CONCISE REVIEW FOR CLINICIANS
Vulvovaginal Atrophy

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Vulvovaginal atrophy (VVA) is a common and underreported condition associated with decreased estrogenization of the vaginal tissue. Symptoms include dryness, irritation, soreness, and dyspareunia with urinary frequency, urgency, and urge incontinence. It can occur at any time in a woman's life cycle, although more commonly in the postmenopausal phase, during which the prevalence is close to 50%. Clinical findings include the presence of pale and dry vulvovaginal mucosa with petechiae. Vaginal rugae disappear, and the cervix may become flush with the vaginal wall. A vaginal pH of 4.6 or more supports the diagnosis of VVA. Even while taking systemic estrogen, 10% to 20% of women may still have residual VVA symptoms. Breast cancer treatment increases the prevalence of VVA because the surgical, endocrine, and chemotherapeutic agents used in its treatment can cause or exacerbate VVA. Local estrogen treatment for this group of women remains controversial.

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PREVALENCE

Vulvovaginal atrophy can occur at any time in a woman's life cycle, although it is more common in the postmenopausal phase, a time of hypoestrogenism. Other causes of a hypoestrogenic state include lactation, various breast cancer treatments, and use of certain medications. In situations other than menopause, VVA may resolve spontaneously when estrogen levels are restored.

Numerous retrospective studies have evaluated the prevalence of symptoms of VVA (Table 1).3, 4, 5, 6, 7, 8, 9, 10 Although

PHYSIOLOGY

Vulvovaginal atrophy occurs under conditions of hypoestrogenism. In the premenopausal state, estradiol levels fluctuate from 10 to 800 pg/mL (to convert to pmol/L, multiply by 3.671),11 depending on when measured during the cycle. In the postmenopausal state, estradiol levels are typically less than 30 pg/mL. After menopause, circulating estradiol derives from estrone, which is peripherally converted in adipose tissue from adrenal androstenedione.

The vaginal epithelium is a stratified squamous

SYMPTOMS

The initial symptom is often lack of lubrication during intercourse. Eventually, persistent vaginal dryness may occur. Thinning of the epithelial lining may also cause pruritus, soreness, and a stinging pain in the vaginal and vulvar area, which, in turn, may further contribute to dyspareunia. Vaginal spotting, due to small tears in the vaginal epithelium, may also occur. Women with VVA may report a thin yellow or grey watery discharge secondary to the rise in pH that accompanies VVA.17

Women

CLINICAL FINDINGS

Clinical findings include atrophy of the labia majora and vaginal introitus. The labia minora may recede. Vulvar andvaginal mucosae may appear pale, shiny, and dry; if there is inflammation, they may appear reddened or pale with petechiae. Vaginal rugae disappear, and the cervix may become flush with the vaginal wall. Vaginal shortening and narrowing tend to occur.20

A thin watery yellow vaginal discharge may be observed. A urethral caruncle, a small, soft, smooth friable red outgrowth along the

CLINICAL TESTS

The diagnosis of VVA is a clinical one. However, 2 tests may be used to support the diagnosis: a vaginal pH and a vaginal maturation index (VMI). To assess pH, a piece of litmus paper is placed on the lateral vaginal wall until moistened. A pH of 4.6 or greater indicates VVA, assuming the patient does not have bacterial vaginosis. Premenopausal women without VVA typically have a pH of 4.5 or less.12

The VMI (Figure 2) is the criterion standard for VVA confirmation but is generally not used or

DIFFERENTIAL DIAGNOSIS

The differential diagnosis includes other conditions that cause chronic vaginal and vulvar itching, discharge, or pain (eg, vaginal infections, irritants, and vulvovaginal dermatoses). Vaginal infections can be caused by bacteria, viruses, protozoa, and fungi. The 3 most common vaginal infections are Candida vulvovaginitis, bacterial vaginosis, and trichomoniasis. Bacterial vaginosis may result from atrophic changes in the vagina. Irritants that can cause chronic vaginal itch include perfumes,

Nonhormonal Treatments

Current over-the-counter treatments include nonhormonal vaginal moisturizers for VVA symptoms and lubricants fordyspareunia. Vaginal moisturizers, which are water based, are available as liquids, gels, or ovules inserted every few days. Vaginal moisturizers can be safely used long term, but they need to be used regularly for optimal effect.

Vaginal lubricants are shorter acting than moisturizers and are applied at the time of sexual activity to reduce dyspareunia. They can be either water or

SYSTEMIC ABSORPTION OF VAGINAL HORMONAL PREPARATIONS

An important concern about treatment safety relates to the extent of systemic absorption of vaginal estrogens. The conclusion from several studies comparing different doses of estradiol vaginal tablets24, 25 or different vaginal estrogen preparations (conjugated estrogens and estradiol vaginal tablets)26 is that systemic absorption occurs, but to a limited extent. Labrie et al26 showed that levels of estradiol increased on average from a baseline (pretreatment) level of 3 pg/mL to 17 pg/mL on

PRACTICAL ISSUES

Because all low-dose vaginal estrogens appear comparable in efficacy for the treatment of VVA, the choice of estrogen formulation is determined by the clinician and by each woman's preferences. Estrogen creams are currently the least costly and most widely used but require commitment to regular use for sustained effect. Dosing vaginal creams can be confusing because the dose of active estrogen cream is specified in milligrams, the dose of base cream in grams, and applicator volume in

SYSTEMIC ESTROGEN AGENTS AND VVA

Systemic estrogen therapy, in the form of patches, oral agents, or a higher-dose vaginal ring, is sometimes used for VVA, especially when the patient also has hot flashes. However, 10% to 20% of women may have residual VVA symptoms even while taking systemic estrogen.27 These women will require administration of local vaginal estrogens alone or along with systemic therapy for relief of VVA symptoms.

Two studies have shown that oral hormone therapy (HT) may worsen symptoms of urinary

BREAST CANCER AND VVA

Currently, more than 2 million women in the United States have a history of breast cancer. In breast cancer survivors, the estimated prevalence of vaginal atrophy, by symptom report, ranges from 23% to 61%.8 Prescribing even very low-dose localized estrogen treatments for these patients can cause concern because of the potential for systemic absorption.

Concern about the provision of any form of estrogen, either systemic or local, to breast cancer survivors contributes to the high incidence of

COMPLEMENTARY AND ALTERNATIVE MEDICINE

Complementary and alternative medicine products have been extensively studied in the treatment of hot flashes, but less information is available on their use in VVA. One study found that Vitamin E and phytoestrogen applied locally as a gel improved the symptoms of VVA.42 An evaluation of VVA was undertaken in a cross-sectional study of 60 women, half of whom had taken 1,25-dihydroxyvitamin D (0.5 μg/d of calcitriol) orally for at least 1 year and half of whom had not. The prevalence of vaginal

FUTURE STUDIES

Future studies will continue to explore the use of even lower doses of vaginal estrogens. The efficacy and safety of 10-μg vaginal tablets of low-dose estradiol for the treatment of VVA were evaluated in a 2009 study; after 12 weeks of therapy, significant improvements in symptoms, pH, and VMI were observed, with no adverse effects.45 In a recent study comparing treatment with 25 μg of estradiol, 10 μg of estradiol, and placebo, Bachmann et al46 found that both active groups experienced

CONCLUSION

Vulvovaginal atrophy, a common and often underreported condition, occurs in women who experience hypoestrogenic states. Systemic treatment, when prescribed for menopausal symptoms, may not be sufficient to control VVA. Local estrogens include creams, tablets, and rings, all of which are equally effective. Thus, patient preference will guide the choice. A growing number of women are at risk of developing VVA because of decreased use of systemic HT and increased use of SERMs, AIs, and

CME Questions About Vulvovaginal Atrophy

  • 1.

    A 58-year-old woman, who has been taking oral hormone therapy (HT) for successful control of hot flashes and night sweats, reports vaginal itching, burning, and dyspareunia. Clinical examination reveals a pale shiny vulva and petechiae in the vagina, consistent with vulvovaginal atrophy (VVA).

    Which one of the following treatments would be most effective for managing this patient's symptoms?

    • a.

      Increase her current dose of oral HT

    • b.

      Decrease her current dose of oral HT, and recommend

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    On completion of this article, you should be able to (1) recognize the common symptoms and signs of vulvovaginal atrophy, (2) evaluate the role of tests used in its identification, and (3) recommend effective treatment options.

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