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

• ClinicalTrials.gov Identifier: NCT03493126
• Recruitment Status: Completed
• First Posted: April 10, 2018
• Results First Posted: December 22, 2021
• Last Update Posted: December 22, 2021
• Sponsor: Ohio State University
• Collaborator: International Urogynecological Association
• Information provided by (Responsible Party): Andrew Hundley, Ohio State University

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 (Clinical Trial)
• 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: October 15, 2018
• Actual Primary Completion Date: September 1, 2020
• Actual Study Completion Date: September 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 Name: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes
• Accepts Healthy Volunteers: Yes

Criteria

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

United States, Ohio

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)

Documents provided by Andrew Hundley, Ohio State University:

Study Protocol and Statistical Analysis Plan  [PDF] January 30, 2018

Informed Consent Form  [PDF] January 30, 2018

More Information

Publications:

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.

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.

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.

• Responsible Party: Andrew Hundley, Associate Professor, Ohio State University
• ClinicalTrials.gov Identifier: NCT03493126
• Other Study ID Numbers: 2018H0006
• First Posted: April 10, 2018
• Results First Posted: December 22, 2021
• Last Update Posted: December 22, 2021
• Last Verified: November 2021

Individual Participant Data (IPD) Sharing Statement:

• 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, Ohio State University:

postpartum, local estrogen

Additional relevant MeSH terms:

Atrophy; Pathological Conditions, Anatomical; Estradiol; Estrogens; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs