Postpartum Vaginal Estrogen for Breastfeeding Patients

Study Overview
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Brief Summary
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Sexual dysfunction is very common in the postpartum period and is more common in people who breastfeed or pump. This research study was designed to help determine whether postpartum patients who use vaginal estrogen cream while breastfeeding have improved sexual function compared to postpartum patients who do not.

Detailed Description
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This will be a prospective, randomized clinical trial of postpartum breastfeeding patients. Postpartum patients at University Hospitals (UH) MacDonald Women's Hospital will be evaluated for inclusion/exclusion by review of their medical record by the study investigators prior to discharge home. The study will then be discussed with the eligible patients privately. If they agree to participate, informed consent will be obtained. At this time, contact information will be obtained for all consenting patients. Between 5 and 6 weeks postpartum, all consented patients will be contacted via their preferred form of communication. Inclusion criteria and desire for continued study participation will be verified prior to randomization. A baseline REDCap questionnaire will be texted or emailed to confirmed study participants. UH REDCap is a HIPAA-certified, secure, web-based data storage platform for research studies. The patient will then be randomized in a 1:1 ratio into two study groups: vaginal estrogen or vaginal moisturizer. Randomization will be performed using blocking with a block size of 10 and a 1:1 allocation ratio. The randomization sequence will be generated using a random number table. After randomization, but not prior to 6 weeks postpartum, the investigational drug service courier service will deliver softgel inserts of vaginal estrogen to the homes of participants randomized to the estrogen arm. Study investigators will deliver vaginal moisturizer to the homes of participants randomized to the placebo arm. Study participants will be provided with an instructional handout including information about how and how often to use the inserts or the moisturizer. Participants will be instructed to start using the inserts or lubricant when they receive the delivery. This will be considered the start of the study period. During the study period, participants will use either estrogen or vaginal moisturizer nightly for two weeks and then twice weekly for ten weeks. Each week during the study period, participants will receive a message via their preferred communication method with five questions: Did you breastfeed or pump this week? Were you sexually active this week? If you were sexually active, did you have vaginal pain with sexual activity? How many times this week did you use the vaginal insert? Did you experience any change in your health this week? 6 and 12 weeks into the study period, the patient will be contacted by their preferred communication method and requested to complete a questionnaire via UH REDCap. The initial study questionnaire will include questions about demographics, gravidity and parity, prior deliveries (including mode of delivery, obstetric lacerations, and infant feeding), baseline sexual activity, prior pelvic surgery, chronic pain disorders, and plans for infant feeding. The 6 and 12-week study questionnaires will include the FSFI, the GAD-7 anxiety questionnaire, the Edinburgh Postnatal Depression Scale (EPDS), and the urinary distress inventory (UDI-6), the vaginal assessment scale (VAS), the Sexual Function Questionnaire Medical Impact Scale (SFQ-MIS), and the Female Sexual Distress Scale-Revised (FSDS-R) as well as questions about sexual activity and plans for infant feeding. Questionnaire responses will be reviewed by a study investigator after completion by the patient. Any patients whose questionnaires indicate possible depression (EPDS score 10+), thoughts of self-harm (any answer other than never on EPDS question 10), or moderate to severe anxiety (GAD-7 score 10+) will be evaluated for safety by a physician study investigator and referred to UH Reproductive Behavioral Health. In order to assess long term benefits of estrogen therapy in the early postpartum period, additional questionnaires will be administered at 6 months and 1 year to patients. The study intervention period will last 12 weeks, after which no additional vaginal estrogen or vaginal moisturizer will be administered to participants. Patients desiring to continue treatment after the 12-week study intervention period will be referred to their postpartum care provider. Patients will be instructed to stop estrogen use after they have completed breastfeeding.

Official Title
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Postpartum Vaginal Estrogen for Sexual Function in Breastfeeding Patients: A Randomized Controlled Trial

Conditions
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Breastfeeding, Postpartum Sexual Dysfunction, Vaginal Atrophy

Intervention / Treatment
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* Drug: Estradiol
* Device: Vaginal Moisturizer


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 or older Sexually active Singleton, term (37 weeks 0 days) birth Planning to breastfeed or pump during the study period History of successful breastfeeding or pumping after a prior pregnancy Between 6 weeks and 6 months postpartum (patients may be recruited at any time during the postpartum period, but the study period will not start until 6 weeks postpartum) Ability to consent in English Not meeting any exclusion criteria Exclusion Criteria: Preterm delivery Perinatal mortality History of difficulty breastfeeding 3rd or 4th degree perineal laceration Any contraindications to estrogen, including, but not limited to, breast cancer or a history of breast cancer, estrogen-dependent neoplasia, active deep vein thrombosis (DVT)/pulmonary embolism (PE) or a history of these conditions, active arterial thromboembolic disease (for example, stroke and MI) or a history of these conditions, known anaphylactic reaction, angioedema, or hypersensitivity to estrogen, hepatic impairment or disease, protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients will be randomized in a 1:1 ratio into two study groups: vaginal estrogen or vaginal moisturizer. Randomization will be performed using blocking with a block size of 10 and a 1:1 allocation ratio. The randomization sequence will be generated using a random number table.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vaginal Estrogen<br>Estradiol 4 mcg vaginal insert, daily for two weeks then twice weekly for ten weeks. | Drug: Estradiol<br>* Imvexxy is an FDA-approved drug produced by TherapeuticsMD.<br>* Other names: Imvexxy;|
| Active Comparator: Vaginal Moisturizer<br>Vaginal moisturizer, daily for two weeks then twice weekly for ten weeks. | Device: Vaginal Moisturizer<br>* Ingredients include hydrogenated coconut and palm oils and natural-source vitamin E (d-alpha tocopheryl acetate and tocopherols).<br>* Other names: Carlson Key-E Suppositories;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Female Sexual Function Index (FSFI) score | Female Sexual Function Index (FSFI) overall score has six domains and a maximum score of 36, with a higher score indicating better functioning. A score of 26 has been validated as a threshold for diagnosing female sexual dysfunction. | Up to 12 weeks into study period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Desire as measured by Female Sexual Function Index (FSFI) | One out of six FSFI domains. Score range of 1.2-6, with a higher score indicating better functioning. | Up to 12 weeks into study period | 
| Arousal as measured by Female Sexual Function Index (FSFI) | One out of six FSFI domains. Score range of 0-6, with a higher score indicating better functioning. | Up to 12 weeks into study period | 
| Lubrication as measured by Female Sexual Function Index (FSFI) | One out of six FSFI domains. Score range of 0-6, with a higher score indicating better functioning. | Up to 12 weeks into study period | 
| Orgasm as measured by Female Sexual Function Index (FSFI) | One out of six FSFI domains. Score range of 0-6, with a higher score indicating better functioning. | Up to 12 weeks into study period | 
| Satisfaction as measured by Female Sexual Function Index (FSFI) | One out of six FSFI domains. Score range of 0.8-6, with a higher score indicating better functioning. | Up to 12 weeks into study period | 
| Pain as measured by Female Sexual Function Index (FSFI) | One out of six FSFI domains. Score range of 0-6, with a higher score indicating better functioning. | Up to 12 weeks into study period | 
| Intercourse resumption | Number of weeks until resumption of intercourse after delivery | Up to 12 weeks into study period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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vaginal atrophy, postpartum, sexual dysfunction, dyspareunia, breastfeeding, pumping, vaginal dryness