Elizabeth G. Stewart, MD

The symptoms are recited every day in gynecologists’ offices around the world: itching, irritation, burning, rawness, pain, dyspareunia. The challenge is tracing these general symptoms to a specific pathology, a task harder than one might expect, because vulvovaginal conditions often represent a complex mix of several problems. Candida and bacterial invasion frequently complicate genital dermatologic conditions. Atrophy and loss of the epithelial barrier worsen the problem. Over-the-counter (OTC) and prescription remedies can lead to contact dermatitis. Vulvodynia may be the ultimate outcome, possibly from central sensitization after chronic inflammation, which in turn can mislead the clinician into thinking appropriate therapy “doesn’t work.” And it is important to remember that any genital complaint has the potential to dampen a woman’s self-esteem and hamper sexual function.

This article covers the fine points of diagnosis and treatment of 4 common vulvovaginal problems:

1. Candidiasis
2. Contact dermatitis
3. Lichen sclerosus
4. Vestibulodynia

Could all 4 problems coexist in 1 patient? They frequently do. As always, a careful history and physical examination with appropriate use of yeast cultures make it possible to manage the complexity.

1. CandidiasisTelephone and self-diagnosis are a waste of time

In vulvovaginal candidiasis (VVC), symptoms can range from none to recurrent. VVC can complicate genital dermatologic conditions and interfere with the treatment of illnesses that call for steroids or antibiotics. Because the symptoms of VVC are nonspecific, diagnosis necessitates consideration of a long list of other potential causes, both infectious and noninfectious.

Candida albicans predominates in 85% to 90% of positive vaginal yeast cultures. Non-albicans species such as C glabrata, parapsilosis, krusei, lusitaniae, and tropicalis are more difficult to treat.

Not all episodes are the same

VVC is uncomplicated when it occurs sporadically or infrequently in a woman in good overall health and involves mild to moderate symptoms; albicans species are likely. VVC is complicated when it is severe or recurrent or occurs in a debilitated, unhealthy, or pregnant woman; non-albicans species often are involved. Proper classification is essential to successful treatment.¹

Phone diagnosis is usually inaccurate

Although phone diagnosis is unreliable,² it is still fairly common, and fewer offices use microscopy and vaginal pH to diagnose vaginal infections because of the tightened (though still simple) requirements of the Clinical Laboratory Improvement Amendment. (Clinicians who do wet mounts and KOH are required to pass a simple test each year to continue the practice.)

Women are poor self-diagnosticians when it comes to Candida infection; only one third of a group purchasing OTC antifungals had accurately identified their condition.³

Clinicians are not exempt from error, either. About 50% of the time, Candida is misdiagnosed,⁴ largely because of the assumption that the wet mount is more specific than it actually is (it is only 40% specific for Candida).

Ask about sex habits, douching, drugs, and diseases

Accurate diagnosis requires a careful history, focusing on risk factors for Candida: a new sexual partner; oral sex; douching; use of antibiotics, steroids, or exogenous estrogen; and uncontrolled diabetes.

Look for signs of vulvar and vaginal erythema, edema, and excoriation.

Classic “cottage cheese” discharge may not be present, and the amount has no correlation with symptom severity.

Vaginal pH of less than 4.5 excludes bacterial vaginosis, trichomoniasis, atrophic vaginitis, desquamative inflammatory vaginitis, and vaginal lichen planus.

Blastospores or pseudohyphae are diagnostic (on 10% KOH microscopy). If they are absent, a yeast culture is essential and will allow speciation. A vaginal culture is especially important in women with recurrent or refractory symptoms.

Always consider testing for sexually transmitted diseases.

Azole antifungals are usual treatment

For uncomplicated VVC, azole antifungals are best (TABLE 1). For complicated VVC, follow this therapy with maintenance fluconazole (150 mg weekly for 6 months), which clears Candida in 90.8% of cases.⁵

Non-albicans infection can be treated with boric acid capsules (inserted vaginally at bedtime for 14 days) or terconazole cream (7 days) or suppositories (3 days). A culture to confirm cure is essential, since non-albicans infection can be difficult to eradicate.

Note that boric acid is not approved for pregnancy.

 

TABLE 1

CDC guidelines for treatment of candidiasis
Any of these intravaginal or oral regimens may be used

	DOSE (NUMBER OF DAYS)
INTRAVAGINAL AGENTS
Butoconazole
2% cream*	5 g (3)
Butoconazole-1 sustained-release cream	5 g (1)
Clotrimazole
1% cream*	5 g (7–14)
100 mg	1 tablet (7)
	2 tablets (3)
500 mg	1 tablet (1)
Miconazole
2% cream*	5 g (7)
100 mg*	1 suppository (7)
200 mg*	1 suppository (3)
Nystatin
100,000 U	1 tablet (14)
Tioconazole
6.5% ointment*	5 g (1)
Terconazole
0.4% cream	5 g (7)
0.8% cream	5 g (3)
80 mg	1 suppository (3)
ORAL AGENT
Fluconazole
150 mg	1 tablet (1)
* Over-the-counter

2. Contact DermatitisNine essentials of treatment

Contact dermatitis, the most common form of vulvar dermatitis, is inflammation of the skin caused by an external agent that acts as an irritant or allergen. The skin reaction may escape notice because changes ranging from minor to extreme are often superimposed on complex preexisting conditions such as lichen simplex chronicus, lichen planus, and lichen sclerosus.⁶

Contact dermatitis occurs readily in the vulvar area because the skin of the vulva reacts more intensely to irritants than other skin, and its barrier function is easily weakened by moisture, friction, urine, and vaginal discharge. The 3 main types of irritant dermatitis are⁷:

• A potent irritant, which may produce the equivalent of a chemical burn.
• A weaker irritant, which may be applied repeatedly before inflammation manifests.
• Stinging and burning, which can occur without detectable skin change, due to chemical exposure.

Many products can cause dermatitis. Even typically harmless products can cause dermatitis if combined with lack of estrogen or use of pads, panty hose, or girdles.

No typical pattern

Patients complain of varying degrees of itching, burning, and irritation. Depending on the agent involved, onset may be sudden or gradual, and the woman may be aware or oblivious of the cause. New reactions to “old” practices or products are also possible.

Ask about personal hygiene, care during menses and after intercourse, and about soap, cleansers, and any product applied to the genital skin, as well as clothing types and exercise habits. Review prescription and OTC products, including topicals, and note which products or actions improve or aggravate symptoms. A history of allergy and atopy should heighten suspicion.

The physical exam may reveal erythema and edema; scaling is possible. Severe cases manifest as erosion, ulceration, or pigment changes. Secondary infection, if any, may involve pustules, crusting, and fissuring. The dermatitis may be localized, but often extends over the area of product spread to the mons, labiocrural folds, and anus. C albicans often complicates genital dermatologic conditions.

9-step treatment

1. Stop the offending product and/or practices.
2. Restore the skin barrier with sitz baths in plain lukewarm water for 5 to 10 minutes twice daily. Compresses or a handheld shower are alternatives.
3. Provide moisture. After hydration, have the patient pat dry and apply a thin film of plain petrolatum.
4. Replace local estrogen if necessary.
5. Control any concomitant Candida with oral fluconazole 150 mg weekly, avoiding the potential irritation caused by topical antifungals.
6. Treat itching and scratching with cool gel packs from the refrigerator, not the freezer (frozen packs can burn). Stop involuntary nighttime scratching with sedation: doxepin or hydroxyzine (10–75 mg at 6 PM).
7. Use topical steroids for dermatitis:
   • Moderate: Triamcinolone, 0.1% ointment twice daily.
   • Severe: A super-potent steroid such as clobetasol, 0.05% ointment, twice daily for 1 to 3 weeks.
   • Extreme: Burst and taper prednisone (0.5–1 mg/kg/day decreased over 14–21 days) or a single dose of intramuscular triamcinolone (1 mg/kg).
8. Order patch testing to rule out or define allergens.
9. Educate the patient about the many potential causes of dermatitis, to prevent recurrence.

FIGURE 1 A mutilating disease of mysterious origin

Though lichen sclerosus is a disfiguring disease, the intensity of symptoms does not necessarily correlate with clinical appearance. Generally, the first change is (A) whitening of an irregular area on the labia, near the clitoris, on the perineum, and/or other vulvar areas. In some cases (A and B), inflammation can alter the anatomy of the vulva by flattening the labia minora, fusing the hood over the clitoris, effectively burying it beneath the skin, and shrinking the skin around the vaginal opening. Images courtesy Lynette Margesson, MD

3. Lichen SclerosusLifelong follow-up is a must

Although it has long been described in medical journals and textbooks, information on lichen sclerosus was often unreliable until recently, and adequate treatment guidelines were lacking. The cause still has not been fully elucidated, but a wealth of information now allows for considerable expertise in the management of this disease.

Lichen sclerosus is a chronic inflammatory and scarring disease that preferentially affects the anogenital area and is 6 to 10 times more prevalent in women than men.⁸ Any cutaneous site may also be affected, but the vagina is never involved.

 

Infection? Autoimmunity? An infectious cause has been proposed but never proven. In some women, an autoimmune component is recognized: Immunoglobulin G antibodies to extracellular matrix protein I have been found in 67% of patients with lichen sclerosus, but whether these antibodies are secondary or pathogenic is unclear.⁹ A genetic component is suggested by the association with autoimmunity and by the link with human leukocyte antigen DQ7 in women¹⁰ and girls.¹¹

Affects 1.7%, or 1 in 60 women.¹² In females, lichen sclerosus peaks in 2 populations: prepubertal girls and postmenopausal women.

No remission after age 70. Although remission of the disease has been reported, a recent study concluded that lichen sclerosus never remits after the age of 70; the average length of remission is 4.7 years, although this figure is still in question.13 Only close follow-up can determine if disease is in remission.

Main symptom is itching

Pruritus is the most common symptom, but dysuria and a sore or burning sensation have also been reported. Some women have no symptoms. When erosions, fissures, or introital narrowing are present, dyspareunia may also occur.

Typical lesions are porcelain-white papules and plaques, often with areas of fissuring or ecchymosis on the vulva or extending around the anus in a figure-of-8 pattern.

Both lichen sclerosus and lichen planus may be seen on the same vulva.

Squamous cell carcinoma can arise in anogenital lichen sclerosus; risk is thought to be 5%. Instruct women in regular self-examination because carcinoma can arise between annual or semiannual visits.

Consider treatment even without biopsy proof

Although a biopsy generally makes the diagnosis, treatment should be considered even in the face of an inconclusive or negative finding if the clinician suspects that lichen sclerosus is present. The reason treatment should proceed in these cases: Loss of the labia or fusion over the clitoris can occur if the disease progresses, as shown in the photos on page.

 

Powerful corticosteroids are treatment of choice

Treatment can control lichen sclerosus, relieve symptoms, and prevent further anatomical changes. Potent or ultrapotent topical corticosteroids in an ointment base are preferred. These drugs are now widely recognized for their efficacy and minimal adverse effects, although no regimen is universally advocated.¹⁴ The patient applies ointment once daily for 1 to 3 months, depending on severity, and then once or twice a week.

Ointments are preferred over creams for vulvar treatment, because creams frequently contain allergens or irritants such as fragrance and propylene glycol preservative.

I continue once-weekly therapy indefinitely in postmenopausal women. If a premenopausal woman is not comfortable using the ointment indefinitely, I will allow her to discontinue treatment but follow her every 3 to 6 months.

Treatment also requires educating the patient about the disease, instructing her in gentle local care, and showing her exactly where to apply the ointment.

In all cases, lifelong follow-up is necessary. Hyperkeratosis, ecchymoses, fissuring, and erosions resolve, but atrophy and color change remain. Scarring usually remains unchanged, but may resolve if treated early in the course of the disease.¹⁵

Testosterone is not as effective as an ultrapotent steroid,¹⁶ and is no more effective than an emollient.¹⁷

Estrogen is valuable for skin integrity, but has no role in the treatment of lichen sclerosus.

Dilator work may be necessary for dyspareunia, once the disease is controlled.

Refer for help with depression and/or negative body image, if present.

4. VestibulodyniaEight treatment options to try

The prevalence of pain in an ethnically diverse population is 16%, and approximately half of this figure (8%) represents vulvodynia.¹⁸ The International Society for the Study of Vulvovaginal Disease now classifies vulvar pain in 3 categories:

• vulvar pain with a known cause, including infection, trauma, and systemic disease (TABLE 2),
• generalized vulvodynia, also known as dysesthetic vulvodynia, essential vulvodynia, or pudendal neuralgia, and
• localized vulvodynia or vestibulodynia, formerly called vestibulitis, vulvar vestibulitis syndrome, and vestibular adenitis.

Terminology is likely to evolve with further study.

Vestibulodynia, the leading cause of dyspareunia in women under age 50,¹⁹ refers to pain on touch within the vestibule. It is primary pain if it has been present since the first tampon use or sexual experience, and it is secondary if it arises after a period of comfortable sexual function.

TABLE 2

Rule out these known causes of vulvar pain

INFECTIONS
Bartholin abscess Candida albicans Herpes Molluscum Trichomonas
TRAUMA
Sexual assault Other physical injury
SYSTEMIC DISEASE
Behçet disease Crohn disease Sjögren syndrome Systemic lupus erythematosus
CANCER AND PRE-CANCER
Vulvar cancer Vulvar intraepithelial neoplasia (VIN)
IRRITANTS
Soaps Sprays Douches Topical anesthetics Antiseptics Suppositories Creams HPV treatment 5-FU Laser treatment
SKIN CONDITIONS
Allergic or contact dermatitis Eczema Psoriasis Hidradenitis suppurativa Lichen planus Lichen sclerosus Pemphigoid and pemphigus
Source: Haefner and Pearlman27

Inflammation starts the cascade

Current theory suggests that inflammatory events such as yeast infection, seminal plasma allergy, and local chemical application release a cascade of cytokines that sensitizes nociceptors in the vestibular epithelium. Prolonged neural firing in turn alters neurons in the dorsal horn, allowing sensitization of mechanoreceptive fibers in the vestibule with sensory allodynia (pain on touch). The proliferation of introital nociceptive fibers is well documented.²⁰

Diagnosis: Report of pain and a positive Q-tip test

When a woman reports superficial dyspareunia with introital contact and clinical examination reveals pain on touch in the vestibule (using a cotton swab), vestibulodynia is diagnosed, provided no other known causes of the vulvar pain are detected during a careful history and examination or after pH measurement, a wet mount, and any indicated cultures.

A careful psychosexual history can help the clinician identify current sexual practices, prior sexual issues, and the impact of the current sexual dysfunction with an eye toward guiding support and counseling.

Multifactorial treatment: 8 options

Because the cause of vestibulodynia is unclear, a multifactorial approach generally is accepted and involves the following:

1. Patient education about the problem and instruction in gentle local care and the elimination of contactants.
2. Referral for support, counseling, and treatment of depression, as indicated.
3. Elimination of any known trigger such as C albicans, although this generally does not lead to remission unless the pain is also treated.
4. Suppression of nociceptor afferent input using topical lidocaine hydrochloride, for which good results have been reported.²¹
5. Systemic oral analgesia with a tricyclic antidepressant modulates the serotonin and epinephrine imbalance associated with persistent pain (TABLE 3).²²
6. Use of anticonvulsants such as gabapentin to increase the amount of stimuli needed for nerves to fire and elevate the central pain threshold.²³
7. Reduction of muscle tension and spasm in the pelvic floor, using physical therapy and biofeedback.²⁴
8. When medical management fails, vulvar vestibulectomy with vaginal advancement yields excellent long-term results,²⁵ but should be a last resort.

TABLE 3

Tricyclic antidepressants modify chemical imbalance associated with persistent pain of vestibulodynia

 

Names of standard agents used	Amitriptyline (Elavil)
	Nortriptyline (Aventyl, Pamelor)
	Desipramine (Norpramin)
	Imipramine (Tofranil)
Standard dosing	Start with 10 mg; increase by 10 mg weekly to 100–150 mg
Side effects	Sedation, often transient
	Constipation, must be actively managed
	Dry mouth
	Palpitations, tachycardia
	Sun sensitivity
Cautions	Obtain EKG over 50 years or with cardiac history
	Contraindicated in glaucoma
	Levels must be monitored if combined with SSRI
Success	Slow change over 6–12 months in sensitivity to touch; ability to use tampon. Minimal pain with dilator use, penetration
Failure	Over 3 months at max dose without any improvement

The symptoms are recited every day in gynecologists’ offices around the world: itching, irritation, burning, rawness, pain, dyspareunia. The challenge is tracing these general symptoms to a specific pathology, a task harder than one might expect, because vulvovaginal conditions often represent a complex mix of several problems. Candida and bacterial invasion frequently complicate genital dermatologic conditions. Atrophy and loss of the epithelial barrier worsen the problem. Over-the-counter (OTC) and prescription remedies can lead to contact dermatitis. Vulvodynia may be the ultimate outcome, possibly from central sensitization after chronic inflammation, which in turn can mislead the clinician into thinking appropriate therapy “doesn’t work.” And it is important to remember that any genital complaint has the potential to dampen a woman’s self-esteem and hamper sexual function.

This article covers the fine points of diagnosis and treatment of 4 common vulvovaginal problems:

1. Candidiasis
2. Contact dermatitis
3. Lichen sclerosus
4. Vestibulodynia

Could all 4 problems coexist in 1 patient? They frequently do. As always, a careful history and physical examination with appropriate use of yeast cultures make it possible to manage the complexity.

1. CandidiasisTelephone and self-diagnosis are a waste of time

In vulvovaginal candidiasis (VVC), symptoms can range from none to recurrent. VVC can complicate genital dermatologic conditions and interfere with the treatment of illnesses that call for steroids or antibiotics. Because the symptoms of VVC are nonspecific, diagnosis necessitates consideration of a long list of other potential causes, both infectious and noninfectious.

Candida albicans predominates in 85% to 90% of positive vaginal yeast cultures. Non-albicans species such as C glabrata, parapsilosis, krusei, lusitaniae, and tropicalis are more difficult to treat.

Not all episodes are the same

VVC is uncomplicated when it occurs sporadically or infrequently in a woman in good overall health and involves mild to moderate symptoms; albicans species are likely. VVC is complicated when it is severe or recurrent or occurs in a debilitated, unhealthy, or pregnant woman; non-albicans species often are involved. Proper classification is essential to successful treatment.¹

Phone diagnosis is usually inaccurate

Although phone diagnosis is unreliable,² it is still fairly common, and fewer offices use microscopy and vaginal pH to diagnose vaginal infections because of the tightened (though still simple) requirements of the Clinical Laboratory Improvement Amendment. (Clinicians who do wet mounts and KOH are required to pass a simple test each year to continue the practice.)

Women are poor self-diagnosticians when it comes to Candida infection; only one third of a group purchasing OTC antifungals had accurately identified their condition.³

Clinicians are not exempt from error, either. About 50% of the time, Candida is misdiagnosed,⁴ largely because of the assumption that the wet mount is more specific than it actually is (it is only 40% specific for Candida).

Ask about sex habits, douching, drugs, and diseases

Accurate diagnosis requires a careful history, focusing on risk factors for Candida: a new sexual partner; oral sex; douching; use of antibiotics, steroids, or exogenous estrogen; and uncontrolled diabetes.

Look for signs of vulvar and vaginal erythema, edema, and excoriation.

Classic “cottage cheese” discharge may not be present, and the amount has no correlation with symptom severity.

Vaginal pH of less than 4.5 excludes bacterial vaginosis, trichomoniasis, atrophic vaginitis, desquamative inflammatory vaginitis, and vaginal lichen planus.

Blastospores or pseudohyphae are diagnostic (on 10% KOH microscopy). If they are absent, a yeast culture is essential and will allow speciation. A vaginal culture is especially important in women with recurrent or refractory symptoms.

Always consider testing for sexually transmitted diseases.

Azole antifungals are usual treatment

For uncomplicated VVC, azole antifungals are best (TABLE 1). For complicated VVC, follow this therapy with maintenance fluconazole (150 mg weekly for 6 months), which clears Candida in 90.8% of cases.⁵

Non-albicans infection can be treated with boric acid capsules (inserted vaginally at bedtime for 14 days) or terconazole cream (7 days) or suppositories (3 days). A culture to confirm cure is essential, since non-albicans infection can be difficult to eradicate.

Note that boric acid is not approved for pregnancy.

 

TABLE 1

CDC guidelines for treatment of candidiasis
Any of these intravaginal or oral regimens may be used

	DOSE (NUMBER OF DAYS)
INTRAVAGINAL AGENTS
Butoconazole
2% cream*	5 g (3)
Butoconazole-1 sustained-release cream	5 g (1)
Clotrimazole
1% cream*	5 g (7–14)
100 mg	1 tablet (7)
	2 tablets (3)
500 mg	1 tablet (1)
Miconazole
2% cream*	5 g (7)
100 mg*	1 suppository (7)
200 mg*	1 suppository (3)
Nystatin
100,000 U	1 tablet (14)
Tioconazole
6.5% ointment*	5 g (1)
Terconazole
0.4% cream	5 g (7)
0.8% cream	5 g (3)
80 mg	1 suppository (3)
ORAL AGENT
Fluconazole
150 mg	1 tablet (1)
* Over-the-counter

2. Contact DermatitisNine essentials of treatment

Contact dermatitis, the most common form of vulvar dermatitis, is inflammation of the skin caused by an external agent that acts as an irritant or allergen. The skin reaction may escape notice because changes ranging from minor to extreme are often superimposed on complex preexisting conditions such as lichen simplex chronicus, lichen planus, and lichen sclerosus.⁶

Contact dermatitis occurs readily in the vulvar area because the skin of the vulva reacts more intensely to irritants than other skin, and its barrier function is easily weakened by moisture, friction, urine, and vaginal discharge. The 3 main types of irritant dermatitis are⁷:

• A potent irritant, which may produce the equivalent of a chemical burn.
• A weaker irritant, which may be applied repeatedly before inflammation manifests.
• Stinging and burning, which can occur without detectable skin change, due to chemical exposure.

Many products can cause dermatitis. Even typically harmless products can cause dermatitis if combined with lack of estrogen or use of pads, panty hose, or girdles.

No typical pattern

Patients complain of varying degrees of itching, burning, and irritation. Depending on the agent involved, onset may be sudden or gradual, and the woman may be aware or oblivious of the cause. New reactions to “old” practices or products are also possible.

Ask about personal hygiene, care during menses and after intercourse, and about soap, cleansers, and any product applied to the genital skin, as well as clothing types and exercise habits. Review prescription and OTC products, including topicals, and note which products or actions improve or aggravate symptoms. A history of allergy and atopy should heighten suspicion.

The physical exam may reveal erythema and edema; scaling is possible. Severe cases manifest as erosion, ulceration, or pigment changes. Secondary infection, if any, may involve pustules, crusting, and fissuring. The dermatitis may be localized, but often extends over the area of product spread to the mons, labiocrural folds, and anus. C albicans often complicates genital dermatologic conditions.

9-step treatment

1. Stop the offending product and/or practices.
2. Restore the skin barrier with sitz baths in plain lukewarm water for 5 to 10 minutes twice daily. Compresses or a handheld shower are alternatives.
3. Provide moisture. After hydration, have the patient pat dry and apply a thin film of plain petrolatum.
4. Replace local estrogen if necessary.
5. Control any concomitant Candida with oral fluconazole 150 mg weekly, avoiding the potential irritation caused by topical antifungals.
6. Treat itching and scratching with cool gel packs from the refrigerator, not the freezer (frozen packs can burn). Stop involuntary nighttime scratching with sedation: doxepin or hydroxyzine (10–75 mg at 6 PM).
7. Use topical steroids for dermatitis:
   • Moderate: Triamcinolone, 0.1% ointment twice daily.
   • Severe: A super-potent steroid such as clobetasol, 0.05% ointment, twice daily for 1 to 3 weeks.
   • Extreme: Burst and taper prednisone (0.5–1 mg/kg/day decreased over 14–21 days) or a single dose of intramuscular triamcinolone (1 mg/kg).
8. Order patch testing to rule out or define allergens.
9. Educate the patient about the many potential causes of dermatitis, to prevent recurrence.

FIGURE 1 A mutilating disease of mysterious origin

Though lichen sclerosus is a disfiguring disease, the intensity of symptoms does not necessarily correlate with clinical appearance. Generally, the first change is (A) whitening of an irregular area on the labia, near the clitoris, on the perineum, and/or other vulvar areas. In some cases (A and B), inflammation can alter the anatomy of the vulva by flattening the labia minora, fusing the hood over the clitoris, effectively burying it beneath the skin, and shrinking the skin around the vaginal opening. Images courtesy Lynette Margesson, MD

3. Lichen SclerosusLifelong follow-up is a must

Although it has long been described in medical journals and textbooks, information on lichen sclerosus was often unreliable until recently, and adequate treatment guidelines were lacking. The cause still has not been fully elucidated, but a wealth of information now allows for considerable expertise in the management of this disease.

Lichen sclerosus is a chronic inflammatory and scarring disease that preferentially affects the anogenital area and is 6 to 10 times more prevalent in women than men.⁸ Any cutaneous site may also be affected, but the vagina is never involved.

 

Infection? Autoimmunity? An infectious cause has been proposed but never proven. In some women, an autoimmune component is recognized: Immunoglobulin G antibodies to extracellular matrix protein I have been found in 67% of patients with lichen sclerosus, but whether these antibodies are secondary or pathogenic is unclear.⁹ A genetic component is suggested by the association with autoimmunity and by the link with human leukocyte antigen DQ7 in women¹⁰ and girls.¹¹

Affects 1.7%, or 1 in 60 women.¹² In females, lichen sclerosus peaks in 2 populations: prepubertal girls and postmenopausal women.

No remission after age 70. Although remission of the disease has been reported, a recent study concluded that lichen sclerosus never remits after the age of 70; the average length of remission is 4.7 years, although this figure is still in question.13 Only close follow-up can determine if disease is in remission.

Main symptom is itching

Pruritus is the most common symptom, but dysuria and a sore or burning sensation have also been reported. Some women have no symptoms. When erosions, fissures, or introital narrowing are present, dyspareunia may also occur.

Typical lesions are porcelain-white papules and plaques, often with areas of fissuring or ecchymosis on the vulva or extending around the anus in a figure-of-8 pattern.

Both lichen sclerosus and lichen planus may be seen on the same vulva.

Squamous cell carcinoma can arise in anogenital lichen sclerosus; risk is thought to be 5%. Instruct women in regular self-examination because carcinoma can arise between annual or semiannual visits.

Consider treatment even without biopsy proof

Although a biopsy generally makes the diagnosis, treatment should be considered even in the face of an inconclusive or negative finding if the clinician suspects that lichen sclerosus is present. The reason treatment should proceed in these cases: Loss of the labia or fusion over the clitoris can occur if the disease progresses, as shown in the photos on page.

 

Powerful corticosteroids are treatment of choice

Treatment can control lichen sclerosus, relieve symptoms, and prevent further anatomical changes. Potent or ultrapotent topical corticosteroids in an ointment base are preferred. These drugs are now widely recognized for their efficacy and minimal adverse effects, although no regimen is universally advocated.¹⁴ The patient applies ointment once daily for 1 to 3 months, depending on severity, and then once or twice a week.

Ointments are preferred over creams for vulvar treatment, because creams frequently contain allergens or irritants such as fragrance and propylene glycol preservative.

I continue once-weekly therapy indefinitely in postmenopausal women. If a premenopausal woman is not comfortable using the ointment indefinitely, I will allow her to discontinue treatment but follow her every 3 to 6 months.

Treatment also requires educating the patient about the disease, instructing her in gentle local care, and showing her exactly where to apply the ointment.

In all cases, lifelong follow-up is necessary. Hyperkeratosis, ecchymoses, fissuring, and erosions resolve, but atrophy and color change remain. Scarring usually remains unchanged, but may resolve if treated early in the course of the disease.¹⁵

Testosterone is not as effective as an ultrapotent steroid,¹⁶ and is no more effective than an emollient.¹⁷

Estrogen is valuable for skin integrity, but has no role in the treatment of lichen sclerosus.

Dilator work may be necessary for dyspareunia, once the disease is controlled.

Refer for help with depression and/or negative body image, if present.

4. VestibulodyniaEight treatment options to try

The prevalence of pain in an ethnically diverse population is 16%, and approximately half of this figure (8%) represents vulvodynia.¹⁸ The International Society for the Study of Vulvovaginal Disease now classifies vulvar pain in 3 categories:

• vulvar pain with a known cause, including infection, trauma, and systemic disease (TABLE 2),
• generalized vulvodynia, also known as dysesthetic vulvodynia, essential vulvodynia, or pudendal neuralgia, and
• localized vulvodynia or vestibulodynia, formerly called vestibulitis, vulvar vestibulitis syndrome, and vestibular adenitis.

Terminology is likely to evolve with further study.

Vestibulodynia, the leading cause of dyspareunia in women under age 50,¹⁹ refers to pain on touch within the vestibule. It is primary pain if it has been present since the first tampon use or sexual experience, and it is secondary if it arises after a period of comfortable sexual function.

TABLE 2

Rule out these known causes of vulvar pain

INFECTIONS
Bartholin abscess Candida albicans Herpes Molluscum Trichomonas
TRAUMA
Sexual assault Other physical injury
SYSTEMIC DISEASE
Behçet disease Crohn disease Sjögren syndrome Systemic lupus erythematosus
CANCER AND PRE-CANCER
Vulvar cancer Vulvar intraepithelial neoplasia (VIN)
IRRITANTS
Soaps Sprays Douches Topical anesthetics Antiseptics Suppositories Creams HPV treatment 5-FU Laser treatment
SKIN CONDITIONS
Allergic or contact dermatitis Eczema Psoriasis Hidradenitis suppurativa Lichen planus Lichen sclerosus Pemphigoid and pemphigus
Source: Haefner and Pearlman27

Inflammation starts the cascade

Current theory suggests that inflammatory events such as yeast infection, seminal plasma allergy, and local chemical application release a cascade of cytokines that sensitizes nociceptors in the vestibular epithelium. Prolonged neural firing in turn alters neurons in the dorsal horn, allowing sensitization of mechanoreceptive fibers in the vestibule with sensory allodynia (pain on touch). The proliferation of introital nociceptive fibers is well documented.²⁰

Diagnosis: Report of pain and a positive Q-tip test

When a woman reports superficial dyspareunia with introital contact and clinical examination reveals pain on touch in the vestibule (using a cotton swab), vestibulodynia is diagnosed, provided no other known causes of the vulvar pain are detected during a careful history and examination or after pH measurement, a wet mount, and any indicated cultures.

A careful psychosexual history can help the clinician identify current sexual practices, prior sexual issues, and the impact of the current sexual dysfunction with an eye toward guiding support and counseling.

Multifactorial treatment: 8 options

Because the cause of vestibulodynia is unclear, a multifactorial approach generally is accepted and involves the following:

1. Patient education about the problem and instruction in gentle local care and the elimination of contactants.
2. Referral for support, counseling, and treatment of depression, as indicated.
3. Elimination of any known trigger such as C albicans, although this generally does not lead to remission unless the pain is also treated.
4. Suppression of nociceptor afferent input using topical lidocaine hydrochloride, for which good results have been reported.²¹
5. Systemic oral analgesia with a tricyclic antidepressant modulates the serotonin and epinephrine imbalance associated with persistent pain (TABLE 3).²²
6. Use of anticonvulsants such as gabapentin to increase the amount of stimuli needed for nerves to fire and elevate the central pain threshold.²³
7. Reduction of muscle tension and spasm in the pelvic floor, using physical therapy and biofeedback.²⁴
8. When medical management fails, vulvar vestibulectomy with vaginal advancement yields excellent long-term results,²⁵ but should be a last resort.

TABLE 3

Tricyclic antidepressants modify chemical imbalance associated with persistent pain of vestibulodynia

 

Names of standard agents used	Amitriptyline (Elavil)
	Nortriptyline (Aventyl, Pamelor)
	Desipramine (Norpramin)
	Imipramine (Tofranil)
Standard dosing	Start with 10 mg; increase by 10 mg weekly to 100–150 mg
Side effects	Sedation, often transient
	Constipation, must be actively managed
	Dry mouth
	Palpitations, tachycardia
	Sun sensitivity
Cautions	Obtain EKG over 50 years or with cardiac history
	Contraindicated in glaucoma
	Levels must be monitored if combined with SSRI
Success	Slow change over 6–12 months in sensitivity to touch; ability to use tampon. Minimal pain with dilator use, penetration
Failure	Over 3 months at max dose without any improvement

The symptoms are recited every day in gynecologists’ offices around the world: itching, irritation, burning, rawness, pain, dyspareunia. The challenge is tracing these general symptoms to a specific pathology, a task harder than one might expect, because vulvovaginal conditions often represent a complex mix of several problems. Candida and bacterial invasion frequently complicate genital dermatologic conditions. Atrophy and loss of the epithelial barrier worsen the problem. Over-the-counter (OTC) and prescription remedies can lead to contact dermatitis. Vulvodynia may be the ultimate outcome, possibly from central sensitization after chronic inflammation, which in turn can mislead the clinician into thinking appropriate therapy “doesn’t work.” And it is important to remember that any genital complaint has the potential to dampen a woman’s self-esteem and hamper sexual function.

This article covers the fine points of diagnosis and treatment of 4 common vulvovaginal problems:

1. Candidiasis
2. Contact dermatitis
3. Lichen sclerosus
4. Vestibulodynia

Could all 4 problems coexist in 1 patient? They frequently do. As always, a careful history and physical examination with appropriate use of yeast cultures make it possible to manage the complexity.

1. CandidiasisTelephone and self-diagnosis are a waste of time

In vulvovaginal candidiasis (VVC), symptoms can range from none to recurrent. VVC can complicate genital dermatologic conditions and interfere with the treatment of illnesses that call for steroids or antibiotics. Because the symptoms of VVC are nonspecific, diagnosis necessitates consideration of a long list of other potential causes, both infectious and noninfectious.

Candida albicans predominates in 85% to 90% of positive vaginal yeast cultures. Non-albicans species such as C glabrata, parapsilosis, krusei, lusitaniae, and tropicalis are more difficult to treat.

Not all episodes are the same

VVC is uncomplicated when it occurs sporadically or infrequently in a woman in good overall health and involves mild to moderate symptoms; albicans species are likely. VVC is complicated when it is severe or recurrent or occurs in a debilitated, unhealthy, or pregnant woman; non-albicans species often are involved. Proper classification is essential to successful treatment.¹

Phone diagnosis is usually inaccurate

Although phone diagnosis is unreliable,² it is still fairly common, and fewer offices use microscopy and vaginal pH to diagnose vaginal infections because of the tightened (though still simple) requirements of the Clinical Laboratory Improvement Amendment. (Clinicians who do wet mounts and KOH are required to pass a simple test each year to continue the practice.)

Women are poor self-diagnosticians when it comes to Candida infection; only one third of a group purchasing OTC antifungals had accurately identified their condition.³

Clinicians are not exempt from error, either. About 50% of the time, Candida is misdiagnosed,⁴ largely because of the assumption that the wet mount is more specific than it actually is (it is only 40% specific for Candida).

Ask about sex habits, douching, drugs, and diseases

Accurate diagnosis requires a careful history, focusing on risk factors for Candida: a new sexual partner; oral sex; douching; use of antibiotics, steroids, or exogenous estrogen; and uncontrolled diabetes.

Look for signs of vulvar and vaginal erythema, edema, and excoriation.

Classic “cottage cheese” discharge may not be present, and the amount has no correlation with symptom severity.

Vaginal pH of less than 4.5 excludes bacterial vaginosis, trichomoniasis, atrophic vaginitis, desquamative inflammatory vaginitis, and vaginal lichen planus.

Blastospores or pseudohyphae are diagnostic (on 10% KOH microscopy). If they are absent, a yeast culture is essential and will allow speciation. A vaginal culture is especially important in women with recurrent or refractory symptoms.

Always consider testing for sexually transmitted diseases.

Azole antifungals are usual treatment

For uncomplicated VVC, azole antifungals are best (TABLE 1). For complicated VVC, follow this therapy with maintenance fluconazole (150 mg weekly for 6 months), which clears Candida in 90.8% of cases.⁵

Non-albicans infection can be treated with boric acid capsules (inserted vaginally at bedtime for 14 days) or terconazole cream (7 days) or suppositories (3 days). A culture to confirm cure is essential, since non-albicans infection can be difficult to eradicate.

Note that boric acid is not approved for pregnancy.

 

TABLE 1

CDC guidelines for treatment of candidiasis
Any of these intravaginal or oral regimens may be used

	DOSE (NUMBER OF DAYS)
INTRAVAGINAL AGENTS
Butoconazole
2% cream*	5 g (3)
Butoconazole-1 sustained-release cream	5 g (1)
Clotrimazole
1% cream*	5 g (7–14)
100 mg	1 tablet (7)
	2 tablets (3)
500 mg	1 tablet (1)
Miconazole
2% cream*	5 g (7)
100 mg*	1 suppository (7)
200 mg*	1 suppository (3)
Nystatin
100,000 U	1 tablet (14)
Tioconazole
6.5% ointment*	5 g (1)
Terconazole
0.4% cream	5 g (7)
0.8% cream	5 g (3)
80 mg	1 suppository (3)
ORAL AGENT
Fluconazole
150 mg	1 tablet (1)
* Over-the-counter

2. Contact DermatitisNine essentials of treatment

Contact dermatitis, the most common form of vulvar dermatitis, is inflammation of the skin caused by an external agent that acts as an irritant or allergen. The skin reaction may escape notice because changes ranging from minor to extreme are often superimposed on complex preexisting conditions such as lichen simplex chronicus, lichen planus, and lichen sclerosus.⁶

Contact dermatitis occurs readily in the vulvar area because the skin of the vulva reacts more intensely to irritants than other skin, and its barrier function is easily weakened by moisture, friction, urine, and vaginal discharge. The 3 main types of irritant dermatitis are⁷:

• A potent irritant, which may produce the equivalent of a chemical burn.
• A weaker irritant, which may be applied repeatedly before inflammation manifests.
• Stinging and burning, which can occur without detectable skin change, due to chemical exposure.

Many products can cause dermatitis. Even typically harmless products can cause dermatitis if combined with lack of estrogen or use of pads, panty hose, or girdles.

No typical pattern

Patients complain of varying degrees of itching, burning, and irritation. Depending on the agent involved, onset may be sudden or gradual, and the woman may be aware or oblivious of the cause. New reactions to “old” practices or products are also possible.

Ask about personal hygiene, care during menses and after intercourse, and about soap, cleansers, and any product applied to the genital skin, as well as clothing types and exercise habits. Review prescription and OTC products, including topicals, and note which products or actions improve or aggravate symptoms. A history of allergy and atopy should heighten suspicion.

The physical exam may reveal erythema and edema; scaling is possible. Severe cases manifest as erosion, ulceration, or pigment changes. Secondary infection, if any, may involve pustules, crusting, and fissuring. The dermatitis may be localized, but often extends over the area of product spread to the mons, labiocrural folds, and anus. C albicans often complicates genital dermatologic conditions.

9-step treatment

1. Stop the offending product and/or practices.
2. Restore the skin barrier with sitz baths in plain lukewarm water for 5 to 10 minutes twice daily. Compresses or a handheld shower are alternatives.
3. Provide moisture. After hydration, have the patient pat dry and apply a thin film of plain petrolatum.
4. Replace local estrogen if necessary.
5. Control any concomitant Candida with oral fluconazole 150 mg weekly, avoiding the potential irritation caused by topical antifungals.
6. Treat itching and scratching with cool gel packs from the refrigerator, not the freezer (frozen packs can burn). Stop involuntary nighttime scratching with sedation: doxepin or hydroxyzine (10–75 mg at 6 PM).
7. Use topical steroids for dermatitis:
   • Moderate: Triamcinolone, 0.1% ointment twice daily.
   • Severe: A super-potent steroid such as clobetasol, 0.05% ointment, twice daily for 1 to 3 weeks.
   • Extreme: Burst and taper prednisone (0.5–1 mg/kg/day decreased over 14–21 days) or a single dose of intramuscular triamcinolone (1 mg/kg).
8. Order patch testing to rule out or define allergens.
9. Educate the patient about the many potential causes of dermatitis, to prevent recurrence.

FIGURE 1 A mutilating disease of mysterious origin

Though lichen sclerosus is a disfiguring disease, the intensity of symptoms does not necessarily correlate with clinical appearance. Generally, the first change is (A) whitening of an irregular area on the labia, near the clitoris, on the perineum, and/or other vulvar areas. In some cases (A and B), inflammation can alter the anatomy of the vulva by flattening the labia minora, fusing the hood over the clitoris, effectively burying it beneath the skin, and shrinking the skin around the vaginal opening. Images courtesy Lynette Margesson, MD

3. Lichen SclerosusLifelong follow-up is a must

Although it has long been described in medical journals and textbooks, information on lichen sclerosus was often unreliable until recently, and adequate treatment guidelines were lacking. The cause still has not been fully elucidated, but a wealth of information now allows for considerable expertise in the management of this disease.

Lichen sclerosus is a chronic inflammatory and scarring disease that preferentially affects the anogenital area and is 6 to 10 times more prevalent in women than men.⁸ Any cutaneous site may also be affected, but the vagina is never involved.

 

Infection? Autoimmunity? An infectious cause has been proposed but never proven. In some women, an autoimmune component is recognized: Immunoglobulin G antibodies to extracellular matrix protein I have been found in 67% of patients with lichen sclerosus, but whether these antibodies are secondary or pathogenic is unclear.⁹ A genetic component is suggested by the association with autoimmunity and by the link with human leukocyte antigen DQ7 in women¹⁰ and girls.¹¹

Affects 1.7%, or 1 in 60 women.¹² In females, lichen sclerosus peaks in 2 populations: prepubertal girls and postmenopausal women.

No remission after age 70. Although remission of the disease has been reported, a recent study concluded that lichen sclerosus never remits after the age of 70; the average length of remission is 4.7 years, although this figure is still in question.13 Only close follow-up can determine if disease is in remission.

Main symptom is itching

Pruritus is the most common symptom, but dysuria and a sore or burning sensation have also been reported. Some women have no symptoms. When erosions, fissures, or introital narrowing are present, dyspareunia may also occur.

Typical lesions are porcelain-white papules and plaques, often with areas of fissuring or ecchymosis on the vulva or extending around the anus in a figure-of-8 pattern.

Both lichen sclerosus and lichen planus may be seen on the same vulva.

Squamous cell carcinoma can arise in anogenital lichen sclerosus; risk is thought to be 5%. Instruct women in regular self-examination because carcinoma can arise between annual or semiannual visits.

Consider treatment even without biopsy proof

Although a biopsy generally makes the diagnosis, treatment should be considered even in the face of an inconclusive or negative finding if the clinician suspects that lichen sclerosus is present. The reason treatment should proceed in these cases: Loss of the labia or fusion over the clitoris can occur if the disease progresses, as shown in the photos on page.

 

Powerful corticosteroids are treatment of choice

Treatment can control lichen sclerosus, relieve symptoms, and prevent further anatomical changes. Potent or ultrapotent topical corticosteroids in an ointment base are preferred. These drugs are now widely recognized for their efficacy and minimal adverse effects, although no regimen is universally advocated.¹⁴ The patient applies ointment once daily for 1 to 3 months, depending on severity, and then once or twice a week.

Ointments are preferred over creams for vulvar treatment, because creams frequently contain allergens or irritants such as fragrance and propylene glycol preservative.

I continue once-weekly therapy indefinitely in postmenopausal women. If a premenopausal woman is not comfortable using the ointment indefinitely, I will allow her to discontinue treatment but follow her every 3 to 6 months.

Treatment also requires educating the patient about the disease, instructing her in gentle local care, and showing her exactly where to apply the ointment.

In all cases, lifelong follow-up is necessary. Hyperkeratosis, ecchymoses, fissuring, and erosions resolve, but atrophy and color change remain. Scarring usually remains unchanged, but may resolve if treated early in the course of the disease.¹⁵

Testosterone is not as effective as an ultrapotent steroid,¹⁶ and is no more effective than an emollient.¹⁷

Estrogen is valuable for skin integrity, but has no role in the treatment of lichen sclerosus.

Dilator work may be necessary for dyspareunia, once the disease is controlled.

Refer for help with depression and/or negative body image, if present.

4. VestibulodyniaEight treatment options to try

The prevalence of pain in an ethnically diverse population is 16%, and approximately half of this figure (8%) represents vulvodynia.¹⁸ The International Society for the Study of Vulvovaginal Disease now classifies vulvar pain in 3 categories:

• vulvar pain with a known cause, including infection, trauma, and systemic disease (TABLE 2),
• generalized vulvodynia, also known as dysesthetic vulvodynia, essential vulvodynia, or pudendal neuralgia, and
• localized vulvodynia or vestibulodynia, formerly called vestibulitis, vulvar vestibulitis syndrome, and vestibular adenitis.

Terminology is likely to evolve with further study.

Vestibulodynia, the leading cause of dyspareunia in women under age 50,¹⁹ refers to pain on touch within the vestibule. It is primary pain if it has been present since the first tampon use or sexual experience, and it is secondary if it arises after a period of comfortable sexual function.

TABLE 2

Rule out these known causes of vulvar pain

INFECTIONS
Bartholin abscess Candida albicans Herpes Molluscum Trichomonas
TRAUMA
Sexual assault Other physical injury
SYSTEMIC DISEASE
Behçet disease Crohn disease Sjögren syndrome Systemic lupus erythematosus
CANCER AND PRE-CANCER
Vulvar cancer Vulvar intraepithelial neoplasia (VIN)
IRRITANTS
Soaps Sprays Douches Topical anesthetics Antiseptics Suppositories Creams HPV treatment 5-FU Laser treatment
SKIN CONDITIONS
Allergic or contact dermatitis Eczema Psoriasis Hidradenitis suppurativa Lichen planus Lichen sclerosus Pemphigoid and pemphigus
Source: Haefner and Pearlman27

Inflammation starts the cascade

Current theory suggests that inflammatory events such as yeast infection, seminal plasma allergy, and local chemical application release a cascade of cytokines that sensitizes nociceptors in the vestibular epithelium. Prolonged neural firing in turn alters neurons in the dorsal horn, allowing sensitization of mechanoreceptive fibers in the vestibule with sensory allodynia (pain on touch). The proliferation of introital nociceptive fibers is well documented.²⁰

Diagnosis: Report of pain and a positive Q-tip test

When a woman reports superficial dyspareunia with introital contact and clinical examination reveals pain on touch in the vestibule (using a cotton swab), vestibulodynia is diagnosed, provided no other known causes of the vulvar pain are detected during a careful history and examination or after pH measurement, a wet mount, and any indicated cultures.

A careful psychosexual history can help the clinician identify current sexual practices, prior sexual issues, and the impact of the current sexual dysfunction with an eye toward guiding support and counseling.

Multifactorial treatment: 8 options

Because the cause of vestibulodynia is unclear, a multifactorial approach generally is accepted and involves the following:

1. Patient education about the problem and instruction in gentle local care and the elimination of contactants.
2. Referral for support, counseling, and treatment of depression, as indicated.
3. Elimination of any known trigger such as C albicans, although this generally does not lead to remission unless the pain is also treated.
4. Suppression of nociceptor afferent input using topical lidocaine hydrochloride, for which good results have been reported.²¹
5. Systemic oral analgesia with a tricyclic antidepressant modulates the serotonin and epinephrine imbalance associated with persistent pain (TABLE 3).²²
6. Use of anticonvulsants such as gabapentin to increase the amount of stimuli needed for nerves to fire and elevate the central pain threshold.²³
7. Reduction of muscle tension and spasm in the pelvic floor, using physical therapy and biofeedback.²⁴
8. When medical management fails, vulvar vestibulectomy with vaginal advancement yields excellent long-term results,²⁵ but should be a last resort.

TABLE 3

Tricyclic antidepressants modify chemical imbalance associated with persistent pain of vestibulodynia

 

Names of standard agents used	Amitriptyline (Elavil)
	Nortriptyline (Aventyl, Pamelor)
	Desipramine (Norpramin)
	Imipramine (Tofranil)
Standard dosing	Start with 10 mg; increase by 10 mg weekly to 100–150 mg
Side effects	Sedation, often transient
	Constipation, must be actively managed
	Dry mouth
	Palpitations, tachycardia
	Sun sensitivity
Cautions	Obtain EKG over 50 years or with cardiac history
	Contraindicated in glaucoma
	Levels must be monitored if combined with SSRI
Success	Slow change over 6–12 months in sensitivity to touch; ability to use tampon. Minimal pain with dilator use, penetration
Failure	Over 3 months at max dose without any improvement

Identifying the cause of a patient’s dyspareunia can be just as challenging as getting her to admit to the problem.

Due in part to underreporting of the condition, the incidence and prevalence of dyspareunia—defined as genital pain experienced just before, during, or after sexual intercourse¹—is uncertain.²

Because it is easy to miss subtle physical findings such as small fissures, periclitoral scarring, or a focus of tender vestibulitis under a hymenal remnant, getting to the root of dyspareunia can present a significant challenge to clinicians. Adding to the difficulty is the fact that intermittent conditions such as cyclical Candida albicans are hard to diagnose.

This review of 5 common but often overlooked causes describes what is known about dyspareunia and how to conduct a complete evaluation, including physical examination, diagnostic tests, and questions to ask the patient.

CAUSE 1Inadequate estrogenization

Vulvovaginal atrophy is the leading cause of sexual dysfunction, affecting up to 50% of women over age 50. It contributes to a lack of vaginal lubrication with sexual arousal and, consequently, dyspareunia and postcoital bleeding.³ Even when a woman is taking oral hormone replacement therapy, the vagina can lack sufficient estrogen.

Younger women also may experience atrophy and lowered estrogen levels. For example, a 34-year-old woman with premature ovarian failure may experience slight burning, dryness, and pain on penetration.

Tamoxifen can be a source of dyspareunia: It can cause vaginal atrophy in the premenopausal woman or estrogenization with Candidal invasion in postmenopausal patients.

Atrophy also can occur:

• with hypothalamic amenorrhea caused by excessive exercise or marked weight loss
  
• during the postpartum period and breast-feeding
  
• with the use of some low-estrogen (20 μg) contraceptives and medroxyprogesterone acetate
  
• after radiation or chemotherapy
  

Resolve the problem with local estrogen.

Fortunately, atrophy is easily reversed with local estrogen in the form of cream, tablets, or the vaginal ring. Because the latter does not elevate circulating estradiol levels after the first 24 hours of use, many oncologists are willing to allow this therapy for breast cancer patients.⁴

When dyspareunia persists despite local estrogen use, we must seek out other causes.

CAUSE 2A skin disease

Dermatitis. There are 2 types of dermatitis: eczematous, in which the irritant is essentially unknown, and contactant, which arises from known irritants or allergens. In some cases, the exposure to an irritant may be fairly recent. In others, the continuing combination of irritants and tight clothing or abrasive activity eventually leads to symptoms.

Physical findings of dermatitis include erythema (with or without scaling) and fissuring—especially of the perineum. A biopsy is diagnostic.

Recommended treatment includes meticulous vulvar hygiene and the use of 2.5% hydrocortisone cream twice daily for 14 to 30 days, followed by twice-weekly “maintenance” applications. For moderate or severe cases, a medium-potency steroid (betamethasone valerate 0.1%) or an ultrapotent steroid (clobetasol 0.05%) may be used in the same manner. In addition, physicians should educate patients with dermatitis about the chronicity of the condition and the importance of eliminating the cause, if possible.

Poorly treated eczema leads to lichen simplex chronicus. One clue to this condition is a history of atopy or eczema elsewhere on the body.

Lichen sclerosus and lichen planus. These dermatoses cause changes in the color and texture of the epithelium.

Because lichen planus can produce erosion of the vestibule, it often is mistaken for vestibulitis. With this condition, erosions are intensely erythematous and vary from small areas to involvement of the entire vestibule. You will also note a serpiginous white border or subtle white reticules adjacent to erosions.

Both lichen sclerosus and lichen planus can produce intense itching or progress without clinical symptoms.

Lichen sclerosus, meanwhile, causes whitened epithelium with the thinned and wrinkled appearance of cigarette paper; areas of hyperkeratosis also may be present. Changes may occur from the periclitoral area to the anus in a keyhole configuration.

Both lichen sclerosus and lichen planus:

• can produce intense itching or progress without clinical symptoms
  
• can scar extensively and cause bridging synechiae at the fourchette, elimination of the labia minora, and fusion of the prepuce over the glans clitoris
  
• can produce anal fissuring and painful defecation
  

 

While lichen sclerosus never involves the vagina, vaginal lichen planus produces inflammatory vaginitis that can scar and reduce the size of the vagina—even obliterate it entirely.

Treatment for both diseases consists of ultrapotent topical steroids to arrest the inflammatory process. Vaginal lichen planus is treated with hydrocortisone suppositories (25 mg at bedtime), with the length of treatment dependent on severity.⁵ More potent steroids may be necessary.

CAUSE 3Candida

This infection can be extremely difficult to diagnose for a variety of reasons. Patients come in partially treated with over-the-counter antifungals. Many have taken a fluconazole tablet with a long half-life of action. Others have a cyclical candidiasis that is seen only in the luteal phase of the cycle. In these cases, fissuring is often attributed to other causes.

Complicating matters further, a wet mount will be negative in the presence of Candida approximately 50% of the time.⁶ For these reasons, a culture is essential when there is an index of clinical suspicion and white blood cells are present on the wet mount.

Uncomplicated Candida is treated by topical -azole creams for 3 or 7 days or a single fluconazole 150-mg tablet.

Complicated Candida (that is, more than 3 infections in a year or infection in a pregnant or immune-compromised host) will require longer courses of therapy.⁷

CAUSE 4Desquamative inflammatory vaginitis

Because the intense inflammation produced by the 2 diseases are similar, some people believe desquamative inflammatory vaginitis is a form of lichen planus⁸—in fact, it is sometimes called lichenoid vaginitis. However, desquamative inflammatory vaginitis does not scar the vagina, suggesting a different cause. Its profusely irritative discharge—microscopically characterized by sheets of white blood cells—resembles Trichomonas and Candida. Sheets of white blood cells and parabasal cells also resemble Trichomonas, Candida, or severe atrophy.

 

The inflammation leads to the loss of the lactobacillus, with bacterial overgrowth and clue cells similar to bacterial vaginosis (though bacterial vaginosis never causes such inflammation).

Vulvodynia consists of unprovoked stinging, burning, irritation, rawness, or pain anywhere on the vulva and can be constant or episodic.

Though antibiotics may yield transient improvement,⁹ management most often consists of 25-mg hydrocortisone suppositories (or compounded as 100 mg for severe cases) at bedtime for 14 days, then every other day for 14 days. After this course of therapy has been completed, clinicians must reevaluate the patient to determine whether she needs extended therapy (in severe cases) or can begin maintenance with a weekly suppository (for cases that are mild but chronic).

If dyspareunia does not resolve after the inflammation abates, superimposed neuroinflammatory pain (vestibulitis) will need treatment.

CAUSE 5Vulvodynia or vulvar vestibulitis

Vulvodynia (generalized vulvar dysesthesia). This condition—which consists of unprovoked stinging, burning, irritation, rawness, or pain anywhere on the vulva—may be constant or episodic. Dyspareunia in these cases may involve postcoital exacerbation of symptoms.

The cause is unknown, but some suspect a lesion of the pudendal nerve in its long course from the spine to the vulva.

There may be virtually no physical findings, or there may be areas of tenderness, hyperesthesia, or hypoesthesia. A biopsy will be nonspecific. Vulvodynia is therefore diagnosed by ruling out infectious, dermatologic, or other causes of genital pain.

The following treatments are usually successful:

• tricyclic antidepressants such as nortriptyline, starting with a bedtime dose of 10 mg and working up to 50 mg to 150 mg
  
• the antiepileptic agent gabapentin, starting with a bedtime dose of 100 mg and working up to as much as 1,000 mg (this is usually substituted for the tricyclic antidepressant if that therapy alone is ineffective)
  

Vulvar vestibulitis (localized vulvar dysesthesia). This condition, consisting of provoked pain in the vestibule on contact, is the leading cause of dyspareunia in women under 50.¹⁰

This condition may be either primary or secondary. With primary vestibulitis, a woman experiences pain with her first use of a tampon, her first exposure to a speculum, and the initiation of sexual relations. For those with secondary vestibulitis, pain on contact results after a period of comfortable sexual relations.

This pain is thought to stem from inflammation or trauma that initially sensitizes nociceptors in the vestibular mucosa, leading to prolonged neuronal firing. This in turn sensitizes the wide-dynamic-range neurons in the dorsal horn to respond abnormally, converting the sensation of touch into pain (allodynia).¹¹ There often is a history of an unresolved irritative event such as Candidal infection, repeated genital infection,¹² topical treatments,¹³ and early and sustained use of oral contraceptives.¹⁴ All are suspected causes.

Diagnosis is made once other pathology has been ruled out and a Q-tip test has demonstrated that contact elicits pain in the vestibule.

Numerous treatment protocols have been described, but current interest focuses on addressing neuroinflammatory pain. This can be done at the peripheral afferents by reducing inflammation and hyperexcitability with topical xylocaine 5% in a compounded sterol-lanolin base 5 times daily; centrally, this is accomplished using tricyclics in doses of 50 mg to 150 mg.

Note that primary vestibulitis is extremely difficult to treat; vestibulectomy and perineoplasty improve the condition by 60% to 90% when medical management fails.¹⁵

• Vaginismus, an involuntary spasm of the perineal and levator muscles, may occur in patients with vestibulitis. While primary vaginismus is psychologic in origin, secondary vaginismus represents a conditioned response to pain,¹⁶ usually vestibulitis. In patients with secondary disease, pelvic-floor motor instability has been well-demonstrated; these women have a reduced ability to contract or relax the pelvic floor and increased muscular instability at rest.¹⁷
  

 

Vaginismus is diagnosed by eliciting muscle spasms in the pelvic floor by depressing the levators. If a woman has primary vaginismus of psychogenic origin, there is no tenderness in the vestibule; note, however, that the exam may be so difficult for her to endure that evaluating the vestibule is not possible.

Pelvic-floor motor instability is treated with physical therapy and biofeedback. In secondary disease, vestibulitis must also be concomitantly addressed. Primary disease, meanwhile, is treated by desensitization techniques that help the patient control the relaxation of her musculature.

The fine points of examination

Asking the right questions. Before you begin the physical exam, it is crucial to get as much information as possible about the patient’s condition. The dyspareunia history includes the following:

• a complete description of the pain problem and any concomitant sexual dysfunction
  
• exploration of potential gynecologic causes
  
• exploration of potential medical causes
  
• psychosocial information¹⁸
  

In addition, a series of open-ended question asked in a nonjudgmental manner will help identify potential anatomic and medical sources of pain (TABLE), as well as psychosocial issues that may be a cause or result of dyspareunia (see “Discussing dyspareunia: Questions crucial to a thorough exam”).

The physical exam. Although guided by the history, the physical examination needs to be as comprehensive as possible. It should include:

• systematic, meticulous inspection of every structure to confirm normal color, texture and architecture, and the presence or absence of lesions.
  
• gentle palpation of all tissues for the source of the discomfort. This should include a Q-tip test of the vestibule for tender foci.
  
• a speculum exam with inspection for mucosal integrity without fissure, erosion, or ulceration, as well as a check for the presence or absence of rugae and discharge. (Testing for pH is done with a reactive cardboard strip while the speculum is in place; then samples for wet mount and cultures are collected.)
  
• gentle single-digit exam of the vestibule to confirm the Q-tip test, as well as single-digit palpation of the pelvic-floor musculature, anterior vaginal wall, urethra, and bladder to confirm superficial pain and avoid confusion with pelvic sources.
  
• bimanual examination to evaluate for any nodularity or masses in the vagina, rectovaginal septum, or pelvis, as well as for mobility and tenderness of the pelvic organs.
  

Before attributing the dyspareunia to a lesion you encounter, it is important to reproduce pain at that lesion site. Whitened skin and some synechiae, for example, are painless; the source of the dyspareunia may be tenderness in the vestibule.

Note that with generalized dysesthesia (vulvodynia), there may be no physical findings.

• Take steps to navigate the pain. Some women cannot tolerate a vulvar or vaginal examination; asking about previous experience will make it easier to tailor the exam appropriately. The following techniques also may be appropriate:
  

• use of premedication
  
• presence of a support person
  
• an agreement to stop the exam if the patient so requests
  
• use of a pediatric speculum
  

In rare cases, examination may need to be deferred until desensitization with a sexual therapist is achieved. Fortunately, most women tolerate the examination well and can identify the troubling areas.

It may not be possible to complete all components of an examination at a single visit. For example, a patient may have to return for a vaginal examination and wet mount if menses are present at the initial appointment.

Cultures for Candida and Trichomonas are important when microscopy is negative.

Essential laboratory studies.

• Vaginal pH. A normal level (3.5 to 4.5) rules out bacterial infection and atrophy. Candida grows at any pH. Elevated pH is nonspecific and can represent recent intercourse or a small amount of blood. However, it also can suggest such causes of dyspareunia as atrophy, vaginal lichen planus, desquamative vaginitis, and Trichomonas.
  
• Wet mount reveals 4 important features:
  1. Epithelial cells. These should be superficial or intermediate. The presence of parabasal cells suggests atrophy regardless of the age group. It also may indicate inflammation from Candida, lichen planus, or desquamative inflammatory vaginitis.
     
  2. Pathogens.Candida or Trichomonas may be identified. Microscopy for Candida lacks sensitivity; a negative examination in a symptomatic woman mandates a culture for Candida.¹⁹
     
  3. Background flora. As mentioned earlier, lactobacillus dominates the normal vagina; when this predominance is seen on microscopy, there is no bacterial infection. A vaginal culture may grow Escherichia coli, group B streptococcus, Gardnerella, and a variety of normal commensals, but these are not the cause of dyspareunia when pH is normal and lactobacilli dominate the slide.
     
  4. White blood cells. Large numbers suggest Candida, lichen planus, Trichomonas, gonorrhea, chlamydia, or desquamative inflammatory vaginitis.
     
  
  
• Cultures for Candida and Trichomonas are important when microscopy is negative. Routine vaginal culture is not recommended. Cultures for herpes, gonorrhea, or chlamydia may be necessary.
  
• Biopsy and blood tests offer data on hormonal levels or type-specific antibodies for herpes. Biopsy of the vulva or vagina is indicated whenever there is a visible lesion that needs identification.
  
• Urine culture, colposcopy, or imaging such as ultrasonography and spine films may be indicated.
  
• Specialty referrals may be helpful for evaluation of the gastrointestinal or genitourinary tract, or for diagnostic laparoscopy for endometriosis.
  

 

Dr. Stewart reports no financial relationship with any companies whose products are mentioned in this article.

Identifying the cause of a patient’s dyspareunia can be just as challenging as getting her to admit to the problem.

Due in part to underreporting of the condition, the incidence and prevalence of dyspareunia—defined as genital pain experienced just before, during, or after sexual intercourse¹—is uncertain.²

Because it is easy to miss subtle physical findings such as small fissures, periclitoral scarring, or a focus of tender vestibulitis under a hymenal remnant, getting to the root of dyspareunia can present a significant challenge to clinicians. Adding to the difficulty is the fact that intermittent conditions such as cyclical Candida albicans are hard to diagnose.

This review of 5 common but often overlooked causes describes what is known about dyspareunia and how to conduct a complete evaluation, including physical examination, diagnostic tests, and questions to ask the patient.

CAUSE 1Inadequate estrogenization

Vulvovaginal atrophy is the leading cause of sexual dysfunction, affecting up to 50% of women over age 50. It contributes to a lack of vaginal lubrication with sexual arousal and, consequently, dyspareunia and postcoital bleeding.³ Even when a woman is taking oral hormone replacement therapy, the vagina can lack sufficient estrogen.

Younger women also may experience atrophy and lowered estrogen levels. For example, a 34-year-old woman with premature ovarian failure may experience slight burning, dryness, and pain on penetration.

Tamoxifen can be a source of dyspareunia: It can cause vaginal atrophy in the premenopausal woman or estrogenization with Candidal invasion in postmenopausal patients.

Atrophy also can occur:

• with hypothalamic amenorrhea caused by excessive exercise or marked weight loss
  
• during the postpartum period and breast-feeding
  
• with the use of some low-estrogen (20 μg) contraceptives and medroxyprogesterone acetate
  
• after radiation or chemotherapy
  

Resolve the problem with local estrogen.

Fortunately, atrophy is easily reversed with local estrogen in the form of cream, tablets, or the vaginal ring. Because the latter does not elevate circulating estradiol levels after the first 24 hours of use, many oncologists are willing to allow this therapy for breast cancer patients.⁴

When dyspareunia persists despite local estrogen use, we must seek out other causes.

CAUSE 2A skin disease

Dermatitis. There are 2 types of dermatitis: eczematous, in which the irritant is essentially unknown, and contactant, which arises from known irritants or allergens. In some cases, the exposure to an irritant may be fairly recent. In others, the continuing combination of irritants and tight clothing or abrasive activity eventually leads to symptoms.

Physical findings of dermatitis include erythema (with or without scaling) and fissuring—especially of the perineum. A biopsy is diagnostic.

Recommended treatment includes meticulous vulvar hygiene and the use of 2.5% hydrocortisone cream twice daily for 14 to 30 days, followed by twice-weekly “maintenance” applications. For moderate or severe cases, a medium-potency steroid (betamethasone valerate 0.1%) or an ultrapotent steroid (clobetasol 0.05%) may be used in the same manner. In addition, physicians should educate patients with dermatitis about the chronicity of the condition and the importance of eliminating the cause, if possible.

Poorly treated eczema leads to lichen simplex chronicus. One clue to this condition is a history of atopy or eczema elsewhere on the body.

Lichen sclerosus and lichen planus. These dermatoses cause changes in the color and texture of the epithelium.

Because lichen planus can produce erosion of the vestibule, it often is mistaken for vestibulitis. With this condition, erosions are intensely erythematous and vary from small areas to involvement of the entire vestibule. You will also note a serpiginous white border or subtle white reticules adjacent to erosions.

Both lichen sclerosus and lichen planus can produce intense itching or progress without clinical symptoms.

Lichen sclerosus, meanwhile, causes whitened epithelium with the thinned and wrinkled appearance of cigarette paper; areas of hyperkeratosis also may be present. Changes may occur from the periclitoral area to the anus in a keyhole configuration.

Both lichen sclerosus and lichen planus:

• can produce intense itching or progress without clinical symptoms
  
• can scar extensively and cause bridging synechiae at the fourchette, elimination of the labia minora, and fusion of the prepuce over the glans clitoris
  
• can produce anal fissuring and painful defecation
  

 

While lichen sclerosus never involves the vagina, vaginal lichen planus produces inflammatory vaginitis that can scar and reduce the size of the vagina—even obliterate it entirely.

Treatment for both diseases consists of ultrapotent topical steroids to arrest the inflammatory process. Vaginal lichen planus is treated with hydrocortisone suppositories (25 mg at bedtime), with the length of treatment dependent on severity.⁵ More potent steroids may be necessary.

CAUSE 3Candida

This infection can be extremely difficult to diagnose for a variety of reasons. Patients come in partially treated with over-the-counter antifungals. Many have taken a fluconazole tablet with a long half-life of action. Others have a cyclical candidiasis that is seen only in the luteal phase of the cycle. In these cases, fissuring is often attributed to other causes.

Complicating matters further, a wet mount will be negative in the presence of Candida approximately 50% of the time.⁶ For these reasons, a culture is essential when there is an index of clinical suspicion and white blood cells are present on the wet mount.

Uncomplicated Candida is treated by topical -azole creams for 3 or 7 days or a single fluconazole 150-mg tablet.

Complicated Candida (that is, more than 3 infections in a year or infection in a pregnant or immune-compromised host) will require longer courses of therapy.⁷

CAUSE 4Desquamative inflammatory vaginitis

Because the intense inflammation produced by the 2 diseases are similar, some people believe desquamative inflammatory vaginitis is a form of lichen planus⁸—in fact, it is sometimes called lichenoid vaginitis. However, desquamative inflammatory vaginitis does not scar the vagina, suggesting a different cause. Its profusely irritative discharge—microscopically characterized by sheets of white blood cells—resembles Trichomonas and Candida. Sheets of white blood cells and parabasal cells also resemble Trichomonas, Candida, or severe atrophy.

 

The inflammation leads to the loss of the lactobacillus, with bacterial overgrowth and clue cells similar to bacterial vaginosis (though bacterial vaginosis never causes such inflammation).

Vulvodynia consists of unprovoked stinging, burning, irritation, rawness, or pain anywhere on the vulva and can be constant or episodic.

Though antibiotics may yield transient improvement,⁹ management most often consists of 25-mg hydrocortisone suppositories (or compounded as 100 mg for severe cases) at bedtime for 14 days, then every other day for 14 days. After this course of therapy has been completed, clinicians must reevaluate the patient to determine whether she needs extended therapy (in severe cases) or can begin maintenance with a weekly suppository (for cases that are mild but chronic).

If dyspareunia does not resolve after the inflammation abates, superimposed neuroinflammatory pain (vestibulitis) will need treatment.

CAUSE 5Vulvodynia or vulvar vestibulitis

Vulvodynia (generalized vulvar dysesthesia). This condition—which consists of unprovoked stinging, burning, irritation, rawness, or pain anywhere on the vulva—may be constant or episodic. Dyspareunia in these cases may involve postcoital exacerbation of symptoms.

The cause is unknown, but some suspect a lesion of the pudendal nerve in its long course from the spine to the vulva.

There may be virtually no physical findings, or there may be areas of tenderness, hyperesthesia, or hypoesthesia. A biopsy will be nonspecific. Vulvodynia is therefore diagnosed by ruling out infectious, dermatologic, or other causes of genital pain.

The following treatments are usually successful:

• tricyclic antidepressants such as nortriptyline, starting with a bedtime dose of 10 mg and working up to 50 mg to 150 mg
  
• the antiepileptic agent gabapentin, starting with a bedtime dose of 100 mg and working up to as much as 1,000 mg (this is usually substituted for the tricyclic antidepressant if that therapy alone is ineffective)
  

Vulvar vestibulitis (localized vulvar dysesthesia). This condition, consisting of provoked pain in the vestibule on contact, is the leading cause of dyspareunia in women under 50.¹⁰

This condition may be either primary or secondary. With primary vestibulitis, a woman experiences pain with her first use of a tampon, her first exposure to a speculum, and the initiation of sexual relations. For those with secondary vestibulitis, pain on contact results after a period of comfortable sexual relations.

This pain is thought to stem from inflammation or trauma that initially sensitizes nociceptors in the vestibular mucosa, leading to prolonged neuronal firing. This in turn sensitizes the wide-dynamic-range neurons in the dorsal horn to respond abnormally, converting the sensation of touch into pain (allodynia).¹¹ There often is a history of an unresolved irritative event such as Candidal infection, repeated genital infection,¹² topical treatments,¹³ and early and sustained use of oral contraceptives.¹⁴ All are suspected causes.

Diagnosis is made once other pathology has been ruled out and a Q-tip test has demonstrated that contact elicits pain in the vestibule.

Numerous treatment protocols have been described, but current interest focuses on addressing neuroinflammatory pain. This can be done at the peripheral afferents by reducing inflammation and hyperexcitability with topical xylocaine 5% in a compounded sterol-lanolin base 5 times daily; centrally, this is accomplished using tricyclics in doses of 50 mg to 150 mg.

Note that primary vestibulitis is extremely difficult to treat; vestibulectomy and perineoplasty improve the condition by 60% to 90% when medical management fails.¹⁵

• Vaginismus, an involuntary spasm of the perineal and levator muscles, may occur in patients with vestibulitis. While primary vaginismus is psychologic in origin, secondary vaginismus represents a conditioned response to pain,¹⁶ usually vestibulitis. In patients with secondary disease, pelvic-floor motor instability has been well-demonstrated; these women have a reduced ability to contract or relax the pelvic floor and increased muscular instability at rest.¹⁷
  

 

Vaginismus is diagnosed by eliciting muscle spasms in the pelvic floor by depressing the levators. If a woman has primary vaginismus of psychogenic origin, there is no tenderness in the vestibule; note, however, that the exam may be so difficult for her to endure that evaluating the vestibule is not possible.

Pelvic-floor motor instability is treated with physical therapy and biofeedback. In secondary disease, vestibulitis must also be concomitantly addressed. Primary disease, meanwhile, is treated by desensitization techniques that help the patient control the relaxation of her musculature.

The fine points of examination

Asking the right questions. Before you begin the physical exam, it is crucial to get as much information as possible about the patient’s condition. The dyspareunia history includes the following:

• a complete description of the pain problem and any concomitant sexual dysfunction
  
• exploration of potential gynecologic causes
  
• exploration of potential medical causes
  
• psychosocial information¹⁸
  

In addition, a series of open-ended question asked in a nonjudgmental manner will help identify potential anatomic and medical sources of pain (TABLE), as well as psychosocial issues that may be a cause or result of dyspareunia (see “Discussing dyspareunia: Questions crucial to a thorough exam”).

The physical exam. Although guided by the history, the physical examination needs to be as comprehensive as possible. It should include:

• systematic, meticulous inspection of every structure to confirm normal color, texture and architecture, and the presence or absence of lesions.
  
• gentle palpation of all tissues for the source of the discomfort. This should include a Q-tip test of the vestibule for tender foci.
  
• a speculum exam with inspection for mucosal integrity without fissure, erosion, or ulceration, as well as a check for the presence or absence of rugae and discharge. (Testing for pH is done with a reactive cardboard strip while the speculum is in place; then samples for wet mount and cultures are collected.)
  
• gentle single-digit exam of the vestibule to confirm the Q-tip test, as well as single-digit palpation of the pelvic-floor musculature, anterior vaginal wall, urethra, and bladder to confirm superficial pain and avoid confusion with pelvic sources.
  
• bimanual examination to evaluate for any nodularity or masses in the vagina, rectovaginal septum, or pelvis, as well as for mobility and tenderness of the pelvic organs.
  

Before attributing the dyspareunia to a lesion you encounter, it is important to reproduce pain at that lesion site. Whitened skin and some synechiae, for example, are painless; the source of the dyspareunia may be tenderness in the vestibule.

Note that with generalized dysesthesia (vulvodynia), there may be no physical findings.

• Take steps to navigate the pain. Some women cannot tolerate a vulvar or vaginal examination; asking about previous experience will make it easier to tailor the exam appropriately. The following techniques also may be appropriate:
  

• use of premedication
  
• presence of a support person
  
• an agreement to stop the exam if the patient so requests
  
• use of a pediatric speculum
  

In rare cases, examination may need to be deferred until desensitization with a sexual therapist is achieved. Fortunately, most women tolerate the examination well and can identify the troubling areas.

It may not be possible to complete all components of an examination at a single visit. For example, a patient may have to return for a vaginal examination and wet mount if menses are present at the initial appointment.

Cultures for Candida and Trichomonas are important when microscopy is negative.

Essential laboratory studies.

• Vaginal pH. A normal level (3.5 to 4.5) rules out bacterial infection and atrophy. Candida grows at any pH. Elevated pH is nonspecific and can represent recent intercourse or a small amount of blood. However, it also can suggest such causes of dyspareunia as atrophy, vaginal lichen planus, desquamative vaginitis, and Trichomonas.
  
• Wet mount reveals 4 important features:
  1. Epithelial cells. These should be superficial or intermediate. The presence of parabasal cells suggests atrophy regardless of the age group. It also may indicate inflammation from Candida, lichen planus, or desquamative inflammatory vaginitis.
     
  2. Pathogens.Candida or Trichomonas may be identified. Microscopy for Candida lacks sensitivity; a negative examination in a symptomatic woman mandates a culture for Candida.¹⁹
     
  3. Background flora. As mentioned earlier, lactobacillus dominates the normal vagina; when this predominance is seen on microscopy, there is no bacterial infection. A vaginal culture may grow Escherichia coli, group B streptococcus, Gardnerella, and a variety of normal commensals, but these are not the cause of dyspareunia when pH is normal and lactobacilli dominate the slide.
     
  4. White blood cells. Large numbers suggest Candida, lichen planus, Trichomonas, gonorrhea, chlamydia, or desquamative inflammatory vaginitis.
     
  
  
• Cultures for Candida and Trichomonas are important when microscopy is negative. Routine vaginal culture is not recommended. Cultures for herpes, gonorrhea, or chlamydia may be necessary.
  
• Biopsy and blood tests offer data on hormonal levels or type-specific antibodies for herpes. Biopsy of the vulva or vagina is indicated whenever there is a visible lesion that needs identification.
  
• Urine culture, colposcopy, or imaging such as ultrasonography and spine films may be indicated.
  
• Specialty referrals may be helpful for evaluation of the gastrointestinal or genitourinary tract, or for diagnostic laparoscopy for endometriosis.
  

 

Dr. Stewart reports no financial relationship with any companies whose products are mentioned in this article.

Identifying the cause of a patient’s dyspareunia can be just as challenging as getting her to admit to the problem.

Due in part to underreporting of the condition, the incidence and prevalence of dyspareunia—defined as genital pain experienced just before, during, or after sexual intercourse¹—is uncertain.²

Because it is easy to miss subtle physical findings such as small fissures, periclitoral scarring, or a focus of tender vestibulitis under a hymenal remnant, getting to the root of dyspareunia can present a significant challenge to clinicians. Adding to the difficulty is the fact that intermittent conditions such as cyclical Candida albicans are hard to diagnose.

This review of 5 common but often overlooked causes describes what is known about dyspareunia and how to conduct a complete evaluation, including physical examination, diagnostic tests, and questions to ask the patient.

CAUSE 1Inadequate estrogenization

Vulvovaginal atrophy is the leading cause of sexual dysfunction, affecting up to 50% of women over age 50. It contributes to a lack of vaginal lubrication with sexual arousal and, consequently, dyspareunia and postcoital bleeding.³ Even when a woman is taking oral hormone replacement therapy, the vagina can lack sufficient estrogen.

Younger women also may experience atrophy and lowered estrogen levels. For example, a 34-year-old woman with premature ovarian failure may experience slight burning, dryness, and pain on penetration.

Tamoxifen can be a source of dyspareunia: It can cause vaginal atrophy in the premenopausal woman or estrogenization with Candidal invasion in postmenopausal patients.

Atrophy also can occur:

• with hypothalamic amenorrhea caused by excessive exercise or marked weight loss
  
• during the postpartum period and breast-feeding
  
• with the use of some low-estrogen (20 μg) contraceptives and medroxyprogesterone acetate
  
• after radiation or chemotherapy
  

Resolve the problem with local estrogen.

Fortunately, atrophy is easily reversed with local estrogen in the form of cream, tablets, or the vaginal ring. Because the latter does not elevate circulating estradiol levels after the first 24 hours of use, many oncologists are willing to allow this therapy for breast cancer patients.⁴

When dyspareunia persists despite local estrogen use, we must seek out other causes.

CAUSE 2A skin disease

Dermatitis. There are 2 types of dermatitis: eczematous, in which the irritant is essentially unknown, and contactant, which arises from known irritants or allergens. In some cases, the exposure to an irritant may be fairly recent. In others, the continuing combination of irritants and tight clothing or abrasive activity eventually leads to symptoms.

Physical findings of dermatitis include erythema (with or without scaling) and fissuring—especially of the perineum. A biopsy is diagnostic.

Recommended treatment includes meticulous vulvar hygiene and the use of 2.5% hydrocortisone cream twice daily for 14 to 30 days, followed by twice-weekly “maintenance” applications. For moderate or severe cases, a medium-potency steroid (betamethasone valerate 0.1%) or an ultrapotent steroid (clobetasol 0.05%) may be used in the same manner. In addition, physicians should educate patients with dermatitis about the chronicity of the condition and the importance of eliminating the cause, if possible.

Poorly treated eczema leads to lichen simplex chronicus. One clue to this condition is a history of atopy or eczema elsewhere on the body.

Lichen sclerosus and lichen planus. These dermatoses cause changes in the color and texture of the epithelium.

Because lichen planus can produce erosion of the vestibule, it often is mistaken for vestibulitis. With this condition, erosions are intensely erythematous and vary from small areas to involvement of the entire vestibule. You will also note a serpiginous white border or subtle white reticules adjacent to erosions.

Both lichen sclerosus and lichen planus can produce intense itching or progress without clinical symptoms.

Lichen sclerosus, meanwhile, causes whitened epithelium with the thinned and wrinkled appearance of cigarette paper; areas of hyperkeratosis also may be present. Changes may occur from the periclitoral area to the anus in a keyhole configuration.

Both lichen sclerosus and lichen planus:

• can produce intense itching or progress without clinical symptoms
  
• can scar extensively and cause bridging synechiae at the fourchette, elimination of the labia minora, and fusion of the prepuce over the glans clitoris
  
• can produce anal fissuring and painful defecation
  

 

While lichen sclerosus never involves the vagina, vaginal lichen planus produces inflammatory vaginitis that can scar and reduce the size of the vagina—even obliterate it entirely.

Treatment for both diseases consists of ultrapotent topical steroids to arrest the inflammatory process. Vaginal lichen planus is treated with hydrocortisone suppositories (25 mg at bedtime), with the length of treatment dependent on severity.⁵ More potent steroids may be necessary.

CAUSE 3Candida

This infection can be extremely difficult to diagnose for a variety of reasons. Patients come in partially treated with over-the-counter antifungals. Many have taken a fluconazole tablet with a long half-life of action. Others have a cyclical candidiasis that is seen only in the luteal phase of the cycle. In these cases, fissuring is often attributed to other causes.

Complicating matters further, a wet mount will be negative in the presence of Candida approximately 50% of the time.⁶ For these reasons, a culture is essential when there is an index of clinical suspicion and white blood cells are present on the wet mount.

Uncomplicated Candida is treated by topical -azole creams for 3 or 7 days or a single fluconazole 150-mg tablet.

Complicated Candida (that is, more than 3 infections in a year or infection in a pregnant or immune-compromised host) will require longer courses of therapy.⁷

CAUSE 4Desquamative inflammatory vaginitis

Because the intense inflammation produced by the 2 diseases are similar, some people believe desquamative inflammatory vaginitis is a form of lichen planus⁸—in fact, it is sometimes called lichenoid vaginitis. However, desquamative inflammatory vaginitis does not scar the vagina, suggesting a different cause. Its profusely irritative discharge—microscopically characterized by sheets of white blood cells—resembles Trichomonas and Candida. Sheets of white blood cells and parabasal cells also resemble Trichomonas, Candida, or severe atrophy.

 

The inflammation leads to the loss of the lactobacillus, with bacterial overgrowth and clue cells similar to bacterial vaginosis (though bacterial vaginosis never causes such inflammation).

Vulvodynia consists of unprovoked stinging, burning, irritation, rawness, or pain anywhere on the vulva and can be constant or episodic.

Though antibiotics may yield transient improvement,⁹ management most often consists of 25-mg hydrocortisone suppositories (or compounded as 100 mg for severe cases) at bedtime for 14 days, then every other day for 14 days. After this course of therapy has been completed, clinicians must reevaluate the patient to determine whether she needs extended therapy (in severe cases) or can begin maintenance with a weekly suppository (for cases that are mild but chronic).

If dyspareunia does not resolve after the inflammation abates, superimposed neuroinflammatory pain (vestibulitis) will need treatment.

CAUSE 5Vulvodynia or vulvar vestibulitis

Vulvodynia (generalized vulvar dysesthesia). This condition—which consists of unprovoked stinging, burning, irritation, rawness, or pain anywhere on the vulva—may be constant or episodic. Dyspareunia in these cases may involve postcoital exacerbation of symptoms.

The cause is unknown, but some suspect a lesion of the pudendal nerve in its long course from the spine to the vulva.

There may be virtually no physical findings, or there may be areas of tenderness, hyperesthesia, or hypoesthesia. A biopsy will be nonspecific. Vulvodynia is therefore diagnosed by ruling out infectious, dermatologic, or other causes of genital pain.

The following treatments are usually successful:

• tricyclic antidepressants such as nortriptyline, starting with a bedtime dose of 10 mg and working up to 50 mg to 150 mg
  
• the antiepileptic agent gabapentin, starting with a bedtime dose of 100 mg and working up to as much as 1,000 mg (this is usually substituted for the tricyclic antidepressant if that therapy alone is ineffective)
  

Vulvar vestibulitis (localized vulvar dysesthesia). This condition, consisting of provoked pain in the vestibule on contact, is the leading cause of dyspareunia in women under 50.¹⁰

This condition may be either primary or secondary. With primary vestibulitis, a woman experiences pain with her first use of a tampon, her first exposure to a speculum, and the initiation of sexual relations. For those with secondary vestibulitis, pain on contact results after a period of comfortable sexual relations.

This pain is thought to stem from inflammation or trauma that initially sensitizes nociceptors in the vestibular mucosa, leading to prolonged neuronal firing. This in turn sensitizes the wide-dynamic-range neurons in the dorsal horn to respond abnormally, converting the sensation of touch into pain (allodynia).¹¹ There often is a history of an unresolved irritative event such as Candidal infection, repeated genital infection,¹² topical treatments,¹³ and early and sustained use of oral contraceptives.¹⁴ All are suspected causes.

Diagnosis is made once other pathology has been ruled out and a Q-tip test has demonstrated that contact elicits pain in the vestibule.

Numerous treatment protocols have been described, but current interest focuses on addressing neuroinflammatory pain. This can be done at the peripheral afferents by reducing inflammation and hyperexcitability with topical xylocaine 5% in a compounded sterol-lanolin base 5 times daily; centrally, this is accomplished using tricyclics in doses of 50 mg to 150 mg.

Note that primary vestibulitis is extremely difficult to treat; vestibulectomy and perineoplasty improve the condition by 60% to 90% when medical management fails.¹⁵

• Vaginismus, an involuntary spasm of the perineal and levator muscles, may occur in patients with vestibulitis. While primary vaginismus is psychologic in origin, secondary vaginismus represents a conditioned response to pain,¹⁶ usually vestibulitis. In patients with secondary disease, pelvic-floor motor instability has been well-demonstrated; these women have a reduced ability to contract or relax the pelvic floor and increased muscular instability at rest.¹⁷
  

 

Vaginismus is diagnosed by eliciting muscle spasms in the pelvic floor by depressing the levators. If a woman has primary vaginismus of psychogenic origin, there is no tenderness in the vestibule; note, however, that the exam may be so difficult for her to endure that evaluating the vestibule is not possible.

Pelvic-floor motor instability is treated with physical therapy and biofeedback. In secondary disease, vestibulitis must also be concomitantly addressed. Primary disease, meanwhile, is treated by desensitization techniques that help the patient control the relaxation of her musculature.

The fine points of examination

Asking the right questions. Before you begin the physical exam, it is crucial to get as much information as possible about the patient’s condition. The dyspareunia history includes the following:

• a complete description of the pain problem and any concomitant sexual dysfunction
  
• exploration of potential gynecologic causes
  
• exploration of potential medical causes
  
• psychosocial information¹⁸
  

In addition, a series of open-ended question asked in a nonjudgmental manner will help identify potential anatomic and medical sources of pain (TABLE), as well as psychosocial issues that may be a cause or result of dyspareunia (see “Discussing dyspareunia: Questions crucial to a thorough exam”).

The physical exam. Although guided by the history, the physical examination needs to be as comprehensive as possible. It should include:

• systematic, meticulous inspection of every structure to confirm normal color, texture and architecture, and the presence or absence of lesions.
  
• gentle palpation of all tissues for the source of the discomfort. This should include a Q-tip test of the vestibule for tender foci.
  
• a speculum exam with inspection for mucosal integrity without fissure, erosion, or ulceration, as well as a check for the presence or absence of rugae and discharge. (Testing for pH is done with a reactive cardboard strip while the speculum is in place; then samples for wet mount and cultures are collected.)
  
• gentle single-digit exam of the vestibule to confirm the Q-tip test, as well as single-digit palpation of the pelvic-floor musculature, anterior vaginal wall, urethra, and bladder to confirm superficial pain and avoid confusion with pelvic sources.
  
• bimanual examination to evaluate for any nodularity or masses in the vagina, rectovaginal septum, or pelvis, as well as for mobility and tenderness of the pelvic organs.
  

Before attributing the dyspareunia to a lesion you encounter, it is important to reproduce pain at that lesion site. Whitened skin and some synechiae, for example, are painless; the source of the dyspareunia may be tenderness in the vestibule.

Note that with generalized dysesthesia (vulvodynia), there may be no physical findings.

• Take steps to navigate the pain. Some women cannot tolerate a vulvar or vaginal examination; asking about previous experience will make it easier to tailor the exam appropriately. The following techniques also may be appropriate:
  

• use of premedication
  
• presence of a support person
  
• an agreement to stop the exam if the patient so requests
  
• use of a pediatric speculum
  

In rare cases, examination may need to be deferred until desensitization with a sexual therapist is achieved. Fortunately, most women tolerate the examination well and can identify the troubling areas.

It may not be possible to complete all components of an examination at a single visit. For example, a patient may have to return for a vaginal examination and wet mount if menses are present at the initial appointment.

Cultures for Candida and Trichomonas are important when microscopy is negative.

Essential laboratory studies.

• Vaginal pH. A normal level (3.5 to 4.5) rules out bacterial infection and atrophy. Candida grows at any pH. Elevated pH is nonspecific and can represent recent intercourse or a small amount of blood. However, it also can suggest such causes of dyspareunia as atrophy, vaginal lichen planus, desquamative vaginitis, and Trichomonas.
  
• Wet mount reveals 4 important features:
  1. Epithelial cells. These should be superficial or intermediate. The presence of parabasal cells suggests atrophy regardless of the age group. It also may indicate inflammation from Candida, lichen planus, or desquamative inflammatory vaginitis.
     
  2. Pathogens.Candida or Trichomonas may be identified. Microscopy for Candida lacks sensitivity; a negative examination in a symptomatic woman mandates a culture for Candida.¹⁹
     
  3. Background flora. As mentioned earlier, lactobacillus dominates the normal vagina; when this predominance is seen on microscopy, there is no bacterial infection. A vaginal culture may grow Escherichia coli, group B streptococcus, Gardnerella, and a variety of normal commensals, but these are not the cause of dyspareunia when pH is normal and lactobacilli dominate the slide.
     
  4. White blood cells. Large numbers suggest Candida, lichen planus, Trichomonas, gonorrhea, chlamydia, or desquamative inflammatory vaginitis.
     
  
  
• Cultures for Candida and Trichomonas are important when microscopy is negative. Routine vaginal culture is not recommended. Cultures for herpes, gonorrhea, or chlamydia may be necessary.
  
• Biopsy and blood tests offer data on hormonal levels or type-specific antibodies for herpes. Biopsy of the vulva or vagina is indicated whenever there is a visible lesion that needs identification.
  
• Urine culture, colposcopy, or imaging such as ultrasonography and spine films may be indicated.
  
• Specialty referrals may be helpful for evaluation of the gastrointestinal or genitourinary tract, or for diagnostic laparoscopy for endometriosis.
  

 

Dr. Stewart reports no financial relationship with any companies whose products are mentioned in this article.