Genitourinary Syndrome of Menopause, Vulvovaginal Atrophy
Conditions
Keywords
Vulvovaginal atrophy, Genitourinary Syndrome of Menopause
Brief summary
Vulvovaginal atrophy (VVA) is a condition characterized by vaginal dryness, itching, burning, irritation and dyspareunia. The condition is mainly due to estrogen deficiency and is common during and after menopause. Furthermore, androgens may have an important function in these symptoms. The purpose of the study is to compare vaginal estrogen with vaginal dehydroepiandrosterone (DHEA, an androgen precursor) on dyspareunia (primary outcome), a symptom of VVA in postmenopausal women. Secondary outcomes are total symptom score of VVA (vaginal dryness, irritation/itching, maturation index, pH), clinical signs of VVA, sexual function, urogenital symptoms, vaginal histomorphology, sex hormone levels and short-term safety. The hypothesis of the study is that the treatments will have a similar effect on dyspareunia while DHEA, through local androgenic effects (eg growth of muscle tissue and nerve density in the vaginal wall), may be more effective in treating other related symptoms such as sexual dysfunction. 170 postmenopausal women will be randomly assigned to treatment with either vaginal estrogen (Vagifem) or vaginal DHEA (Intrarosa). The women are examined at the start of the study, after 4 weeks of daily application and after another 8 weeks of treatment with twice a week application of the vaginal treatment. The study is expected to provide increased knowledge about the effect of the treatments of VVA in postmenopausal women as well as whether vaginal DHEA has additional positive effects on sexual function compared to vaginal estrogen.
Interventions
DRUGvaginal estradiol 10 μg
Vagifem® (estradiol), vaginal tablets
DRUGvaginal DHEA 6.5 mg
Intrarosa® (dehydroepiandrosterone; DHEA; prasterone), pessaries
Sponsors
Angelica Lindén Hirschberg
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
40 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Postmenopausal women (non-hysterectomized or hysterectomized) must satisfy either: a) No menses for at least one year for non-hysterectomized women, or b) Follicle stimulating hormone (FSH) levels \>40 IU/L * Women who have self-identified at screening and baseline (Day 1) as experiencing moderate to severe dyspareunia, using VASQ questionnaire (section 1) * Between 40 and 80 years of age * Body mass index (BMI) 19-35 * Women having a vaginal pH above 5 at screening and baseline (Day 1) * Women who currently have intercourse or other sexual activity, at least once a month, with a partner * Normal mammogram within 12 months (of Day 1) * A normal PAP smear (which includes inflammatory changes) within the last 12 months (of Day 1) for both non-hysterectomized and hysterectomized women. * Understands Swedish and is willing to participate in the study and sign an informed consent
Exclusion criteria
* Undiagnosed abnormal vaginal bleeding * Previous diagnosis of cancer, except skin cancer (non-melanoma) * Lichen Sclerosis and other pathological conditions in vulva and/or vagina * Active or history of thromboembolic disease * Clinically significant metabolic or endocrine disease (including diabetes mellitus) not controlled by medication * Oral estrogen, progestin or DHEA exposure or intrauterine progestin therapy in the 8 weeks prior to baseline assessments (screening visit) * Vaginal hormonal products (rings, creams, gels or tablets) or transdermal estrogen alone or estrogen/progestin products in the 4 weeks prior to baseline assessments (screening visit) * Use of testosterone or other anabolic steroid within 6 months prior to screening visit * Natural oral estrogenic products in the 4 weeks prior to baseline assessments * Confirmed clinically significant depression (not controlled by standard therapy) or confirmed history of severe psychiatric disturbance * The administration of any investigational drug within 30 days of screening visit
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dyspareunia, a symptom of VVA in postmenopausal women | Primary endpoint will be evaluated as change in dyspareunia (VASQ section 1) from baseline to Week 12 | Patient reports in the Vaginal Atrophy Symptoms Questionnaire (VASQ, section 1). A 4-point scale, where a higher point means more symptoms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Sexual function | Change from baseline to Week 4 and 12 | Profile of Female Sexual Function (PFSF) and its seven domains desire, arousal, orgasm, pleasure, concern, responsiveness and self-image (range from 0 to 100, where a lower score means more dysfunction) |
| Urinary incontinence | Change from baseline to Week 4 and 12 | The Incontinence Impact Questionnaire (IIQ-7, a 4-point scale, where a higher point means more symptoms) |
| Histomorphology of the vaginal wall | Change from baseline to Week 4 and 12 | Histomorphology (thickness of epithelium, lamina propria and muscle layer in vaginal biopsies) |
| Sex hormone levels | Change from baseline to Week 4 and 12 | Sex hormone levels (estradiol and testosterone) |
| Total symptom score of VVA | Change from baseline to Week 4 and 12 | Vaginal dryness and irritation/itching (VASQ, section 2 and 3, a 4-point scale, where a higher point means more symptoms) |
| Clinical signs of VVA | Change from baseline to Week 4 and 12 | Examination of vaginal atrophy symptoms (VAX). A 4-point scale, where a higher point means more symptoms. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Urogenital distress | Change from baseline to Week 4 and 12 | Urogenital Distress Inventory (UDI-6, a 4-point scale, where a higher point means more symptoms) |
| Sexual activity | Change from baseline to Week 4 and 12 | Sexual activity log (SAL, the number of satisfying sexual episodes over a 1-week period) |
| Sexual distress | Change from baseline to Week 4 and 12 | the Personal Distress Scale (PDS, 0 \[no distress\] to 100 \[maximum distress\]). |
Countries
Sweden
Outcome results
None listed