Clinical trial NCT05586711: Local DHEA and Estradiol on Dyspareunia in Postmenopausal Women
Official title: Effects of Local Dehydroepiandrosterone (DHEA) and Estradiol on Moderate to Severe Dyspareunia, a Symptom of Vulvovaginal Atrophy in Postmenopausal Women - a Randomized, Controlled Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Vulvovaginal Atrophy
Genitourinary Syndrome of Menopause
Keywords: Vulvovaginal atrophy
Genitourinary Syndrome of Menopause
Lead sponsor: Karolinska University Hospital
Sponsor class: OTHER
First posted: 2022-10-19
Enrollment: 170
Sex: FEMALE
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Dyspareunia, a symptom of VVA in postmenopausal women
timeFrame: Primary endpoint will be evaluated as change in dyspareunia (VASQ section 1) from baseline to Week 12
Secondary outcomes:
measure: Total symptom score of VVA
timeFrame: Change from baseline to Week 4 and 12
measure: Clinical signs of VVA
timeFrame: Change from baseline to Week 4 and 12
measure: Sexual function
timeFrame: Change from baseline to Week 4 and 12
measure: Urinary incontinence
timeFrame: Change from baseline to Week 4 and 12
measure: Histomorphology of the vaginal wall
timeFrame: Change from baseline to Week 4 and 12
measure: Sex hormone levels
timeFrame: Change from baseline to Week 4 and 12
Other outcomes:
measure: Sexual activity
timeFrame: Change from baseline to Week 4 and 12
measure: Sexual distress
timeFrame: Change from baseline to Week 4 and 12
measure: Urogenital distress
timeFrame: Change from baseline to Week 4 and 12
Locations:
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
Study officials:
References: