Dyspareunia
Conditions
Keywords
Post-menopause dyspareunia, Vulvar vestibular pain, Genitourinary syndrome of menopause, Sexual pain
Brief summary
The purpose of this study is to compare the effectiveness of two low doses of estrogen cream applied to a new location for the treatment of moderate or severe pain during sexual intercourse in postmenopausal women.
Detailed description
Estrogen cream is FDA-approved for vaginal use for the treatment of sexual pain, but its use in a new location is experimental. Pain with sex is a common problem experienced by women after menopause and the relationship of pain to sexual difficulties is well established. The cause has been assumed to be atrophy and the location has been assumed to be the vagina. Recent focused studies have shown that the location of pain is the vulvar vestibule and usually not the vagina. This study will look at pain before and after therapy with estrogen when only the vulvar entryway area is treated. This will be a study focused on sexual dysfunction in postmenopausal women.
Interventions
DRUG50mcg estradiol cream
Use of study drug nightly applied to vulvar vestibule
DRUG100mcg estradiol cream
Use of study drug nightly
Sponsors
Oregon Health and Science University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double Blind
Eligibility
Sex/Gender
FEMALE
Age
40 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
1. Postmenopausal women aged 40 to 70 years old. 2. Postmenopausal, demonstrated by at least one of the following: i. Cessation of menses for ≥1 years if age is \>50 ii. Bilateral oophorectomy iii. A history of climacteric symptoms if below age 50, having an ovary and scarred or absent uterus. 3. Onset of dyspareunia after menopause.\* 4. Stable heterosexual partnership ≥2 years (or by investigator discretion if less than 2 years) and both partners want to have more satisfying penetrative intimacy. 5. No estrogen product use, local or systemic, for 6 months.\* 6. More than 6 months of consistent insertional pain with intercourse (may have stopped having intercourse due to this consistent experience of pain).\* 7. Willingness to enter a study where she will receive low-dose local estrogen.\* 8. Willingness to enter a study that requires application of cream on a frequent schedule for 3 months. \* 9. Willingness to evaluate the progress of therapies by use of the Tampon Test as many as 2 times per week, and willingness to attempt intercourse if the Tampon Test indicates tolerable penetrative pain.\* * n/a for reference group
Exclusion criteria
1. Consistently has pain in the pelvis or low abdomen during or after intercourse (deep dyspareunia). 2. Negative cotton-swab touch test in the vulvar vestibule or vestibular tenderness that is not extinguishable by application of lidocaine 4% topical solution applied for 3 minutes. 3. Partner with sexual dysfunction limiting his performance or making it inconsistent. (The use of male therapy for erectile dysfunction is acceptable.) 4. Diagnosis by a physical therapist or clinician of significant pelvic floor muscle tension causing pain (pelvic floor myalgia) or has been found on screening examination to have pelvic floor tenderness or bladder tenderness. 5. Constant burning pain localized to the vulva. 6. Allergy to local estrogen products or lidocaine numbing agents. 7. Previous estrogen receptor positive breast cancer or endometrial cancer. 8. Endometrial thickness ≥5mm on screening via transvaginal ultrasound.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Median Dyspareunia Pain Scores After 4 Weeks Using Study Drug | Baseline to 4 weeks | Change in median dyspareunia pain scores between baseline and 4 weeks of use of nightly use of study medication. Pain will be assessed using 11-point Numerical Rating Scale (NRS) where 0 = no pain and 10 = worst possible pain. |
| Change in Median Pain Scores for Intercourse After 12 Weeks Using Study Drug | Baseline and 12 weeks | Difference in median dyspareunia pain scores between arms for intercourse at 12 weeks after use of nightly study medication for 90d. Pain will be assessed using 11-point Numerical Rating Scale (NRS) where 0 = no pain and 10 = worst possible pain. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 50mcg Estradiol Cream Subjects randomized to 50mcg of study medication will be issued a pump that will dispense 0.5gm of cream with each pump
50mcg estradiol cream: Use of study drug nightly | 25 |
| 100mcg Estradiol Cream Subjects randomized to 100mcg of study medication will be issued a pump that will dispense 0.5gm of cream with each pump
100mcg estradiol cream: Use of study drug nightly | 25 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 2 |
Baseline characteristics
| Characteristic | Total | 50mcg Estradiol Cream | 100mcg Estradiol Cream |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 11 Participants | 4 Participants | 7 Participants |
| Age, Categorical Between 18 and 65 years | 39 Participants | 21 Participants | 18 Participants |
| Age, Continuous | 59.69 years STANDARD_DEVIATION 6.9 | 59.24 years STANDARD_DEVIATION 6.16 | 60.17 years STANDARD_DEVIATION 7.7 |
| BMI | 25.23 kg/m^2 STANDARD_DEVIATION 4.61 | 24.59 kg/m^2 STANDARD_DEVIATION 4.04 | 25.91 kg/m^2 STANDARD_DEVIATION 7.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 50 Participants | 25 Participants | 25 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 48 Participants | 24 Participants | 24 Participants |
| Region of Enrollment United States | 50 participants | 25 participants | 25 participants |
| Sex: Female, Male Female | 50 Participants | 25 Participants | 25 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 / 25 | 0 / 25 |
| other Total, other adverse events | 13 / 25 | 6 / 25 |
| serious Total, serious adverse events | 0 / 25 | 0 / 25 |
Outcome results
Primary
Change in Median Dyspareunia Pain Scores After 4 Weeks Using Study Drug
Change in median dyspareunia pain scores between baseline and 4 weeks of use of nightly use of study medication. Pain will be assessed using 11-point Numerical Rating Scale (NRS) where 0 = no pain and 10 = worst possible pain.
Time frame: Baseline to 4 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 50mcg Estradiol Cream | Change in Median Dyspareunia Pain Scores After 4 Weeks Using Study Drug | -1.5 score on a scale |
| 100mcg Estradiol Cream | Change in Median Dyspareunia Pain Scores After 4 Weeks Using Study Drug | -3 score on a scale |
p-value: 0.08Wilcoxon (Mann-Whitney)
Primary
Change in Median Pain Scores for Intercourse After 12 Weeks Using Study Drug
Difference in median dyspareunia pain scores between arms for intercourse at 12 weeks after use of nightly study medication for 90d. Pain will be assessed using 11-point Numerical Rating Scale (NRS) where 0 = no pain and 10 = worst possible pain.
Time frame: Baseline and 12 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 50mcg Estradiol Cream | Change in Median Pain Scores for Intercourse After 12 Weeks Using Study Drug | -4 score on a scale |
| 100mcg Estradiol Cream | Change in Median Pain Scores for Intercourse After 12 Weeks Using Study Drug | -5.5 score on a scale |
p-value: 0.95Wilcoxon (Mann-Whitney)