What is the mechanism of action of this treatment?

The most common treatments for painful intercourse, such as estradiol vaginal inserts, work by addressing the underlying causes of vulvar and vaginal atrophy, which often contribute to dyspareunia. Estradiol, a form of estrogen, is absorbed through the vaginal mucosa, where it helps to restore the thickness and elasticity of the vaginal epithelium, increase lubrication, and reduce inflammation. This is crucial for patients as it directly alleviates the symptoms of dryness and irritation that cause pain during intercourse. Topical treatments like lidocaine can also be used to numb the area and provide immediate pain relief by blocking nerve signals. These mechanisms are essential for improving the quality of life and sexual health of patients suffering from painful intercourse.

What side effects are associated with this type of intervention?

Common treatments for painful intercourse, such as estradiol vaginal inserts, can have side effects including local irritation, vaginal discharge, and yeast infections. Systemic absorption of estradiol may also lead to side effects like breast tenderness, headache, and nausea. It is important for patients to discuss these potential side effects with their healthcare provider to determine the most appropriate treatment for their condition.

What prior FDA approvals exist?

The FDA has approved several treatments for dyspareunia, particularly in postmenopausal women. One notable approval is for estradiol vaginal inserts, such as IMVEXXY®, which are designed to treat vulvar and vaginal atrophy by delivering low doses of estradiol directly to the vaginal tissue. These inserts work by replenishing estrogen locally, which helps to restore the vaginal epithelium, increase lubrication, and reduce pain during intercourse. The pharmacokinetics involve minimal systemic absorption, focusing the effect on the vaginal area, while the pharmacodynamics involve estrogen receptor activation leading to tissue regeneration and symptom relief.

What other types of research exist?

Promising novel alternatives for treating painful intercourse in 2024 include advanced hormonal therapies such as estradiol vaginal inserts and GnRH antagonists like Elagolix. These treatments aim to address hormonal imbalances and tissue changes associated with conditions like vulvar and vaginal atrophy and endometriosis.

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Hormone Therapy

Estradiol Inserts for Painful Intercourse

Phase 3

Waitlist Available

Research Sponsored by Teva Pharmaceuticals USA

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Moderate to severe symptom of vaginal pain associated with sexual activity considered the most bothersome vaginal symptom (dyspareunia) of VVA by the patient at screening visit. (i.e., a VVA Symptom Self-Assessment Questionnaire score of 2 or 3) (Appendix B).

Females aged 40-75 years inclusive who are postmenopausal, with at least:

Must not have

Premenopasual, perimenopausal, pregnant or lactating patient or planning a pregnancy

History of Protein C, Protein S, or antithrombin deficiency, or other thrombophilic disorder

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 15 days

Awards & highlights

Pivotal Trial

Summary

This trial tests a new version of a drug to ensure it works just as well as an existing one for patients who need it. It checks if the new drug is equally effective and safe.

Who is the study for?

This trial is for postmenopausal women aged 40-75 experiencing painful intercourse due to vaginal atrophy. Participants must have a stable blood pressure, normal PAP smear and mammogram results, be sexually active, and not have used certain hormonal treatments recently. Women with a history of certain cancers, significant heart or liver disease, drug abuse within the last year, or those who are pregnant cannot participate.

What is being tested?

The study tests if Estradiol Vaginal Inserts (4mcg) are as effective as IMVEXXY® in treating dyspareunia caused by vulvar and vaginal atrophy. It's randomized and double-blind; participants will receive either the test medication or placebo without knowing which one they're getting to compare outcomes fairly.

What are the potential side effects?

Potential side effects may include typical estrogen-related reactions such as nausea, headaches, breast tenderness, spotting or bleeding from the vagina. There could also be local irritation where the product is applied. Serious but rare risks involve blood clots or stroke.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

I experience moderate to severe pain during sex, which is my main concern.

Select...

I am a woman aged 40-75 and have gone through menopause.

Select...

I experience moderate to severe pain during sex, which is my main concern.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I am premenopausal, perimenopausal, pregnant, breastfeeding, or planning to become pregnant.

Select...

I have a history of blood clotting disorders.

Select...

I do not have any current vaginal infections.

Select...

I have been diagnosed with endometrial hyperplasia in the past or currently.

Select...

I have or might have had breast cancer.

Select...

I have had unexplained vaginal bleeding or am at high risk for endometrial cancer.

Select...

I have had a cancer that grows with estrogen, like endometrial cancer.

Select...

I do not have liver or kidney problems.

Select...

I have a history of blood clots.

Select...

I have had a stroke or a mini-stroke in the past.

Select...

I have had a heart attack or heart disease.

Select...

I have a skin condition affecting my vulva or vagina.

Select...

I have unusual growths in my vulva or vagina not caused by thinning tissues.

Select...

I have a history of ongoing or frequent pelvic pain.

Select...

I have painful genital warts or sores.

Select...

I have been diagnosed with interstitial cystitis.

Select...

I have unclear or suspicious breast exam or mammogram results.

Select...

My uterus is intact with an endometrial thickness of 4mm or more.

Select...

I haven't used any treatments for vaginal dryness or irritation in the last 2 weeks.

Select...

I am not taking any medication that affects how my body processes drugs.

Select...

I am not taking any strong CYP3A4 inhibitors like certain antibiotics, antifungals, HIV drugs, or consuming grapefruit juice.

Select...

I have used hormone patches within the last 4 weeks.

Select...

I have used hormone therapy with estrogen or progestin in the last 6 months.

Select...

I understand and can follow the study's requirements.

Select...

I am unable or unwilling to give informed consent.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 15 days

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~15 days

This trial's timeline: 3 weeks for screening, Varies for treatment, and 15 days for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Change in Most Bothersome Symptom

Responder

Secondary study objectives

Treatment Success in Most bothersome symptom

Side effects data

From 2018 Phase 4 trial • 64 Patients • NCT02255175

18%

Breast Tenderness

15%

Cramps

15%

Itchiness at patch site

12%

Headaches

Nausea

Acne

Lower Back Pain

Hot Flashes

Menstrual Bleeding

Bloating

Dizziness

100%

80%

60%

40%

20%

Study treatment Arm

Perimenopausal Women, Depressed

Perimenopausal Women, Non-depressed

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

3Treatment groups

Experimental Treatment

Active Control

Placebo Group

Group I: Estradiol vaginal inserts, 4 mcgExperimental Treatment1 Intervention

Estradiol vaginal inserts, 4 mcg. Insert vaginally once daily for 14 days.

Group II: IMVEXXY® (estradiol vaginal inserts) 4 mcgActive Control1 Intervention

IMVEXXY® (estradiol vaginal inserts) 4 mcg. Insert vaginally once for 14 days.

Group III: Placebo vaginal insertsPlacebo Group1 Intervention

Placebo vaginal inserts. Insert vaginally once for 14 days.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Estradiol

2008

Completed Phase 4

~3960

0 / 28Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for painful intercourse, such as estradiol vaginal inserts, work by addressing the underlying causes of vulvar and vaginal atrophy, which often contribute to dyspareunia. Estradiol, a form of estrogen, is absorbed through the vaginal mucosa, where it helps to restore the thickness and elasticity of the vaginal epithelium, increase lubrication, and reduce inflammation. This is crucial for patients as it directly alleviates the symptoms of dryness and irritation that cause pain during intercourse. Topical treatments like lidocaine can also be used to numb the area and provide immediate pain relief by blocking nerve signals. These mechanisms are essential for improving the quality of life and sexual health of patients suffering from painful intercourse.

Vulvodynia--An Evidence-Based Literature Review and Proposed Treatment Algorithm.