Vaginal Atrophy
Conditions
Keywords
postpartum, local estrogen
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.
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.
Interventions
DRUGEstradiol
17β-estradiol vaginal cream
OTHERPlacebo
Compounded placebo cream
Sponsors
International Urogynecological Association
Ohio State University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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? |
| 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. |
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Estradiol Estrace: pea sized amount 2 times per week from week 1 postpartum to 3 months postpartum.
Estradiol: 17β-estradiol vaginal cream | 31 |
| Placebo Placebo: pea sized amount 2 times per week from week 1 postpartum to 3 months postpartum.
Placebo: Compounded placebo cream | 28 |
| Total | 59 |
Baseline characteristics
| Characteristic | Estradiol | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 29.3 years STANDARD_DEVIATION 5.1 | 28.0 years STANDARD_DEVIATION 4.1 | 28.6 years STANDARD_DEVIATION 4.6 |
| Race/Ethnicity, Customized Race/Ethnicity Black non-hispanic | 2 Participants | 3 Participants | 5 Participants |
| Race/Ethnicity, Customized Race/Ethnicity Hispanic | 1 Participants | 5 Participants | 6 Participants |
| Race/Ethnicity, Customized Race/Ethnicity missing | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Race/Ethnicity Other race/ethnicity | 2 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Race/Ethnicity White non-hispanic | 26 Participants | 18 Participants | 44 Participants |
| Sex: Female, Male Female | 31 Participants | 28 Participants | 59 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 31 | 0 / 28 |
| other Total, other adverse events | 0 / 31 | 0 / 28 |
| serious Total, serious adverse events | 0 / 31 | 0 / 28 |
Outcome results
Primary
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.
Time frame: 3 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Estradiol | Vulvar Assessment Scale (VUAS) | 0.10 score on a scale | Standard Deviation 0.25 |
| Placebo | Vulvar Assessment Scale (VUAS) | 0.20 score on a scale | Standard Deviation 0.22 |
Secondary
Adverse Outcomes
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Estradiol | Adverse Outcomes | 0 Participants |
| Placebo | Adverse Outcomes | 1 Participants |
Secondary
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.
Time frame: 3 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Estradiol | Depression | 4.07 score on a scale | Standard Deviation 3.71 |
| Placebo | Depression | 4.07 score on a scale | Standard Deviation 2.99 |
Secondary
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.
Time frame: 3 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Estradiol | Fecal Incontinence | 16.5 score on a scale | Standard Deviation 14.3 |
| Placebo | Fecal Incontinence | 15.4 score on a scale | Standard Deviation 12.4 |
Secondary
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?
Time frame: 3 months
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Estradiol | Satisfaction Via Likert Scale | Neutral/unsure | 8 Participants |
| Estradiol | Satisfaction Via Likert Scale | Very satisfied | 14 Participants |
| Estradiol | Satisfaction Via Likert Scale | somewhat dissatisfied | 0 Participants |
| Estradiol | Satisfaction Via Likert Scale | Somewhat satisfied | 5 Participants |
| Placebo | Satisfaction Via Likert Scale | somewhat dissatisfied | 1 Participants |
| Placebo | Satisfaction Via Likert Scale | Neutral/unsure | 11 Participants |
| Placebo | Satisfaction Via Likert Scale | Somewhat satisfied | 6 Participants |
| Placebo | Satisfaction Via Likert Scale | Very satisfied | 9 Participants |
Secondary
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.
Time frame: 3 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Estradiol | Sexual Function | 25.4 score on a scale | Standard Deviation 8.1 |
| Placebo | Sexual Function | 20.5 score on a scale | Standard Deviation 10.8 |
Secondary
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.
Time frame: 3 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Estradiol | Urinary Symptoms | 5.6 score on a scale | Standard Deviation 10.2 |
| Placebo | Urinary Symptoms | 10.5 score on a scale | Standard Deviation 23.5 |