Local Estrogen Treatment Options for Vaginal Atrophy

CLINICAL ACTIONS:

A growing number of estrogen treatment options are available for postmenopausal vaginal atrophy. Vulvovaginal atrophy is a common symptom of atrophic vaginitis (also referred to as the genitourinary syndrome of menopause or GSM) and can occur in both perimenopausal and postmenopausal women. If a patient reports vaginal dryness, consider the following

• Establish a diagnosis of postmenopausal atrophy based on thorough history and physical exam
  • Confirm with an appropriate pelvic/ vaginal exam
• Discuss use of estrogen, understanding that for some women based on medical history, systemic estrogen might not be an appropriate option
  • Even with a personal history of cancer, local estrogen may be an appropriate treatment (see ‘Key Points’ and ‘Related ObG Topics’ below) depending on the clinical scenario
• Vaginal estrogens can be prescribed as
  • A cream inserted twice weekly using an applicator
  • A tablet inserted with an applicator
  • A soft gel pellet inserted twice weekly with no applicator (FDA approved May, 2018)
  • Ring made of silicone elastomere containing a drug core of estradiol hemihydrate (replaced every 3 months)

Local Estrogen Routes and Dosing for GSM

• Estradiol-17β ring (releases 7.5 micrograms/d)
  • Replace every 3 months
• Estradiol vaginal tablet (10 micrograms/d)
  • Place nightly for 2 weeks
  • Maintenance is one tablet 2 times/week
  • Note: this is the corrected dose in ACOG PB 141
• Estradiol-17β cream (0.1 mg active ingredient/g)
  • 2-4 g/d for 1 to 2 weeks
  • Gradually reduce to ½ initial dosage for 1 – 2 weeks
  • Maintenance is 1 g, 1 to 3 times/week
• Conjugated estrogen cream (0.625 mg/g)
  • 0.5–2 g/d for 21 days then off for 7 days
  • In practice during maintenance therapy, most women apply 1 – 3 times /week
• Vaginal inserts (4-μg and 10-μg)
  • 1 vaginal insert daily for 2 weeks
  • Maintenance is 1 insert twice weekly

SYNOPSIS:

Patients may experience vaginal atrophy as itching, dryness or pain during sexual activity. Vaginal estrogen has been shown to improve moderate to severe menopausal vaginal atrophy. Options for topical estrogen treatment are increasing. Women’s healthcare professionals need to confirm appropriate use of estrogen and help patients identify which treatment option will work best for their situation and lifestyle.

KEY POINTS:

• During perimenopause and menopause, estrogen levels decline in vaginal tissues
  • Referred to as vulvovaginal atrophy (VVA), this may result in discomfort or pain during intercourse or general dryness and discomfort
• If patient complains of dyspareunia, and clinical examination is consistent with postmenopausal vaginal atrophy / atrophic vaginitis, local estrogen is the first line and most effective treatment
  • Estrogen treatment may not be appropriate or desired by all patients
• Ascertain if estrogen is an appropriate option for the patient
  • Screen for a history of breast or uterine cancer
  • History of blood clots
  • Liver conditions
• If patient is appropriate for treatment with local estrogen, offering the spectrum of choices can help a patient identify the product that will work best for them
• While there is a theoretical concern regarding systemic estrogen absorption and risk for uterine cancer, based on evidence, professional organizations  consider “the addition of progestin for endometrial protection is not needed” (ACOG)

Differentiating factors include

• Creams
  • Can be used on the vulva as well as internally in the vagina
• Tablets or caplets
  • Some can be used during the day
  • Some tablets may need to be used at night because of the way they dissolve
• Applicators
  • May be an issue of patient preference and warrants discussion
• Ring
  • Benefits include ease of use
  • For some women, there may be structural issues related to comfort and/or retention  (e.g., short or narrow vagina / prolapse)
• Make patients aware that there are non-estrogen options available for use by women who are not appropriate candidates for local estrogen including
  • Prasterone | Ospemifene
• Laser Treatments have been advocated as a possible treatment, however VVA not a currently FDA-approved indication

Learn More – Primary Sources:

ACOG Practice Bulletin 141: Management of Menopausal Symptoms

Practice Bulletin 141: Management of Menopausal Symptoms: Correction

A Randomized, Multicenter, Double-Blind, Study to Evaluate the Safety and Efficacy of Estradiol Vaginal Cream 0.003% in Postmenopausal Women with Vaginal Dryness as the Most Bothersome Symptom.

FDA Highlights of Prescribing Information for IMVEXXY

Drugs@FDA: Estring

Drugs@FDA: Estrace Cream

Drugs@FDA: Premarin Vaginal Cream 

Drugs@FDA: Vagifem Tablet 

Estradiol vaginal inserts (4 µg and 10 µg) for treating moderate to severe vulvar and vaginal atrophy: a review of phase 3 safety, efficacy and pharmacokinetic data

Reviewing the options for local estrogen treatment of vaginal atrophy