Definition
Vaginal oestrogen refers to topical estrogen therapy administered directly into the vaginal canal, vulva, or lower urinary tract to manage urogenital symptoms of menopause. Unlike systemic estrogen therapy, vaginal estrogens deliver low-dose, localized hormone exposure with minimal systemic absorption, aiming to restore the estrogen-deficient vaginal epithelium in postmenopausal women.
Forms of Vaginal Oestrogen
Multiple pharmaceutical preparations exist
Vaginal Creams
Conjugated estrogens (Premarin Vaginal Cream)
Estradiol (Estrace Cream)
Apply intravaginally using applicator
Vaginal Tablets
Estradiol (Vagifem, Vagirux)
Insert using a disposable applicator
Vaginal Rings
Estradiol (Estring)
Delivers consistent dose over 90 days
Placed and left inside the vagina
Vaginal Gels or Inserts
Ospemifene and other novel SERMs available orally but designed to impact vaginal epithelium
DHEA (prasterone vaginal insert) acts as precursor to estrogen and androgen
Mechanism of Action
Estrogen deficiency following menopause leads to thinning of the vaginal epithelium
Reduces glycogen content, increases vaginal pH, decreases lactobacilli, and predisposes to inflammation and infection
Vaginal estrogen binds to estrogen receptors ER-α and ER-β in urogenital tissues
Stimulates proliferation and maturation of epithelial cells
Increases local blood flow and collagen synthesis
Restores normal vaginal pH by promoting lactic acid-producing bacteria
Reduces local inflammation and improves secretory function
Indications
Genitourinary Syndrome of Menopause (GSM)
Vaginal dryness
Vulvovaginal atrophy
Dyspareunia
Burning and itching
Vaginal irritation
Postcoital bleeding
Recurrent urinary tract infections
Urinary urgency and frequency
Urinary incontinence
Not indicated for systemic menopausal symptoms like hot flashes or night sweats unless used with systemic therapy
Dosage and Administration
Vaginal Creams
Estradiol cream
Initial 0.5 to 1 g daily for 2 weeks
Maintenance 0.5 g two to three times weekly
Conjugated estrogens
Initial 0.5 g daily for 21 days then 7-day break
Maintenance 0.5 g two to three times per week
Vaginal Tablets (Estradiol 10 mcg)
Initial one tablet daily for 2 weeks
Maintenance one tablet twice weekly
Administered via disposable applicator
Vaginal Ring (Estring 7.5 mcg/24h)
Inserted once every 90 days
No removal required until replacement
Vaginal Insert (Prasterone 6.5 mg)
Daily insertion before bedtime
Treatment Duration
Can be continued long term
Lowest effective dose for the shortest duration
Regular evaluation to reassess need
Pharmacokinetics
Systemic absorption is minimal
Estradiol levels typically remain within postmenopausal range
Vaginal ring provides steady release
Creams and tablets have transient peaks
Higher doses or damaged epithelium may increase systemic exposure
Little impact on hepatic metabolism or clotting proteins
Contraindications
Undiagnosed abnormal genital bleeding
Known or suspected estrogen-dependent malignancy
Active or history of breast cancer
Active deep vein thrombosis or pulmonary embolism
Active arterial thromboembolic disease
Liver dysfunction or disease
Known hypersensitivity to product ingredients
Pregnancy
Warnings and Precautions
Should not be used for cardiovascular protection
Systemic risks may increase if high doses are used
Minimal systemic absorption reduces but does not eliminate risks
Patients with a history of estrogen-sensitive cancers should consult oncology
Use caution in women with predisposition to thromboembolism
Endometrial safety
Unopposed estrogen may stimulate endometrium
However, low-dose vaginal estrogens have not shown increased risk in studies
Progestogen co-therapy not routinely needed at low doses
Adverse Effects
Local
Vaginal irritation or discharge
Burning or itching
Spotting or breakthrough bleeding
Urinary tract discomfort
Pelvic cramping
Systemic
Rare but may include nausea headache breast tenderness
Minimal risk of thromboembolism or endometrial hyperplasia with low-dose regimens
Overdose
No serious toxicity expected from local use
Overuse may increase systemic estrogen levels
Symptoms include breast tenderness fluid retention nausea
Treatment involves dose reduction or discontinuation
Drug Interactions
Minimal systemic absorption leads to low interaction potential
Concomitant use with vaginal antifungals or lubricants may alter absorption
Strong CYP3A4 inducers may reduce systemic estradiol levels if significant absorption occurs
Tamoxifen or aromatase inhibitors may have antagonistic effect on local estrogenic activity
Use in Special Populations
Pregnancy
Contraindicated
Lactation
Minimal data
Not recommended as estrogen can reduce milk production
Geriatrics
Well tolerated and indicated for postmenopausal urogenital symptoms
Renal Impairment
No specific dose adjustment
Hepatic Impairment
Avoid in severe impairment due to altered estrogen metabolism
Monitoring Parameters
Symptom relief assessment vaginal dryness dyspareunia
Periodic pelvic exams
Assessment for signs of endometrial stimulation if systemic symptoms occur
Monitor for vaginal bleeding or discharge
Evaluate need for continued treatment periodically
Breast exams and mammography per national guidelines
Comparative Pharmacology
Compared to systemic estrogen therapy
Vaginal route has lower systemic risk profile
Minimal hepatic first-pass effect
Fewer systemic side effects
Compared to lubricants
More effective for moderate to severe vaginal atrophy
Lubricants provide only temporary symptom relief
Compared to ospemifene
Ospemifene is oral SERM with systemic activity
May be preferred when estrogen is contraindicated
Compared to prasterone
Prasterone (DHEA) provides hormonal precursor to local estrogen and androgen synthesis
Less estrogenic but beneficial in vulvovaginal atrophy
Clinical Guidelines
North American Menopause Society NAMS recommends vaginal estrogen as first-line therapy for GSM
Progestin not required when using low-dose local estrogen
FDA advises lowest effective dose for shortest duration
European Menopause and Andropause Society EMAS supports extended use in symptomatic women with regular reassessment
NICE UK supports use for vaginal atrophy regardless of time since menopause onset
Formulations Available
Creams
Estradiol cream 005%
Conjugated estrogen cream 0625 mg/g
Tablets
Vagifem 10 mcg
Vagirux
Rings
Estring 75 mcgday estradiol
Femring 005 mgday or 01 mgday (systemic effect)
Inserts
Prasterone DHEA 65 mg daily
Regulatory and Legal Status
Prescription-only medication
FDA and EMA approved for GSM
Not a controlled substance
Widely available globally
Over-the-counter lubricants may be used adjunctively
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