Vaginal Estrogen on Postpartum Atrophy, Perineal Pain, and Sexual Function

• Sponsor: Ohio State University (Other)
• Overall Status: Completed
• CT.gov ID: NCT03493126
• Collaborator: International Urogynecological Association (Other)
• Enrollment: 59
• Location: 1
• Arms: 2
• Actual Duration (Months): 22.6
• Patients Per Site Per Month: 2.6

Study Details

Study Description

Brief Summary

Pilot randomized, placebo-controlled trial of nulliparous postpartum women with a perineal laceration following a term vaginal delivery comparing vulvovaginal atrophy symptoms between women using vaginal estrogen in the postpartum period with those using placebo.

Condition or Disease	Intervention/Treatment	Phase
Vaginal Atrophy	Drug: Estradiol; Other: Placebo	Phase 4

Detailed Description

The overall goal of this study is to determine whether there are benefits to use of low-dose vaginal estrogen in the postpartum period. Dyspareunia and vaginal/perineal pain are well-known sequelae after vaginal delivery. However, the contribution of postpartum vaginal atrophy to these issues is largely unknown. Although the relationship between lactation, relative estrogen deprivation, and vulvovaginal atrophy has been established, there is a paucity of data regarding on the prevalence of vulvovaginal atrophy symptoms in the postpartum period. Additionally, although the benefits of vaginal estrogen in postmenopausal atrophy are well-established, the benefits in the postpartum period are unknown.

Study Design

• Study Type: Interventional
• Actual Enrollment: 59 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Pilot Randomized Controlled Trial of Vaginal Estrogen on Postpartum Atrophy, Perineal Pain, and Sexual Function
• Actual Study Start Date: Oct 15, 2018
• Actual Primary Completion Date: Sep 1, 2020
• Actual Study Completion Date: Sep 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Estradiol Estrace: pea sized amount 2 times per week from week 1 postpartum to 3 months postpartum.	Drug: Estradiol; 17β-estradiol vaginal cream; Other Names: Estrace
Placebo Comparator: Placebo Placebo: pea sized amount 2 times per week from week 1 postpartum to 3 months postpartum.	Other: Placebo; Compounded placebo cream

Outcome Measures

Primary Outcome Measures

1. Vulvar Assessment Scale (VUAS) [3 months]

   The VUAS is a four-item measurement administered by a clinical provider that quantifies and rates the patient's responses to questions of dryness, soreness, irritation and pain to external stimulation. Patients are asked whether they have experienced specific symptoms ("yes/no") during the past 4 weeks and rate symptom severity ("none," "mild," "moderate," "severe"). The first 3 items assess dryness, soreness, and irritation during routine activities excluding sexual intercourse and the fourth item assesses pain with external manual stimulation. An option for "no attempt" indicates a patient has not been sexually active within the past 4 weeks. Each item in the VuAS is scored from 0 (none) to 3 (severe) with composite scores calculated by taking the mean of the items when at least two of four items are not missing. Higher scores indicate worse symptoms. The minimum composite score is 0 and maximum composite score is 3.

Secondary Outcome Measures

1. Depression [3 months]

   Edinburgh Postnatal Depression Scale (EPDS) The EPDS is a validated 10-question depression assessment for postpartum women, which includes anxiety symptoms and excludes constitutional symptoms associated with depression common in the postpartum period, such as changes in sleeping patterns. Questions 1, 2, & 4 are scored 0, 1, 2 or 3 with top box scored as 0 and the bottom box scored as 3. Questions 3 and 5--10 are reverse scored, with the top box scored as a 3 and the bottom box scored as 0. Minimum total score: 0 Maximum total score: 30. Total score of 10 or higher may be indicative of postpartum depression.

2. Urinary Symptoms [3 months]

   Urinary Distress Inventory (UDI-6) The UDI-6 is a questionnaire that includes 6 items evaluating bother from urinary symptoms with higher scores indicating more disability. Each item is scored from 0-3. The total score is the average individual score multiplied by 25. The minimal score is 0 and maximum score is 100.

3. Fecal Incontinence [3 months]

   Fecal Incontinence Severity Index (FISI) for bowel symptoms The FISI evaluates patient responses symptom severity to fecal incontinence with higher scores indicating more bothersome anal incontinence symptoms. The FISI score ranges from 0 to 61 with higher score indicating higher severity of the fecal incontinence.

4. Sexual Function [3 months]

   Female Sexual Function Index (FSFI) The FSFI is a validated questionnaire to assess sexual function in six domains of sexual function, including desire, arousal, lubrication, orgasm, satisfaction, and pain over the 4 weeks prior to administration of questionnaire with lower scores indicating more sexual dysfunction. The FSFI score ranges from 2-36 with LOWER score indicating worse sexual dysfunction.

5. Satisfaction Via Likert Scale [3 months]

   Likert scale Satisfaction will be assessed using the patient satisfaction questionnaire in response to the question, "How satisfied were you with your progress with this treatment?"

6. Adverse Outcomes [3 months]

   At each clinical/research visit the participant will be asked about any adverse events (AEs). AEs will be reported with study outcomes.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• females >18 years old with at least one prior prenatal care appointment affiliated with The Ohio State University Wexner Medical Center; nulliparous; 1-2 days status post >37 weeks and 0 day vaginal delivery with at least a second degree perineal laceration; English-speaking and able to provide informed consent.

Exclusion Criteria:

• allergies to estradiol cream or its constituents; a vaginal delivery associated with a intrauterine fetal demise or neonatal death; inability to complete questionnaires in English or comply with study protocol; and inability to apply vaginal cream independently. The following medical conditions and diagnoses are also exempted: undiagnosed abnormal vaginal bleeding, known or suspected estrogen-dependent neoplasia, active or history of deep venous thrombosis or pulmonary embolism, active arterial thromboembolic disease, known liver dysfunction or disease, known protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Ohio State University Urogynecology Clinic	Columbus	Ohio	United States	43215

Sponsors and Collaborators

• Ohio State University
• International Urogynecological Association

Investigators

• Principal Investigator: Andrew F Hundley, MD, The Ohio State University, Female Pelvic Medicine and Reconstructive Surgery

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jan 30, 2018
• Informed Consent Form - Jan 30, 2018

More Information

Publications

• Eaton AA, Baser RE, Seidel B, Stabile C, Canty JP, Goldfrank DJ, Carter J. Validation of Clinical Tools for Vaginal and Vulvar Symptom Assessment in Cancer Patients and Survivors. J Sex Med. 2017 Jan;14(1):144-151. doi: 10.1016/j.jsxm.2016.11.317. Epub 2016 Dec 20.
• Haran C, van Driel M, Mitchell BL, Brodribb WE. Clinical guidelines for postpartum women and infants in primary care-a systematic review. BMC Pregnancy Childbirth. 2014 Jan 29;14:51. doi: 10.1186/1471-2393-14-51. Review.
• Rahn DD, Carberry C, Sanses TV, Mamik MM, Ward RM, Meriwether KV, Olivera CK, Abed H, Balk EM, Murphy M; Society of Gynecologic Surgeons Systematic Review Group. Vaginal estrogen for genitourinary syndrome of menopause: a systematic review. Obstet Gynecol. 2014 Dec;124(6):1147-1156. doi: 10.1097/AOG.0000000000000526. Review.
• Tennfjord MK, Hilde G, Stær-Jensen J, Ellström Engh M, Bø K. Dyspareunia and pelvic floor muscle function before and during pregnancy and after childbirth. Int Urogynecol J. 2014 Sep;25(9):1227-35. doi: 10.1007/s00192-014-2373-2. Epub 2014 Apr 1.
• Wisniewski PM, Wilkinson EJ. Postpartum vaginal atrophy. Am J Obstet Gynecol. 1991 Oct;165(4 Pt 2):1249-54.

• Responsible Party: Andrew Hundley, Associate Professor, Ohio State University
• ClinicalTrials.gov Identifier: NCT03493126
• Other Study ID Numbers: 2018H0006
• First Posted: Apr 10, 2018
• Last Update Posted: Dec 22, 2021
• Last Verified: Nov 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by Andrew Hundley, Associate Professor, Ohio State University: postpartum, local estrogen
• Additional relevant MeSH terms: Atrophy; Estradiol

Study Results

Participant Flow

Arm/Group Title	Estradiol	Placebo
Arm/Group Description	Estrace: pea sized amount 2 times per week from week 1 postpartum to 3 months postpartum. Estradiol: 17β-estradiol vaginal cream	Placebo: pea sized amount 2 times per week from week 1 postpartum to 3 months postpartum. Placebo: Compounded placebo cream
Period Title: Overall Study
STARTED	31	28
COMPLETED	28	28
NOT COMPLETED	3	0

Baseline Characteristics

Arm/Group Title	Estradiol	Placebo	Total
Arm/Group Description	Estrace: pea sized amount 2 times per week from week 1 postpartum to 3 months postpartum. Estradiol: 17β-estradiol vaginal cream	Placebo: pea sized amount 2 times per week from week 1 postpartum to 3 months postpartum. Placebo: Compounded placebo cream	Total of all reporting groups
Overall Participants	31	28	59
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	29.3 (5.1)	28.0 (4.1)	28.6 (4.6)
Sex: Female, Male (Count of Participants)
Female	31 100%	28 100%	59 100%
Male	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
White non-hispanic	26 83.9%	18 64.3%	44 74.6%
Black non-hispanic	2 6.5%	3 10.7%	5 8.5%
Hispanic	1 3.2%	5 17.9%	6 10.2%
Other race/ethnicity	2 6.5%	1 3.6%	3 5.1%
missing	0 0%	1 3.6%	1 1.7%

Outcome Measures

1. Primary Outcome

Title	Vulvar Assessment Scale (VUAS)
Description	The VUAS is a four-item measurement administered by a clinical provider that quantifies and rates the patient's responses to questions of dryness, soreness, irritation and pain to external stimulation. Patients are asked whether they have experienced specific symptoms ("yes/no") during the past 4 weeks and rate symptom severity ("none," "mild," "moderate," "severe"). The first 3 items assess dryness, soreness, and irritation during routine activities excluding sexual intercourse and the fourth item assesses pain with external manual stimulation. An option for "no attempt" indicates a patient has not been sexually active within the past 4 weeks. Each item in the VuAS is scored from 0 (none) to 3 (severe) with composite scores calculated by taking the mean of the items when at least two of four items are not missing. Higher scores indicate worse symptoms. The minimum composite score is 0 and maximum composite score is 3.
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Estradiol	Placebo
Arm/Group Description	Estrace: pea sized amount 2 times per week from week 1 postpartum to 3 months postpartum. Estradiol: 17β-estradiol vaginal cream	Placebo: pea sized amount 2 times per week from week 1 postpartum to 3 months postpartum. Placebo: Compounded placebo cream
Measure Participants	31	28
Mean (Standard Deviation) [score on a scale]	0.10 (0.25)	0.20 (0.22)

2. Secondary Outcome

Title	Depression
Description	Edinburgh Postnatal Depression Scale (EPDS) The EPDS is a validated 10-question depression assessment for postpartum women, which includes anxiety symptoms and excludes constitutional symptoms associated with depression common in the postpartum period, such as changes in sleeping patterns. Questions 1, 2, & 4 are scored 0, 1, 2 or 3 with top box scored as 0 and the bottom box scored as 3. Questions 3 and 5--10 are reverse scored, with the top box scored as a 3 and the bottom box scored as 0. Minimum total score: 0 Maximum total score: 30. Total score of 10 or higher may be indicative of postpartum depression.
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Estradiol	Placebo
Arm/Group Description	Estrace: pea sized amount 2 times per week from week 1 postpartum to 3 months postpartum. Estradiol: 17β-estradiol vaginal cream	Placebo: pea sized amount 2 times per week from week 1 postpartum to 3 months postpartum. Placebo: Compounded placebo cream
Measure Participants	31	28
Mean (Standard Deviation) [score on a scale]	4.07 (3.71)	4.07 (2.99)

3. Secondary Outcome

Title	Urinary Symptoms
Description	Urinary Distress Inventory (UDI-6) The UDI-6 is a questionnaire that includes 6 items evaluating bother from urinary symptoms with higher scores indicating more disability. Each item is scored from 0-3. The total score is the average individual score multiplied by 25. The minimal score is 0 and maximum score is 100.
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Estradiol	Placebo
Arm/Group Description	Estrace: pea sized amount 2 times per week from week 1 postpartum to 3 months postpartum. Estradiol: 17β-estradiol vaginal cream	Placebo: pea sized amount 2 times per week from week 1 postpartum to 3 months postpartum. Placebo: Compounded placebo cream
Measure Participants	31	28
Mean (Standard Deviation) [score on a scale]	5.6 (10.2)	10.5 (23.5)

4. Secondary Outcome

Title	Fecal Incontinence
Description	Fecal Incontinence Severity Index (FISI) for bowel symptoms The FISI evaluates patient responses symptom severity to fecal incontinence with higher scores indicating more bothersome anal incontinence symptoms. The FISI score ranges from 0 to 61 with higher score indicating higher severity of the fecal incontinence.
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Estradiol	Placebo
Arm/Group Description	Estrace: pea sized amount 2 times per week from week 1 postpartum to 3 months postpartum. Estradiol: 17β-estradiol vaginal cream	Placebo: pea sized amount 2 times per week from week 1 postpartum to 3 months postpartum. Placebo: Compounded placebo cream
Measure Participants	31	28
Mean (Standard Deviation) [score on a scale]	16.5 (14.3)	15.4 (12.4)

5. Secondary Outcome

Title	Sexual Function
Description	Female Sexual Function Index (FSFI) The FSFI is a validated questionnaire to assess sexual function in six domains of sexual function, including desire, arousal, lubrication, orgasm, satisfaction, and pain over the 4 weeks prior to administration of questionnaire with lower scores indicating more sexual dysfunction. The FSFI score ranges from 2-36 with LOWER score indicating worse sexual dysfunction.
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Estradiol	Placebo
Arm/Group Description	Estrace: pea sized amount 2 times per week from week 1 postpartum to 3 months postpartum. Estradiol: 17β-estradiol vaginal cream	Placebo: pea sized amount 2 times per week from week 1 postpartum to 3 months postpartum. Placebo: Compounded placebo cream
Measure Participants	31	28
Mean (Standard Deviation) [score on a scale]	25.4 (8.1)	20.5 (10.8)

6. Secondary Outcome

Title	Satisfaction Via Likert Scale
Description	Likert scale Satisfaction will be assessed using the patient satisfaction questionnaire in response to the question, "How satisfied were you with your progress with this treatment?"
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Estradiol	Placebo
Arm/Group Description	Estrace: pea sized amount 2 times per week from week 1 postpartum to 3 months postpartum. Estradiol: 17β-estradiol vaginal cream	Placebo: pea sized amount 2 times per week from week 1 postpartum to 3 months postpartum. Placebo: Compounded placebo cream
Measure Participants	27	27
Very satisfied	14 45.2%	9 32.1%
Somewhat satisfied	5 16.1%	6 21.4%
Neutral/unsure	8 25.8%	11 39.3%
somewhat dissatisfied	0 0%	1 3.6%

7. Secondary Outcome

Title	Adverse Outcomes
Description	At each clinical/research visit the participant will be asked about any adverse events (AEs). AEs will be reported with study outcomes.
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Estradiol	Placebo
Arm/Group Description	Estrace: pea sized amount 2 times per week from week 1 postpartum to 3 months postpartum. Estradiol: 17β-estradiol vaginal cream	Placebo: pea sized amount 2 times per week from week 1 postpartum to 3 months postpartum. Placebo: Compounded placebo cream
Measure Participants	31	28
Count of Participants [Participants]	0 0%	1 3.6%

Adverse Events

Time Frame	6 months
Arm/Group Title	Estradiol		Placebo
Arm/Group Description	Estrace: pea sized amount 2 times per week from week 1 postpartum to 3 months postpartum. Estradiol: 17β-estradiol vaginal cream		Placebo: pea sized amount 2 times per week from week 1 postpartum to 3 months postpartum. Placebo: Compounded placebo cream
All Cause Mortality
	Estradiol		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/31 (0%)		0/28 (0%)
Serious Adverse Events
	Estradiol		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/31 (0%)		0/28 (0%)
Other (Not Including Serious) Adverse Events
	Estradiol		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/31 (0%)		0/28 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.