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Vulvovaginal Issues in Mature Women

      Abstract

      Mature women often present with symptomatic vulvovaginal atrophy and vulvar dermatoses, causing noncoital pain, dyspareunia, and sexual changes. Diagnosis of these conditions can be challenging, and long-term management is required to decrease morbidity and enhance quality of life. Vaginal estrogen therapies remain safe and effective for treating symptomatic vulvovaginal atrophy. A vulvar biopsy is easy to perform and generally well tolerated when indicated for the diagnosis of lichen simplex chronicus, lichen sclerosus, and lichen planus. Therapy with moderate- to high-potency corticosteroids is effective for these frequently debilitating conditions.

      Abbreviations and Acronyms:

      GSM (genitourinary syndrome of menopause), LP (lichen planus), LS (lichen sclerosus), LSC (lichen simplex chronicus), OTC (over-the-counter), SCC (squamous cell carcinoma)
      CME Activity
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      Learning Objectives: On completion of this article, you should be able to: (1) identify and treat genitourinary syndrome of menopause; (2) assess women for vulvar dermatitis/lichen simplex chronicus; and (3) recognize the differences between lichen sclerosus and lichen planus and begin management of these conditions.
      Disclosures: As a provider accredited by ACCME, Mayo Clinic College of Medicine and Science (Mayo School of Continuous Professional Development) must ensure balance, independence, objectivity, and scientific rigor in its educational activities. Course Director(s), Planning Committee members, Faculty, and all others who are in a position to control the content of this educational activity are required to disclose all relevant financial relationships with any commercial interest related to the subject matter of the educational activity. Safeguards against commercial bias have been put in place. Faculty also will disclose any off-label and/or investigational use of pharmaceuticals or instruments discussed in their presentation.
      Disclosure of this information will be published in course materials so that those participants in the activity may formulate their own judgments regarding the presentation. In their editorial and administrative roles, William L. Lanier, Jr, MD, Terry L. Jopke, Kimberly D. Sankey, and Nicki M. Smith, MPA, have control of the content of this program but have no relevant financial relationship(s) with industry.
      The authors report no competing interests.
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      Questions? Contact [email protected] .
      Vulvovaginal concerns become common with age and range from atrophic changes associated with declining estrogen levels to immune-based vulvar dermatoses, such as lichen sclerosus (LS) and lichen planus (LP). It is important to identify the atrophic vulvovaginal changes related to menopause, as well as the abnormal changes associated with vulvar dermatoses, and clinicians should become familiar with well-tolerated therapies that have been proven safe and effective for these conditions. Therefore, in this review, we discuss the genitourinary syndrome of menopause (GSM; vulvovaginal atrophy), and vulvar dermatitis/lichen simplex chronicus (LSC), LS, and LP.

      The Genitourinary Syndrome of Menopause

      Genitourinary syndrome of menopause, formerly vulvovaginal atrophy, refers to the symptoms and signs associated with decreasing hormone levels.
      • Portman D.J.
      • Gass M.L.
      Vulvovaginal Atrophy Terminology Consensus Conference Panel
      Genitourinary syndrome of menopause: new terminology for vulvovaginal atrophy from the International Society for the Study of Women's Sexual Health and the North American Menopause Society.
      It affects up to 50% of postmenopausal women and includes vaginal dryness, dyspareunia, decreased lubrication, postcoital bleeding, sexual dysfunction along with vulvovaginal irritation, burning, pruritus, urinary urgency, and frequency.
      • Mac Bride M.B.
      • Rhodes D.J.
      • Shuster L.T.
      Vulvovaginal atrophy.
      Signs of GSM include decreased moisture and elasticity, mild labial minora reabsorption, pallor or erythema, loss of vaginal rugae, tissue fragility with fissuring and petechiae, and introital retraction. Urinary signs include urethral eversion or prolapse, prominence of the urethral meatus, and recurrent urinary tract infections.
      • Portman D.J.
      • Gass M.L.
      Vulvovaginal Atrophy Terminology Consensus Conference Panel
      Genitourinary syndrome of menopause: new terminology for vulvovaginal atrophy from the International Society for the Study of Women's Sexual Health and the North American Menopause Society.
      Although vulvovaginal atrophy does not cause symptoms in all women, the symptoms can be long-term and progressive and are unlikely to improve over time.
      Management of symptomatic vulvovaginal atrophy: 2013 position statement of The North American Menopause Society.
      Systemic estrogens are helpful, but local or topical estrogens are most beneficial for women without vasomotor symptoms (hot flashes) and at least moderate to severe GSM.
      • Portman D.J.
      • Gass M.L.
      Vulvovaginal Atrophy Terminology Consensus Conference Panel
      Genitourinary syndrome of menopause: new terminology for vulvovaginal atrophy from the International Society for the Study of Women's Sexual Health and the North American Menopause Society.
      Vulvovaginal low-dose estrogens are supplied in several forms: cream (estradiol [Estrace; Allergan] or conjugated estrogen [Premarin; Pfizer Inc], 0.5-1.0 g twice weekly), tablet (estradiol [Vagifem; Novo Nordisk Health Care AG],10 μg twice weekly), or ring (estradiol [Estring; Pfizer Inc], 2 mg every 3 months). Vagifem and Estring had the least systemic absorption compared with vaginal creams.
      • Pruthi S.
      • Simon J.A.
      • Early A.P.
      Current overview of the management of urogenital atrophy in women with breast cancer.
      For women with an intact uterus, progestogens are not additionally required with these doses.
      • Portman D.J.
      • Gass M.L.
      Vulvovaginal Atrophy Terminology Consensus Conference Panel
      Genitourinary syndrome of menopause: new terminology for vulvovaginal atrophy from the International Society for the Study of Women's Sexual Health and the North American Menopause Society.
      Vaginal estrogen may be beneficial for symptomatic survivors of estrogen-dependent cancers; however, the patient's oncologist should be consulted before this therapy is prescribed. Oral ospemifene, a selective estrogen receptor modulator, is effective for GSM but is not recommended for women with a history of breast or endometrial cancer. For women who decline estrogen, over-the-counter (OTC) vaginal moisturizers (Replens [Church & Dwight Co Inc] and Luvena [Laclede Inc]) can be applied in the vagina every 2 to 3 days. Organic or silicone-based lubricants and moisturizers are available for sexual intimacy and often do not contain propylene glycol, glycerine, and parabens, which can be irritants. For women with vaginal stenosis from GSM, daily lubricant-coated graduated vaginal dilators, combined with vaginal estrogen twice weekly, may be helpful for accomplishing comfortable examinations and sexual intimacy.
      • Portman D.J.
      • Gass M.L.
      Vulvovaginal Atrophy Terminology Consensus Conference Panel
      Genitourinary syndrome of menopause: new terminology for vulvovaginal atrophy from the International Society for the Study of Women's Sexual Health and the North American Menopause Society.

      Vulvar Dermatitis/LSC

      Vulvar dermatitis is common.
      • Lynch P.J.
      Lichen simplex chronicus (atopic/neurodermatitis) of the anogenital region.
      Exogenous vulvar dermatitis is induced by external factors and is called contact dermatitis. It results 80% of the time from an irritant trigger that damages vulvar skin and 20% of the time from an allergen trigger that causes an antigen-specific immune response.
      • Pincus S.H.
      Vulvar dermatoses and pruritus vulvae.
      Common culprits include fragranced and antibacterial soaps, bath products, feminine sprays, and OTC anti-itch formulations containing benzocaine (eg, Vagisil [Combe Inc] and vagicaine products).
      • Marren P.
      • Wojnarowska F.
      • Powell S.
      Allergic contact dermatitis and vulvar dermatoses.
      • Virgili A.
      • Bacilieri S.
      • Corazza M.
      Evaluation of contact sensitization in vulvar lichen simplex chronicus: a proposal for a battery of selected allergens.
      Symptoms include intense pruritus, burning, and irritation. The vulva may be erythematous, edematous, scaly, fissured, hypopigmented, or hyperpigmented, with hyperkeratosis and lichenification from chronic scratching.
      • Lynch P.J.
      Lichen simplex chronicus (atopic/neurodermatitis) of the anogenital region.
      • Marren P.
      • Wojnarowska F.
      • Powell S.
      Allergic contact dermatitis and vulvar dermatoses.
      Lichen simplex chronicus occurs when chronic irritation, pruritus, or both evolve into a recalcitrant itch-scratch cycle (Figure 1).
      • Lynch P.J.
      Lichen simplex chronicus (atopic/neurodermatitis) of the anogenital region.
      A thorough history and examination are required. Further evaluation may include patch testing for allergens and cultures to exclude the possibility of secondary bacterial or Candida infections.
      • Virgili A.
      • Bacilieri S.
      • Corazza M.
      Evaluation of contact sensitization in vulvar lichen simplex chronicus: a proposal for a battery of selected allergens.
      • Sobel J.D.
      • Faro S.
      • Force R.W.
      • et al.
      Vulvovaginal candidiasis: epidemiologic, diagnostic, and therapeutic considerations.
      • Herbst R.
      Perineal streptococcal dermatitis/disease: recognition and management.
      A vulvar biopsy should be performed if the diagnosis remains unclear from the history and physical examination findings.
      • Lynch P.J.
      Lichen simplex chronicus (atopic/neurodermatitis) of the anogenital region.
      • Pincus S.H.
      Vulvar dermatoses and pruritus vulvae.
      Management of LSC includes patient education, avoidance measures, topical mid- to high-potency corticosteroids, topical anesthetic agents, and nighttime sedation. If a secondary infection is identified, systemic therapies are preferred to avoid further irritation caused by additional topical preparations. Recommendations include avoiding irritants and allergens indefinitely (improvement may not be noted for several months after avoidance); using minimal, unscented soaps (eg, Dove Sensitive Skin [Unilever] or Olay Sensitive Unscented [Procter & Gamble]); wearing cotton-lined underclothing that has been rinsed twice; and using nonsedating OTC antihistamines to break the scratch-itch cycle. Of the topical medications, creams are used for hair-bearing, keratinized epithelium, and ointments are used for modified mucous membranes. For mild symptoms, the recommended therapy is topical hydrocortisone, 2.5%, daily for 4 weeks; the dosage is then tapered to 2 to 3 times weekly.
      • Green C.
      • Colquitt J.L.
      • Kirby J.
      • Davidson P.
      Topical corticosteroids for atopic eczema: clinical and cost effectiveness of once-daily vs. more frequent use.
      For patients with moderate to severe symptoms, clobetasol propionate, 0.05%, or betamethasone dipropionate, 0.05%, is recommended to be used nightly, with reevaluation for tapering therapy after 1 month.
      • Neill S.M.
      Vulvar lichen sclerosus.
      For women who have superimposed vaginal yeast infections (positive results from culture or KOH testing), oral fluconazole (150-mg dose, repeated in 3-7 days) is recommended over topical azole antifungal agents because the latter may be irritating to the vulva.
      • Sobel J.D.
      • Faro S.
      • Force R.W.
      • et al.
      Vulvovaginal candidiasis: epidemiologic, diagnostic, and therapeutic considerations.
      Recurrent Candida albicans infections can be treated with weekly doses of fluconazole for 3 to 6 months. For the management of unusual strains of Candida that cause symptoms, sensitivities can be obtained and expertise gained from dermatologists and infectious disease experts. Heavy growth of Staphylococcus or Streptococcus species on culture should be treated with a 500-mg dose of cephalexin 3 times a day or a 500-mg dose of cefadroxil twice a day for 5 to 7 days. Alternatively, patients with penicillin allergy should be treated with azithromycin, 500 mg, on day 1 and then 250 mg daily for another 4 days.
      • Herbst R.
      Perineal streptococcal dermatitis/disease: recognition and management.
      Lichen simplex chronicus tends to persist or recur, so plans for ongoing assessment are necessary.

      Lichen Sclerosus

      Vulvar LS is a common, chronic, progressive dermatosis that causes intense pruritus, noncoital pain, dyspareunia, dysuria, and perianal discomfort (Figure 2).
      • Neill S.M.
      Vulvar lichen sclerosus.
      It is estimated to affect 1:30 to 1:59 perimenopausal/menopausal women.
      • Goldstein A.T.
      • Marinoff S.C.
      • Christopher K.
      • Srodon M.
      Prevalence of vulvar lichen sclerosus in a general gynecology practice.
      The disease extends beyond the vulvar region to involve the anogenital region in a figure-of-eight pattern in 85% to 90% of patients, with extragenital lesions noted in up to 15%.
      • Dalziel K.L.
      • Wojnarowska F.
      Long-term control of vulval lichen sclerosus after treatment with a potent topical steroid cream.
      A characteristic finding is thin, white, wrinkled skin. In active disease, ecchymoses, excoriations, fissuring, edema, and, occasionally, erosive changes are noted around the vaginal introitus and rectum. Chronic inflammation can lead to reabsorption or agglutination of the labia minora, clitoral hooding, burying of the clitoris, and introital stenosis. The vagina is rarely affected.
      • Longinotti M.
      • Schieffer Y.M.
      • Kaufman R.H.
      Lichen sclerosus involving the vagina.
      A genetic predisposition has been reported and an autoimmune cause suggested because LS has been associated with alopecia areata, vitiligo, thyroid disorders, pernicious anemia, and diabetes.
      • Cooper S.M.
      • Ali I.
      • Baldo M.
      • Wojnarowska F.
      The association of lichen sclerosus and erosive lichen planus of the vulva with autoimmune disease: a case-control study.
      A history and physical examination may be sufficient to diagnose LS; however, a biopsy may be required to exclude other causes of vulvar whitening, particularly vulvar intraepithelial neoplasia or a malignant neoplasm. The risk of vulvar squamous cell carcinoma (SCC) is estimated to be up to 5% in women with LS.
      • Neill S.M.
      • Lewis F.M.
      • Tatnall F.M.
      • Cox N.H.
      British Association of Dermatologists
      British Association of Dermatologists' guidelines for the management of lichen sclerosus 2010.
      Long-term monitoring should include vulvar examinations every 6 to 12 months indefinitely. Concerning lesions and persistent localized thickening require biopsy(s). Clinical signs of additional autoimmune conditions should prompt appropriate laboratory evaluations.
      • Cooper S.M.
      • Ali I.
      • Baldo M.
      • Wojnarowska F.
      The association of lichen sclerosus and erosive lichen planus of the vulva with autoimmune disease: a case-control study.
      An ultrapotent topical corticosteroid ointment (clobetasol) is the gold standard of therapy for LS.
      • Dalziel K.L.
      • Wojnarowska F.
      Long-term control of vulval lichen sclerosus after treatment with a potent topical steroid cream.
      The aim of treatment is to reduce symptoms (pruritus and pain) and signs (thinning, dyspigmentation, fissuring, ecchymoses, and hyperkeratosis) of active inflammation.
      • Neill S.M.
      • Lewis F.M.
      • Tatnall F.M.
      • Cox N.H.
      British Association of Dermatologists
      British Association of Dermatologists' guidelines for the management of lichen sclerosus 2010.
      A recent report provided evidence that long-term treatment of LS can reduce disease-associated risk of SCC.
      • Lee A.
      • Bradford J.
      • Fischer G.
      Long-term management of adult vulvar lichen sclerosus: a prospective cohort study of 507 women.
      Therefore, patient education regarding ongoing therapy is imperative. A treatment plan should include (1) good vulvar hygiene to eliminate irritants and overwashing the area and (2) clobetasol propionate, 0.05%, ointment (not cream) applied once to twice daily in a thin layer (pea-sized amount) for 4 to 6 weeks, followed by once-daily use at bedtime for 2 to 4 weeks, then treatment 2 to 3 times weekly continually.
      • Neill S.M.
      • Lewis F.M.
      • Tatnall F.M.
      • Cox N.H.
      British Association of Dermatologists
      British Association of Dermatologists' guidelines for the management of lichen sclerosus 2010.
      Long-term use of ultrapotent topical corticosteroids is safe because the modified mucous membranes of the vulva are resistant to the adverse effects of corticosteroids. Perianal skin is less resistant, so the frequency of application, the strength of the corticosteroid, or both should be reduced for treating perianal disease. An alternative therapy is topical tacrolimus, 0.1%, ointment applied twice daily.
      • Luesley D.M.
      • Downey G.P.
      Topical tacrolimus in the management of lichen sclerosus.
      Tacrolimus may initially cause burning on application, which often resolves in 4 to 5 days. Petroleum jelly or zinc oxide applied between applications of clobetasol or tacrolimus can provide an effective barrier, particularly if urinary incontinence is an issue. Occasionally, bacterial or Candida infections may become superimposed on vulvar dermatoses and should be treated as discussed previously herein for LSC.
      • Sobel J.D.
      • Faro S.
      • Force R.W.
      • et al.
      Vulvovaginal candidiasis: epidemiologic, diagnostic, and therapeutic considerations.
      • Herbst R.
      Perineal streptococcal dermatitis/disease: recognition and management.
      Rarely, LS is resistant to topical therapies attempted for 3 to 6 months; in this case, the patient should be promptly referred to a dermatologist with expertise in vulvar disease for consideration of systemic therapies, including methotrexate or mycophenolate mofetil.
      • Nayeemuddin F.
      • Yates V.M.
      Lichen sclerosus et atrophicus responding to methotrexate.
      • Deen K.
      • McMeniman E.
      Mycophenolate mofetil in erosive genital lichen planus: a case and review of the literature.

      Lichen Planus

      Lichen planus is an uncommon, debilitating vulvovaginal dermatosis occurring most often in women in their 50s and 60s (Figure 3). It is thought to arise from a T-cell–mediated autoimmune response against basal keratinocytes and is often associated with other autoimmune diseases.
      • Cooper S.M.
      • Ali I.
      • Baldo M.
      • Wojnarowska F.
      The association of lichen sclerosus and erosive lichen planus of the vulva with autoimmune disease: a case-control study.
      It can also affect the skin, oral mucosa, nails, scalp, esophagus, trachea, eyes, and ears.
      • Eisen D.
      The evaluation of cutaneous, genital, scalp, nail, esophageal, and ocular involvement in patients with oral lichen planus.
      Patients may have severe noncoital vulvar pain, burning, pruritus, dyspareunia, postcoital bleeding, dysuria, occasional vaginal discharge,
      • Eisen D.
      The evaluation of cutaneous, genital, scalp, nail, esophageal, and ocular involvement in patients with oral lichen planus.
      • Cooper S.M.
      • Haefner H.K.
      • Abrahams-Gessel S.
      • Margesson L.J.
      Vulvovaginal lichen planus treatment: a survey of current practices.
      and brightly erythematous erosions with white or violaceous borders.
      • Neill S.M.
      Erosive Lichen Planus: Diagnosis and Management.
      Erosive changes at the introitus are a common vulvar finding.
      • Neill S.M.
      Erosive Lichen Planus: Diagnosis and Management.
      Marked architectural changes, including loss of the labial minora, narrowing of the introitus, and vaginal agglutination, may occur. Although anal involvement is rare, vaginal involvement occurs in up to 70% of women with erosive LP.
      • Neill S.M.
      Erosive Lichen Planus: Diagnosis and Management.
      • Pelisse M.
      Erosive vulvar lichen planus and desquamative vaginitis.
      The vaginal epithelium can be friable, inflamed, and denuded, with a serosanguineous discharge. Adhesions and synechiae may develop, leading to narrowing or obliteration of the vagina. We recommend a complete examination for systemic disease and a biopsy of the vulvovaginal disease. The histologic-pathologic features of LP include degenerative changes of basal cells and bandlike subepithelial infiltration by lymphocytes.
      • Neill S.M.
      Erosive Lichen Planus: Diagnosis and Management.
      A biopsy for direct immunofluorescence studies may be helpful in the diagnosis.
      The goals of treatment for LP are controlling symptoms, slowing vulvovaginal architectural changes, and providing regular follow-up every 6 to 12 months indefinitely because LP carries a small risk of vulvar SCC.
      • Neill S.M.
      Erosive Lichen Planus: Diagnosis and Management.
      First-line therapy is a pea-sized amount of clobetasol, 0.05%, ointment applied once to twice daily to affected tissues.
      • Pelisse M.
      Erosive vulvar lichen planus and desquamative vaginitis.
      • Jensen J.T.
      • Bird M.
      • Leclair C.M.
      Patient satisfaction after the treatment of vulvovaginal erosive lichen planus with topical clobetasol and tacrolimus: a survey study.
      After 2 to 3 months, if the LP is responding to therapy, clobetasol use can be decreased to 2 to 3 times weekly continually. In resistant cases, second-line therapy is tacrolimus, 0.03% to 0.1%, ointment once to twice daily; however, burning on application may limit its use.
      • Jensen J.T.
      • Bird M.
      • Leclair C.M.
      Patient satisfaction after the treatment of vulvovaginal erosive lichen planus with topical clobetasol and tacrolimus: a survey study.
      If tolerated and effective, tacrolimus can be used once or twice daily for maintenance therapy. Various oral immunomodulatory and immunosuppressive agents, such as methotrexate, mycophenolate mofetil, acitretin, cyclosporine, and short courses of oral or intramuscular corticosteroids, have been tried, but reported results of treatment are limited.
      • Nayeemuddin F.
      • Yates V.M.
      Lichen sclerosus et atrophicus responding to methotrexate.
      • Deen K.
      • McMeniman E.
      Mycophenolate mofetil in erosive genital lichen planus: a case and review of the literature.
      The use of these therapies should be under the guidance of a vulvar dermatologist. For vaginal involvement, daily hydrocortisone suppositories (25 mg) at bedtime may be used, tapering to 2 to 3 times weekly.
      • Cooper S.M.
      • Haefner H.K.
      • Abrahams-Gessel S.
      • Margesson L.J.
      Vulvovaginal lichen planus treatment: a survey of current practices.
      • Neill S.M.
      Erosive Lichen Planus: Diagnosis and Management.
      Alternatively, we have used triamcinolone, 0.1%, ointment or clobetasol, 0.05%, ointment (pea-sized amount) applied onto a vaginal dilator and inserted into the vagina every other night with beneficial results. If the patient has substantial vaginal synechiae and desires vaginal penetration, a gynecologist or urogynecologist should be consulted regarding possible surgical separation of the synechiae, which would be followed by having the patient use a gentle dilator long-term (daily to every other day) to maintain vaginal patency. Women with LP, given its substantial morbidity, need regular follow-up assessment for disease progression, possible development of vulvar intraepithelial neoplasia or SCC, and ongoing emotional support.

      Conclusion

      Vulvovaginal changes related to hormonal decline and vulvar dermatoses are common. Clinicians should become comfortable inquiring about vulvovaginal symptoms and their effect on quality of life and sexual function. Careful physical assessment for signs of GSM and vulvar dermatoses should be performed, and long-term follow-up is important. Culture and biopsy samples should be obtained when indicated. The first-line therapies outlined previously herein are safe and effective tools for primary care physicians to use in managing the care of patients. If patients have treatment-resistant disease, we recommend referral to a dermatologist or a gynecologist with expertise in vulvovaginal disease.

      Supplemental Online Material

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