Atrophic Vaginitis

Etiology

A hypoestrogenic state may be part of natural physiological menopause or induced (secondary to surgical, radiation, or chemotherapy treatments). Premenopausal women may develop a temporary hypoestrogenic state while lactating. Other conditions, such as exposure to medications, radiation therapy, chemotherapy, or hypothalamic dysfunction, may also result in a hypoestrogenic state. Medications that may induce a hypoestrogenic state include selective estrogen receptor modulators, selective estrogen receptor degraders, and antigonadotropins. Decreased estrogen levels lead to changes in the vaginal environment, which causes a shift in the normal flora. Typically, there is a decrease in Lactobacillus spp. resulting in overgrowth of skin and rectal pathogens.

Epidemiology

An estimated 10% to 50% of all postmenopausal women develop atrophic vaginitis.[1][2][3] Additionally, 15% of premenopausal women develop genitourinary syndrome symptoms. While these numbers are high, the prevalence may be significantly higher than reported, and many women do not discuss their symptoms.[4]

Pathophysiology

The female genitalia, the lower urinary tract, and the surrounding vasculature develop from the same embryologic tissue with similar estrogen receptors. Estrogen receptor alpha is primarily found in the uterus and pituitary gland. The estrogen receptor alpha is present during premenopause and postmenopause. Estrogen receptor beta is primarily found in the ovary. The estrogen receptor beta is present predominately in the premenopausal state, leading to the ovarian failure state experienced in menopause.[4] Hypoestrogenic state results in the fusion of collagen fibers and fragmentation of elastin fibers in vulvovaginal tissue and decreased squamous cells, resulting in decreased mucosal elasticity and decreased rugae, and narrowing of the vagina.

Premenopausal vaginal tissues mature in normal estrogen ranges of 30 to 40 pg/ml, which allows for adequate growth of vaginal epithelium with superficial squamous cells containing glycogen. Lactobacilli spp. utilize the glycogen from the cells and convert it into lactic acid, creating a slightly acidic environment with a pH of 3.5 to 5.0. Free glycogen is also associated with lower pH and higher levels of lactobacillus. In menopause, vaginal tissue is exposed to estrogen less than 20pg/ml resulting in fewer superficial squamous epithelial cells with an increase in parabasal cells. The higher concentration of parabasal cells and reduced Lactobacillus spp. leads to decreased lactic acid conversion, producing a higher pH of 5.0 to 7.5 environment. (1,2) The consequence of elevated vaginal pH is a shift in normal flora, Lactobacilli spp., and more susceptible to other pathogens such as Gardnerella, Prevoltella, Atopobium, and Streptococcus.[2][5][3]

Histopathology

Atrophic pattern histologic findings demonstrate decreased superficial squamous cells, increased parabasal cells, and decreased lactobacilli. However, there are normal to low numbers of neutrophils.[6] Increased neutrophils are noted in atrophic vaginitis when compared to the vaginal atrophy pattern.[1] The hypoestrogenic state results in the loss of dermal collagen, elastin fibers, and blood vessels in the lamina propria. These changes result in decreased elasticity and vascularity. Decreased vascularity, in response to low estrogen levels, results in thin friable vaginal mucosa and decreased secretions.

History and Physical

Postmenopausal women are typically older than 50 years old unless they incur induced menopause. Postmenopausal women have low estrogen levels, precipitating genitourinary syndrome symptoms. Symptoms appear in the early to late postmenopausal stage. The STRAW staging system is useful for healthcare members and patients to evaluate menstrual transition and postmenopause.[7] Atrophic vaginitis symptoms include vulvovaginal dryness, pruritis, dyspareunia, abnormal vaginal discharge, post-coital pain of the labia minora or deeper in the vaginal vault, recurrent urinary tract infections, urethral pain, hematuria, urinary incontinence.[1][8][9] These symptoms may be progressive, or the patient may have just noticed the changes.

Evaluation

Age-related changes include a decrease in hair distribution and pigment of the hair. Decreased subcutaneous fat leads to a decreased volume of the mons pubis, labia majora, and labia minora. There may be fissuring or other signs of friction of the external genitalia or the introitus. Inflammation may occur, resulting in erythematous patches with or without petechia or friable tissue. Collection of pH, vaginal swabs for the Vaginal Maturation Index, and cultures are obtained before the speculum exam. The exam reveals hypoestrogenic tissue with decreased secretions and elasticity, narrowing the introitus and being more susceptible to friction. Vaginal tissue is pale pink with diminished vaginal secretions. pH greater than 5.0 or decreased Follicular stimulating hormone is consistent with lower estrogen states. The pH of vaginal secretions should be obtained before the speculum exam. The vaginal maturation index (VMI) is the proportional relationship between the superficial, intermediate, and parabasal cells of the vaginal tissue. A decrease in estrogen is associated with increased parabasal cells, resulting in lower VMI. The hypoestrogenic state is noted as a VMI of 0 to 49, however, the hyperestrogenic state is noted as a VMI 65 to 100.[1][10]

Treatment / Management

Treatment of atrophic vaginitis begins with a trial of intravaginal estrogen. Intravaginal estrogen products, Conjugated estrogen cream, estradiol cream, estradiol tablet, estradiol vaginal ring, and estradiol transdermal patch show equivocal relief of symptoms and improvement in acidification of vaginal tissues.[6][7] Use the lowest effective dose to reduce systemic estrogen exposure. Taper the estrogen therapy after symptoms and function improve.[8] Some patients may require maintenance therapy indefinitely. Contraindications to estrogen therapy include a history of estrogen receptor-positive breast cancer, other estrogen-dependent cancers (subtypes of breast and uterine cancers), thromboembolism disorders, liver disease, undiagnosed vaginal bleeding, endometrial hyperplasia, heart disease, pregnancy, migraines with aura, or allergy to the estrogen or the carrier product.[11] The vaginal maturation index may be used as a clinical measurement to evaluate the response to estrogen therapy. Lactobacillus predominance is associated with fewer genital symptoms compared to a change in pH.[2] Additional or alternative therapy includes selective estrogen receptor modulators, tissue-selective estrogen complexes, estriol, platelet-rich plasma, herbals, and other natural products.[9] Ospemifene, a selective estrogen receptor modulator, is approved by the FDA for adjunctive therapy in patients with dyspareunia or for use in patients who are not candidates for estrogen therapy. A patient may use lubricants for symptomatic improvement or if contraindicated to estrogen therapy. Lubricants can improve symptoms; however, no chemical or histologic changes occur. Other non-hormonal forms of treatments include fractional micro-ablative carbon-dioxide laser therapy and transcutaneous temperature-controlled radiofrequency with external and internal treatments that improve vaginal dryness, vulvovaginal laxity, and dyspareunia for 6 to 12 months.[12][13][14][15][16](A1)

Differential Diagnosis

Differentials include vaginal atrophy, vulvovaginal atrophy, vulvovaginal lichen planus or sclerosis, vulvar dermatitis, vulvovaginal candidiasis, vulvodynia, inflammatory vaginitis without atrophy, desquamative inflammatory vaginitis, vulvovaginal neoplasm, sexually transmitted infection, other infections, and urogenital dysfunction.

Pertinent Studies and Ongoing Trials

Microablative carbon-dioxide laser therapy has been noted to improve histologic changes in the lamina propria with the remodeling of collagen fibers and blood vessels and improve the vaginal flora with increased Lactobacillus spp.[15][17]

Radiofrequency temperature therapy shows potential as an alternative treatment for atrophic vaginitis. However, due to the small study sizes, follow-up studies are needed to evaluate the histological changes that improved the regeneration of collagen and blood vessels.[12][13][14]

Prognosis

Many women see improvement with the use of intravaginal estrogen. Those refractory to treatment or who experience incomplete resolution may start adjunctive therapy with ospemifene. Risk factors include no vaginal births, therefore, no stretching of the vaginal canal. Cigarette smoking causes vasoconstriction, which decreases secretions and exacerbates symptoms.

Complications

Untreated atrophic vaginitis leads to persistent pruritis, which may cause scarring from scratching. Thinned mucosa may result in abrasions or fissures. The patient may continue to have other genitourinary complaints.