetic mesh. However, because of concern about a higher risk of complications relative to other approaches, the use of transvaginal mesh for prolapse repair has come under increased scrutiny by the FDA. At this time, almost one quarter of all prolapse repairs involve placement of transvaginal mesh.³

Details of the trial

Withagen and colleagues enrolled 194 women from 13 Dutch medical centers. All women had recurrent pelvic organ prolapse and were randomized to either trocar-guided transvaginal mesh repair (Prolift) or conventional vaginal prolapse repair without mesh (i.e., native-tissue repair).

As in several other trials evaluating transvaginal mesh for anterior vaginal prolapse, the investigators found that it led to improved anatomic outcomes, compared with native-tissue repair, but at the expense of a higher complication rate. In this study, women in the mesh group experienced a cumulative rate of vaginal mesh exposure of 16.9% by 12 months and had a higher rate of hematoma and greater voiding dysfunction in the immediate postoperative period.

The most clinically relevant outcome to patients who have prolapse is resolution of their symptom of vaginal bulging; this symptom improved similarly in both treatment groups.⁴

Strengths and weakness of the study

This study has a number of strengths:

• an excellent rate of follow-up (98%)
• a large number of study sites
• use of multiple validated outcome measures.

The principal weakness is the use of strict anatomic criteria as the primary outcome measure. In the general population, 40% of asymptomatic women who present for annual gynecologic examination have vaginal support of Stage 2 or higher and would have been considered failures by this definition.⁵ Prolapse beyond the hymen appears to be a more clinically relevant threshold for defining anatomic success.

FDA gets involved

In July 2011, the FDA issued a safety update on the use of transvaginal mesh for prolapse repair. Its principal findings:

• Serious adverse events are not rare
• Transvaginally placed mesh in prolapse repair does not conclusively improve clinical outcomes over traditional non-mesh repair.³

The FDA noted that patients who undergo prolapse repair with mesh are subject to a unique set of complications, including erosion and mesh contraction, which can be life-altering and, in some women, may require multiple surgeries to correct.

Given the safety concerns regarding transvaginal mesh, the FDA is considering changing the regulatory process for the introduction of new transvaginal mesh devices.

We want to hear from you!  Tell us what you think.

A woman’s lifetime risk of surgery for pelvic organ prolapse is approximately 7%; more than 300,000 prolapse surgeries are performed annually in the United States alone.¹ Of the women who undergo surgery, an estimated 13% will require re-operation within 5 years, and as many as 29% will undergo another surgery for genital prolapse or a related condition at some point during their life.²

In the hope of improving the effectiveness and durability of vaginal prolapse repairs, many pelvic reconstructive surgeons have turned to reinforcement with synthetic mesh. However, because of concern about a higher risk of complications relative to other approaches, the use of transvaginal mesh for prolapse repair has come under increased scrutiny by the FDA. At this time, almost one quarter of all prolapse repairs involve placement of transvaginal mesh.³

Details of the trial

Withagen and colleagues enrolled 194 women from 13 Dutch medical centers. All women had recurrent pelvic organ prolapse and were randomized to either trocar-guided transvaginal mesh repair (Prolift) or conventional vaginal prolapse repair without mesh (i.e., native-tissue repair).

As in several other trials evaluating transvaginal mesh for anterior vaginal prolapse, the investigators found that it led to improved anatomic outcomes, compared with native-tissue repair, but at the expense of a higher complication rate. In this study, women in the mesh group experienced a cumulative rate of vaginal mesh exposure of 16.9% by 12 months and had a higher rate of hematoma and greater voiding dysfunction in the immediate postoperative period.

The most clinically relevant outcome to patients who have prolapse is resolution of their symptom of vaginal bulging; this symptom improved similarly in both treatment groups.⁴

Strengths and weakness of the study

This study has a number of strengths:

• an excellent rate of follow-up (98%)
• a large number of study sites
• use of multiple validated outcome measures.

The principal weakness is the use of strict anatomic criteria as the primary outcome measure. In the general population, 40% of asymptomatic women who present for annual gynecologic examination have vaginal support of Stage 2 or higher and would have been considered failures by this definition.⁵ Prolapse beyond the hymen appears to be a more clinically relevant threshold for defining anatomic success.

FDA gets involved

In July 2011, the FDA issued a safety update on the use of transvaginal mesh for prolapse repair. Its principal findings:

• Serious adverse events are not rare
• Transvaginally placed mesh in prolapse repair does not conclusively improve clinical outcomes over traditional non-mesh repair.³

The FDA noted that patients who undergo prolapse repair with mesh are subject to a unique set of complications, including erosion and mesh contraction, which can be life-altering and, in some women, may require multiple surgeries to correct.

Given the safety concerns regarding transvaginal mesh, the FDA is considering changing the regulatory process for the introduction of new transvaginal mesh devices.

We want to hear from you!  Tell us what you think.

Although the incidence of vulvar pain has increased over the past decade—thanks to both greater awareness and increasing numbers of affected women—the phenomenon is not a recent development. As early as 1874, T. Galliard Thomas wrote, “[T]his disorder, although fortunately not very frequent, is by no means very rare.”1 He went on to express “surprise” that it had not been “more generally and fully described.”

Despite the focus Thomas directed to the issue, vulvar pain did not get much attention until the 21st century, when a number of studies began to gauge its prevalence. For example, in a study in Boston of about 5,000 women, the lifetime prevalence of chronic vulvar pain was 16%.² And in a study in Texas, the prevalence of vulvar pain in an urban, largely minority population was estimated to be 11%.³ The Boston study also reported that “nearly 40% of women chose not to seek treatment, and, of those who did, 60% saw three or more doctors, many of whom could not provide a diagnosis.”²

Clearly, there is a need for comprehensive information on vulvar pain and its causes, symptoms, diagnosis, and treatment. To address the lack of guidance, OBG Management Contributing Editor Neal M. Lonky, MD, assembled a panel of experts on vulvar pain syndromes and invited them to share their considerable knowledge. The ensuing discussion, presented in three parts, offers a gold mine of information.

In this opening article, the panel focuses on causes, symptomatology, and diagnosis of this common complaint. In Part 2, which will appear in the October issue of this journal, the focus is the bounty of treatment options. Part 3 follows in November, when the discussion shifts to vestibulodynia.

The lower vagina and vulva are richly supplied with peripheral nerves and are, therefore, sensitive to pain, particularly the region of the hymeneal ring. Although the pudendal nerve (arrow) courses through the area, it is an uncommon source of vulvar pain.

Common diagnoses—and misdiagnoses

Dr. Lonky: What are the most common diagnoses when vulvar pain is the complaint?

Dr. Gunter: The most common cause of chronic vulvar pain is vulvodynia, although lichen simplex chronicus, chronic yeast infections, and non-neoplastic epithelial disorders, such as lichen sclerosus and lichen planus, can also produce irritation and pain. In postmenopausal women, atrophic vaginitis can also cause a burning pain, although symptoms are typically more vaginal than vulvar. Yeast and lichen simplex chronicus typically produce itching, although sometimes they can present with irritation and pain, so they must be considered in the differential diagnosis. It is important to remember that many women with vulvodynia have used multiple topical agents and may have developed complex hygiene rituals in an attempt to treat their symptoms, which can result in a secondary lichen simplex chronicus.

That said, there is a high frequency of misdiagnosis with yeast. For example, in a study by Nyirjesy and colleagues, two thirds of women who were referred to a tertiary clinic for chronic vulvovaginal candidiasis were found to have a noninfectious entity instead—most commonly lichen simplex chronicus and vulvodynia.⁴

Dr. Edwards: The most common “diagnosis” for vulvar pain is vulvodynia. However, the definition of vulvodynia is pain—i.e., burning, rawness, irritation, soreness, aching, or stabbing or stinging sensations—in the absence of skin disease, infection, or specific neurologic disease. Therefore, even though the usual cause of vulvar pain is vulvodynia, it is a diagnosis of exclusion, and skin disease, infection, and neurologic disease must be ruled out.

In regard to infection, Candida albicans and bacterial vaginosis (BV) are usually the first conditions that are considered when a patient complains of vulvar pain, but they are not common causes of vulvar pain and are never causes of chronic vulvar pain. Very rarely they may cause recurrent pain that clears, at least briefly, with treatment.

Candida albicans is usually primarily pruritic, and BV produces discharge and odor, sometimes with minor symptoms. Non-albicans Candida (e.g., Candida glabrata) is nearly always asymptomatic, but it occasionally causes irritation and burning.

Group B streptococcus is another infectious entity that very, very occasionally causes irritation and dyspareunia but is usually only a colonizer.

Herpes simplex virus is a cause of recurrent but not chronic pain.

Chronic pain is more likely to be caused by skin disease than by infection. Lichen simplex chronicus causes itching; any pain is due to erosions from scratching.

Dr. Haefner: Several other infectious conditions or their treatments can cause vulvar pain. For example, herpes (particularly primary herpes infection) is classically associated with vulvar pain. The pain is so great that, at times, the patient requires admission for pain control. Surprisingly, despite the known pain of herpes, approximately 80% of patients who have it are unaware of their diagnosis.

Although condyloma is generally a painless condition, many patients complain of pain following treatment for it, whether treatment involves topical medications or laser surgery.

Chancroid is a painful vulvar ulcer. Trichomonas can sometimes be associated with vulvar pain.

Dr. Lonky: What terminology do we use when we discuss vulvar pain?

Dr. Haefner: The current terminology used to describe vulvar pain was published in 2004, after years of debate over nomenclature within the International Society for the Study of Vulvovaginal Disease.⁵ The terminology lists two major categories of vulvar pain:

• pain related to a specific disorder. This category encompasses numerous conditions that feature an abnormal appearance of the vulva (Table 1).

TABLE 1

Terminology and classification of vulvar pain from the International Society for the Study of Vulvovaginal Disease

• vulvodynia, in which the vulva appears normal, other than occasional erythema, which is most prominent at the duct openings (vestibular ducts—Bartholin’s and Skene’s).

As for vulvar pain, there are two major forms:

• hyperalgesia (a low threshold for pain)
• allodynia (pain in response to light touch).

Some diseases that are associated with vulvar pain do not qualify for the diagnosis of vulvodynia (Table 2) because they are associated with an abnormal appearance of the vulva.

TABLE 2

Conditions other than vulvodynia that are associated with vulvar pain

What needs to be ruled out for a diagnosis of vulvodynia?

Dr. Lonky: What skin diseases need to be ruled out before vulvodynia can be diagnosed?

Dr. Edwards: Skin diseases that affect the vulva are usually pruritic—pain is a later sign. Lichen simplex chronicus (also known as eczema) is pruritus caused by any irritant; any pain that arises is produced by visible excoriations from scratching.

Lichen sclerosus manifests as white epithelium that has a crinkling, shiny, or waxy texture. It can produce pain, especially dyspareunia. The pain is caused by erosions that arise from fragility and introital narrowing and inelasticity.

Vulvovaginal lichen planus is usually erosive and preferentially affects mucous membranes, especially the vestibule; it sometimes affects the vagina and mouth, as well.

Desquamative inflammatory vaginitis is most likely a skin disease that affects only the vagina. It involves introital redness and a clinically and microscopically purulent vaginal discharge that also reveals parabasal cells and absent lactobacilli.

Dr. Lonky: You mentioned that neurologic diseases can sometimes cause vulvar pain. Which ones?

Dr. Edwards: Pudendal neuralgia, diabetic neuropathy, and post-herpetic neuralgia are the most common specific neurologic causes of vulvar pain. Multiple sclerosis can also produce pain syndromes. Post-herpetic neuralgia follows herpes zoster—not herpes simplex—virus infection.

Dr. Lonky: Any other conditions that can cause vulvar pain?

Dr. Haefner: Aphthous ulcers are common and are often flared by stress.

Non-neoplastic epithelial disorders are also seen frequently in health-care providers’ offices; many patients who experience them report pain on the vulva.

It is always important to consider cancer when a patient has an abnormal vulvar appearance and pain that has persisted despite treatment.

What are the most common vulvar pain syndromes?

Dr. Lonky: If you were to rank vulvar pain syndromes according to their prevalence, what would the most common syndromes be?

Dr. Gunter: Given the misdiagnosis of many women, who are told they have chronic yeast infection, as I mentioned, it’s hard to know which vulvar pain syndromes are most prevalent. I suspect that lichen simplex chronicus is most common, followed by vulvodynia, with chronic yeast infection a distant third.

My experience reflects what Nyirjesy and colleagues⁴ found: 65% to 75% of women referred to my clinic with chronic yeast actually have lichen simplex chronicus or vulvodynia. In postmenopausal women, atrophic vaginitis is also a consideration; it’s becoming more common now that the use of systemic hormone replacement therapy is decreasing.

Dr. Lonky: What about subsets of vulvodynia? Which ones are most common?

Dr. Edwards: There is good evidence of marked overlap among subsets of vulvodynia. The vast majority of women who have vulvodynia experience primarily provoked vestibular pain, regardless of age. However, I find that almost all patients also report pain that extends beyond the vestibule at times, as well as occasional unprovoked pain.

The diagnosis requires the exclusion of other causes of vulvar pain, and the subset is identified by the location of pain (that is, is it strictly localized or generalized or even migratory?) and its provoked or unprovoked nature.

Localized clitoral pain and vulvar pain localized to one side of the vulva are extremely uncommon, but they do occur. And although I rarely encounter teenagers and prepubertal children who have vulvodynia, I do have patients in both age groups who have vulvodynia.

Dr. Lonky: Are there racial differences in the prevalence of vulvodynia?

Dr. Edwards: Although several good studies show that women of African descent and white patients are equally likely to experience vulvodynia, the vast majority (99%) of my patients who have vulvodynia are white. My patients of African descent consult me primarily for itching or discharge.

My local demographics prevent me from judging the likelihood of Asians having vulvodynia, and our Hispanic population has limited access to health care.

In general, I don’t think that demographics are useful in making the diagnosis of vulvodynia.

Do women who have vulvar pain tend to have comorbidities?

Dr. Lonky: Do your patients who have vulvodynia or another vulvar pain syndrome tend to have comorbidities? If so, is this information helpful in establishing the diagnosis and planning therapy?

Dr. Haefner: Women who have vulvodynia often have other medical problems as well. In my practice, when new patients who have vulvodynia complete their intake survey, they often report a history of headache, irritable bowel syndrome, interstitial cystitis, fibromyalgia,⁶ chronic fatigue syndrome, back pain, and temporomandibular joint (TMJ) disorder. These comorbidities are not particularly helpful in establishing the diagnosis of vulvodynia, but they are an important consideration when choosing therapy for the patient. Often, the medications chosen to treat one condition will also benefit another condition. However, it’s important to check for potential interactions between drugs before prescribing a new treatment.

Dr. Gunter: A significant number of women who have vulvodynia also have other chronic pain syndromes. For example, the incidence of bladder pain syndrome–interstitial cystitis is 68% to 82% among women who have vulvodynia, compared with a baseline rate among all women of 6% to 11%.^7-10 The rate of irritable bowel syndrome is more than doubled among women who have vulvodynia, compared with the general population (27% versus 12%).⁸ Another common comorbidity, hypertonic somatic dysfunction of the pelvic floor, is identified in 10% to 90% of women who have chronic vulvar pain.^8,11,12 These women also have a higher incidence of nongenital pain syndromes, such as fibromyalgia, migraine, and TMJ dysfunction, than the general population, as Dr. Haefner noted.^8,12,13

Many studies have evaluated psychological and emotional contributions to chronic vulvar pain. Pain and depression are intimately related—the incidence of depression among all people who experience chronic pain ranges from 27% to 54%, compared with 5% to 17% among the general population.^14-16 The relationship is complex because chronic illness in general is associated with depression. Nevertheless, several studies have noted an increase in anxiety, stress, and depression among women who have vulvodynia.^17-19

I screen every patient for depression using a Patient Health Questionnaire (PHQ-9); I also screen for anxiety. I find that a significant percentage of patients in my clinic are depressed or have an anxiety disorder. Failure to address these comorbidities makes treatment very difficult. I typically prescribe citalopram (Celexa), although there is some question whether it can safely be combined with a tricyclic antidepressant. We also offer stress-reduction classes, teach every patient the value of diaphragmatic breathing, offer mind-body classes for anxiety and stress, and provide intensive programs where the patient can learn important self-care skills, such as pacing (spacing activities throughout the day in a manner that avoids aggravating the pain), and address her anxiety and stress in a more guided manner. We also have a psychologist who specializes in pain for any patient who may need one-on-one counseling.

Dr. Edwards: The presence of comorbidities is somewhat useful in making the diagnosis of vulvodynia. I question my diagnosis, in fact, when a patient who has vulvodynia does not have headaches, low energy, depression, anxiety, irritable bowel syndrome, constipation, fibromyalgia, chronic fatigue, sensitivity to medications, TMJ dysfunction, or urinary symptoms.

How common is pudendal neuralgia?

Dr. Lonky: How prevalent is a finding of pudendal neuralgia?

Dr. Edwards: The prevalence and incidence of pudendal neuralgia are not known. Those who specialize in this condition think it is relatively common. I do not identify or suspect it very often. Its definitive diagnosis and management are outside the purview of the general gynecologist, but the general gynecologist should recognize the symptoms of pudendal neuralgia and refer the patient for evaluation and therapy.

Dr. Lonky: What are those symptoms?

Dr. Haefner: Pudendal neuralgia often occurs following trauma to the pudendal nerve. The pudendal nerve arises from sacral nerves, generally sacral nerves 2 to 4. Several tests can be utilized to diagnose this condition, including quantitative sensor tests, pudendal nerve motor latency tests, electromyography (EMG), and pudendal nerve blocks.²⁰

Nantes Criteria allow for making a diagnosis of pudendal neuralgia (Table 3).²¹

TABLE 3

Nantes Criteria for pudendal neuralgia by pudendal nerve entrapment

Initial treatments for pudendal neuralgia should be conservative. Treatments consist of lifestyle changes to prevent flare of disease. Physical therapy, medical management, nerve blocks, and alternative treatments may be beneficial.

Pudendal nerve entrapment is often exacerbated by sitting (not on a toilet seat, however) and is reduced in a standing position. It tends to increase in intensity throughout the day.²² The final treatment for pudendal nerve entrapment is surgery if the nerve is compressed. By this time, the generalist is not generally the provider who performs the surgery.

Dr. Gunter: I believe pudendal neuralgia is sometimes overdiagnosed. EMG studies of the pudendal nerve, often touted as a diagnostic tool, are unreliable (they can be abnormal after vaginal delivery or vaginal hysterectomy, for example). In my experience, bilateral pain is less likely to be pudendal neuralgia; spontaneous bilateral compression neuropathy at exactly the same level is not a common phenomenon in chronic pain.

I reserve the diagnosis of pudendal neuralgia for women who have allodynia in the distribution of the pudendal nerve with severe pain on sitting, and who have exquisite tenderness when pressure is applied over the pudendal nerve (at the level of the ischial spine on vaginal examination). Typically, the vaginal sidewall on the affected side is very sensitive to light touch. I do see pudendal nerve pain after vaginal surgery when there has been some compromise of the pudendal nerve or the sacral plexus. This is typically unilateral pain.

Dr. Lonky: Thank you all. We’ll continue our discussion, with a focus on treatment, in the October 2011 issue.

We want to hear from you! Tell us what you think.

Although the incidence of vulvar pain has increased over the past decade—thanks to both greater awareness and increasing numbers of affected women—the phenomenon is not a recent development. As early as 1874, T. Galliard Thomas wrote, “[T]his disorder, although fortunately not very frequent, is by no means very rare.”1 He went on to express “surprise” that it had not been “more generally and fully described.”

Despite the focus Thomas directed to the issue, vulvar pain did not get much attention until the 21st century, when a number of studies began to gauge its prevalence. For example, in a study in Boston of about 5,000 women, the lifetime prevalence of chronic vulvar pain was 16%.² And in a study in Texas, the prevalence of vulvar pain in an urban, largely minority population was estimated to be 11%.³ The Boston study also reported that “nearly 40% of women chose not to seek treatment, and, of those who did, 60% saw three or more doctors, many of whom could not provide a diagnosis.”²

Clearly, there is a need for comprehensive information on vulvar pain and its causes, symptoms, diagnosis, and treatment. To address the lack of guidance, OBG Management Contributing Editor Neal M. Lonky, MD, assembled a panel of experts on vulvar pain syndromes and invited them to share their considerable knowledge. The ensuing discussion, presented in three parts, offers a gold mine of information.

In this opening article, the panel focuses on causes, symptomatology, and diagnosis of this common complaint. In Part 2, which will appear in the October issue of this journal, the focus is the bounty of treatment options. Part 3 follows in November, when the discussion shifts to vestibulodynia.

The lower vagina and vulva are richly supplied with peripheral nerves and are, therefore, sensitive to pain, particularly the region of the hymeneal ring. Although the pudendal nerve (arrow) courses through the area, it is an uncommon source of vulvar pain.

Common diagnoses—and misdiagnoses

Dr. Lonky: What are the most common diagnoses when vulvar pain is the complaint?

Dr. Gunter: The most common cause of chronic vulvar pain is vulvodynia, although lichen simplex chronicus, chronic yeast infections, and non-neoplastic epithelial disorders, such as lichen sclerosus and lichen planus, can also produce irritation and pain. In postmenopausal women, atrophic vaginitis can also cause a burning pain, although symptoms are typically more vaginal than vulvar. Yeast and lichen simplex chronicus typically produce itching, although sometimes they can present with irritation and pain, so they must be considered in the differential diagnosis. It is important to remember that many women with vulvodynia have used multiple topical agents and may have developed complex hygiene rituals in an attempt to treat their symptoms, which can result in a secondary lichen simplex chronicus.

That said, there is a high frequency of misdiagnosis with yeast. For example, in a study by Nyirjesy and colleagues, two thirds of women who were referred to a tertiary clinic for chronic vulvovaginal candidiasis were found to have a noninfectious entity instead—most commonly lichen simplex chronicus and vulvodynia.⁴

Dr. Edwards: The most common “diagnosis” for vulvar pain is vulvodynia. However, the definition of vulvodynia is pain—i.e., burning, rawness, irritation, soreness, aching, or stabbing or stinging sensations—in the absence of skin disease, infection, or specific neurologic disease. Therefore, even though the usual cause of vulvar pain is vulvodynia, it is a diagnosis of exclusion, and skin disease, infection, and neurologic disease must be ruled out.

In regard to infection, Candida albicans and bacterial vaginosis (BV) are usually the first conditions that are considered when a patient complains of vulvar pain, but they are not common causes of vulvar pain and are never causes of chronic vulvar pain. Very rarely they may cause recurrent pain that clears, at least briefly, with treatment.

Candida albicans is usually primarily pruritic, and BV produces discharge and odor, sometimes with minor symptoms. Non-albicans Candida (e.g., Candida glabrata) is nearly always asymptomatic, but it occasionally causes irritation and burning.

Group B streptococcus is another infectious entity that very, very occasionally causes irritation and dyspareunia but is usually only a colonizer.

Herpes simplex virus is a cause of recurrent but not chronic pain.

Chronic pain is more likely to be caused by skin disease than by infection. Lichen simplex chronicus causes itching; any pain is due to erosions from scratching.

Dr. Haefner: Several other infectious conditions or their treatments can cause vulvar pain. For example, herpes (particularly primary herpes infection) is classically associated with vulvar pain. The pain is so great that, at times, the patient requires admission for pain control. Surprisingly, despite the known pain of herpes, approximately 80% of patients who have it are unaware of their diagnosis.

Although condyloma is generally a painless condition, many patients complain of pain following treatment for it, whether treatment involves topical medications or laser surgery.

Chancroid is a painful vulvar ulcer. Trichomonas can sometimes be associated with vulvar pain.

Dr. Lonky: What terminology do we use when we discuss vulvar pain?

Dr. Haefner: The current terminology used to describe vulvar pain was published in 2004, after years of debate over nomenclature within the International Society for the Study of Vulvovaginal Disease.⁵ The terminology lists two major categories of vulvar pain:

• pain related to a specific disorder. This category encompasses numerous conditions that feature an abnormal appearance of the vulva (Table 1).

TABLE 1

Terminology and classification of vulvar pain from the International Society for the Study of Vulvovaginal Disease

• vulvodynia, in which the vulva appears normal, other than occasional erythema, which is most prominent at the duct openings (vestibular ducts—Bartholin’s and Skene’s).

As for vulvar pain, there are two major forms:

• hyperalgesia (a low threshold for pain)
• allodynia (pain in response to light touch).

Some diseases that are associated with vulvar pain do not qualify for the diagnosis of vulvodynia (Table 2) because they are associated with an abnormal appearance of the vulva.

TABLE 2

Conditions other than vulvodynia that are associated with vulvar pain

What needs to be ruled out for a diagnosis of vulvodynia?

Dr. Lonky: What skin diseases need to be ruled out before vulvodynia can be diagnosed?

Dr. Edwards: Skin diseases that affect the vulva are usually pruritic—pain is a later sign. Lichen simplex chronicus (also known as eczema) is pruritus caused by any irritant; any pain that arises is produced by visible excoriations from scratching.

Lichen sclerosus manifests as white epithelium that has a crinkling, shiny, or waxy texture. It can produce pain, especially dyspareunia. The pain is caused by erosions that arise from fragility and introital narrowing and inelasticity.

Vulvovaginal lichen planus is usually erosive and preferentially affects mucous membranes, especially the vestibule; it sometimes affects the vagina and mouth, as well.

Desquamative inflammatory vaginitis is most likely a skin disease that affects only the vagina. It involves introital redness and a clinically and microscopically purulent vaginal discharge that also reveals parabasal cells and absent lactobacilli.

Dr. Lonky: You mentioned that neurologic diseases can sometimes cause vulvar pain. Which ones?

Dr. Edwards: Pudendal neuralgia, diabetic neuropathy, and post-herpetic neuralgia are the most common specific neurologic causes of vulvar pain. Multiple sclerosis can also produce pain syndromes. Post-herpetic neuralgia follows herpes zoster—not herpes simplex—virus infection.

Dr. Lonky: Any other conditions that can cause vulvar pain?

Dr. Haefner: Aphthous ulcers are common and are often flared by stress.

Non-neoplastic epithelial disorders are also seen frequently in health-care providers’ offices; many patients who experience them report pain on the vulva.

It is always important to consider cancer when a patient has an abnormal vulvar appearance and pain that has persisted despite treatment.

What are the most common vulvar pain syndromes?

Dr. Lonky: If you were to rank vulvar pain syndromes according to their prevalence, what would the most common syndromes be?

Dr. Gunter: Given the misdiagnosis of many women, who are told they have chronic yeast infection, as I mentioned, it’s hard to know which vulvar pain syndromes are most prevalent. I suspect that lichen simplex chronicus is most common, followed by vulvodynia, with chronic yeast infection a distant third.

My experience reflects what Nyirjesy and colleagues⁴ found: 65% to 75% of women referred to my clinic with chronic yeast actually have lichen simplex chronicus or vulvodynia. In postmenopausal women, atrophic vaginitis is also a consideration; it’s becoming more common now that the use of systemic hormone replacement therapy is decreasing.

Dr. Lonky: What about subsets of vulvodynia? Which ones are most common?

Dr. Edwards: There is good evidence of marked overlap among subsets of vulvodynia. The vast majority of women who have vulvodynia experience primarily provoked vestibular pain, regardless of age. However, I find that almost all patients also report pain that extends beyond the vestibule at times, as well as occasional unprovoked pain.

The diagnosis requires the exclusion of other causes of vulvar pain, and the subset is identified by the location of pain (that is, is it strictly localized or generalized or even migratory?) and its provoked or unprovoked nature.

Localized clitoral pain and vulvar pain localized to one side of the vulva are extremely uncommon, but they do occur. And although I rarely encounter teenagers and prepubertal children who have vulvodynia, I do have patients in both age groups who have vulvodynia.

Dr. Lonky: Are there racial differences in the prevalence of vulvodynia?

Dr. Edwards: Although several good studies show that women of African descent and white patients are equally likely to experience vulvodynia, the vast majority (99%) of my patients who have vulvodynia are white. My patients of African descent consult me primarily for itching or discharge.

My local demographics prevent me from judging the likelihood of Asians having vulvodynia, and our Hispanic population has limited access to health care.

In general, I don’t think that demographics are useful in making the diagnosis of vulvodynia.

Do women who have vulvar pain tend to have comorbidities?

Dr. Lonky: Do your patients who have vulvodynia or another vulvar pain syndrome tend to have comorbidities? If so, is this information helpful in establishing the diagnosis and planning therapy?

Dr. Haefner: Women who have vulvodynia often have other medical problems as well. In my practice, when new patients who have vulvodynia complete their intake survey, they often report a history of headache, irritable bowel syndrome, interstitial cystitis, fibromyalgia,⁶ chronic fatigue syndrome, back pain, and temporomandibular joint (TMJ) disorder. These comorbidities are not particularly helpful in establishing the diagnosis of vulvodynia, but they are an important consideration when choosing therapy for the patient. Often, the medications chosen to treat one condition will also benefit another condition. However, it’s important to check for potential interactions between drugs before prescribing a new treatment.

Dr. Gunter: A significant number of women who have vulvodynia also have other chronic pain syndromes. For example, the incidence of bladder pain syndrome–interstitial cystitis is 68% to 82% among women who have vulvodynia, compared with a baseline rate among all women of 6% to 11%.^7-10 The rate of irritable bowel syndrome is more than doubled among women who have vulvodynia, compared with the general population (27% versus 12%).⁸ Another common comorbidity, hypertonic somatic dysfunction of the pelvic floor, is identified in 10% to 90% of women who have chronic vulvar pain.^8,11,12 These women also have a higher incidence of nongenital pain syndromes, such as fibromyalgia, migraine, and TMJ dysfunction, than the general population, as Dr. Haefner noted.^8,12,13

Many studies have evaluated psychological and emotional contributions to chronic vulvar pain. Pain and depression are intimately related—the incidence of depression among all people who experience chronic pain ranges from 27% to 54%, compared with 5% to 17% among the general population.^14-16 The relationship is complex because chronic illness in general is associated with depression. Nevertheless, several studies have noted an increase in anxiety, stress, and depression among women who have vulvodynia.^17-19

I screen every patient for depression using a Patient Health Questionnaire (PHQ-9); I also screen for anxiety. I find that a significant percentage of patients in my clinic are depressed or have an anxiety disorder. Failure to address these comorbidities makes treatment very difficult. I typically prescribe citalopram (Celexa), although there is some question whether it can safely be combined with a tricyclic antidepressant. We also offer stress-reduction classes, teach every patient the value of diaphragmatic breathing, offer mind-body classes for anxiety and stress, and provide intensive programs where the patient can learn important self-care skills, such as pacing (spacing activities throughout the day in a manner that avoids aggravating the pain), and address her anxiety and stress in a more guided manner. We also have a psychologist who specializes in pain for any patient who may need one-on-one counseling.

Dr. Edwards: The presence of comorbidities is somewhat useful in making the diagnosis of vulvodynia. I question my diagnosis, in fact, when a patient who has vulvodynia does not have headaches, low energy, depression, anxiety, irritable bowel syndrome, constipation, fibromyalgia, chronic fatigue, sensitivity to medications, TMJ dysfunction, or urinary symptoms.

How common is pudendal neuralgia?

Dr. Lonky: How prevalent is a finding of pudendal neuralgia?

Dr. Edwards: The prevalence and incidence of pudendal neuralgia are not known. Those who specialize in this condition think it is relatively common. I do not identify or suspect it very often. Its definitive diagnosis and management are outside the purview of the general gynecologist, but the general gynecologist should recognize the symptoms of pudendal neuralgia and refer the patient for evaluation and therapy.

Dr. Lonky: What are those symptoms?

Dr. Haefner: Pudendal neuralgia often occurs following trauma to the pudendal nerve. The pudendal nerve arises from sacral nerves, generally sacral nerves 2 to 4. Several tests can be utilized to diagnose this condition, including quantitative sensor tests, pudendal nerve motor latency tests, electromyography (EMG), and pudendal nerve blocks.²⁰

Nantes Criteria allow for making a diagnosis of pudendal neuralgia (Table 3).²¹

TABLE 3

Nantes Criteria for pudendal neuralgia by pudendal nerve entrapment

Initial treatments for pudendal neuralgia should be conservative. Treatments consist of lifestyle changes to prevent flare of disease. Physical therapy, medical management, nerve blocks, and alternative treatments may be beneficial.

Pudendal nerve entrapment is often exacerbated by sitting (not on a toilet seat, however) and is reduced in a standing position. It tends to increase in intensity throughout the day.²² The final treatment for pudendal nerve entrapment is surgery if the nerve is compressed. By this time, the generalist is not generally the provider who performs the surgery.

Dr. Gunter: I believe pudendal neuralgia is sometimes overdiagnosed. EMG studies of the pudendal nerve, often touted as a diagnostic tool, are unreliable (they can be abnormal after vaginal delivery or vaginal hysterectomy, for example). In my experience, bilateral pain is less likely to be pudendal neuralgia; spontaneous bilateral compression neuropathy at exactly the same level is not a common phenomenon in chronic pain.

I reserve the diagnosis of pudendal neuralgia for women who have allodynia in the distribution of the pudendal nerve with severe pain on sitting, and who have exquisite tenderness when pressure is applied over the pudendal nerve (at the level of the ischial spine on vaginal examination). Typically, the vaginal sidewall on the affected side is very sensitive to light touch. I do see pudendal nerve pain after vaginal surgery when there has been some compromise of the pudendal nerve or the sacral plexus. This is typically unilateral pain.

Dr. Lonky: Thank you all. We’ll continue our discussion, with a focus on treatment, in the October 2011 issue.

We want to hear from you! Tell us what you think.

Although the incidence of vulvar pain has increased over the past decade—thanks to both greater awareness and increasing numbers of affected women—the phenomenon is not a recent development. As early as 1874, T. Galliard Thomas wrote, “[T]his disorder, although fortunately not very frequent, is by no means very rare.”1 He went on to express “surprise” that it had not been “more generally and fully described.”

Despite the focus Thomas directed to the issue, vulvar pain did not get much attention until the 21st century, when a number of studies began to gauge its prevalence. For example, in a study in Boston of about 5,000 women, the lifetime prevalence of chronic vulvar pain was 16%.² And in a study in Texas, the prevalence of vulvar pain in an urban, largely minority population was estimated to be 11%.³ The Boston study also reported that “nearly 40% of women chose not to seek treatment, and, of those who did, 60% saw three or more doctors, many of whom could not provide a diagnosis.”²

Clearly, there is a need for comprehensive information on vulvar pain and its causes, symptoms, diagnosis, and treatment. To address the lack of guidance, OBG Management Contributing Editor Neal M. Lonky, MD, assembled a panel of experts on vulvar pain syndromes and invited them to share their considerable knowledge. The ensuing discussion, presented in three parts, offers a gold mine of information.

In this opening article, the panel focuses on causes, symptomatology, and diagnosis of this common complaint. In Part 2, which will appear in the October issue of this journal, the focus is the bounty of treatment options. Part 3 follows in November, when the discussion shifts to vestibulodynia.

The lower vagina and vulva are richly supplied with peripheral nerves and are, therefore, sensitive to pain, particularly the region of the hymeneal ring. Although the pudendal nerve (arrow) courses through the area, it is an uncommon source of vulvar pain.

Common diagnoses—and misdiagnoses

Dr. Lonky: What are the most common diagnoses when vulvar pain is the complaint?

Dr. Gunter: The most common cause of chronic vulvar pain is vulvodynia, although lichen simplex chronicus, chronic yeast infections, and non-neoplastic epithelial disorders, such as lichen sclerosus and lichen planus, can also produce irritation and pain. In postmenopausal women, atrophic vaginitis can also cause a burning pain, although symptoms are typically more vaginal than vulvar. Yeast and lichen simplex chronicus typically produce itching, although sometimes they can present with irritation and pain, so they must be considered in the differential diagnosis. It is important to remember that many women with vulvodynia have used multiple topical agents and may have developed complex hygiene rituals in an attempt to treat their symptoms, which can result in a secondary lichen simplex chronicus.

That said, there is a high frequency of misdiagnosis with yeast. For example, in a study by Nyirjesy and colleagues, two thirds of women who were referred to a tertiary clinic for chronic vulvovaginal candidiasis were found to have a noninfectious entity instead—most commonly lichen simplex chronicus and vulvodynia.⁴

Dr. Edwards: The most common “diagnosis” for vulvar pain is vulvodynia. However, the definition of vulvodynia is pain—i.e., burning, rawness, irritation, soreness, aching, or stabbing or stinging sensations—in the absence of skin disease, infection, or specific neurologic disease. Therefore, even though the usual cause of vulvar pain is vulvodynia, it is a diagnosis of exclusion, and skin disease, infection, and neurologic disease must be ruled out.

In regard to infection, Candida albicans and bacterial vaginosis (BV) are usually the first conditions that are considered when a patient complains of vulvar pain, but they are not common causes of vulvar pain and are never causes of chronic vulvar pain. Very rarely they may cause recurrent pain that clears, at least briefly, with treatment.

Candida albicans is usually primarily pruritic, and BV produces discharge and odor, sometimes with minor symptoms. Non-albicans Candida (e.g., Candida glabrata) is nearly always asymptomatic, but it occasionally causes irritation and burning.

Group B streptococcus is another infectious entity that very, very occasionally causes irritation and dyspareunia but is usually only a colonizer.

Herpes simplex virus is a cause of recurrent but not chronic pain.

Chronic pain is more likely to be caused by skin disease than by infection. Lichen simplex chronicus causes itching; any pain is due to erosions from scratching.

Dr. Haefner: Several other infectious conditions or their treatments can cause vulvar pain. For example, herpes (particularly primary herpes infection) is classically associated with vulvar pain. The pain is so great that, at times, the patient requires admission for pain control. Surprisingly, despite the known pain of herpes, approximately 80% of patients who have it are unaware of their diagnosis.

Although condyloma is generally a painless condition, many patients complain of pain following treatment for it, whether treatment involves topical medications or laser surgery.

Chancroid is a painful vulvar ulcer. Trichomonas can sometimes be associated with vulvar pain.

Dr. Lonky: What terminology do we use when we discuss vulvar pain?

Dr. Haefner: The current terminology used to describe vulvar pain was published in 2004, after years of debate over nomenclature within the International Society for the Study of Vulvovaginal Disease.⁵ The terminology lists two major categories of vulvar pain:

• pain related to a specific disorder. This category encompasses numerous conditions that feature an abnormal appearance of the vulva (Table 1).

TABLE 1

Terminology and classification of vulvar pain from the International Society for the Study of Vulvovaginal Disease

• vulvodynia, in which the vulva appears normal, other than occasional erythema, which is most prominent at the duct openings (vestibular ducts—Bartholin’s and Skene’s).

As for vulvar pain, there are two major forms:

• hyperalgesia (a low threshold for pain)
• allodynia (pain in response to light touch).

Some diseases that are associated with vulvar pain do not qualify for the diagnosis of vulvodynia (Table 2) because they are associated with an abnormal appearance of the vulva.

TABLE 2

Conditions other than vulvodynia that are associated with vulvar pain

What needs to be ruled out for a diagnosis of vulvodynia?

Dr. Lonky: What skin diseases need to be ruled out before vulvodynia can be diagnosed?

Dr. Edwards: Skin diseases that affect the vulva are usually pruritic—pain is a later sign. Lichen simplex chronicus (also known as eczema) is pruritus caused by any irritant; any pain that arises is produced by visible excoriations from scratching.

Lichen sclerosus manifests as white epithelium that has a crinkling, shiny, or waxy texture. It can produce pain, especially dyspareunia. The pain is caused by erosions that arise from fragility and introital narrowing and inelasticity.

Vulvovaginal lichen planus is usually erosive and preferentially affects mucous membranes, especially the vestibule; it sometimes affects the vagina and mouth, as well.

Desquamative inflammatory vaginitis is most likely a skin disease that affects only the vagina. It involves introital redness and a clinically and microscopically purulent vaginal discharge that also reveals parabasal cells and absent lactobacilli.

Dr. Lonky: You mentioned that neurologic diseases can sometimes cause vulvar pain. Which ones?

Dr. Edwards: Pudendal neuralgia, diabetic neuropathy, and post-herpetic neuralgia are the most common specific neurologic causes of vulvar pain. Multiple sclerosis can also produce pain syndromes. Post-herpetic neuralgia follows herpes zoster—not herpes simplex—virus infection.

Dr. Lonky: Any other conditions that can cause vulvar pain?

Dr. Haefner: Aphthous ulcers are common and are often flared by stress.

Non-neoplastic epithelial disorders are also seen frequently in health-care providers’ offices; many patients who experience them report pain on the vulva.

It is always important to consider cancer when a patient has an abnormal vulvar appearance and pain that has persisted despite treatment.

What are the most common vulvar pain syndromes?

Dr. Lonky: If you were to rank vulvar pain syndromes according to their prevalence, what would the most common syndromes be?

Dr. Gunter: Given the misdiagnosis of many women, who are told they have chronic yeast infection, as I mentioned, it’s hard to know which vulvar pain syndromes are most prevalent. I suspect that lichen simplex chronicus is most common, followed by vulvodynia, with chronic yeast infection a distant third.

My experience reflects what Nyirjesy and colleagues⁴ found: 65% to 75% of women referred to my clinic with chronic yeast actually have lichen simplex chronicus or vulvodynia. In postmenopausal women, atrophic vaginitis is also a consideration; it’s becoming more common now that the use of systemic hormone replacement therapy is decreasing.

Dr. Lonky: What about subsets of vulvodynia? Which ones are most common?

Dr. Edwards: There is good evidence of marked overlap among subsets of vulvodynia. The vast majority of women who have vulvodynia experience primarily provoked vestibular pain, regardless of age. However, I find that almost all patients also report pain that extends beyond the vestibule at times, as well as occasional unprovoked pain.

The diagnosis requires the exclusion of other causes of vulvar pain, and the subset is identified by the location of pain (that is, is it strictly localized or generalized or even migratory?) and its provoked or unprovoked nature.

Localized clitoral pain and vulvar pain localized to one side of the vulva are extremely uncommon, but they do occur. And although I rarely encounter teenagers and prepubertal children who have vulvodynia, I do have patients in both age groups who have vulvodynia.

Dr. Lonky: Are there racial differences in the prevalence of vulvodynia?

Dr. Edwards: Although several good studies show that women of African descent and white patients are equally likely to experience vulvodynia, the vast majority (99%) of my patients who have vulvodynia are white. My patients of African descent consult me primarily for itching or discharge.

My local demographics prevent me from judging the likelihood of Asians having vulvodynia, and our Hispanic population has limited access to health care.

In general, I don’t think that demographics are useful in making the diagnosis of vulvodynia.

Do women who have vulvar pain tend to have comorbidities?

Dr. Lonky: Do your patients who have vulvodynia or another vulvar pain syndrome tend to have comorbidities? If so, is this information helpful in establishing the diagnosis and planning therapy?

Dr. Haefner: Women who have vulvodynia often have other medical problems as well. In my practice, when new patients who have vulvodynia complete their intake survey, they often report a history of headache, irritable bowel syndrome, interstitial cystitis, fibromyalgia,⁶ chronic fatigue syndrome, back pain, and temporomandibular joint (TMJ) disorder. These comorbidities are not particularly helpful in establishing the diagnosis of vulvodynia, but they are an important consideration when choosing therapy for the patient. Often, the medications chosen to treat one condition will also benefit another condition. However, it’s important to check for potential interactions between drugs before prescribing a new treatment.

Dr. Gunter: A significant number of women who have vulvodynia also have other chronic pain syndromes. For example, the incidence of bladder pain syndrome–interstitial cystitis is 68% to 82% among women who have vulvodynia, compared with a baseline rate among all women of 6% to 11%.^7-10 The rate of irritable bowel syndrome is more than doubled among women who have vulvodynia, compared with the general population (27% versus 12%).⁸ Another common comorbidity, hypertonic somatic dysfunction of the pelvic floor, is identified in 10% to 90% of women who have chronic vulvar pain.^8,11,12 These women also have a higher incidence of nongenital pain syndromes, such as fibromyalgia, migraine, and TMJ dysfunction, than the general population, as Dr. Haefner noted.^8,12,13

Many studies have evaluated psychological and emotional contributions to chronic vulvar pain. Pain and depression are intimately related—the incidence of depression among all people who experience chronic pain ranges from 27% to 54%, compared with 5% to 17% among the general population.^14-16 The relationship is complex because chronic illness in general is associated with depression. Nevertheless, several studies have noted an increase in anxiety, stress, and depression among women who have vulvodynia.^17-19

I screen every patient for depression using a Patient Health Questionnaire (PHQ-9); I also screen for anxiety. I find that a significant percentage of patients in my clinic are depressed or have an anxiety disorder. Failure to address these comorbidities makes treatment very difficult. I typically prescribe citalopram (Celexa), although there is some question whether it can safely be combined with a tricyclic antidepressant. We also offer stress-reduction classes, teach every patient the value of diaphragmatic breathing, offer mind-body classes for anxiety and stress, and provide intensive programs where the patient can learn important self-care skills, such as pacing (spacing activities throughout the day in a manner that avoids aggravating the pain), and address her anxiety and stress in a more guided manner. We also have a psychologist who specializes in pain for any patient who may need one-on-one counseling.

Dr. Edwards: The presence of comorbidities is somewhat useful in making the diagnosis of vulvodynia. I question my diagnosis, in fact, when a patient who has vulvodynia does not have headaches, low energy, depression, anxiety, irritable bowel syndrome, constipation, fibromyalgia, chronic fatigue, sensitivity to medications, TMJ dysfunction, or urinary symptoms.

How common is pudendal neuralgia?

Dr. Lonky: How prevalent is a finding of pudendal neuralgia?

Dr. Edwards: The prevalence and incidence of pudendal neuralgia are not known. Those who specialize in this condition think it is relatively common. I do not identify or suspect it very often. Its definitive diagnosis and management are outside the purview of the general gynecologist, but the general gynecologist should recognize the symptoms of pudendal neuralgia and refer the patient for evaluation and therapy.

Dr. Lonky: What are those symptoms?

Dr. Haefner: Pudendal neuralgia often occurs following trauma to the pudendal nerve. The pudendal nerve arises from sacral nerves, generally sacral nerves 2 to 4. Several tests can be utilized to diagnose this condition, including quantitative sensor tests, pudendal nerve motor latency tests, electromyography (EMG), and pudendal nerve blocks.²⁰

Nantes Criteria allow for making a diagnosis of pudendal neuralgia (Table 3).²¹

TABLE 3

Nantes Criteria for pudendal neuralgia by pudendal nerve entrapment

Initial treatments for pudendal neuralgia should be conservative. Treatments consist of lifestyle changes to prevent flare of disease. Physical therapy, medical management, nerve blocks, and alternative treatments may be beneficial.

Pudendal nerve entrapment is often exacerbated by sitting (not on a toilet seat, however) and is reduced in a standing position. It tends to increase in intensity throughout the day.²² The final treatment for pudendal nerve entrapment is surgery if the nerve is compressed. By this time, the generalist is not generally the provider who performs the surgery.

Dr. Gunter: I believe pudendal neuralgia is sometimes overdiagnosed. EMG studies of the pudendal nerve, often touted as a diagnostic tool, are unreliable (they can be abnormal after vaginal delivery or vaginal hysterectomy, for example). In my experience, bilateral pain is less likely to be pudendal neuralgia; spontaneous bilateral compression neuropathy at exactly the same level is not a common phenomenon in chronic pain.

I reserve the diagnosis of pudendal neuralgia for women who have allodynia in the distribution of the pudendal nerve with severe pain on sitting, and who have exquisite tenderness when pressure is applied over the pudendal nerve (at the level of the ischial spine on vaginal examination). Typically, the vaginal sidewall on the affected side is very sensitive to light touch. I do see pudendal nerve pain after vaginal surgery when there has been some compromise of the pudendal nerve or the sacral plexus. This is typically unilateral pain.

Dr. Lonky: Thank you all. We’ll continue our discussion, with a focus on treatment, in the October 2011 issue.

We want to hear from you! Tell us what you think.

Obstetric care providers have two patients: the mother and the fetus. Although it is relatively easy to tell when the mother is unwell, determining the well-being of the fetus is far more difficult.

Several tests have been developed to confirm fetal well-being during labor. The most widely used is electronic fetal heart rate monitoring (EFM), also referred to as fetal cardiotocography. EFM was introduced by Hon and Lee in the 1960s, and is now the most common obstetric procedure in the United States.^1,2 It is noninvasive, simple to perform, inexpensive, and readily available in almost all obstetric units. However, despite our best efforts, we have little objective evidence that EFM has improved perinatal outcomes.

A 2006 Cochrane review of 12 randomized, controlled trials (RCTs) involving more than 37,000 women concluded that, compared with intermittent auscultation—the only acceptable control because randomization to no intrapartum monitoring would be unethical—the only benefit of intrapartum EFM was a reduction in the incidence of seizures in the early neonatal period (the number needed to treat to prevent one event was 661). However, this finding did not translate into a diminished risk of seizures after the first week of life. There was otherwise no significant difference in perinatal outcomes, including no difference in the rates of cerebral palsy or death, although EFM was associated with an increased risk of obstetric intervention and operative delivery.³

It is this contradiction between the almost routine use of intrapartum EFM in the United States and the lack of evidence supporting its use that the authors hoped to address in their analysis.

What did Chen et al find?

In the lead-up to their analysis, the authors make a compelling argument that the existing data—including the 12 RCTs summarized in the Cochrane review³—are flawed. They raise specific concerns about such issues as “low-quality” study design, insufficient data in low-risk populations, and the use of pathologic antecedents (such as newborn encephalopathy) instead of cerebral palsy as a clinical endpoint. These are all reasonable and valid critiques.

So how did Chen and colleagues proceed? Did they design and execute a high-quality prospective study to address these issues? Did they reanalyze the existing RCTs using more sophisticated statistical methodology in an effort to correct for these deficiencies?

They did neither. They simply carried out another retrospective study using a large but poorly validated data set. In doing so, they transgressed and indeed aggravated all of the concerns they themselves raised about the existing literature. Specifically:

• Their retrospective analysis is a far inferior study design, compared with the RCTs they criticized
• Their efforts to distinguish between high-risk and low-risk pregnancies were rudimentary at best and relied on reported birth/death certificate data, which—as the authors themselves and the accompanying editorial concede⁴—is a notoriously unreliable source
• They made no effort to look at any medium- or long-term measures of neurologic injury.

The observation that EFM was associated with a decreased risk of neonatal seizures and 5-minute Apgar scores below 4 is not novel. Neither is the observation that EFM is associated with an increased risk of operative delivery—both cesarean and operative vaginal delivery. The only novel observation in this study is that, in a cohort of 1.7 million singleton pregnancies, EFM appeared to be associated with a decrease in the risk of early neonatal death (defined as death within the first 6 days of life), although no such association was noted for deaths in the late neonatal (7–27 days) or postneonatal (28–364 days) periods.

Limitations of the study design

RCTs remain the gold standard for clinical trials, and for good reason. The absence of randomization in the current study poses significant limitations. It prevents us from understanding why some women received intrapartum EFM while others did not. This makes it impossible to determine if we are comparing two equal groups, a limitation that cannot be overcome even with the most elegant of statistical analyses.

More concerning, however, is the lack of an adequate control group. The authors conclude that “the use of electronic fetal heart rate monitoring was associated with a substantial decrease in early neonatal mortality and morbidity.” This begs the question: compared with what? In the numerous RCTs on this topic, intrapartum EFM was compared head-to-head with a standardized protocol of intermittent auscultation, whereas the comparison group in the current study was women who did not receive EFM.³ Stated differently, the absence of EFM is not equivalent to intermittent auscultation. An alternative and, in my opinion, far more likely explanation for the observed difference in mortality is that the current study compares women who received intrapartum EFM with those who simply had inadequate fetal monitoring in labor. And I am not aware of any report or, for that matter, any obstetric care provider who believes that it is unnecessary to monitor fetal well-being in labor.

The conclusion of this study should have been that adequate monitoring of the fetus in labor can prevent early neonatal death, not that adequate monitoring of the fetus in labor with EFM can prevent early neonatal death. Moreover, the authors’ attempt to deflect this issue by referring to the current study as an example of “reality-based medicine” as opposed to “evidence-based medicine” undermines the very foundation of scientific investigation.

More questions than answers

The major conclusion of this study is that EFM protects against early neonatal death. So why is there no information about cause of death? These data should be readily available from a linked birth/death certificate data set. Such information might help to determine whether the excess early neonatal deaths were related to EFM or, more likely, to other variables surrounding or related to the delivery, such as the inability to perform an emergency cesarean, if indicated, or the lack of providers skilled in neonatal resuscitation.

We want to hear from you!  Tell us what you think.

Obstetric care providers have two patients: the mother and the fetus. Although it is relatively easy to tell when the mother is unwell, determining the well-being of the fetus is far more difficult.

Several tests have been developed to confirm fetal well-being during labor. The most widely used is electronic fetal heart rate monitoring (EFM), also referred to as fetal cardiotocography. EFM was introduced by Hon and Lee in the 1960s, and is now the most common obstetric procedure in the United States.^1,2 It is noninvasive, simple to perform, inexpensive, and readily available in almost all obstetric units. However, despite our best efforts, we have little objective evidence that EFM has improved perinatal outcomes.

A 2006 Cochrane review of 12 randomized, controlled trials (RCTs) involving more than 37,000 women concluded that, compared with intermittent auscultation—the only acceptable control because randomization to no intrapartum monitoring would be unethical—the only benefit of intrapartum EFM was a reduction in the incidence of seizures in the early neonatal period (the number needed to treat to prevent one event was 661). However, this finding did not translate into a diminished risk of seizures after the first week of life. There was otherwise no significant difference in perinatal outcomes, including no difference in the rates of cerebral palsy or death, although EFM was associated with an increased risk of obstetric intervention and operative delivery.³

It is this contradiction between the almost routine use of intrapartum EFM in the United States and the lack of evidence supporting its use that the authors hoped to address in their analysis.

What did Chen et al find?

In the lead-up to their analysis, the authors make a compelling argument that the existing data—including the 12 RCTs summarized in the Cochrane review³—are flawed. They raise specific concerns about such issues as “low-quality” study design, insufficient data in low-risk populations, and the use of pathologic antecedents (such as newborn encephalopathy) instead of cerebral palsy as a clinical endpoint. These are all reasonable and valid critiques.

So how did Chen and colleagues proceed? Did they design and execute a high-quality prospective study to address these issues? Did they reanalyze the existing RCTs using more sophisticated statistical methodology in an effort to correct for these deficiencies?

They did neither. They simply carried out another retrospective study using a large but poorly validated data set. In doing so, they transgressed and indeed aggravated all of the concerns they themselves raised about the existing literature. Specifically:

• Their retrospective analysis is a far inferior study design, compared with the RCTs they criticized
• Their efforts to distinguish between high-risk and low-risk pregnancies were rudimentary at best and relied on reported birth/death certificate data, which—as the authors themselves and the accompanying editorial concede⁴—is a notoriously unreliable source
• They made no effort to look at any medium- or long-term measures of neurologic injury.

The observation that EFM was associated with a decreased risk of neonatal seizures and 5-minute Apgar scores below 4 is not novel. Neither is the observation that EFM is associated with an increased risk of operative delivery—both cesarean and operative vaginal delivery. The only novel observation in this study is that, in a cohort of 1.7 million singleton pregnancies, EFM appeared to be associated with a decrease in the risk of early neonatal death (defined as death within the first 6 days of life), although no such association was noted for deaths in the late neonatal (7–27 days) or postneonatal (28–364 days) periods.

Limitations of the study design

RCTs remain the gold standard for clinical trials, and for good reason. The absence of randomization in the current study poses significant limitations. It prevents us from understanding why some women received intrapartum EFM while others did not. This makes it impossible to determine if we are comparing two equal groups, a limitation that cannot be overcome even with the most elegant of statistical analyses.

More concerning, however, is the lack of an adequate control group. The authors conclude that “the use of electronic fetal heart rate monitoring was associated with a substantial decrease in early neonatal mortality and morbidity.” This begs the question: compared with what? In the numerous RCTs on this topic, intrapartum EFM was compared head-to-head with a standardized protocol of intermittent auscultation, whereas the comparison group in the current study was women who did not receive EFM.³ Stated differently, the absence of EFM is not equivalent to intermittent auscultation. An alternative and, in my opinion, far more likely explanation for the observed difference in mortality is that the current study compares women who received intrapartum EFM with those who simply had inadequate fetal monitoring in labor. And I am not aware of any report or, for that matter, any obstetric care provider who believes that it is unnecessary to monitor fetal well-being in labor.

The conclusion of this study should have been that adequate monitoring of the fetus in labor can prevent early neonatal death, not that adequate monitoring of the fetus in labor with EFM can prevent early neonatal death. Moreover, the authors’ attempt to deflect this issue by referring to the current study as an example of “reality-based medicine” as opposed to “evidence-based medicine” undermines the very foundation of scientific investigation.

More questions than answers

The major conclusion of this study is that EFM protects against early neonatal death. So why is there no information about cause of death? These data should be readily available from a linked birth/death certificate data set. Such information might help to determine whether the excess early neonatal deaths were related to EFM or, more likely, to other variables surrounding or related to the delivery, such as the inability to perform an emergency cesarean, if indicated, or the lack of providers skilled in neonatal resuscitation.

We want to hear from you!  Tell us what you think.

Obstetric care providers have two patients: the mother and the fetus. Although it is relatively easy to tell when the mother is unwell, determining the well-being of the fetus is far more difficult.

Several tests have been developed to confirm fetal well-being during labor. The most widely used is electronic fetal heart rate monitoring (EFM), also referred to as fetal cardiotocography. EFM was introduced by Hon and Lee in the 1960s, and is now the most common obstetric procedure in the United States.^1,2 It is noninvasive, simple to perform, inexpensive, and readily available in almost all obstetric units. However, despite our best efforts, we have little objective evidence that EFM has improved perinatal outcomes.

A 2006 Cochrane review of 12 randomized, controlled trials (RCTs) involving more than 37,000 women concluded that, compared with intermittent auscultation—the only acceptable control because randomization to no intrapartum monitoring would be unethical—the only benefit of intrapartum EFM was a reduction in the incidence of seizures in the early neonatal period (the number needed to treat to prevent one event was 661). However, this finding did not translate into a diminished risk of seizures after the first week of life. There was otherwise no significant difference in perinatal outcomes, including no difference in the rates of cerebral palsy or death, although EFM was associated with an increased risk of obstetric intervention and operative delivery.³

It is this contradiction between the almost routine use of intrapartum EFM in the United States and the lack of evidence supporting its use that the authors hoped to address in their analysis.

What did Chen et al find?

In the lead-up to their analysis, the authors make a compelling argument that the existing data—including the 12 RCTs summarized in the Cochrane review³—are flawed. They raise specific concerns about such issues as “low-quality” study design, insufficient data in low-risk populations, and the use of pathologic antecedents (such as newborn encephalopathy) instead of cerebral palsy as a clinical endpoint. These are all reasonable and valid critiques.

So how did Chen and colleagues proceed? Did they design and execute a high-quality prospective study to address these issues? Did they reanalyze the existing RCTs using more sophisticated statistical methodology in an effort to correct for these deficiencies?

They did neither. They simply carried out another retrospective study using a large but poorly validated data set. In doing so, they transgressed and indeed aggravated all of the concerns they themselves raised about the existing literature. Specifically:

• Their retrospective analysis is a far inferior study design, compared with the RCTs they criticized
• Their efforts to distinguish between high-risk and low-risk pregnancies were rudimentary at best and relied on reported birth/death certificate data, which—as the authors themselves and the accompanying editorial concede⁴—is a notoriously unreliable source
• They made no effort to look at any medium- or long-term measures of neurologic injury.

The observation that EFM was associated with a decreased risk of neonatal seizures and 5-minute Apgar scores below 4 is not novel. Neither is the observation that EFM is associated with an increased risk of operative delivery—both cesarean and operative vaginal delivery. The only novel observation in this study is that, in a cohort of 1.7 million singleton pregnancies, EFM appeared to be associated with a decrease in the risk of early neonatal death (defined as death within the first 6 days of life), although no such association was noted for deaths in the late neonatal (7–27 days) or postneonatal (28–364 days) periods.

Limitations of the study design

RCTs remain the gold standard for clinical trials, and for good reason. The absence of randomization in the current study poses significant limitations. It prevents us from understanding why some women received intrapartum EFM while others did not. This makes it impossible to determine if we are comparing two equal groups, a limitation that cannot be overcome even with the most elegant of statistical analyses.

More concerning, however, is the lack of an adequate control group. The authors conclude that “the use of electronic fetal heart rate monitoring was associated with a substantial decrease in early neonatal mortality and morbidity.” This begs the question: compared with what? In the numerous RCTs on this topic, intrapartum EFM was compared head-to-head with a standardized protocol of intermittent auscultation, whereas the comparison group in the current study was women who did not receive EFM.³ Stated differently, the absence of EFM is not equivalent to intermittent auscultation. An alternative and, in my opinion, far more likely explanation for the observed difference in mortality is that the current study compares women who received intrapartum EFM with those who simply had inadequate fetal monitoring in labor. And I am not aware of any report or, for that matter, any obstetric care provider who believes that it is unnecessary to monitor fetal well-being in labor.

The conclusion of this study should have been that adequate monitoring of the fetus in labor can prevent early neonatal death, not that adequate monitoring of the fetus in labor with EFM can prevent early neonatal death. Moreover, the authors’ attempt to deflect this issue by referring to the current study as an example of “reality-based medicine” as opposed to “evidence-based medicine” undermines the very foundation of scientific investigation.

More questions than answers

The major conclusion of this study is that EFM protects against early neonatal death. So why is there no information about cause of death? These data should be readily available from a linked birth/death certificate data set. Such information might help to determine whether the excess early neonatal deaths were related to EFM or, more likely, to other variables surrounding or related to the delivery, such as the inability to perform an emergency cesarean, if indicated, or the lack of providers skilled in neonatal resuscitation.

We want to hear from you!  Tell us what you think.

The evolution of the laparoscope from diagnostic tool to operative instrument came as quite a shake-up to some. For example, when Professor Kurt Semm pioneered efforts in operative laparoscopy in Germany in the late 1960s and early 1970s, one of his peers suggested he undergo a scan to rule out brain damage!¹ (Until then, the laparoscope had been used only to perform tubal sterilization.)

Fast forward to 1988, when Harry Reich, MD, performed the first laparoscopic hysterectomy.² Within 5 years of that milestone, the literature was replete with information on laparoscopic-assisted vaginal hysterectomy and total laparoscopic hysterectomy. Surgeons such as Tom Lyons, MD, and Harry Hasson, MD, described the advantages, relative ease, and safety profile of laparoscopic supracervical hysterectomy. However, despite accumulating evidence of the benefits of minimally invasive hysterectomy, including speedier recovery and fewer complications, the president of ACOG felt compelled to question, in a 1992 editorial in Obstetrics & Gynecology, whether operative laparoscopy was a “surgical advance” or a “technical gimmick.”³

By 2007, a Cochrane review of hysterectomy for benign gynecologic disease had concluded that the laparoscopic approach is associated with less intraoperative blood loss, a smaller decline in hemoglobin levels, faster recovery, and fewer wound and abdominal infections and febrile episodes than the abdominal approach is.

Moreover, the laparoscopic approach to hysterectomy is more cost-effective than the abdominal route. In a 2009 study, unadjusted expenditures for laparoscopic hysterectomy averaged $10,868 per case, compared with $12,086 for abdominal hysterectomy and $9,544 for vaginal hysterectomy. Adjusted expenditures for outpatient minimally invasive hysterectomy (laparoscopic or vaginal) were markedly lower than for inpatient abdominal hysterectomy.⁴

Nevertheless, as I noted in my 2008 presidential address to the 37^th Global Congress of Minimally Invasive Gynecology of the AAGL, we have not yet achieved widespread adoption of laparoscopic hysterectomy in the United States. Although more than 95% of cholecystectomy cases are performed laparoscopically—as well as 70% of hernia repairs and 80% of bariatric procedures—only 15% of hysterectomies are laparoscopic, and nearly two thirds are completed using an open abdominal technique.

Jonsdottir et al: Details of the study

Enter the current study: a retrospective analysis from the Division of Minimally Invasive Gynecologic Surgery at Brigham and Women’s Hospital in Boston. It may finally deliver the much-needed death knell for open abdominal hysterectomy. The study of 2,133 women who underwent hysterectomy (1,054 in 2006 and 1,079 in 2009) found that the total number of hysterectomies remained stable while the percentages of abdominal and laparoscopic cases changed markedly. The percentage of hysterectomies that were performed abdominally declined from 64.7% in 2006 to 35.8% in 2009, and the percentage of laparoscopic procedures rose from 17.7% to 46% over the same period.

Along with this change, the overall rate of intraoperative complications decreased significantly—from 7.2% to 4%—and so did the mean percentage of postoperative complications—from 18% to 5.7%. Although operative costs did increase significantly, there was no change in the mean total cost.

Jonsdottir and colleagues cite various reasons for the shift toward minimally invasive hysterectomy:

• a nationwide change in practice patterns
  
• increasing awareness among patients of the benefits of minimally invasive procedures
  
• establishment of a minimally invasive gynecologic surgery program at Brigham and Women’s Hospital in 2006
  
• a preponderance of hysterectomies performed by the gynecologic oncology service or the minimally invasive gynecologic surgery group, both of which are adept in minimally invasive hysterectomy.
  

Use of the robot increased dramatically

Although robotic hysterectomy was the least common approach identified in this study, the rate nearly tripled over 3 years. This trend toward increasing use of robotic assistance in hysterectomy is seen nationally; according to industry estimates, 26% of all hysterectomy procedures are performed via the robot, as opposed to 18% performed via laparoscopy, 15% performed vaginally, and 38% performed via the open abdominal approach. Although a study by Pasic and colleagues noted increased hospital costs per case with use of the robot for hysterectomy, Jonsdottir and coworkers found the calculated cost to society to be lowest with robotic hysterectomy.⁵

These findings in context

In another retrospective study that evaluated the use of minimally invasive hysterectomy over a 20-year period at my institution—a tertiary-care, community teaching hospital—Moen and colleagues noted a decrease in the percentage of abdominal hysterectomy from 77% to 35%, whereas minimally invasive hysterectomy (vaginal and laparoscopic approaches) increased from 23% to 64.8%.⁶ By 2009, 13.6% of hysterectomies at my institution were completed with robotic assistance.

Interestingly, the majority of abdominal, laparoscopic supracervical, and robotic-assisted hysterectomies were performed by generalists, whereas the majority of vaginal and total laparoscopic hysterectomies were performed by fellowship-trained specialists.⁶

The evolution of the laparoscope from diagnostic tool to operative instrument came as quite a shake-up to some. For example, when Professor Kurt Semm pioneered efforts in operative laparoscopy in Germany in the late 1960s and early 1970s, one of his peers suggested he undergo a scan to rule out brain damage!¹ (Until then, the laparoscope had been used only to perform tubal sterilization.)

Fast forward to 1988, when Harry Reich, MD, performed the first laparoscopic hysterectomy.² Within 5 years of that milestone, the literature was replete with information on laparoscopic-assisted vaginal hysterectomy and total laparoscopic hysterectomy. Surgeons such as Tom Lyons, MD, and Harry Hasson, MD, described the advantages, relative ease, and safety profile of laparoscopic supracervical hysterectomy. However, despite accumulating evidence of the benefits of minimally invasive hysterectomy, including speedier recovery and fewer complications, the president of ACOG felt compelled to question, in a 1992 editorial in Obstetrics & Gynecology, whether operative laparoscopy was a “surgical advance” or a “technical gimmick.”³

By 2007, a Cochrane review of hysterectomy for benign gynecologic disease had concluded that the laparoscopic approach is associated with less intraoperative blood loss, a smaller decline in hemoglobin levels, faster recovery, and fewer wound and abdominal infections and febrile episodes than the abdominal approach is.

Moreover, the laparoscopic approach to hysterectomy is more cost-effective than the abdominal route. In a 2009 study, unadjusted expenditures for laparoscopic hysterectomy averaged $10,868 per case, compared with $12,086 for abdominal hysterectomy and $9,544 for vaginal hysterectomy. Adjusted expenditures for outpatient minimally invasive hysterectomy (laparoscopic or vaginal) were markedly lower than for inpatient abdominal hysterectomy.⁴

Nevertheless, as I noted in my 2008 presidential address to the 37^th Global Congress of Minimally Invasive Gynecology of the AAGL, we have not yet achieved widespread adoption of laparoscopic hysterectomy in the United States. Although more than 95% of cholecystectomy cases are performed laparoscopically—as well as 70% of hernia repairs and 80% of bariatric procedures—only 15% of hysterectomies are laparoscopic, and nearly two thirds are completed using an open abdominal technique.

Jonsdottir et al: Details of the study

Enter the current study: a retrospective analysis from the Division of Minimally Invasive Gynecologic Surgery at Brigham and Women’s Hospital in Boston. It may finally deliver the much-needed death knell for open abdominal hysterectomy. The study of 2,133 women who underwent hysterectomy (1,054 in 2006 and 1,079 in 2009) found that the total number of hysterectomies remained stable while the percentages of abdominal and laparoscopic cases changed markedly. The percentage of hysterectomies that were performed abdominally declined from 64.7% in 2006 to 35.8% in 2009, and the percentage of laparoscopic procedures rose from 17.7% to 46% over the same period.

Along with this change, the overall rate of intraoperative complications decreased significantly—from 7.2% to 4%—and so did the mean percentage of postoperative complications—from 18% to 5.7%. Although operative costs did increase significantly, there was no change in the mean total cost.

Jonsdottir and colleagues cite various reasons for the shift toward minimally invasive hysterectomy:

• a nationwide change in practice patterns
  
• increasing awareness among patients of the benefits of minimally invasive procedures
  
• establishment of a minimally invasive gynecologic surgery program at Brigham and Women’s Hospital in 2006
  
• a preponderance of hysterectomies performed by the gynecologic oncology service or the minimally invasive gynecologic surgery group, both of which are adept in minimally invasive hysterectomy.
  

Use of the robot increased dramatically

Although robotic hysterectomy was the least common approach identified in this study, the rate nearly tripled over 3 years. This trend toward increasing use of robotic assistance in hysterectomy is seen nationally; according to industry estimates, 26% of all hysterectomy procedures are performed via the robot, as opposed to 18% performed via laparoscopy, 15% performed vaginally, and 38% performed via the open abdominal approach. Although a study by Pasic and colleagues noted increased hospital costs per case with use of the robot for hysterectomy, Jonsdottir and coworkers found the calculated cost to society to be lowest with robotic hysterectomy.⁵

These findings in context

In another retrospective study that evaluated the use of minimally invasive hysterectomy over a 20-year period at my institution—a tertiary-care, community teaching hospital—Moen and colleagues noted a decrease in the percentage of abdominal hysterectomy from 77% to 35%, whereas minimally invasive hysterectomy (vaginal and laparoscopic approaches) increased from 23% to 64.8%.⁶ By 2009, 13.6% of hysterectomies at my institution were completed with robotic assistance.

Interestingly, the majority of abdominal, laparoscopic supracervical, and robotic-assisted hysterectomies were performed by generalists, whereas the majority of vaginal and total laparoscopic hysterectomies were performed by fellowship-trained specialists.⁶

The evolution of the laparoscope from diagnostic tool to operative instrument came as quite a shake-up to some. For example, when Professor Kurt Semm pioneered efforts in operative laparoscopy in Germany in the late 1960s and early 1970s, one of his peers suggested he undergo a scan to rule out brain damage!¹ (Until then, the laparoscope had been used only to perform tubal sterilization.)

Fast forward to 1988, when Harry Reich, MD, performed the first laparoscopic hysterectomy.² Within 5 years of that milestone, the literature was replete with information on laparoscopic-assisted vaginal hysterectomy and total laparoscopic hysterectomy. Surgeons such as Tom Lyons, MD, and Harry Hasson, MD, described the advantages, relative ease, and safety profile of laparoscopic supracervical hysterectomy. However, despite accumulating evidence of the benefits of minimally invasive hysterectomy, including speedier recovery and fewer complications, the president of ACOG felt compelled to question, in a 1992 editorial in Obstetrics & Gynecology, whether operative laparoscopy was a “surgical advance” or a “technical gimmick.”³

By 2007, a Cochrane review of hysterectomy for benign gynecologic disease had concluded that the laparoscopic approach is associated with less intraoperative blood loss, a smaller decline in hemoglobin levels, faster recovery, and fewer wound and abdominal infections and febrile episodes than the abdominal approach is.

Moreover, the laparoscopic approach to hysterectomy is more cost-effective than the abdominal route. In a 2009 study, unadjusted expenditures for laparoscopic hysterectomy averaged $10,868 per case, compared with $12,086 for abdominal hysterectomy and $9,544 for vaginal hysterectomy. Adjusted expenditures for outpatient minimally invasive hysterectomy (laparoscopic or vaginal) were markedly lower than for inpatient abdominal hysterectomy.⁴

Nevertheless, as I noted in my 2008 presidential address to the 37^th Global Congress of Minimally Invasive Gynecology of the AAGL, we have not yet achieved widespread adoption of laparoscopic hysterectomy in the United States. Although more than 95% of cholecystectomy cases are performed laparoscopically—as well as 70% of hernia repairs and 80% of bariatric procedures—only 15% of hysterectomies are laparoscopic, and nearly two thirds are completed using an open abdominal technique.

Jonsdottir et al: Details of the study

Enter the current study: a retrospective analysis from the Division of Minimally Invasive Gynecologic Surgery at Brigham and Women’s Hospital in Boston. It may finally deliver the much-needed death knell for open abdominal hysterectomy. The study of 2,133 women who underwent hysterectomy (1,054 in 2006 and 1,079 in 2009) found that the total number of hysterectomies remained stable while the percentages of abdominal and laparoscopic cases changed markedly. The percentage of hysterectomies that were performed abdominally declined from 64.7% in 2006 to 35.8% in 2009, and the percentage of laparoscopic procedures rose from 17.7% to 46% over the same period.

Along with this change, the overall rate of intraoperative complications decreased significantly—from 7.2% to 4%—and so did the mean percentage of postoperative complications—from 18% to 5.7%. Although operative costs did increase significantly, there was no change in the mean total cost.

Jonsdottir and colleagues cite various reasons for the shift toward minimally invasive hysterectomy:

• a nationwide change in practice patterns
  
• increasing awareness among patients of the benefits of minimally invasive procedures
  
• establishment of a minimally invasive gynecologic surgery program at Brigham and Women’s Hospital in 2006
  
• a preponderance of hysterectomies performed by the gynecologic oncology service or the minimally invasive gynecologic surgery group, both of which are adept in minimally invasive hysterectomy.
  

Use of the robot increased dramatically

Although robotic hysterectomy was the least common approach identified in this study, the rate nearly tripled over 3 years. This trend toward increasing use of robotic assistance in hysterectomy is seen nationally; according to industry estimates, 26% of all hysterectomy procedures are performed via the robot, as opposed to 18% performed via laparoscopy, 15% performed vaginally, and 38% performed via the open abdominal approach. Although a study by Pasic and colleagues noted increased hospital costs per case with use of the robot for hysterectomy, Jonsdottir and coworkers found the calculated cost to society to be lowest with robotic hysterectomy.⁵

These findings in context

In another retrospective study that evaluated the use of minimally invasive hysterectomy over a 20-year period at my institution—a tertiary-care, community teaching hospital—Moen and colleagues noted a decrease in the percentage of abdominal hysterectomy from 77% to 35%, whereas minimally invasive hysterectomy (vaginal and laparoscopic approaches) increased from 23% to 64.8%.⁶ By 2009, 13.6% of hysterectomies at my institution were completed with robotic assistance.

Interestingly, the majority of abdominal, laparoscopic supracervical, and robotic-assisted hysterectomies were performed by generalists, whereas the majority of vaginal and total laparoscopic hysterectomies were performed by fellowship-trained specialists.⁶

Shoulder dystocia occurs in 0.6% to 1.4% of vaginal births and is highly unpredictable. It can cause maternal lacerations, increase the risk of postpartum hemorrhage, and lead to major neonatal injuries such as fractures of the clavicle or humerus, palsies of the brachial plexus, hypoxic-ischemic encephalopathy (HIE), and, even, death. It is also a leading cause of monetary awards in obstetric-related malpractice litigation.

Hoffman and colleagues analyzed 2,018 cases of shoulder dystocia, 101 of which (5.2%) incurred neonatal injury. A total of 3,751 maneuvers were performed, with an average number of maneuvers per case of 1.86. The total number of maneuvers performed in any given case of shoulder dystocia correlated significantly with the rate of neonatal injury.

When five or more maneuvers were used, the rate of neonatal injury exceeded 20%. The authors did not specify whether the neonatal injuries reflected in this figure included bone fracture as well as peripheral nerve injury, or only the latter. They also failed to specify how many brachial plexus injuries resolved spontaneously.

As for which maneuvers were most effective, delivery of the posterior arm and shoulder had a higher rate of success (84%), compared with the McRoberts maneuver, suprapubic pressure, and other maneuvers (24.3% to 72.0% success rate). However, the authors continue to recommend that the McRoberts maneuver and suprapubic pressure be the first maneuvers utilized when shoulder dystocia occurs.

Large study size was a strength

This study, emanating from 12 centers that make up the Consortium on Safe Labor, is probably the largest to date to examine issues related to shoulder dystocia. The sheer magnitude of this study lends great credence to the findings. Another significant strength: Trained obstetric abstractors reviewed the entire medical record of both the mother and newborn.

That said, as with most studies related to shoulder dystocia, there is the possibility of ascertainment bias. Moreover, the study was not randomized. Nor was there uniformity among cases in terms of the maneuvers used or the order in which they were performed, both of which were based largely on provider preference, theoretical models, and expert opinion.

This analysis encompassed the following maneuvers to manage shoulder dystocia:

• McRoberts maneuver
• suprapubic pressure
• Rubin maneuver
• delivery of the posterior arm
• Woods corkscrew maneuver
• Gaskin maneuver (delivery in the maternal knee-chest position)
• Zavanelli maneuver
• fundal pressure.

ACOG recommends the McRoberts maneuver as an initial intervention, followed by suprapubic pressure, when shoulder dystocia occurs.¹

The rate of injury was low

At 5.2%, the rate of clinically relevant injury resulting from shoulder dystocia in this study was low. As the authors note, the reported rate of injury in shoulder dystocia cases in general ranges from 4% to as high as 40%.

In this study, if one excludes the 41 cases of bone fracture (either clavicular or humeral) that occurred, which will heal without long-term sequelae, the rate of injury (i.e., neonatal peripheral nerve injury) was just 3%—60 cases of Erb’s palsy and four cases of Klumpke’s palsy among 2,018 cases of shoulder dystocia.

In general, the rate of HIE related to intractable shoulder dystocia is also exceedingly low. In this study, the authors reported only six cases (0.29%). However, the mean head-to-body delivery time in the cases involving HIE was 10.75 minutes, which is troubling. One case of HIE occurred within a reported time frame of 3 minutes.

No real differences between providers were identified

No significant differences in the rate of injury were observed when shoulder dystocia was managed primarily by a resident physician (7.4%), compared with a midwife (2.9%) or attending physician (5.2%). This finding is somewhat confusing because the authors attributed “primary” management to the individual who delivered the newborn and “thus initiated the maneuvers.” I suspect that when a case was managed by a resident, an attending physician was actively involved.

No causal relationship was established

The authors have made a valiant argument that delivery of the posterior arm should be a priority when shoulder dystocia occurs. However, their findings do not confirm a cause-effect relationship between delivery of the posterior arm and resolution of dystocia, for the following reasons:

• Patients were not randomized to a uniform series of maneuvers.
• The order in which the maneuvers were employed could be determined in only 65.7% of cases.
• Management of shoulder dystocia at the study centers was heterogeneous in nature.

We want to hear from you!  Tell us what you think.

Shoulder dystocia occurs in 0.6% to 1.4% of vaginal births and is highly unpredictable. It can cause maternal lacerations, increase the risk of postpartum hemorrhage, and lead to major neonatal injuries such as fractures of the clavicle or humerus, palsies of the brachial plexus, hypoxic-ischemic encephalopathy (HIE), and, even, death. It is also a leading cause of monetary awards in obstetric-related malpractice litigation.

Hoffman and colleagues analyzed 2,018 cases of shoulder dystocia, 101 of which (5.2%) incurred neonatal injury. A total of 3,751 maneuvers were performed, with an average number of maneuvers per case of 1.86. The total number of maneuvers performed in any given case of shoulder dystocia correlated significantly with the rate of neonatal injury.

When five or more maneuvers were used, the rate of neonatal injury exceeded 20%. The authors did not specify whether the neonatal injuries reflected in this figure included bone fracture as well as peripheral nerve injury, or only the latter. They also failed to specify how many brachial plexus injuries resolved spontaneously.

As for which maneuvers were most effective, delivery of the posterior arm and shoulder had a higher rate of success (84%), compared with the McRoberts maneuver, suprapubic pressure, and other maneuvers (24.3% to 72.0% success rate). However, the authors continue to recommend that the McRoberts maneuver and suprapubic pressure be the first maneuvers utilized when shoulder dystocia occurs.

Large study size was a strength

This study, emanating from 12 centers that make up the Consortium on Safe Labor, is probably the largest to date to examine issues related to shoulder dystocia. The sheer magnitude of this study lends great credence to the findings. Another significant strength: Trained obstetric abstractors reviewed the entire medical record of both the mother and newborn.

That said, as with most studies related to shoulder dystocia, there is the possibility of ascertainment bias. Moreover, the study was not randomized. Nor was there uniformity among cases in terms of the maneuvers used or the order in which they were performed, both of which were based largely on provider preference, theoretical models, and expert opinion.

This analysis encompassed the following maneuvers to manage shoulder dystocia:

• McRoberts maneuver
• suprapubic pressure
• Rubin maneuver
• delivery of the posterior arm
• Woods corkscrew maneuver
• Gaskin maneuver (delivery in the maternal knee-chest position)
• Zavanelli maneuver
• fundal pressure.

ACOG recommends the McRoberts maneuver as an initial intervention, followed by suprapubic pressure, when shoulder dystocia occurs.¹

The rate of injury was low

At 5.2%, the rate of clinically relevant injury resulting from shoulder dystocia in this study was low. As the authors note, the reported rate of injury in shoulder dystocia cases in general ranges from 4% to as high as 40%.

In this study, if one excludes the 41 cases of bone fracture (either clavicular or humeral) that occurred, which will heal without long-term sequelae, the rate of injury (i.e., neonatal peripheral nerve injury) was just 3%—60 cases of Erb’s palsy and four cases of Klumpke’s palsy among 2,018 cases of shoulder dystocia.

In general, the rate of HIE related to intractable shoulder dystocia is also exceedingly low. In this study, the authors reported only six cases (0.29%). However, the mean head-to-body delivery time in the cases involving HIE was 10.75 minutes, which is troubling. One case of HIE occurred within a reported time frame of 3 minutes.

No real differences between providers were identified

No significant differences in the rate of injury were observed when shoulder dystocia was managed primarily by a resident physician (7.4%), compared with a midwife (2.9%) or attending physician (5.2%). This finding is somewhat confusing because the authors attributed “primary” management to the individual who delivered the newborn and “thus initiated the maneuvers.” I suspect that when a case was managed by a resident, an attending physician was actively involved.

No causal relationship was established

The authors have made a valiant argument that delivery of the posterior arm should be a priority when shoulder dystocia occurs. However, their findings do not confirm a cause-effect relationship between delivery of the posterior arm and resolution of dystocia, for the following reasons:

• Patients were not randomized to a uniform series of maneuvers.
• The order in which the maneuvers were employed could be determined in only 65.7% of cases.
• Management of shoulder dystocia at the study centers was heterogeneous in nature.

We want to hear from you!  Tell us what you think.

Shoulder dystocia occurs in 0.6% to 1.4% of vaginal births and is highly unpredictable. It can cause maternal lacerations, increase the risk of postpartum hemorrhage, and lead to major neonatal injuries such as fractures of the clavicle or humerus, palsies of the brachial plexus, hypoxic-ischemic encephalopathy (HIE), and, even, death. It is also a leading cause of monetary awards in obstetric-related malpractice litigation.

Hoffman and colleagues analyzed 2,018 cases of shoulder dystocia, 101 of which (5.2%) incurred neonatal injury. A total of 3,751 maneuvers were performed, with an average number of maneuvers per case of 1.86. The total number of maneuvers performed in any given case of shoulder dystocia correlated significantly with the rate of neonatal injury.

When five or more maneuvers were used, the rate of neonatal injury exceeded 20%. The authors did not specify whether the neonatal injuries reflected in this figure included bone fracture as well as peripheral nerve injury, or only the latter. They also failed to specify how many brachial plexus injuries resolved spontaneously.

As for which maneuvers were most effective, delivery of the posterior arm and shoulder had a higher rate of success (84%), compared with the McRoberts maneuver, suprapubic pressure, and other maneuvers (24.3% to 72.0% success rate). However, the authors continue to recommend that the McRoberts maneuver and suprapubic pressure be the first maneuvers utilized when shoulder dystocia occurs.

Large study size was a strength

This study, emanating from 12 centers that make up the Consortium on Safe Labor, is probably the largest to date to examine issues related to shoulder dystocia. The sheer magnitude of this study lends great credence to the findings. Another significant strength: Trained obstetric abstractors reviewed the entire medical record of both the mother and newborn.

That said, as with most studies related to shoulder dystocia, there is the possibility of ascertainment bias. Moreover, the study was not randomized. Nor was there uniformity among cases in terms of the maneuvers used or the order in which they were performed, both of which were based largely on provider preference, theoretical models, and expert opinion.

This analysis encompassed the following maneuvers to manage shoulder dystocia:

• McRoberts maneuver
• suprapubic pressure
• Rubin maneuver
• delivery of the posterior arm
• Woods corkscrew maneuver
• Gaskin maneuver (delivery in the maternal knee-chest position)
• Zavanelli maneuver
• fundal pressure.

ACOG recommends the McRoberts maneuver as an initial intervention, followed by suprapubic pressure, when shoulder dystocia occurs.¹

The rate of injury was low

At 5.2%, the rate of clinically relevant injury resulting from shoulder dystocia in this study was low. As the authors note, the reported rate of injury in shoulder dystocia cases in general ranges from 4% to as high as 40%.

In this study, if one excludes the 41 cases of bone fracture (either clavicular or humeral) that occurred, which will heal without long-term sequelae, the rate of injury (i.e., neonatal peripheral nerve injury) was just 3%—60 cases of Erb’s palsy and four cases of Klumpke’s palsy among 2,018 cases of shoulder dystocia.

In general, the rate of HIE related to intractable shoulder dystocia is also exceedingly low. In this study, the authors reported only six cases (0.29%). However, the mean head-to-body delivery time in the cases involving HIE was 10.75 minutes, which is troubling. One case of HIE occurred within a reported time frame of 3 minutes.

No real differences between providers were identified

No significant differences in the rate of injury were observed when shoulder dystocia was managed primarily by a resident physician (7.4%), compared with a midwife (2.9%) or attending physician (5.2%). This finding is somewhat confusing because the authors attributed “primary” management to the individual who delivered the newborn and “thus initiated the maneuvers.” I suspect that when a case was managed by a resident, an attending physician was actively involved.

No causal relationship was established

The authors have made a valiant argument that delivery of the posterior arm should be a priority when shoulder dystocia occurs. However, their findings do not confirm a cause-effect relationship between delivery of the posterior arm and resolution of dystocia, for the following reasons:

• Patients were not randomized to a uniform series of maneuvers.
• The order in which the maneuvers were employed could be determined in only 65.7% of cases.
• Management of shoulder dystocia at the study centers was heterogeneous in nature.

We want to hear from you!  Tell us what you think.

AGC is a relatively uncommon cytologic finding, with a mean reporting rate in 2003 of just 0.4% in the United States, according to guidelines from the ASCCP, the society for lower genital tract disease.¹

“Although AGC is frequently caused by benign conditions, such as reactive changes and polyps, clinicians should be aware that it is not uncommon for AGC to be associated with a significant underlying neoplastic condition, including adenocarcinomas of the cervix, endometrium, ovary, and fallopian tube. Recent series have reported that 9%–38% of women with AGC have significant neoplasia…and 3%–17% have invasive cancer,” the guidelines state.¹

In recent years, evidence-based guidelines such as this one have helped clinicians improve the care that they offer to their patients. Nevertheless, the cytologic diagnosis of AGC presents a dilemma. The significant rate of neoplasia associated with this finding, combined with the lack of sensitivity of methods of evaluation, is responsible for this quandary. Although clinicians try to avoid over-testing, there is a real concern about missing a critical diagnosis.

As ASCCP guidelines point out, all of the diagnostic testing done to investigate this cytologic finding lack sensitivity.¹ This observation led to the recommendation that multiple modalities be combined in the evaluation of these patients.¹ Previously published data suggest that women with AGC cytology are under-managed in both their initial and secondary evaluations.²

Authors explore management in women found to have cancer

Cheng and colleagues report on a large series of women who had a first-time diagnosis of AGC. These patients were drawn from an extensive, heterogeneous screening population in Taiwan. The report focuses only on patients who were ultimately found to have a diagnosis of invasive cancer—not those who had premalignant conditions such as cervical intraepithelial neoplasia (CIN) 2, CIN 3, adenocarcinoma in situ, or endometrial hyperplasia. The study confirms a high relative risk (RR) of gynecologic malignancy among women with a cytologic finding of AGC. The greatest risk is cervical cancer (RR, 17.85), followed by uterine cancer (RR, 5.68) and ovarian cancer (RR, 2.04).

Should we include US imaging in our assessment?

Current guidelines recommend colposcopy, endocervical curettage, cervical biopsy, and human papillomavirus (HPV) DNA testing (for high-risk types only) in women who have AGC. They also call for endometrial assessment among women at risk of uterine malignancy, including all women older than 35 years and those younger than 35 who have risk factors, such as unexplained vaginal bleeding, or a condition that suggests chronic anovulation.

Cheng and colleagues also include a recommendation for US imaging in women who have AGC, because of the risk of ovarian cancer. However, although the relative risk of ovarian cancer is roughly doubled among women who have AGC, compared with women with normal cytology, the absolute risk remains quite low. In this sample of 8,281 patients, for example, there were only 12 cases (0.14%).

Nor do the data presented by Cheng and colleagues make a compelling case for the addition of routine US in these patients. However, based on the results of this study, it may be prudent to consider US in certain risk groups when evaluation of the cervix and uterus is negative, such as women who have a family history of ovarian cancer, women who have breast cancer, or women who have a cytologic finding of adenocarcinoma.

HPV DNA testing was not included in this study

The authors suggest, instead, that this modality could be used for triage. However, both of the studies they cite to back this recommendation precede the 2006 ASCCP guidelines, which recommend testing for high-risk HPV types as part of the initial evaluation of women who have AGC but advise against using HPV DNA testing for triage.

More recent studies have confirmed that the sensitivity of HPV DNA testing is only approximately 80%, which is not sufficient for triage in this population.³ Such testing may reassure clinicians—but only after complete evaluation of the cervix and uterus. It can be used to guide subsequent surveillance after diagnostic studies, however.

We want to hear from you!  Tell us what you think.

AGC is a relatively uncommon cytologic finding, with a mean reporting rate in 2003 of just 0.4% in the United States, according to guidelines from the ASCCP, the society for lower genital tract disease.¹

“Although AGC is frequently caused by benign conditions, such as reactive changes and polyps, clinicians should be aware that it is not uncommon for AGC to be associated with a significant underlying neoplastic condition, including adenocarcinomas of the cervix, endometrium, ovary, and fallopian tube. Recent series have reported that 9%–38% of women with AGC have significant neoplasia…and 3%–17% have invasive cancer,” the guidelines state.¹

In recent years, evidence-based guidelines such as this one have helped clinicians improve the care that they offer to their patients. Nevertheless, the cytologic diagnosis of AGC presents a dilemma. The significant rate of neoplasia associated with this finding, combined with the lack of sensitivity of methods of evaluation, is responsible for this quandary. Although clinicians try to avoid over-testing, there is a real concern about missing a critical diagnosis.

As ASCCP guidelines point out, all of the diagnostic testing done to investigate this cytologic finding lack sensitivity.¹ This observation led to the recommendation that multiple modalities be combined in the evaluation of these patients.¹ Previously published data suggest that women with AGC cytology are under-managed in both their initial and secondary evaluations.²

Authors explore management in women found to have cancer

Cheng and colleagues report on a large series of women who had a first-time diagnosis of AGC. These patients were drawn from an extensive, heterogeneous screening population in Taiwan. The report focuses only on patients who were ultimately found to have a diagnosis of invasive cancer—not those who had premalignant conditions such as cervical intraepithelial neoplasia (CIN) 2, CIN 3, adenocarcinoma in situ, or endometrial hyperplasia. The study confirms a high relative risk (RR) of gynecologic malignancy among women with a cytologic finding of AGC. The greatest risk is cervical cancer (RR, 17.85), followed by uterine cancer (RR, 5.68) and ovarian cancer (RR, 2.04).

Should we include US imaging in our assessment?

Current guidelines recommend colposcopy, endocervical curettage, cervical biopsy, and human papillomavirus (HPV) DNA testing (for high-risk types only) in women who have AGC. They also call for endometrial assessment among women at risk of uterine malignancy, including all women older than 35 years and those younger than 35 who have risk factors, such as unexplained vaginal bleeding, or a condition that suggests chronic anovulation.

Cheng and colleagues also include a recommendation for US imaging in women who have AGC, because of the risk of ovarian cancer. However, although the relative risk of ovarian cancer is roughly doubled among women who have AGC, compared with women with normal cytology, the absolute risk remains quite low. In this sample of 8,281 patients, for example, there were only 12 cases (0.14%).

Nor do the data presented by Cheng and colleagues make a compelling case for the addition of routine US in these patients. However, based on the results of this study, it may be prudent to consider US in certain risk groups when evaluation of the cervix and uterus is negative, such as women who have a family history of ovarian cancer, women who have breast cancer, or women who have a cytologic finding of adenocarcinoma.

HPV DNA testing was not included in this study

The authors suggest, instead, that this modality could be used for triage. However, both of the studies they cite to back this recommendation precede the 2006 ASCCP guidelines, which recommend testing for high-risk HPV types as part of the initial evaluation of women who have AGC but advise against using HPV DNA testing for triage.

More recent studies have confirmed that the sensitivity of HPV DNA testing is only approximately 80%, which is not sufficient for triage in this population.³ Such testing may reassure clinicians—but only after complete evaluation of the cervix and uterus. It can be used to guide subsequent surveillance after diagnostic studies, however.

We want to hear from you!  Tell us what you think.

AGC is a relatively uncommon cytologic finding, with a mean reporting rate in 2003 of just 0.4% in the United States, according to guidelines from the ASCCP, the society for lower genital tract disease.¹

“Although AGC is frequently caused by benign conditions, such as reactive changes and polyps, clinicians should be aware that it is not uncommon for AGC to be associated with a significant underlying neoplastic condition, including adenocarcinomas of the cervix, endometrium, ovary, and fallopian tube. Recent series have reported that 9%–38% of women with AGC have significant neoplasia…and 3%–17% have invasive cancer,” the guidelines state.¹

In recent years, evidence-based guidelines such as this one have helped clinicians improve the care that they offer to their patients. Nevertheless, the cytologic diagnosis of AGC presents a dilemma. The significant rate of neoplasia associated with this finding, combined with the lack of sensitivity of methods of evaluation, is responsible for this quandary. Although clinicians try to avoid over-testing, there is a real concern about missing a critical diagnosis.

As ASCCP guidelines point out, all of the diagnostic testing done to investigate this cytologic finding lack sensitivity.¹ This observation led to the recommendation that multiple modalities be combined in the evaluation of these patients.¹ Previously published data suggest that women with AGC cytology are under-managed in both their initial and secondary evaluations.²

Authors explore management in women found to have cancer

Cheng and colleagues report on a large series of women who had a first-time diagnosis of AGC. These patients were drawn from an extensive, heterogeneous screening population in Taiwan. The report focuses only on patients who were ultimately found to have a diagnosis of invasive cancer—not those who had premalignant conditions such as cervical intraepithelial neoplasia (CIN) 2, CIN 3, adenocarcinoma in situ, or endometrial hyperplasia. The study confirms a high relative risk (RR) of gynecologic malignancy among women with a cytologic finding of AGC. The greatest risk is cervical cancer (RR, 17.85), followed by uterine cancer (RR, 5.68) and ovarian cancer (RR, 2.04).

Should we include US imaging in our assessment?

Current guidelines recommend colposcopy, endocervical curettage, cervical biopsy, and human papillomavirus (HPV) DNA testing (for high-risk types only) in women who have AGC. They also call for endometrial assessment among women at risk of uterine malignancy, including all women older than 35 years and those younger than 35 who have risk factors, such as unexplained vaginal bleeding, or a condition that suggests chronic anovulation.

Cheng and colleagues also include a recommendation for US imaging in women who have AGC, because of the risk of ovarian cancer. However, although the relative risk of ovarian cancer is roughly doubled among women who have AGC, compared with women with normal cytology, the absolute risk remains quite low. In this sample of 8,281 patients, for example, there were only 12 cases (0.14%).

Nor do the data presented by Cheng and colleagues make a compelling case for the addition of routine US in these patients. However, based on the results of this study, it may be prudent to consider US in certain risk groups when evaluation of the cervix and uterus is negative, such as women who have a family history of ovarian cancer, women who have breast cancer, or women who have a cytologic finding of adenocarcinoma.

HPV DNA testing was not included in this study

The authors suggest, instead, that this modality could be used for triage. However, both of the studies they cite to back this recommendation precede the 2006 ASCCP guidelines, which recommend testing for high-risk HPV types as part of the initial evaluation of women who have AGC but advise against using HPV DNA testing for triage.

More recent studies have confirmed that the sensitivity of HPV DNA testing is only approximately 80%, which is not sufficient for triage in this population.³ Such testing may reassure clinicians—but only after complete evaluation of the cervix and uterus. It can be used to guide subsequent surveillance after diagnostic studies, however.

We want to hear from you!  Tell us what you think.

The Food and Drug Administration (FDA) should remove the black-box warning regarding skeletal health that the agency inserted into labeling for the injectable contraceptive depot medroxyprogesterone acetate (DMPA; Depo-Provera) in 2004. The black box 1) indicates that use of DMPA for longer than 2 years may reduce peak bone mass and place a woman at increased risk of osteoporotic fracture and 2) suggests that ObGyns order bone-density assessment in women who use DMPA long-term.

This warning is not based on scientific evidence. By depriving women of long-term use of a safe, effective contraceptive, the black-box warning damages women’s health and the public health.

The scientific argument for removing the black box

Although DMPA does cause reduced ovarian estradiol production, with a decline in bone mineral density (BMD), complete recovery of BMD occurs approximately 1 or 2 years after discontinuation in adolescent girls^1,2 and 3 years after discontinuation in adult women.^3,4 BMD trends observed with the use of DMPA parallel those associated with another normal but hypoestrogenic state: breastfeeding. Although BMD declines noted in nursing mothers are similar to those associated with DMPA, breastfeeding one or more infants has not been reported to increase the risk of subsequent osteoporotic fractures.⁵ The FDA does not warn women against breastfeeding for fear of a theoretical negative impact on skeletal health.

BMD can help predict a risk of osteoporotic fracture in menopausal women, but it is not a valid surrogate endpoint for fracture in women of reproductive age.⁶ Basing clinical recommendations on invalid surrogate endpoints can cause harm.^7-9 Clinical recommendations, including those from the FDA, should be based on sound studies that address important clinical outcomes.

No convincing evidence links the use of DMPA for contraception to fracture. Studies of menopausal women have not suggested that prior use of DMPA increased their risk of osteoporosis.^10-12 Two recently published case-control studies, one using a Danish National Patient Registry¹³ and one based on the United Kingdom Family Practice Research database,¹⁴ have demonstrated that DMPA is associated with an elevated risk of fracture in reproductive-age women. However, a cohort analysis using the same British Family Practice database clarifies that the elevated fracture risk observed in women using DMPA occurred before initiation of injectable contraception and was not the result of DMPA use.¹⁵

A clearly harmful effect on women’s health

The black-box warning for DMPA has caused clinicians and women to reduce use of this effective method of contraception. The 2008 National Survey of Family Growth shows that the overall percentage of US women, 15 to 44 years of age, who now use DMPA has declined—from 3.3% in 2002 to 2.0% in 2006 to 2008.¹⁶

In fact, a survey of ObGyns in Florida found that 1) almost one half of respondents place a time limit on duration of DMPA and 2) two thirds of those respondents base that restriction on the black-box warning.¹⁷ Restricting the use of DMPA can lead to more unintended pregnancies and induced abortions.

In the Florida survey, two thirds of respondents order BMD assessment in women who use DMPA, with 58% of those physicians who do so attributing their decision to, again, the black-box warning. Indeed, more than 5% of respondents reported that they selectively prescribe bisphosphonates to women of reproductive age who use DMPA—an expensive practice that is not evidence-based and is potentially dangerous.

FDA guidance is far out of step

The black-box warning for DMPA is not in accord with the guidance provided major medical and public health organizations. The World Health Organization,⁶ the American College of Obstetricians and Gynecologists,¹⁸ the Society for Adolescent Medicine,¹⁹ and the Society of Obstetrics and Gynecology of Canada,²⁰ have all stated that skeletal health concerns shouldn’t restrict the use of DMPA, including the duration of use.

In the US Medical Eligibility Criteria for contraceptive use, the Centers for Disease Control and Prevention declared that use of DMPA is Category 1 (no restriction on use) in women 18 to 45 years of age and Category 2 (advantages of the method generally outweigh theoretical or proven risks) in younger women.²¹ The FDA’s black-box warning is therefore inconsistent with the recommendation of its sister agency.

An opportunity to improve the health of women

The FDA appropriately takes action when a pharmaceutical company mislabels a product or promotes it in a way that isn’t based on sound evidence. Shouldn’t the FDA apply the same scientific standards to itself? Guidance included in DMPA’s black box is not evidence-based—and that reduces use of DMPA in US women and increases the potential for harm. Removing the black box would encourage use of this convenient, effective, and safe contraceptive²² and, in turn, improve the health of women and their families.

Again: We urge the FDA to promptly remove the black-box warning from labeling for DMPA.

Do you agree? We want to hear your opinion: Write to us in care of The Editors, at [email protected]!

Has the FDA’s warning about DMPA had a chilling effect? Does the black-box warning prevent you from prescribing DMPA? Or does it alter your approach to using it? How?
To tell us, click here

The Food and Drug Administration (FDA) should remove the black-box warning regarding skeletal health that the agency inserted into labeling for the injectable contraceptive depot medroxyprogesterone acetate (DMPA; Depo-Provera) in 2004. The black box 1) indicates that use of DMPA for longer than 2 years may reduce peak bone mass and place a woman at increased risk of osteoporotic fracture and 2) suggests that ObGyns order bone-density assessment in women who use DMPA long-term.

This warning is not based on scientific evidence. By depriving women of long-term use of a safe, effective contraceptive, the black-box warning damages women’s health and the public health.

The scientific argument for removing the black box

Although DMPA does cause reduced ovarian estradiol production, with a decline in bone mineral density (BMD), complete recovery of BMD occurs approximately 1 or 2 years after discontinuation in adolescent girls^1,2 and 3 years after discontinuation in adult women.^3,4 BMD trends observed with the use of DMPA parallel those associated with another normal but hypoestrogenic state: breastfeeding. Although BMD declines noted in nursing mothers are similar to those associated with DMPA, breastfeeding one or more infants has not been reported to increase the risk of subsequent osteoporotic fractures.⁵ The FDA does not warn women against breastfeeding for fear of a theoretical negative impact on skeletal health.

BMD can help predict a risk of osteoporotic fracture in menopausal women, but it is not a valid surrogate endpoint for fracture in women of reproductive age.⁶ Basing clinical recommendations on invalid surrogate endpoints can cause harm.^7-9 Clinical recommendations, including those from the FDA, should be based on sound studies that address important clinical outcomes.

No convincing evidence links the use of DMPA for contraception to fracture. Studies of menopausal women have not suggested that prior use of DMPA increased their risk of osteoporosis.^10-12 Two recently published case-control studies, one using a Danish National Patient Registry¹³ and one based on the United Kingdom Family Practice Research database,¹⁴ have demonstrated that DMPA is associated with an elevated risk of fracture in reproductive-age women. However, a cohort analysis using the same British Family Practice database clarifies that the elevated fracture risk observed in women using DMPA occurred before initiation of injectable contraception and was not the result of DMPA use.¹⁵

A clearly harmful effect on women’s health

The black-box warning for DMPA has caused clinicians and women to reduce use of this effective method of contraception. The 2008 National Survey of Family Growth shows that the overall percentage of US women, 15 to 44 years of age, who now use DMPA has declined—from 3.3% in 2002 to 2.0% in 2006 to 2008.¹⁶

In fact, a survey of ObGyns in Florida found that 1) almost one half of respondents place a time limit on duration of DMPA and 2) two thirds of those respondents base that restriction on the black-box warning.¹⁷ Restricting the use of DMPA can lead to more unintended pregnancies and induced abortions.

In the Florida survey, two thirds of respondents order BMD assessment in women who use DMPA, with 58% of those physicians who do so attributing their decision to, again, the black-box warning. Indeed, more than 5% of respondents reported that they selectively prescribe bisphosphonates to women of reproductive age who use DMPA—an expensive practice that is not evidence-based and is potentially dangerous.

FDA guidance is far out of step

The black-box warning for DMPA is not in accord with the guidance provided major medical and public health organizations. The World Health Organization,⁶ the American College of Obstetricians and Gynecologists,¹⁸ the Society for Adolescent Medicine,¹⁹ and the Society of Obstetrics and Gynecology of Canada,²⁰ have all stated that skeletal health concerns shouldn’t restrict the use of DMPA, including the duration of use.

In the US Medical Eligibility Criteria for contraceptive use, the Centers for Disease Control and Prevention declared that use of DMPA is Category 1 (no restriction on use) in women 18 to 45 years of age and Category 2 (advantages of the method generally outweigh theoretical or proven risks) in younger women.²¹ The FDA’s black-box warning is therefore inconsistent with the recommendation of its sister agency.

An opportunity to improve the health of women

The FDA appropriately takes action when a pharmaceutical company mislabels a product or promotes it in a way that isn’t based on sound evidence. Shouldn’t the FDA apply the same scientific standards to itself? Guidance included in DMPA’s black box is not evidence-based—and that reduces use of DMPA in US women and increases the potential for harm. Removing the black box would encourage use of this convenient, effective, and safe contraceptive²² and, in turn, improve the health of women and their families.

Again: We urge the FDA to promptly remove the black-box warning from labeling for DMPA.

Do you agree? We want to hear your opinion: Write to us in care of The Editors, at [email protected]!

Has the FDA’s warning about DMPA had a chilling effect? Does the black-box warning prevent you from prescribing DMPA? Or does it alter your approach to using it? How?
To tell us, click here

The Food and Drug Administration (FDA) should remove the black-box warning regarding skeletal health that the agency inserted into labeling for the injectable contraceptive depot medroxyprogesterone acetate (DMPA; Depo-Provera) in 2004. The black box 1) indicates that use of DMPA for longer than 2 years may reduce peak bone mass and place a woman at increased risk of osteoporotic fracture and 2) suggests that ObGyns order bone-density assessment in women who use DMPA long-term.

This warning is not based on scientific evidence. By depriving women of long-term use of a safe, effective contraceptive, the black-box warning damages women’s health and the public health.

The scientific argument for removing the black box

Although DMPA does cause reduced ovarian estradiol production, with a decline in bone mineral density (BMD), complete recovery of BMD occurs approximately 1 or 2 years after discontinuation in adolescent girls^1,2 and 3 years after discontinuation in adult women.^3,4 BMD trends observed with the use of DMPA parallel those associated with another normal but hypoestrogenic state: breastfeeding. Although BMD declines noted in nursing mothers are similar to those associated with DMPA, breastfeeding one or more infants has not been reported to increase the risk of subsequent osteoporotic fractures.⁵ The FDA does not warn women against breastfeeding for fear of a theoretical negative impact on skeletal health.

BMD can help predict a risk of osteoporotic fracture in menopausal women, but it is not a valid surrogate endpoint for fracture in women of reproductive age.⁶ Basing clinical recommendations on invalid surrogate endpoints can cause harm.^7-9 Clinical recommendations, including those from the FDA, should be based on sound studies that address important clinical outcomes.

No convincing evidence links the use of DMPA for contraception to fracture. Studies of menopausal women have not suggested that prior use of DMPA increased their risk of osteoporosis.^10-12 Two recently published case-control studies, one using a Danish National Patient Registry¹³ and one based on the United Kingdom Family Practice Research database,¹⁴ have demonstrated that DMPA is associated with an elevated risk of fracture in reproductive-age women. However, a cohort analysis using the same British Family Practice database clarifies that the elevated fracture risk observed in women using DMPA occurred before initiation of injectable contraception and was not the result of DMPA use.¹⁵

A clearly harmful effect on women’s health

The black-box warning for DMPA has caused clinicians and women to reduce use of this effective method of contraception. The 2008 National Survey of Family Growth shows that the overall percentage of US women, 15 to 44 years of age, who now use DMPA has declined—from 3.3% in 2002 to 2.0% in 2006 to 2008.¹⁶

In fact, a survey of ObGyns in Florida found that 1) almost one half of respondents place a time limit on duration of DMPA and 2) two thirds of those respondents base that restriction on the black-box warning.¹⁷ Restricting the use of DMPA can lead to more unintended pregnancies and induced abortions.

In the Florida survey, two thirds of respondents order BMD assessment in women who use DMPA, with 58% of those physicians who do so attributing their decision to, again, the black-box warning. Indeed, more than 5% of respondents reported that they selectively prescribe bisphosphonates to women of reproductive age who use DMPA—an expensive practice that is not evidence-based and is potentially dangerous.

FDA guidance is far out of step

The black-box warning for DMPA is not in accord with the guidance provided major medical and public health organizations. The World Health Organization,⁶ the American College of Obstetricians and Gynecologists,¹⁸ the Society for Adolescent Medicine,¹⁹ and the Society of Obstetrics and Gynecology of Canada,²⁰ have all stated that skeletal health concerns shouldn’t restrict the use of DMPA, including the duration of use.

In the US Medical Eligibility Criteria for contraceptive use, the Centers for Disease Control and Prevention declared that use of DMPA is Category 1 (no restriction on use) in women 18 to 45 years of age and Category 2 (advantages of the method generally outweigh theoretical or proven risks) in younger women.²¹ The FDA’s black-box warning is therefore inconsistent with the recommendation of its sister agency.

An opportunity to improve the health of women

The FDA appropriately takes action when a pharmaceutical company mislabels a product or promotes it in a way that isn’t based on sound evidence. Shouldn’t the FDA apply the same scientific standards to itself? Guidance included in DMPA’s black box is not evidence-based—and that reduces use of DMPA in US women and increases the potential for harm. Removing the black box would encourage use of this convenient, effective, and safe contraceptive²² and, in turn, improve the health of women and their families.

Again: We urge the FDA to promptly remove the black-box warning from labeling for DMPA.

Do you agree? We want to hear your opinion: Write to us in care of The Editors, at [email protected]!

Has the FDA’s warning about DMPA had a chilling effect? Does the black-box warning prevent you from prescribing DMPA? Or does it alter your approach to using it? How?
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