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

A Pilot Randomized Controlled Trial of Vaginal Estrogen on Postpartum Atrophy, Perineal Pain, and Sexual Function

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.

Study Overview

• Status: Completed
• Conditions: Vaginal Atrophy
• Intervention / Treatment: Drug: Estradiol; Other: Placebo

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 Type: Interventional
• Enrollment (Actual): 59
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Columbus, Ohio, United States, 43215
      • The Ohio State University Urogynecology Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vulvar Assessment Scale (VUAS)	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.	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Depression	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.	3 months
Urinary Symptoms	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 months
Fecal Incontinence	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.	3 months
Sexual Function	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.	3 months
Satisfaction Via Likert Scale	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?"	3 months
Adverse Outcomes	At each clinical/research visit the participant will be asked about any adverse events (AEs). AEs will be reported with study outcomes.	3 months

Collaborators and Investigators

• Sponsor: Ohio State University
• Collaborators: International Urogynecological Association
• Investigators: Principal Investigator: Andrew F Hundley, MD, The Ohio State University, Female Pelvic Medicine and Reconstructive Surgery

Publications and helpful links

General Publications

• Tennfjord MK, Hilde G, Staer-Jensen J, Ellstrom Engh M, Bo 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. doi: 10.1016/s0002-9378(12)90737-1.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): October 15, 2018
• Primary Completion (Actual): September 1, 2020
• Study Completion (Actual): September 1, 2020

Study Registration Dates

• First Submitted: March 16, 2018
• First Submitted That Met QC Criteria: April 2, 2018
• First Posted (Actual): April 10, 2018

Study Record Updates

• Last Update Posted (Actual): December 22, 2021
• Last Update Submitted That Met QC Criteria: November 23, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: postpartum, local estrogen
• Additional Relevant MeSH Terms: Pathological Conditions, Anatomical; Atrophy; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Estrogens; Estradiol
• Other Study ID Numbers: 2018H0006

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• 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