Vaginal Estrogen Cream for Postpartum Recovery

Overseen By Hannah L Chapman, MD

Age: 18+

Sex: Female

Trial Phase: Phase 4

Sponsor: University of Alabama at Birmingham

Disqualifiers: DVT, Stroke, Breast cancer, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 15

Duration: 6 months

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a vaginal estrogen cream (Estradiol 0.01% Vag Cream) can improve sexual function and reduce issues like urinary and anal incontinence in women who have experienced severe tears during childbirth. Participants will use either the estrogen cream or a placebo starting two weeks postpartum and continuing for six months. Women who had 3rd or 4th degree tears during childbirth and can apply the cream themselves may be suitable candidates. The goal is to determine if the cream enhances recovery and quality of life for these women. As a Phase 4 trial, this research aims to understand how an already FDA-approved and effective treatment can benefit more patients, potentially improving recovery and quality of life.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What is the safety track record for these treatments?

Research has shown that estradiol 0.01% vaginal cream is generally safe for women after childbirth. Studies indicate it is well-tolerated and acceptable during this period. While it may only slightly alleviate symptoms like vaginal dryness and itching, it does not pose major safety risks. Already approved for other uses, its safety profile is well-established. Participants in previous studies have not reported serious side effects, making it a promising option for those considering joining a clinical trial. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about vaginal estrogen cream for postpartum recovery because it offers a targeted approach to alleviate symptoms like discomfort and vaginal dryness that many new mothers experience. Unlike systemic hormone therapies, which affect the whole body, this cream delivers estradiol directly where it's needed, maximizing local benefits while potentially minimizing systemic side effects. Additionally, the phased dosing schedule—starting with nightly applications and transitioning to twice weekly—could offer sustained relief over the critical postpartum period, providing a convenient and potentially more effective option for mothers during their recovery.

What evidence suggests that this treatment might be an effective treatment for postpartum recovery?

This trial will compare the effects of vaginal estrogen cream with a placebo cream for postpartum recovery. Research has shown that vaginal estrogen cream can aid recovery after childbirth, particularly for women with severe tears. Studies have found that this cream helps heal wounds in the vaginal area and is considered safe and acceptable for postpartum use. Although past research on vaginal dryness showed only small benefits, this cream primarily aims to improve tissue quality and healing. This improvement may enhance sexual health and reduce incontinence, which is the inability to control urination or bowel movements, for new mothers. ^{1 2 4 6 7}

Who Is on the Research Team?

Hannah L Chapman, MD

Principal Investigator

University of Alabama at Birmingham

Are You a Good Fit for This Trial?

This trial is for women aged 18 or older who have experienced severe tears during childbirth (3rd or 4th degree lacerations) and can apply vaginal cream themselves. It's not suitable for those with a history of blood clots, stroke, hormone-sensitive breast cancer, tobacco use, allergies to estradiol cream or its ingredients, or if they have an infection at the site of injury.

Inclusion Criteria

Women who have had severe tears during childbirth.

I can apply vaginal cream by myself.

I have experienced severe tearing during childbirth.

Exclusion Criteria

I cannot use intra-vaginal estrogen due to a history of DVT, stroke, or hormone-sensitive breast cancer.

I had complications with my perineal wound 2 weeks after giving birth.

You smoke or use tobacco products.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

1 visit (in-person)

Treatment

Participants receive intravaginal estrogen therapy or placebo starting at 2 weeks postpartum, continuing for 6 months

6 months

Initial visit at 2 weeks postpartum, followed by regular follow-ups

Follow-up

Participants are monitored for sexual function and incontinence symptom distress and impact

6 months

Follow-up visits at 12 weeks and 6 months postpartum

What Are the Treatments Tested in This Trial?

Interventions

• Estradiol 0.01% Vag Cream
• Placebo vaginal cream

Trial Overview The study tests whether applying a topical vaginal estrogen cream (Estradiol 0.01%) after childbirth helps with recovery from obstetric anal sphincter injuries compared to a placebo cream. The focus is on improving sexual function and reducing distress from urinary and bowel incontinence.

How Is the Trial Designed?

Group I: Topical vaginal estrogen group Active Control 1 Intervention

Estradiol vaginal cream 0.01% 1g will be administered vaginally, initiated at 2 weeks postpartum and continued until 6 months postpartum. Beginning at 2 weeks postpartum, 1g estradiol vaginal cream 0.01% will be administered by participants nightly for 2 weeks then twice weekly to complete 6 months therapy

Group II: Placebo group Placebo Group 1 Intervention

Placebo cream, 1g will be administered vaginally, initiated at 2 weeks postpartum and continued until 6 months postpartum. Beginning at 2 weeks postpartum, 1g of placebo cream will be administered by participants nightly for 2 weeks then twice weekly to complete 6 months therapy.

Estradiol 0.01% Vag Cream is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Estradiol 0.01% Vag Cream for:

• Moderate to severe dyspareunia due to vaginal atrophy
• Vaginal dryness and pain during sexual intercourse

Approved in European Union as Vagifem for:

• Vaginal atrophy symptoms including vaginal dryness and pain during sexual intercourse

Approved in Canada as Estrace for:

• Moderate to severe dyspareunia due to vaginal atrophy
• Vaginal dryness and pain during sexual intercourse

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

Published Research Related to This Trial

In a study involving 40 high-risk obstetric patients, a topical cervical gel containing 200 mg of estradiol valerate did not improve cervical ripening compared to a placebo, as measured by the Bishop score and other labor outcomes.

The sequential use of estradiol followed by prostaglandin E2 did not lead to effective cervical ripening, as only 85% of patients showed uterine activity after prostaglandin application, indicating this regimen may not be suitable for inducing labor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The sequential use of estradiol and prostaglandin E2 topical gels for cervical ripening in high-risk term pregnancies requiring induction of labor. Williams, JK., Lewis, ML., Cohen, GR., et al.[2019]

Both 25-microg 17beta-estradiol vaginal tablets and 1.25-mg conjugated equine estrogen vaginal cream effectively relieve symptoms of atrophic vaginitis in menopausal women, as shown in a study with 159 participants over 24 weeks.

The vaginal tablets were associated with fewer systemic side effects, lower rates of endometrial proliferation, and higher patient satisfaction, leading to a lower withdrawal rate compared to the vaginal cream.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

17beta-estradiol vaginal tablet versus conjugated equine estrogen vaginal cream to relieve menopausal atrophic vaginitis. Rioux, JE., Devlin, C., Gelfand, MM., et al.[2022]

In a study of 99 women with a very unfavorable cervix (Bishop score < 4) requiring labor induction, no significant differences were found in the effectiveness of oxytocin, prostaglandin E2 gel, and estradiol cream for cervical ripening, as cesarean delivery rates and maximum cervical dilation were similar across all groups.

However, among those who delivered vaginally, oxytocin showed a significant improvement in Bishop score, indicating it may be more effective for cervical ripening in that specific subset of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cervical ripening before medical induction of labor: a comparison of prostaglandin E2, estradiol, and oxytocin. Magann, EF., Perry, KG., Dockery, JR., et al.[2019]

Both 25-μg 17β-estradiol vaginal tablets and 1.25-mg conjugated equine estrogen vaginal cream effectively relieve symptoms of atrophic vaginitis in menopausal women, as shown in a study of 159 participants over 24 weeks.

The vaginal tablets resulted in fewer systemic side effects and lower rates of endometrial proliferation compared to the cream, along with higher patient satisfaction and lower withdrawal rates, indicating they may be a safer and more acceptable option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

17β-estradiol vaginal tablet versus conjugated equine estrogen vaginal cream to relieve menopausal atrophic vaginitis. Rioux, JE., Devlin, MC., Gelfand, MM., et al.[2022]

In a study of 160 postmenopausal women, both Vagifem (an estradiol vaginal tablet) and vaginal estrogen cream effectively improved symptoms of atrophic vaginitis, showing no significant difference in treatment effectiveness.

Vagifem was associated with a significantly lower rate of hygienic issues (0% vs. 23%) and was reported as easier to use by 90% of patients compared to 55% for estrogen cream, making it a more user-friendly option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparative study of vaginal estrogen cream and sustained-release estradiol vaginal tablet (Vagifem) in the treatment of atrophic vaginitis in Isfahan, Iran in 2010-2012. Hosseinzadeh, P., Ghahiri, A., Daneshmand, F., et al.[2020]

In a study of 75 primigravid patients with unripe cervixes, the use of Prostaglandin E2 gel for labor induction resulted in a significant improvement in the Bishop score, indicating increased cervical readiness for labor, with 92% of patients entering spontaneous labor within 12 hours.

The overall success rate for vaginal delivery was high at 81.33%, with a low incidence of failed induction at 1.33%, suggesting that Prostaglandin E2 gel is an effective and safe option for inducing labor in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prostaglandin E2 gel In ripening of cervix in induction of labour. Warke, HS., Saraogi, RM., Sanjwalla, SM.[2013]

In a 12-week study involving 117 women, Vagisan® Moisturising Cream (CREAM) was found to be non-inferior to a non-hormonal vaginal gel (GEL) for relieving symptoms of vulvovaginal atrophy (VVA), and it even showed superior efficacy in reducing both subjective and objective symptoms.

CREAM demonstrated better tolerability than GEL, with fewer reports of burning and itching, and it significantly improved vaginal pH, indicating it may be a safer and more effective option for VVA symptom relief.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of non-hormonal remedies for vaginal dryness: open, prospective, randomized trial. Stute, P., May, TW., Masur, C., et al.[2015]

In a study involving 423 postmenopausal women, low-dose conjugated estrogens (CE) cream significantly improved vaginal health markers, such as vaginal maturation index and pH, compared to placebo after 12 weeks, with effects sustained for up to 52 weeks.

Both daily and twice-weekly applications of CE cream effectively reduced symptoms of vaginal atrophy, including dryness and pain during intercourse, without any reported cases of endometrial hyperplasia or carcinoma, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of low-dose regimens of conjugated estrogens cream administered vaginally. Bachmann, G., Bouchard, C., Hoppe, D., et al.[2022]

In a study of 54 postmenopausal women, daily intravaginal application of 0.2 mg of 17 beta-estradiol cream for one to two months significantly improved symptoms of atrophic vaginitis and related menopausal symptoms, such as hot flashes and vaginal dryness (P < 0.01).

The treatment was well-tolerated with low incidence of side effects, primarily breast tenderness and abdominal cramping, and did not cause significant changes in hematologic or biochemical parameters.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of micronized estradiol vaginal cream. Gordon, WE., Hermann, HW., Hunter, DC.[2019]

In a study of 29 postmenopausal women, both conjugated estrogen cream and estradiol cream significantly relieved vasomotor and vaginal symptoms after 14 days of daily use.

Estradiol cream was more effective than conjugated estrogen cream in achieving plasma hormone levels similar to those of premenopausal women, suggesting it may provide better symptom relief due to its direct action and metabolism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of estradiol vaginal cream in postmenopausal women. Dickerson, J., Bressler, R., Christian, CD., et al.[2019]

The controlled release hydrogel polymer pessary effectively delivers PGE2, leading to a significant increase in PGEM levels within two hours, indicating that the drug is absorbed and active in the body.

The study suggests that this method of delivery may offer better control for labor induction compared to other methods, although further clinical trials are needed to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prostaglandin metabolite levels during cervical ripening with a controlled-release hydrogel polymer prostaglandin E2 pessary. Taylor, AV., Boland, J., Bernal, AL., et al.[2019]

In a study of 520 women with a previous caesarean section, vaginal delivery rates were similar across groups receiving oxytocin (65%), prostaglandins (67%), and those with spontaneous labor (72%), indicating that labor induction methods are effective.

The study found no maternal deaths or cases of complete uterine rupture, suggesting that with careful monitoring, inducing labor in women with a history of caesarean section is safe and can lead to successful vaginal deliveries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vaginal delivery following caesarean section-the use of oxytocin and prostaglandins. Goldman, GA., Kaplan, B., Rabinerson, D., et al.[2004]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9020152/

A pilot randomized controlled trial of vaginal estrogen on ... Use of local estradiol showed minimal clinical benefit in vulvovaginal atrophy and related symptoms but appears to be acceptable and safe for postpartum use.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05317364

Topical Vaginal Estrogen for Postpartum Obstetric Anal ... The objective of this study is to determine if intra-vaginal estrogen therapy improves sexual function and incontinence symptom distress and impact for ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5484719/

Vaginal estrogen: a dual-edged sword in postoperative ... Postoperative administration of local estrogen, direct injection of mesenchymal stem cells (MSCs), or both lead to improved wound healing of the injured vagina.

4. withpower.com withpower.com/trial/phase-4-sexual-dysfunctions-6-2022-af115

Vaginal Estrogen Cream for Postpartum Recovery This trial is testing whether applying estrogen cream inside the vagina can help women who have had severe tears during childbirth.

5. outbreak.info outbreak.info/resources/pmid35441854

A pilot randomized controlled trial of vaginal estrogen ... The primary outcome was a validated measure of vulvovaginal symptoms at 12 weeks postpartum. Secondary outcomes included measures of perineal pain, quality of ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35441854/

A pilot randomized controlled trial of vaginal estrogen on ... Use of local estradiol showed minimal clinical benefit in vulvovaginal atrophy and related symptoms but appears to be acceptable and safe for postpartum use.

7. mayoclinic.org mayoclinic.org/drugs-supplements/estradiol-vaginal-route/description/drg-20075648

Estradiol (vaginal route) - Side effects & dosage Estradiol vaginal gel, insert, and ring are used to treat changes in and around the vagina (such as vaginal dryness, itching, and burning) ...