Introduction

Genitourinary syndrome of menopause, a group of chronic, progressive, hypoestrogenic conditions, includes vulvovaginal atrophy, atrophic vaginitis, and bladder and urethral dysfunction. Urogenital tissues, derived from similar embryologic tissues, develop and mature in response to estrogen. In hypoestrogenic states, these tissues undergo physiologic changes. Atrophic vaginal changes include thinning of the vaginal epithelium, decreased vaginal rugae and elasticity, and decreased vaginal secretions. Atrophic vaginitis is a symptomatic inflammatory process involving the thinned vaginal epithelium affecting some pre-menopausal and up to 50% of post-menopausal women.

Etiology

A hypoestrogenic state may be part of natural physiologic menopause or induced menopause secondary to surgical, radiation, or chemotherapy treatments. Premenopausal women may develop a temporary hypoestrogenic state while lactating. Medications that may cause 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 cause a shift in the normal vaginal flora.

Epidemiology

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

Besides natural menopause, risk factors for atrophic vaginitis include low estrogen levels and elevated prolactin in the postpartum time frame, lack of vaginal childbirth, low frequency of sexual intercourse, sedentary lifestyle, autoimmune diseases, previous radiation or chemotherapy, smoking, and alcohol abuse.[5]

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 found mainly 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.

The normal estrogen ranges in premenopausal vaginal tissue are 30 to 40 pg/ml. This 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 normal vaginal 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 levels of less than 20 pg/ml resulting in fewer superficial squamous epithelial cells and 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. (1,2) The consequence of this elevated vaginal pH is a shift in normal flora from Lactobacilli spp. This makes the vagina more susceptible to other pathogens such as Gardnerella, Prevoltella, Atopobium, and Streptococcus.[2][6][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.[7] 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 over 51 years old unless they incur induced menopause at an earlier age. 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.[8] Atrophic vaginitis symptoms include vulvovaginal dryness, burning, irritation, pruritis, dyspareunia, abnormal vaginal discharge, post-coital pain, recurrent urinary tract infections, urethral pain, hematuria, and urinary incontinence.[1][9][10] These symptoms may be progressive over time. Urinary symptoms such as frequency, urgency, and recurrent urinary tract infections may also be present.

On physical exam, atrophic vaginitis frequently presents with vaginal dryness, vaginal shortening and stenosis, the fragility of tissues, labial fusion, clitoral hood retraction, loss of vaginal rugae, erythema or petechiae, and leukorrhea.[5]

Evaluation

Age-related changes include a decrease in hair distribution and pigment of the hair in the pubic area. 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 vaginal pH, vaginal swabs for the Vaginal Maturation Index, and vaginal pathogen swabs may be obtained. The exam of a patient with atrophic vaginitis reveals hypoestrogenic tissue with decreased secretions and elasticity, narrowing of the introitus. Vaginal tissue is pale pink with diminished vaginal secretions. A 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 of 65 to 100.[1][11]

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.[7][8] Use the lowest effective dose to reduce systemic estrogen exposure. Taper the estrogen therapy after symptoms and function improve.[9] 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.[12] 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.[10] 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.[13][14][15][16][17]

Differential Diagnosis

The differential diagnosis of vaginal atrophy includes vulvovaginal lichen planus or sclerosis, other vulvar dermatoses, vulvovaginal candidiasis, vulvodynia, inflammatory vaginitis without atrophy, desquamative inflammatory vaginitis, vulvovaginal neoplasms, sexually transmitted infections, and other infections.

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.[16][18]

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.[13][14][15]

Prognosis

Many women see improvement with the use of intravaginal moisturizers and local estrogen. Those people who are refractory to treatment or who experience incomplete resolution may start a trial of therapy with oral 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 may lead to persistent pruritis, dyspareunia, and scarring from scratching. Thinned vaginal mucosa may result in abrasions or fissures. The patient may also continue to have other genitourinary complaints, especially dysparuenia.

Deterrence and Patient Education

Atrophic vaginitis is an inflammatory condition associated with low estrogen levels. Pre-menopausal women may experience symptoms that postmenopausal women more commonly experience. Treatment is typically initiated with localized estrogen therapy to provide symptom relief. Adjunctive therapy with estrogen modulator receptors or radiofrequency treatment may further improve symptoms.

Patient education plays a crucial role in managing atrophic vaginitis, a condition characterized by thinning, drying, and inflammation of the vaginal walls due to decreased estrogen levels. Educating patients about the importance of regular gynecological check-ups can aid in early detection and treatment. Preventive measures include lifestyle modifications such as avoiding irritants like harsh soaps and perfumed products, which can exacerbate symptoms. Additionally, informing patients about the benefits of using vaginal moisturizers and lubricants can help alleviate discomfort. Emphasizing the role of hormone replacement therapy or other medical treatments tailored by healthcare providers ensures patients are well-informed about their options, fostering proactive management and improved quality of life.

Pearls and Other Issues

Patients should be encouraged to have regular gynecological exams to detect early signs of atrophic vaginitis, as atrophic vaginitis not only affects physical health but can also impact psychological well-being and sexual relationships. Addressing these aspects in patient education and treatment plans is important. Cultural and individual differences in perceptions of menopausal symptoms and treatments should be considered to provide personalized and effective care. Some patients may be hesitant to use hormone therapy due to concerns about potential risks. It's crucial to provide clear information about the safety and benefits of low-dose, localized treatments. Regular follow-up is essential to monitor the effectiveness of the treatment and adjust as needed.Over-reliance on non-hormonal treatments may lead to insufficient relief of symptoms in patients who require estrogen therapy.

Enhancing Healthcare Team Outcomes

Atrophic vaginitis is not a life-threatening disease, but it can significantly negatively affect patients' quality of life if not diagnosed and treated appropriately. Interprofessional communication and patient education are essential. The condition can be recognized and treated by multiple clinicians, including primary care, obstetricians/gynecologists, dermatologists, and surgeons. A proper diagnosis can be challenging without a dedicated history taking and physical exam, and misdiagnosis can lead to unnecessary referrals and procedures. With adequate interprofessional communication and patient education, atrophic vaginitis can be diagnosed and treated for improved patient outcomes.

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Disclosure: Shelley Flores declares no relevant financial relationships with ineligible companies.

Disclosure: Carrie Hall declares no relevant financial relationships with ineligible companies.