Local DHEA and Estradiol on Dyspareunia in Postmenopausal Women

Vulvovaginal Atrophy Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05586711
• Other study ID #: 2020-003254-76
• Status: Recruiting
• Phase: Phase 4
• Start date: December 18, 2020
• Est. completion date: December 2024

Study information

• Verified date: October 2022
• Source: Karolinska University Hospital
• Contact: Angelica L Hirschberg, MD, PhD
• Phone: +46 70 255 99 24
• Email: angelica.linden-hirschberg[@]regionstockholm.se
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 170
• Est. completion date: December 2024
• Est. primary completion date: December 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 40 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Atrophy
• Dyspareunia
• Genitourinary Syndrome of Menopause
• Vulvovaginal Atrophy

Intervention

Drug:
• vaginal estradiol 10 µg
Vagifem® (estradiol), vaginal tablets
• vaginal DHEA 6.5 mg
Intrarosa® (dehydroepiandrosterone; DHEA; prasterone), pessaries

Locations

Country	Name	City	State
Sweden	Karolinska University Hospital	Stockholm

Sponsors (1)

Lead Sponsor	Collaborator
Angelica Lindén Hirschberg

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Sexual activity	Sexual activity log (SAL, the number of satisfying sexual episodes over a 1-week period)	Change from baseline to Week 4 and 12
Other	Sexual distress	the Personal Distress Scale (PDS, 0 [no distress] to 100 [maximum distress]).	Change from baseline to Week 4 and 12
Other	Urogenital distress	Urogenital Distress Inventory (UDI-6, a 4-point scale, where a higher point means more symptoms)	Change from baseline to Week 4 and 12
Primary	Dyspareunia, a symptom of VVA in postmenopausal women	Patient reports in the Vaginal Atrophy Symptoms Questionnaire (VASQ, section 1). A 4-point scale, where a higher point means more symptoms.	Primary endpoint will be evaluated as change in dyspareunia (VASQ section 1) from baseline to Week 12
Secondary	Total symptom score of VVA	Vaginal dryness and irritation/itching (VASQ, section 2 and 3, a 4-point scale, where a higher point means more symptoms)	Change from baseline to Week 4 and 12
Secondary	Clinical signs of VVA	Examination of vaginal atrophy symptoms (VAX). A 4-point scale, where a higher point means more symptoms.	Change from baseline to Week 4 and 12
Secondary	Sexual function	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)	Change from baseline to Week 4 and 12
Secondary	Urinary incontinence	The Incontinence Impact Questionnaire (IIQ-7, a 4-point scale, where a higher point means more symptoms)	Change from baseline to Week 4 and 12
Secondary	Histomorphology of the vaginal wall	Histomorphology (thickness of epithelium, lamina propria and muscle layer in vaginal biopsies)	Change from baseline to Week 4 and 12
Secondary	Sex hormone levels	Sex hormone levels (estradiol and testosterone)	Change from baseline to Week 4 and 12