Sexual Dysfunction, Physiological
Conditions
Keywords
Female Sexual Arousal Disorder, FSAD
Brief summary
This randomized, double-blind, placebo-controlled clinical trial investigated the effect of once daily oral administration of 20 mg estetrol monohydrate tablet for 12 weeks in postmenopausal women who experienced sexual arousal disorder. Specifically, the main aim was to evaluate whether estetrol (E4) is effective in the treatment of female sexual arousal disorder (FSAD) in women after their menopause.
Detailed description
Female Sexual Arousal Disorder (FSAD), a subtype of female sexual dysfunction, is an inability to attain or to maintain an adequate lubrication-swelling response of sexual excitement. FSAD may manifest as a decrease in vaginal lubrication and a decrease in genital sensation related to blood flow and can cause marked distress and/or interpersonal difficulty (Diagnostic and Statistical Manual (DSM) of Mental Disorders, 4th edition \[DSMIV\]). Estrogen has a role in maintaining genital tissue structural integrity and pelvic nerve-stimulated genital blood flow. This study was conducted with estetrol (E4), assessing the efficacy and safety of estetrol monohydrate 20 mg (E4 20 mg), equivalent to estetrol 18.9 mg, for the treatment of FSAD associated with menopause in hysterectomized postmenopausal women. The design of this Phase 2, Proof of Concept (POC) study was: randomized, double-blind, placebo-controlled, two-arm parallel group. Eligible subjects were randomized in a 1:1 ratio and received either an oral tablet of E4 20 mg or placebo, once daily for 12 weeks. Placebo tablet looked identical to E4 but had no active ingredient. During the study, participants visited the clinic 7 times and completed a daily e-diary. The results were evaluated regarding the effect of E4 and placebo on the sexual arousal of the participants, using several validated questionnaires. The primary efficacy endpoints were the change from Baseline to Week 12: * in feeling concerned by difficulties with sexual arousal, assessed by Female Sexual Distress Scale-Desire/Arousal/Orgasm (FSDS-DAO) Item 14; * in the Sexual Function Questionnaire (SFQ-28) Arousal-Sensation Domain (Questions 6 to 9). Secondary efficacy endpoints were the change from Baseline to Week 12: * in arousal and lubrication assessed by Patient-Reported Outcomes Measurement Information System-Sexual Function and Satisfaction (PROMIS-SexFS) Questionnaire; * in sexual function assessed by FSDS-DAO - total score and by percentage of Satisfying Sexual Event (SSE) captured in e-diary; * in sexual function assessed by SFQ-28 - total score; * in sexual function assessed by PROMIS-SexFS; * in severity of sexual arousal disorder as assessed by Patient Global Impression of Severity (PGIS). The secondary efficacy endpoint Patient Global Impression of Change (PGIC) was assessed at Week 12.
Interventions
DRUGEstetrol
Estetrol monohydrate 20 mg, equivalent to estetrol 18.9 mg
OTHERPlacebo
Matching Placebo to E4
Sponsors
Estetra
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
40 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Main Inclusion Criteria: • Hysterectomized postmenopausal women, ≥40 up to ≤65 years, diagnosed with Female Sexual Arousal Disorder Main
Exclusion criteria
* Not willing to stop any hormonal products during their participation in the study * History of unresolved sexual trauma or abuse that is contributing to any sexual dysfunction problem * Have experienced a recent major life stress or relationship discord that could interfere with sexual activity * Clinically significant abnormal gynecological findings * History of malignancy, with the exception of basal cell or squamous cell carcinoma of the skin * Systolic BP higher than 140 mmHg, diastolic BP higher than 90 mmHg * Is judged by the investigator to be unsuitable for any reason
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 12 in Feeling Concerned by Difficulties With Sexual Arousal, Assessed by Female Sexual Distress Scale-Desire/Arousal/Orgasm (FSDS-DAO), Item 14 | Baseline, Week 12. | The Female Sexual Distress Scale-Desire/Arousal/Orgasm (FSDS-DAO) is a validated 15-item self-assessment where each item is scored from 0 (never) to 4 (always). Higher scores on this scale, which has a total range of 0-60, indicate greater distress. Item 14 assesses how often the subject has felt concerned by difficulties with sexual arousal during the past 30 days. |
| Change From Baseline to Week 12 in the Sexual Function Questionnaire 28 (SFQ-28) Arousal-Sensation Domain (Questions 6 to 9) | Baseline, Week 12. | The 28-item Sexual Function Questionnaire (SFQ-28) is a validated self-assessment tool to assess female sexual function. It has 8 domains, including domains for desire, arousal (sensation/lubrication/cognitive), orgasm, pain, enjoyment, and partner relationship. Questions are scored on a Likert scale (e.g., 0 to 5 or 1 to 5), where lower scores indicate higher levels of dysfunction. Questions 6, 7, 8, and 9 deal with the domain "Arousal-sensation". Score range for this domain is: 4-20 (=sum of Questions 6-9). Total score range is: 24-141 (=sum of all Questions 1-28). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 12 in Arousal and Lubrication Assessed by Patient Reported Outcomes Measurement Information System (PROMIS) Sexual Function and Satisfaction (SexFS) Measures (PROMIS-SexFS Questionnaire) | Baseline, Week 12. | The PROMIS-SexFS is an instrument to measure self-reported sexual function and satisfaction. In total, 24 questions (out of 26) are rated on a 5-point scale each, so that for each question, the score range may be 1-5 or 0-5 (0=not applicable). Questions (Q) can be grouped by domains; their scores are summed to calculate the domain score. There are 11 domains in total. A higher score indicates a better outcome in the following domains: arousal and lubrication (3Q; 3-15), interest in sexual activity (2Q, score range: 2-10), orgasm-pleasure (2Q; 0-10), orgasm-ability (1Q; 0-5), and satisfaction with sex life (4Q; 3-20). A higher score indicates a worse outcome in the following domains: vaginal discomfort (2Q; 2-10), vulvar discomfort (2Q; 2-10), vulvar dysfunction (2Q; 2-10), oral discomfort (2Q; 2-10), oral dryness (2Q; 2-10), anal discomfort (2Q; 2-10). The 2 remaining questions of the questionnaire are for screening purposes. |
| Change From Baseline to Week 12 in Sexual Function Assessed by FSDS-DAO -- Total Score | Baseline, Week 12. | The Female Sexual Distress Scale-Desire/Arousal/Orgasm (FSDS-DAO) is a validated 15-item self-assessment where each item is scored from 0 (never) to 4 (always). Higher scores on this scale, which has a total range of 0-60, indicate greater distress. |
| Change From Baseline to Week 12 in Sexual Function Assessed by Percentage of Satisfying Sexual Events (SSE) -- Captured in Arousal Electronic Diary (Ediary) | Baseline, Week 12. | A higher number of Satisfying Sexual Events (SSE) indicates an improvement in sexual function. The arousal electronic diary contains a questionnaire to be completed by the subject within 24 hours of a sexual event. |
| Change From Baseline to Week 12 in Sexual Function Assessed by the Sexual Function Questionnaire 28 (SFQ-28) -- Total Score | Baseline, Week 12. | The 28-item Sexual Function Questionnaire (SFQ-28) is a validated self-assessment tool to assess female sexual function. It has 8 domains, including domains for desire, arousal (sensation/lubrication/cognitive), orgasm, pain, enjoyment, and partner relationship. Questions are scored on a Likert scale (e.g., 0 to 5 or 1 to 5), where lower scores indicate higher levels of dysfunction. Questions 6, 7, 8, and 9 deal with the domain "Arousal-sensation". Score range for this domain is: 4-20 (=sum of Questions 6-9). Total score range is: 24-141 (=sum of all Questions 1-28). |
| Change From Baseline to Week 12 in Sexual Function Assessed by PROMIS-SexFS | Baseline, Week 12. | Refer to Description of Outcome Measure #3. |
| Patient Global Impression of Change (PGIC) at Week 12 | Week 12. | Patient Global Impression of Change (PGIC) was used to measure changes in sexual arousal disorder. At Week 12, each enrolled subject was asked to rate their change in sexual arousal on 7-point Likert scale. The results are presented as the number of participants. The grading of responses were from 'No Change' to 'A Great Deal Better', as shown in the results table below. |
| Change From Baseline to Week 12 in Severity of Sexual Arousal Disorder as Assessed by Patient Global Impression of Severity (PGIS) | Baseline, Week 12. | Patient Global Impression of Severity (PGIS) was used to evaluate the severity of sexual arousal disorder at a given time. The subject is asked to rate the severity of their sexual arousal dysfunction on 7-point Likert scale (1=not present, 2=very mild, 3=mild, 4=moderate, 5=moderately severe, 6=severe, and 7=extremely severe). A lower score indicates an improvement. |
Countries
United States
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 56.07 years STANDARD_DEVIATION 5.21 |
| Arousal and Lubrication Assessed by PROMIS-SexFS Questionnaire | 7.2 scores on a scale STANDARD_DEVIATION 3.25 |
| Body Mass Index (BMI) | 29.41 kg/m^2 STANDARD_DEVIATION 4.607 |
| FSDS-DAO, Item 14 | 3.5 score STANDARD_DEVIATION 0.6 |
| FSDS-DAO -- Total Score | 43.0 score STANDARD_DEVIATION 9.95 |
| Patient Global Impression of Severity (PGIS) | 5.3 scores on a scale STANDARD_DEVIATION 1.44 |
| Percentage of Satisfying Sexual Events (SSE) | 31.2 Percentage of SSE STANDARD_DEVIATION 38.44 |
| PROMIS-SexFS: Anal Discomfort | 2.3 scores on a scale STANDARD_DEVIATION 0.93 |
| PROMIS-SexFS: Interest in Sexual Activity | 4.9 scores on a scale STANDARD_DEVIATION 1.46 |
| PROMIS-SexFS: Oral Discomfort | 2.8 scores on a scale STANDARD_DEVIATION 1.55 |
| PROMIS-SexFS: Oral Dryness | 3.4 scores on a scale STANDARD_DEVIATION 1.83 |
| PROMIS-SexFS: Orgasm- ability | 2.0 scores on a scale STANDARD_DEVIATION 1.1 |
| PROMIS-SexFS: Orgasm- pleasure | 3.4 scores on a scale STANDARD_DEVIATION 2.71 |
| PROMIS-SexFS: Satisfaction with Sex Life | 6.9 scores on a scale STANDARD_DEVIATION 3.19 |
| PROMIS-SexFS: Vaginal Discomfort for Sexual Activity | 5.5 scores on a scale STANDARD_DEVIATION 2.21 |
| PROMIS-SexFS: Vulvar Discomfort with Sexual Activity - clitoral | 3.3 scores on a scale STANDARD_DEVIATION 1.9 |
| PROMIS-SexFS: Vulvar Discomfort with Sexual Activity - labial | 4.6 scores on a scale STANDARD_DEVIATION 2.44 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 19 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 23 Participants |
| Region of Enrollment United States | 73 participants |
| Sex: Female, Male Female | 37 Participants |
| Sex: Female, Male Male | 0 Participants |
| Sexual Function Questionnaire 28 (SFQ-28) Arousal-Sensation Domain (Questions 6 to 9) | 7.0 scores on a scale STANDARD_DEVIATION 2.28 |
| Sexual Function Questionnaire 28 (SFQ-28) -- Total Score | 64.1 scores on a scale STANDARD_DEVIATION 12.89 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 41 | 0 / 41 |
| other Total, other adverse events | 18 / 41 | 10 / 41 |
| serious Total, serious adverse events | 0 / 41 | 0 / 41 |
Outcome results
None listed