Atrophic vaginitis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Dima Nimri, M.D. [2] Aravind Kuchkuntla, M.B.B.S[3]

Synonyms and keywords: Atrophic vulvovaginitis; vaginal atrophy; urogenital atrophy; genitourinary syndrome of menopause

Overview

Atrophic vaginitis is defined as inflammation of the vaginal epithelium due to atrophy secondary to decreased levels of circulating estrogen. The features of this disease are estimated to be seen in 15% of premenopausal and 50% menopausal women. Patients present with the symptoms of vaginal dryness, itching, irritation, and dyspareunia. Diagnosis of atrophic vaginitis requires subjective assessment of the severity of symptoms to be correlated with the physical examination findings. The prominent physical examination findings include atrophic vaginal or vulvar tissue, pale, smooth and shiny vaginal epithelium with increased friability and inflammation with patchy erythema. The characteristic findings to confirm the diagnosis are: a left shift of the vaginal maturation index on a vaginal smear and a alkaline pH of the vagina. However, other secondary causes such as lichen sclerosus and lichen planus must be ruled before the confirmation of the diagnosis. The therapeutic management is based on the severity of the symptoms: lubricants are the first line of therapy for mild symptoms, in patients unresponsive to lubricants and with moderate to severe symptoms topical or oral estrogen therapy is effective for the management of patients . Majority of the patients have resolution of symptoms but due to the chronic nature of the condition it requires continuous treatment.

Historical Perspective

• In 1898, Charles B. Penrose described vaginitis in elderly women as senile Vaginitis. The areas of patchy inflammation were treated with 5% silver nitrate solution.
• In 1940, Jacob described the use of vaginal pH in determination of hypoestrogenic state.
• In 1947, Racoff gave a description the efficacy and safety of a synthetic estrogen, dienestrol for the treatment of menopausal syndrome and atrophic vaginitis is described.
• In 1963, topical Dinesterol vaginal cream was used for the treatment of senile vaginitis.
• In 1967, the relationship between the vaginal maturation index and estrogen therapy was described.
• In 2013, vulvovaginal atrophy is renamed as genitourinary syndrome of menopause.

Classification

Atrophic vaginitis is classified based on the symptom severity into:

• Mild: Patients present with symptoms related to sexual activity.
• Moderate to severe: Patients with persistent symptoms not related to sexual activity.

Pathophysiology

Pathogenesis

The pathogenesis of atrophic vaginitis is due to decreased estrogen levels. Estrogen is a vasoactive hormone, which increases blood flow and maintains vaginal lubrication through fluid transudation from blood vessels. The following are the manifestations of decreased estrogen levels:

• A hypoestrogenic state causes the breakdown of collagen and elastic fibres in the vagina resulting in vaginal epithelium to lose its rugae to become thin and pale or erythematous with fine petechial hemorrhages.
• Decreased glycogen content within the epithelium due to decreased thickness leads to less glycogen content available for the lactobacilli to utilize and turn it into lactic acid. Vaginal pH rises with a resultant overgrowth of other bacteria, such as group B streptococci, staphylococci and diptheroids leading to recurrent vaginal infections and UTI.

Genetics

There are no genetic factors associated with atrophic vaginitis.

Gross Pathology

Gross pathology findings in atrophic vaginitis include:

• Vaginal dryness
• Loss of vaginal rugae
• Changes in vaginal mucosa: pallor and friability or redness and petechiae of the mucosa

Microscopic Pathology

• Cytology of the vaginal cells show an increase in the parabasal cells and decreased superficial cells. In situations of low estrogen levels the vaginal epithelium ceases to produce superficial and intermediate squamous cells, leaving only the parabasal and basal cells lining the vaginal wall.

Associated Conditions

• Atrophic vaginitis is characterized with pale dry vaginal epithelium and increased pH. This predisposes the patients to recurrent vaginal infections with common pathogens such as candida, gardnerella vaginalis and trichomonas, therefore it is essential to rule out these infections.
• Scarring and atrophy are features of lichen sclerosis and lichen planus which can co-exist with atrophic vaginitis.

Causes

Atrophic vaginitis is caused by any condition that may lead to decreased circulating estrogen levels. A hypoestrogenic state may be due to ovarian failure or other causes:

Ovarian Failure	Other causes
Menopause	Elevated Prolactin during the Postpartum period
Premature Ovarian Failure Bilateral oophorectomy	Pituitary Adenoma
Chemotherapy and Radiation	Medications with anti-estrogenic effect

Epidemiology and Demographics

• Atrophic vaginitis is often an underdiagnosed condition and exact prevalence estimation is difficult because of the following reasons:
  • Majority of women are embarrassed to discuss their symptoms with doctors and few others think the symptoms associated with atrophic vaginitis as a process of natural aging.
  • Only 25% of patients with symptoms seek medical care.
  • Inadequate relief of symptoms with treatment.
• The features of atrophic vaginitis are estimated to be seen in 15% of premenopausal women and 40-54% of post-menopausal women.
• Based on self-reported symptoms of vaginal dryness, the prevalence of atrophic vaginitis ranged from 4% to 47%, depending on the stage of menopause (early or late menopause).

Risk Factors

The risk factors associated with vaginal atrophy are related to decreased estrogen levels, which can be due to menopause (most common cause) or other causes that may lead to hypoestrogenism or vaginal atrophy. These include:

• Menopause (most common cause)
• Bilateral oophorectomy
• Premature ovarian failure
• Decreased ovarian function, due to chemotherapy or radiation
• Medications with an anti-estrogenic side effect:
  • Tamoxifen
  • Danazol
  • Medroxyprogesterone acetate
  • GnRH agonsists: leuprolide, nafarelin, goserelin
  • GnRH antagonists: ganirelix
• Elevated prolactin levels during lactation
• Sexual abstinence
• Vaginal nulliparity
• Smoking
• Alcohol abuse
• Lack of exercise

Screening

There are no screening recommendations for atrophic vaginitis.

Differentiating atrophic vaginitis from other diseases

Atrophic vaginitis must be differentiated from other disease processes that may present with similar symptoms. These can be divided into 4 categories:

• Vaginal infections: Candida vulvovaginitis, bacterial vaginosis and trichomoniasis
• Vulvovaginal dermatoses: Lichen sclerosus, lichen planus and lichen simplex chronicus
• Cancer and precancerous lesions: Vulvar intraepithelial neoplasia, vulvar cancer and extramammary paget disease
• Others: Foreign body, sexual trauma and contact irritants

The conditions which may need to be differentiated from the atrophic vagintis and presents as vulvar or vaginal pruritus, dryness, discharge and dyspareunia include the following:

Disease	Findings
Atrophic vaginitis	Progressive symptoms Presents with yellow and malodorous vaginal discharge, vaginal dryness, postcoital bleeding, and dyspareunia with the signs of vaginal inflammation and elevated vaginal pH (>5) Diagnosis is critical and laboratory tests help to confirm hypoestrogenic state
Trichomoniasis	Presents with purulent, malodorous, thin discharge associated with burning, pruritus, and dysuria, with the signs of vaginal inflammation and elevated vaginal pH (>4.5) Motile trichomonads on wet mount are demonstrated Positive culture(Gold standard) Positive nucleic acid amplification test (NAAT)
Bacterial Vaginosis	Presents with dysuria, vaginal discharge Fishy odor on whiff test Normal vaginal PH (<4.5) On speculum examination signs of vaginal inflammation are demonstrated
Candida Vulvovaginitis	Presents with vulvar pruritus and cottage cheese-like vaginal discharge with no or minimal odor with normal vaginal pH (4-4.5) Presence of Candida on wet mount (adding 10% KOH destroys the cellular elements and facilitates recognition of budding yeast, pseudohyphae, and hyphae)
Lichen Sclerosus	Affects pre-pubertal and post-menopausal women, reflecting its nature of occurrence in low estrogen states Pruritus is the predominant symptom, burning with urination and dyspareunia can also be seen On examination characteristically the lesions follow a figure of eight pattern affecting the areas around the vagina and anus Signs of active disease include white atrophic plaques with cigarette-paper wrinkling, petechiae, fissures and erosions can be demonstrated Examination findings of chronic disease include clitoral hood phimosis and labia minora resorption Diagnosis confirmed with skin punch biopsy
Lichen Planus	Affects pre-menopausal and post menopausal women T-cell mediated inflammatory disease affecting mucosal membranes In erosive form patients present with vulvar pain, dyspareunia and dysuria Non-erosive form presents with pruritus On examination, lesions appear as red plaques or erosions, with overlying white violaceous or reticular plaques( Wickham Striae) Diagnosis confirmed by shave or punch biopsy
Lichen simplex chronicus	On examination, the lesion appear as thick, erythematous lichenified skin (epidermal thickening and accentuation of skin markings) Due to long-term rubbing or scratching secondary to conditions such as recurrent yeast infections, contact dermatitis, psychiatric illness
Contact dermatitis	It could be allergic or irritant contact dermatitis Presents with redness, swelling, and pruritus Ocassionally blistering and painful bright red swelling can be seen
Vulvar intraepithelial neoplasm	Bimodal peak is observed between 40-44 years and above 55 years Red, white, or dark raised or eroded multifocal lesions
Vulvar Cancer	Presents as a solitary ulcer with raised or indurated edge Histologically it can be a melanoma, squamous cell carcinoma, basal cell carcinoma or neuroendocrine cancer
Extramammary Paget disease	Seen in postmenopausal women On examination it appears as a erythematous plaque with typical white scaling known as “cake-icing scaling” Biopsy is characterized by the presence of intraepithelial mucin-producing neoplastic cells known as Paget cells

Natural History, Complications and Prognosis

Natural History

Atrophic vaginitis is a chronic progressive medical problem affecting postmenopausal women and in younger women with low estrogen levels. Women present with vaginal dryness, pruritus, urinary disturbances and dyspareunia.

Prognosis

Atrophic vagnitis is a chronic disease and requires continuous treatment with estrogen or other alternatives. Majority of the patients have significant resolution of the symptoms with treatment, however the symptoms recur once the treatment is stopped.

Complications

Complications of atrophic vaginitis include:

• If left untreated, the greatest impact is the lack of sexual enjoyment and other effects such as sleep disturbances.
• Stress urinary incontinence
• Urge incontinence
• Pelvic organ prolapse
• Recurrent urinary tract infections

Diagnosis

History and Symptoms

Symptoms of atrophic vaginitis can be divided into three categories:

• External genital symptoms:
  • Vaginal dryness
  • Vaginal irritation
  • Vaginal pruritus
  • Yellowish or brown vaginal discharge
• Sexual symptoms:
  • Painful sexual intercourse (dyspareunia)
  • Postcoital bleeding
  • Lack of arousal
  • Pelvic pain
• Urological symptoms:
  • Burning on urination (dysuria)
  • Increased Urinary frequency
  • Increased Urinary urgency
  • Nocturia
  • Urinary incontinence
  • Recurrent urinary tract infections (UTI)

Physical Examination

Physical examination in women with atrophic vaginitis includes a general inspection of the external genitalia, a speculum examination.

• Physical examination in women with atrophic vaginitis begins with inspection of the external genitalia. Findings include sparsity of pubic hair, dryness of the labia and/or fusion of the labia minora.
• Gynecologic examination is carried using a small speculum to avoid damage to the atrophic vaginal or vulvar tissue. Vaginal epithelium may be atrophic and appear pale, smooth and shiny. Other findings include increased friability, inflamed epithelium with patchy erythema and petechiae.
• Other findings may include: pelvic organ prolapse, such as cystocele and/or rectocele, urethral polyps or eversion of the urethral mucosa.

Laboratory Findings

Assessment of Vaginal Atrophy

• Vaginal Cytology: It demonstrates a decrease in the superficial squamous cells and an increased parabasal cells.
• Vaginal Maturation Index(VMI): It represents the percentage of the parabasal, intermediate and superficial squamous cells. It read from left to right as follows, for example if its represented as 0/35/65-it means the smear has 0% parabasal cells, 35% intermediate cells and 65% superficial cells. A shift to the left indicates vaginal atrophy.
• Vaginal Maturation Value (VMV): It is calculated using a formula: 0 * %parabasal cells + 0.5 * %intermediate cells + 1.0 * superficial cells divided by 2.
  • A lower VMV indicates a low number of superficial cells indicating hypoestrogenic state.
• Vaginal pH : Normal vaginal pH is acidic and is maintained by the lactobacillus flora by the breakdown of glucose (from the vaginal epithelial cell glycogen-the level of which is based on the estrogen) to lactic acid.
  • In lower estrogen states, the vaginal pH is typically greater then 5; higher than normal due to lower levels of glycogen in the epithelial cells. It is a useful and inexpensive test in the absence of bacterial vaginosis to indicate vaginal atrophy.
• Wet mount of vaginal smear : Demonstrates the paucity of lactobacillus.
• FSH Level: Estimation of FSH is not neccessary for the diagnosis of hypoestrogenic state as alkaline pH of vaginal secretions is equally sensitive.

Ultrasound

An ultrasound of the uterus may demonstrate thinning of the endometrium lining to 4-5mm.

Treatment

Medical Therapy

Atrophic vaginitis is a chronic condition requiring continuous treatment. The choice of therapy is based on the severity of the symptoms and associated factors such as history of hormone dependent cancer.

• In patients with mild symptoms, the vaginal lubricants are the first line therapeutic choice to relieve symptoms.
• In patients with moderate to severe symptoms unresponsive to lubricants, the topical estrogen or oral estrogen therapy is preferred. In patients with menopause, the topical agents are preferred over systemic therapy.
• In patients with the history of harmone dependent cancer, discuss the risks and benefits with the patient and the oncologist before initiation of therapy.
• Progesterone is not indicated in patients with topical low dose estrogen therapy, however endometrial safety studies are lacking in this group who receive treatment greater than a year.
• Patients at a higher risk of developing endometrial cancer secondary to estrogen therapy, annual transvaginal ultrasound is recommended .
• All the patients with post-menopausal bleeding with a uterus, should be evaluated with transvaginal ultrasound and endometrial biopsy.
• The following table is the description of available options for the treatment of atrophic vaginitis:

Treatment Modality	Improvement in symptoms	Advantages	Limitations
Topical Estrogen (Creams and Estradiol releasing vaginal rings)	Restores vaginal epithelium and associated vaginal vasculature Improves vaginal secretions Lowers vaginal pH and restores healthy vaginal flora Relieves urinary symptoms Effective resolution of dyspareunia, vaginal itching, and dryness	No systemic absorption 80 to 90% patients have symptomatic improvement	Creams can be messy to use Rings are expelled in patients with cystocele and rectocele Side effects include vaginal secretion, vaginal spotting, and genital pruritus
Oral Estrogen Therapy	In addition to the changes with topical estrogen other actions include: Relief from hot flashes and protection from osteoporosis	Treats menopausal symptoms like hot flashes	Adverse effects include: Breast tenderness with or without enlargement, vaginal bleeding or spotting, nausea, and weight gain Contraindications to estrogen inlcude: known or suspected cases of breast cancer, estrogen-dependent cancers, undiagnosed vaginal bleeding, history of thromboembolism, endometrial hyperplasia or cancer, hypertension, hyperlipidemia, liver disease,history of stroke, coronary heart disease, pregnancy, smoking in those age >35 years, migraines with neurologic symptoms, and acute cholecystitis/cholangitis.
Selective estrogen receptor modulator Ospemifene	Safe in treating vulvovaginal atrophy Treats dyspareunia by improving vaginal structure and pH	Less than 1% risk of developing endometrial hyperplasia after treatment for 52 weeks	Increased risk of venous thromboembolism
Laser Therapy	Fractional microablative carbondioxide laser improves vascularity, glycogen storage, extracellular matrix production cellular proliferation Improvement of vaginal epithelial thickness and viability	Improvement of symptoms sustained at 12 weeks after therapy Improved sexual activity	Lack of long term evidence on efficacy and safety Common adverse effect is hot flashes Contraindicated in patients with DVT
Tibolone Synthetic steriod	Improves VMI, sexual desire with the androgenic activity Improvement in urinary symptoms	Improvement of urinary symptoms No endometrial hyperplasia	Lack of long term evidence on efficacy Increases recurrence risk of breast cancer in patients with history of breast cancer Vaginal spotting and bleeding
Oxytocin	Oxytocin gel improves vaginal secretions and epithelial thickness and pH	No endometrial hyperplasia	No long term evidence
Intravaginal dehydroepiandrosterone	Improves vaginal epithelium thickness and secretions	None	Lacks long term studies
Moisturizers and lubricants	Polymers adhere to the epithelial and mucin improving vaginal lubrication	Temporary relief for patients with mild symptoms	No effect on reversal of atrophic changes

Assessment of Response to treatment

• Atrophic vaginitis being a chronic disease, continuous therapy is recommended. Response to treatment is assessed by the following:
  • Vaginal Maturation Index(VMI) assessment
  • Vaginal pH assessment

Prevention

Primary Prevention

There are no primary preventive measures for atrophic vaginitis.

Secondary Prevention

The following behavioral changes are advised to slow down the progression of atrophic vaginitis, and also help in maintenance of normal vaginal tissue:

• Encouraging sexual activity helps in the maintenance of vaginal elasticity and lubrication in response to sexual stimulation.
• Stress reduction therapy is helpful in patients with non-organic causes of vaginal dryness.
• Cessation of smoking
• Encourage the use of looser undergarments; it increases the vascularity and prevents infections.

References

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