Genitourinary Syndrome of Menopause
A comprehensive clinical guide to understanding, diagnosing, and managing vulvovaginal atrophy and related menopausal changes affecting the urogenital system.
Department of Obstetrics and gynecology
prof Mykhailo Medvediev
Understanding GSM
What is GSM?
Genitourinary syndrome of menopause encompasses symptoms and signs caused by hypoestrogenic changes to the vulva, vagina, urethra, and bladder in menopausal patients.
The syndrome includes genital symptoms (dryness, burning, irritation), sexual symptoms (lack of lubrication, discomfort, impaired function), and urinary symptoms (urgency, dysuria, recurrent infections).
Patients may present with some or all signs and symptoms, which must be bothersome and not better explained by another diagnosis.
Evolution of Terminology
The term GSM was introduced in 2014, replacing "vaginal atrophy." However, controversy remains as it includes normal age-related changes and symptoms not necessarily attributable to menopause.
The Core OutcoMes in MenopAuse (COMMA) consortium developed a Core Outcome Set based on international consensus across 21 countries, identifying eight key outcomes for clinical trials.
Core Outcomes of Interest
Sexual Function
Pain with sex and vulvovaginal dryness
Comfort Measures
Vulvovaginal discomfort, irritation, and urinary symptoms
Patient Experience
Most bothersome symptom changes and distress levels
Treatment Response
Satisfaction with treatment and side effects
Pathophysiology: The Role of Estrogen
GSM results predominantly from declining serum estrogen levels, most commonly due to natural or surgical menopause. Androgens also play a role in maintaining genitourinary tissue structure and function.
Steroid receptor locations vary within the genitourinary system. Estrogen receptor density is higher in the vagina compared with external genitalia, while androgen receptor density shows the opposite pattern.
Premenopausal Estrogen Levels
In premenopausal patients, estradiol is the predominant circulating estrogen. Serum concentrations fluctuate throughout the menstrual cycle, with peaks during ovulation and the mid-luteal phase.
Estrogen's Essential Functions
Structural Integrity
Maintains collagen content affecting thickness and elasticity
Tissue Hydration
Maintains acid mucopolysaccharides and hyaluronic acid for moist surfaces
Vascular Support
Maintains optimal genital blood flow
Microbiome Health
Maintains healthy vaginal microbiome
The Healthy Premenopausal Vagina
The nonkeratinized stratified squamous epithelium of the vagina is thick, rugated, and rich in glycogen. Glycogen from sloughed cells serves as substrate for Döderlein lactobacilli.
These lactobacilli convert glucose into lactic acid, creating an acidic vaginal environment. This acidity maintains normal vaginal flora and protects against vaginal and urinary tract infections.
Impact of Menopause on Estrogen
95%
Estradiol Decline
Approximate reduction from premenopausal to postmenopausal state
5
Postmenopausal Level
Average estradiol concentration in pg/mL after menopause
Most estradiol assays lack sufficient sensitivity to accurately detect postmenopausal levels. Therefore, measurement of estradiol levels should not be routine in clinical care.
Hypoestrogenic Changes to Vaginal Tissue
01
Epithelial Thinning
Loss of superficial epithelial cell layer, potentially absent in severe atrophy
02
Structural Changes
Loss of rugae and elasticity, with increased subepithelial connective tissue
03
Dimensional Changes
Shortening and narrowing of vaginal canal with loss of distensibility
04
Secretion Reduction
Vaginal secretions decrease from 3-4 g/4 hours to 1.7 g/4 hours
05
pH Elevation
Increase in vaginal pH to ≥5
Consequences of Epithelial Thinning
Thinning of the vaginal epithelium increases susceptibility to trauma, resulting in bleeding, petechiae, and ulceration with pressure from sexual activity or Pap testing.
The thinned epithelium exposes underlying connective tissue, which is more vulnerable to inflammation or infection. Low glycogen content leads to reduced lactic acid production by lactobacilli.
Microbiome Shift and pH Changes
The Cascade Effect
Reduced glycogen leads to decreased lactic acid production, causing vaginal pH to rise. This pH change encourages overgrowth of nonacidophilic coliforms and reduction of lactobacillus species.
The altered environment predisposes patients to infection by skin and rectal flora including Gardnerella vaginalis, streptococci, staphylococci, coliforms, and diphtheroids.
Clinical Implications
These shifting flora and resulting inflammatory changes were the source of the older term "atrophic vaginitis."
However, interventions to treat through vaginal microbiome manipulation remain limited.
Urinary Tract Involvement
Urinary tract structures derive from the same embryologic origin as the genital tract and contain estrogen receptors. The bladder, urethra, pelvic floor musculature, and endopelvic fascia are all affected by hypoestrogenism.
Possible consequences include urethral discomfort, urinary frequency, hematuria, dysuria, and increased frequency of urinary tract infection.
Menopause and Pelvic Floor Disorders
Increased Risks
Menopause increases risk for both pelvic organ prolapse and stress urinary incontinence
Oral Estrogen Concerns
May result in development or exacerbation of urinary incontinence
Vaginal Estrogen Benefits
May improve continence, decrease urgency/frequency, and reduce recurrent UTIs
Prolapse Treatment
Neither systemic nor vaginal estrogen appears effective for pelvic organ prolapse
The Role of Androgens
While estrogen's effects are well-described, emerging data suggest androgens also play a role in urogenital health. Androgen receptors have been reported in the mucosa, muscularis, and adventitial layers of the vagina.
Both estrogen and androgen receptors exist in the genitourinary tract, and androgens are precursors to estrogen synthesis. Evidence suggests androgens like testosterone may have direct effects on tissue, not just through aromatization.
Epidemiology: Prevalence of GSM
85%
Vaginal Dryness
Affects women over 40 years of age
59%
Dyspareunia
Additional women reporting painful intercourse
77%
Irritation
Women reporting vaginal itching and irritation
Internet surveys reveal high prevalence rates, though actual numbers vary by study population and methodology.
Age Distribution of Symptoms
A longitudinal study illustrated how vaginal dryness symptoms increase dramatically through the menopausal transition, with the highest rates occurring three years after menopause.
Quality of Life Impact
An international survey of over 4,000 menopausal patients found that 39 percent experienced menopause-related vaginal discomfort. Of those with discomfort, 52 percent reported their quality of life had been affected.
A systematic review of 27 studies found GSM symptoms were reported by 40 to 60 percent of peri- and postmenopausal females, with many endorsing four or five symptoms simultaneously.
Etiologies of Hypoestrogenism
Natural Menopause
The most common cause of hypoestrogenism
Bilateral Oophorectomy
Surgical removal of both ovaries
Primary Ovarian Insufficiency
Early loss of ovarian function
Treatment-Induced
Ovarian failure from radiation, chemotherapy, or uterine artery embolization
Medication-Induced Hypoestrogenism
Antiestrogenic Medications
  • Tamoxifen
  • Aromatase inhibitors
  • Danazol
  • Medroxyprogesterone acetate
  • GnRH agonists (leuprolide, nafarelin, goserelin)
  • GnRH antagonists (ganirelix)
Other Causes
  • Postpartum reduction, especially during lactation
  • Prolactin elevation from hypothalamic-pituitary disorders
  • Hypothalamic amenorrhea
  • Severe systemic lupus or rheumatoid arthritis with glucocorticoid therapy
Transgender Considerations
Transgender women with neovaginas created through penile inversion vaginoplasty lack mucus-producing glands. Those with colovaginoplasty experience mucus production, but not in response to sexual stimulation.
The impact of hormonal and surgical gender-affirming treatment on microbiota is not yet well understood. Whether non-Lactobacillus dominant microbiome in trans people constitutes BV requiring treatment needs further study.
Modifying Factors Beyond Estrogen
Vaginal Nulliparity
May intensify vaginal atrophy symptoms
Sexual Activity
Abstinence exacerbates changes; activity helps preserve epithelium
Cigarette Smoking
Causes relative estrogen deficiency and may reduce vaginal perfusion
Comorbidities
Depression and urinary incontinence may worsen symptom impact
Clinical Presentation of GSM
By definition, patients with GSM are symptomatic. However, not all patients with atrophic changes on pelvic examination are symptomatic.
Up to 70 percent of patients with symptoms do not discuss their condition with a healthcare provider. Many believe symptoms are an expected part of aging, while cultural, religious, and societal beliefs may create embarrassment.
Common Symptoms of GSM
Vulvovaginal dryness
The most common symptom during daily activities
Decreased vaginal lubrication
Particularly noticeable during sexual activity
Dyspareunia
Vulvar or vaginal pain at introitus or within vagina
Vulvovaginal bleeding
Including postcoital bleeding and labial fissures
Sexual dysfunction
Decreased arousal, orgasm, or sexual desire
Urinary symptoms
Frequency, urgency, dysuria, and recurrent infections
Symptom Progression
Symptoms accompanying vaginal atrophy are usually progressive and worsen with duration of hypoestrogenism. Early signs include decreased lubrication upon sexual arousal, often one of the first indicators of estrogen insufficiency.
Evaluation: Taking a Comprehensive History
Patients who are peri- or postmenopausal should be asked about GSM symptoms during routine clinical visits. Many patients do not bring symptoms to clinician attention.
Medical history should include obstetric and gynecologic history, menstrual history, and assessment of menopausal status. Clinicians should ask about response to previous interventions and take a pertinent sexual history.
Key History Components
Symptom Assessment
Painful vulvar symptoms and those suggesting infection or inflammatory conditions
Irritant Exposure
Use of perfumes, powders, panty liners, soaps, deodorants, spermicides, lubricants, tight clothing
Treatment History
Including pelvic radiation exposure
Quality of Life
Degree of discomfort, behavioral responses, impact on daily activities and relationships
Pelvic Examination Findings
External Genitalia
  • Labia minora resorption or fusion
  • Tissue fragility, fissures, petechiae
  • Introital retraction
  • Loss of hymenal remnants
  • Prominence of urethral meatus
  • Urethral eversion or prolapse
Vaginal Assessment
  • Vulvovaginal pallor or erythema
  • Loss of vaginal rugae
  • Decreased secretions and lubrication
  • Decreased elasticity
  • Thin, white, nonodorous discharge
  • Spasm of levator muscles
Examination Considerations
Exercise caution when performing speculum and bimanual examinations in patients with severe atrophic changes, as gentle contact can cause pain and bleeding. Assess for introital stenosis before attempting speculum insertion.
A one-finger gloved examination is often better tolerated than a two-finger exam. Use a lubricated narrow speculum, typically a Pederson rather than Graves speculum.
When Examination is Too Uncomfortable
01
Stop and Assess
If insertion is too distressing, stop and ask if patient is too uncomfortable to continue
02
Consider Treatment First
For some patients, treatment of vaginal atrophy may be necessary before complete examination
03
Alternative Evaluation
Rectal examination or transabdominal pelvic ultrasound may allow evaluation when vagina is too stenotic
04
Examination Under Anesthesia
May be necessary when office examination cannot be completed and is deemed essential
Classic Vaginal Findings
Classic findings include a pale, dry vaginal epithelium that is smooth and shiny with loss of most rugation. If inflammation is present, there may be patchy erythema, petechiae, visible blood vessels, friability, bleeding, and discharge.
The vagina may be shortened, narrowed, and poorly distensible. The cervix may become flush with the vault, making it difficult to identify the cervical os. Vaginal fornices may become obliterated.
Laboratory Testing: Limited Role
Generally Not Necessary
Laboratory tests usually not needed for diagnosis and evaluation of GSM
Exclusion Testing
May be used to exclude other etiologies under consideration
Research Applications
Used to assess efficacy of treatments in research studies
Vaginal pH Testing
Normal Estrogenized Vagina
pH typically ranges from 4.0 to 4.5, though broader ranges (3.5 to 5) have been reported
Postmenopausal Changes
Vaginal pH may reach 5.5 to 6.8 or higher, especially in those not on estrogen therapy
A pH ≥5 in absence of other causes can indicate vaginal atrophy
Maturation Index
The maturation index represents the proportion of parabasal, intermediate, and superficial cells in each 100 cells counted on a vaginal smear. It quantifies cell types of the vaginal epithelium.
In premenopausal patients with adequate estrogen, intermediate and superficial cells predominate. In patients with vaginal atrophy, parabasal cells increase while superficial cells decrease.
Maturation Index Values
0
Parabasal Cells
Typical count in premenopausal patients
65
Early Menopause
Parabasal cell count in early menopausal patients
100
Advanced Atrophy
Maturation index may consist entirely of parabasal cells
Making the Diagnosis
GSM is a clinical diagnosis made in patients who are in a hypoestrogenic state and have characteristic symptoms and findings on pelvic examination.
Patients may present with some or all signs and symptoms, which must be bothersome and should not be better accounted for by another diagnosis. The presence of symptoms in a perimenopausal or postmenopausal patient is sufficient.
Differential Diagnosis
Vaginitis and Vaginosis
Candidiasis, bacterial vaginosis, trichomoniasis, desquamative inflammatory vaginitis
Vulvar Dermatitis
Response to environmental agents causing contact or irritant dermatitis
Vulvar Lichen Sclerosus
Chronic inflammatory condition affecting vulvar tissue
Vulvovaginal Lichen Planus
Inflammatory condition with distinct clinical features
Additional Differential Considerations
Genital Tract Ulcers
May be due to herpes lesions or systemic disease like Crohn disease
Genital Tract Bleeding
May result from trauma, infection, or malignancy requiring evaluation
Vulvodynia
Chronic vulvar pain of unknown cause
Urinary Tract Issues
Frequent UTIs from anatomic, hygiene issues, or bladder pain syndrome
Department of Obstetrics and gynecology
prof Mykhailo Medvediev