What is the recommended dosing schedule for Vagifem (estradiol vaginal tablet) in post‑menopausal women with vulvovaginal atrophy, including initial and maintenance dosing?

Vagifem Dosing for Postmenopausal Vulvovaginal Atrophy

Vagifem (10 μg estradiol vaginal tablet) should be administered once daily for 2 weeks as initial therapy, followed by twice-weekly maintenance dosing thereafter. 1, 2, 3

Initial (Loading) Phase

• Administer one 10 μg estradiol tablet intravaginally daily for the first 2 weeks to rapidly restore vaginal tissue health and achieve symptom relief 1, 2, 3
• This loading phase allows for adequate tissue response before transitioning to maintenance therapy 3

Maintenance Phase

• After the initial 2-week period, reduce frequency to one 10 μg tablet twice weekly (e.g., Monday and Thursday) for ongoing symptom control 1, 2, 3
• This maintenance regimen provides an annual estradiol exposure of only 1.14 mg, representing an ultra-low dose with minimal systemic absorption 4

Clinical Reassessment Timeline

• Reassess symptom improvement at 6–12 weeks after initiating therapy to determine treatment efficacy 1, 5
• Optimal symptom relief typically requires 6–12 weeks of consistent use as vaginal tissue restoration is gradual 1

Safety Profile of This Regimen

• Low-dose vaginal estradiol tablets do not raise serum estradiol concentrations, demonstrating minimal systemic absorption 1
• No increased risk of endometrial hyperplasia or endometrial carcinoma has been documented with this dosing schedule 1
• Endometrial thickness may increase slightly (approximately 1.1 mm) during the initial 2-week daily dosing phase but returns to baseline levels once twice-weekly maintenance dosing begins 3

Comparative Efficacy and User Preference

• Vagifem tablets are as effective as vaginal estrogen creams for symptom relief but offer superior user-friendliness 2, 6
• 90% of patients report Vagifem as easier to use compared to 55% for estrogen cream, with significantly fewer hygienic problems (0% vs 23%) 2
• Vagifem demonstrates greater acceptability, hygiene, and ease of use compared to vaginal promestriene cream at both 4 and 12 weeks 6

Important Clinical Considerations

• Continue water-based or silicone-based lubricants during sexual activity throughout the initial treatment period to provide immediate comfort while vaginal tissue restoration is ongoing 1
• For women who have undergone hysterectomy, estrogen-only vaginal therapy (like Vagifem) is specifically recommended due to its more favorable risk-benefit profile 1
• Do not prescribe if contraindications exist: history of hormone-dependent cancers, undiagnosed abnormal vaginal bleeding, active liver disease, recent thromboembolic events, or active/recent pregnancy 1, 5

Special Population: Breast Cancer Survivors

• Non-hormonal options (moisturizers 3–5 times weekly plus lubricants) must be tried first for at least 4–6 weeks before considering vaginal estrogen in women with hormone-positive breast cancer 1
• If non-hormonal measures fail, low-dose vaginal estrogen may be considered after thorough discussion of risks and benefits with the patient and oncologist 1
• A large cohort study of nearly 50,000 breast cancer patients followed for up to 20 years showed no increased risk of breast cancer-specific mortality with vaginal estrogen use 1
• For women on aromatase inhibitors specifically, vaginal DHEA (prasterone) may be preferable as an alternative to estradiol 1