Pelvic Floor Disorders
Conditions
Keywords
pelvic floor dysfunction, pelvic organ prolapse, vaginal estrogen effects
Brief summary
Our primary aim in the current study is to determine important tissue differences, including muscle and connective tissue changes, between postmenopausal women and reproductive age women with pelvic floor dysfunction to help develop targeted and noninvasive treatments.
Detailed description
Our primary aim in the current study is to determine important tissue differences, including muscle and connective tissue changes, between postmenopausal women and reproductive age women with pelvic floor dysfunction to help develop targeted and noninvasive treatments. We will perform in vivo evaluations with colposcopy and OCT to determine epithelial thickness and overall mucosal health prior to surgery. At the time of surgery, we will obtain tissue for histologic and imaging analysis.
Interventions
DRUGPostmenopausal, topical vaginal estrogen cream
Topical vaginal estrogen cream is commonly but not universally used to improve the health of vaginal tissue prior to surgery. This study will provide data regarding estrogen effects for post-menopausal women undergoing pelvic organ prolapse.
DRUGPlacebo Comparator: Postmenopausal, topical placebo cream
Postmenopausal participants randomized to topical vaginal placebo for about one month's use prior to scheduled surgery.
Sponsors
The University of Texas Medical Branch, Galveston
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
21 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* 21 to 70 years of age * Stage II or greater pelvic organ prolapse (POP) * Individuals electing surgery to treat their POP * Willing and able to comply with study procedures * Willing and able to provide written informed consent
Exclusion criteria
* Contraindication for estrogen cream * Any medical condition that in the opinion of the investigator would place the subject at increased risk for participation * History of connective tissue disease * Previous hysterectomy or pelvic organ prolapse surgery * Known allergic reaction to any agent required by the protocol * Use of hormone therapy in postmenopausal women in the last 90 days * Pregnant or lactating females * History of prior noncompliance or the presence or history of psychiatric condition that would in the opinion of the investigator make it difficult for the subject to comply with study procedures or follow instructions
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Vaginal Epithelial Thickness | Change in thickness visit 1 to visit 2 for the postmenopausal group (approximately 1 month apart), and change in thickness from follicular to luteal phase for premenopausal group (approximately 1 month apart). | Measure of vaginal epithelial thickness obtained by optical coherence tomography |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Histologic Assessment of Excised Tissue | 1 month after visit 1 (3-17days after visit 2) | Evaluated tissue samples obtained during surgery to examine collagen. Collagen score (Masson trichrome): 3=abundant collagen (dark blue stain), 2=collagen present (light blue stain), 1=scant collagen (minimal blue stain) Higher scores indicate more collagen, or better outcome. (note that study vaginal drug was stopped at visit 2 for postmenopausal subjects except in one subject who used active topical vaginal cream but stopped after 2 weeks due to AE. Her OCT score was obtained after 2 weeks of active cream, however the histology was obtained 2 weeks after discontinuation of study drug because Visit 2 was scheduled at the time of the AE and at the time of stopping the active cream. The OCT and histology results are not concordant due to being taken at different timepoints (visit 2 on active cream vs surgery 16 days later off cream) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Postmenopausal, Topical Vaginal Cream Postmenopausal participants randomized to topical vaginal cream containing estrogen or placebo for about one month's use prior to scheduled surgery. These will include those women randomized to estrogen cream.
Postmenopausal, topical vaginal estrogen cream: Topical vaginal estrogen cream is commonly but not universally used to improve the health of vaginal tissue prior to surgery. This study will provide data regarding estrogen effects for post-menopausal women undergoing pelvic organ prolapse. | 2 |
| Pre-menopausal, no Topical Vaginal Cream Pre-menopausal, no topical vaginal cream. These women will be examined at different stages in their menstrual cycle in order to compare characteristics of the cycle at high and lower estrogen timepoints. | 3 |
| Postmenopausal, Topical Placebo Cream Postmenopausal participants randomized to topical vaginal cream containing estrogen or placebo for about one month's use prior to scheduled surgery. These will include those women randomized to placebo.
Placebo Comparator: Postmenopausal, topical placebo cream: Postmenopausal participants randomized to topical vaginal placebo for about one month's use prior to scheduled surgery. | 2 |
| Total | 7 |
Baseline characteristics
| Characteristic | Postmenopausal, Topical Vaginal Cream | Pre-menopausal, no Topical Vaginal Cream | Postmenopausal, Topical Placebo Cream | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 3 Participants | 1 Participants | 5 Participants |
| Age, Continuous | 63.5 years STANDARD_DEVIATION 4.5 | 44.7 years STANDARD_DEVIATION 4.5 | 65.5 years STANDARD_DEVIATION 1.5 | 56 years STANDARD_DEVIATION 10.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 3 Participants | 2 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 2 Participants | 2 Participants | 6 Participants |
| Region of Enrollment United States | 2 participants | 3 participants | 2 participants | 7 participants |
| Sex: Female, Male Female | 2 Participants | 3 Participants | 2 Participants | 7 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 2 | 0 / 3 | 0 / 2 |
| other Total, other adverse events | 2 / 2 | 0 / 3 | 1 / 2 |
| serious Total, serious adverse events | 0 / 2 | 0 / 3 | 0 / 2 |
Outcome results
Primary
Vaginal Epithelial Thickness
Measure of vaginal epithelial thickness obtained by optical coherence tomography
Time frame: Change in thickness visit 1 to visit 2 for the postmenopausal group (approximately 1 month apart), and change in thickness from follicular to luteal phase for premenopausal group (approximately 1 month apart).
Population: All participants who enrolled were analyzed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Postmenopausal, Topical Vaginal Cream | Vaginal Epithelial Thickness | 80 micrometers | Standard Deviation 23 |
| Pre-menopausal, no Topical Vaginal Cream | Vaginal Epithelial Thickness | 25.5 micrometers | Standard Deviation 2.5 |
| Postmenopausal, Topical Placebo Cream | Vaginal Epithelial Thickness | -11 micrometers | Standard Deviation 5 |
Secondary
Histologic Assessment of Excised Tissue
Evaluated tissue samples obtained during surgery to examine collagen. Collagen score (Masson trichrome): 3=abundant collagen (dark blue stain), 2=collagen present (light blue stain), 1=scant collagen (minimal blue stain) Higher scores indicate more collagen, or better outcome. (note that study vaginal drug was stopped at visit 2 for postmenopausal subjects except in one subject who used active topical vaginal cream but stopped after 2 weeks due to AE. Her OCT score was obtained after 2 weeks of active cream, however the histology was obtained 2 weeks after discontinuation of study drug because Visit 2 was scheduled at the time of the AE and at the time of stopping the active cream. The OCT and histology results are not concordant due to being taken at different timepoints (visit 2 on active cream vs surgery 16 days later off cream)
Time frame: 1 month after visit 1 (3-17days after visit 2)
Population: Histology was performed for the postmenopausal, topical vaginal cream, and the pre-menopausal, no topical vaginal cream group. There was no histology available from the 2 postmenopausal subjects randomly assigned to the placebo cream group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Postmenopausal, Topical Vaginal Cream | Histologic Assessment of Excised Tissue | 2.0 score on a scale | Standard Deviation 1 |
| Pre-menopausal, no Topical Vaginal Cream | Histologic Assessment of Excised Tissue | 2.3 score on a scale | Standard Deviation 0.5 |