Local DHEA and Estradiol on Dyspareunia in Postmenopausal Women

Effects of Local Dehydroepiandrosterone (DHEA) and Estradiol on Moderate to Severe Dyspareunia, a Symptom of Vulvovaginal Atrophy in Postmenopausal Women - a Randomized, Controlled Study

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.

Study Overview

• Status: Recruiting
• Conditions: Vulvovaginal Atrophy; Genitourinary Syndrome of Menopause
• Intervention / Treatment: Drug: vaginal estradiol 10 μg; Drug: vaginal DHEA 6.5 mg

• Study Type: Interventional
• Enrollment (Anticipated): 170
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Angelica L Hirschberg, MD, PhD; Phone Number: +46 70 255 99 24; Email: angelica.linden-hirschberg@regionstockholm.se

Study Locations

• Sweden
  • Stockholm, Sweden, 171 76
    • Recruiting
    • Karolinska University Hospital
    • Contact: Angelica L Hirschberg, MD, PhD; Phone Number: +46 70 255 99 24; Email: angelica.linden-hirschberg@regionstockholm.se
    • Sub-Investigator: Moa Strandberg, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 38 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Vaginal estradiol 10 μg	Drug: vaginal estradiol 10 μg; Vagifem® (estradiol), vaginal tablets
Active Comparator: Vaginal DHEA 6,5 mg	Drug: vaginal DHEA 6.5 mg; Intrarosa® (dehydroepiandrosterone; DHEA; prasterone), pessaries

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
Sex hormone levels	Sex hormone levels (estradiol and testosterone)	Change from baseline to Week 4 and 12

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Sexual distress	the Personal Distress Scale (PDS, 0 [no distress] to 100 [maximum distress]).	Change from baseline to Week 4 and 12
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

Collaborators and Investigators

• Sponsor: Angelica Lindén Hirschberg

Study record dates

Study Major Dates

• Study Start (Actual): December 18, 2020
• Primary Completion (Anticipated): December 1, 2023
• Study Completion (Anticipated): December 1, 2024

Study Registration Dates

• First Submitted: October 9, 2022
• First Submitted That Met QC Criteria: October 15, 2022
• First Posted (Actual): October 19, 2022

Study Record Updates

• Last Update Posted (Actual): October 19, 2022
• Last Update Submitted That Met QC Criteria: October 15, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Genitourinary Syndrome of Menopause; Vulvovaginal atrophy
• Additional Relevant MeSH Terms: Mental Disorders; Pathological Conditions, Anatomical; Sexual Dysfunctions, Psychological; Sexual Dysfunction, Physiological; Atrophy; Dyspareunia; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Estrogens; Estradiol
• Other Study ID Numbers: 2020-003254-76

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No