What is Imvexxy?
Imvexxy is an FDA-approved, ultra-low-dose 17β-estradiol vaginal softgel insert (available in 4 μg and 10 μg doses) specifically designed to treat moderate to severe dyspareunia (painful intercourse) associated with postmenopausal vulvar and vaginal atrophy (VVA), with the key advantage of providing effective local vaginal estrogen therapy without increasing systemic estrogen levels. 1, 2
Formulation and Mechanism
Imvexxy consists of small softgel capsules containing solubilized estradiol that are inserted vaginally twice weekly (every 3-4 days). 2
The formulation uses MIGLYOL 812 N to keep the estradiol in solution, which allows for effective local delivery to vaginal tissues. 2
Pharmacokinetic studies demonstrate that these low doses of estradiol do not increase systemic blood levels of estrogens above baseline values, greatly reducing the likelihood of unwanted systemic effects. 2
Clinical Efficacy
In the REJOICE trial, responder rates (defined as having ≥2 of the following: vaginal superficial cells >5%, vaginal pH <5.0, or dyspareunia improvement of ≥1 category) were 74-82% with Imvexxy versus 24% with placebo at week 2, and 72-80% versus 33% at week 12. 1
Positive treatment responses were 9- to 14-fold higher with vaginal estradiol than with placebo at week 2, and 5- to 8-fold higher at week 12. 1
A positive response at week 2 predicted a positive response at week 12 (odds ratio 13.1; 95% CI, 8.8-19.7), indicating rapid onset of action. 1
Place in Treatment Algorithm
Imvexxy represents a second-line treatment option for postmenopausal women with moderate to severe dyspareunia who have not responded adequately to first-line non-hormonal therapies (vaginal moisturizers 3-5 times weekly and water-based lubricants during sexual activity). 3
For women with hormone-positive breast cancer who are symptomatic and not responding to conservative measures, low-dose vaginal estrogen like Imvexxy can be considered only after thorough discussion of risks and benefits. 3, 4
For women on aromatase inhibitors, estriol-containing preparations may be preferable to estradiol formulations, as estriol cannot be converted to estradiol, though vaginal DHEA (prasterone) is another alternative option. 3
Safety Profile
The ultra-low doses (4 μg and 10 μg) represent the lowest approved estradiol doses available, with annual estradiol exposure of only 1.14 mg for the 10 μg tablet formulation. 5
Minimal estradiol absorption occurs with these ultra-low doses, causing no increased risk of endometrial hyperplasia or carcinoma. 5
Large studies of topical vaginal estrogen show no concerning safety signals regarding stroke, venous thromboembolism, invasive breast cancer, or colorectal cancer. 4
Contraindications
History of hormone-dependent cancers (particularly breast cancer) remains a contraindication, though individual risk-benefit discussions may allow use in select breast cancer survivors with severe symptoms unresponsive to non-hormonal options. 3, 4
Undiagnosed abnormal vaginal bleeding, active or recent pregnancy, and active liver disease are contraindications. 3
Advantages Over Other Formulations
The softgel insert format provides convenient twice-weekly dosing compared to daily applications required by some vaginal creams. 2
The solubilized estradiol formulation allows for effective local delivery without the messiness associated with traditional vaginal creams. 2
The ultra-low doses minimize systemic absorption concerns while maintaining clinical efficacy for vaginal symptoms. 5, 2