Vulvovaginal Signs and SymptomsPhase 4EROSNCT04677491
Effects of Ospemifene on Brain Activation Patterns in Women With Sexual Interest-arousal Disorders
A Phase 4 study testing Ospemifene 60 mg and fMRI experiments in people with Vulvovaginal Signs and Symptoms and Genitourinary Syndrome of Menopause, run by Hospital Clinic of Barcelona at 1 site in Spain.
Trial summary
Ospemifene is the first oral and non-hormonal treatment for moderate or severe vulvo-vaginal atrophy (VVA) in postmenopausal women who are not candidates to treatment with local oestrogens. Read more about this study
- Who is it for?
- Any age, women only
- Conditions the study is for
- Vulvovaginal Signs and Symptoms, Genitourinary Syndrome of Menopause, Sexual; Disorder, Arousal, Female
- What is being tested?
- Ospemifene 60 mg and fMRI experiments
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 25 participants
- Where
- 1 siteSpain
- Study dates
- 1 Nov 2021to 1 Dec 2023
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- Women only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Women 40 year old or older who have been diagnosed with menopause (either chemical, surgical or natural menopause)
- No menstruation for at least a year.
- Moderate or severe VVA diagnosis (defined by the presence of ≤ 5% of superficial cells and vaginal pH > 5).
- For homogenisation of brain patterns, women had to be right-handed.
- Women should be strictly heterosexual, in a stable relationship of at least 1 year duration (with expectations of remaining with the same relationship), and have had experience viewing sexually explicit images
- For the FSIAD groups, women will be included if they are diagnosed with FSIAD, defined according to the criteria of DSM-V and confirmed by a structured clinical interview and by means of the scores of the SFQ and the FSDS-R (with a score of ≤20 for FSFI and ≥15 for the FSDS-R, respectively). These criteria will be an exclusion criterion for women without FSIAD.
- Informed written consent of the patient.
Who cannot join
- Women with known history of mental illness, history of drug or alcohol abuse.
- Women with VVA treatment (oestrogens or ospemifene) at any time during the last 6 months, and/or laser treatment at any time during the last year.
- Use of medication or herbal preparations at any time during the last 3 months for the purpose of improving sexual performance.
- Women who have received any medication previous to the study inclusion, that may alter or interfere with brain activation patterns (psychoactive drugs).
- Women with history of sexual offenses.
- Women with abnormal vision that would impair the visualisation of the images and the olfactory stimuli.
Show all 16Show fewer
- Women with claustrophobia or implants that would preclude fMRI procedures.
- Women with diagnosis of depression assessed by PHQ self-administered questionnaire.
- Patients who had undergone vaginal surgery in the last 12 months.
- Women who did not sign the written informed consent.
- Hypersensitivity to the active substance or to any of the excipients included in Senshio.
- Past or active history of venous thromboembolic events (VTE), including deep vein thrombosis, pulmonary embolism and retinal vein thrombosis.
- Unexplained vaginal bleeding.
- Patients with suspected breast cancer or who are receiving active treatment (including adjuvant treatment) for breast cancer.
- Suspicion of neoplasia or active neoplasia dependent on sex hormones (eg endometrial cancer).
- Patients with signs or symptoms of endometrial hyperplasia; In this group of patients, safety has not been studied.
Trial locations and contacts
1 site in 1 country.
About this study
Ospemifene is the first oral and non-hormonal treatment for moderate or severe vulvo-vaginal atrophy (VVA) in postmenopausal women who are not candidates to treatment with local oestrogens. Its effects are mediated though the regeneration of the proportion of superficial and intermediate cells of the vagina, improving menopausal symptomatology such as dryness and dyspareunia.
Only two studies to date have directly compared brain activation patterns in women with normal sexual function with women complaining with hypoactive sexual desire disorder. Arnow et al. demonstrated that women with normal sexual function showed brain activations in multiple regions different from women with FSIAD. When comparing the two groups, women with normal sexual function showed greater activation of the bilateral entorhinal cortex while women with FSIAD exhibited greater activation of the medial frontal gyrus, right inferior frontal gyrus, and bilateral putamen. The medial frontal gyrus activation has been associated with self-monitoring; thus, it is possible that women with FSIAD allocate more attention to monitoring their response, which may be inhibitory to sexual functioning. The other study was done by Woodard and colleges showing that women with normal sexual function showed significantly differences on cerebral activation in comparison with women with FSIAD.
Read more
These differences observed in women with FSIAD could suggest that they may have alterations in activation of limbic and cortical structures responsible for acquiring, encoding, and retrieving memory, the processing and memory of emotional reactions, and areas responsible for heightened attention to one's own physical state.
For this reason the authors believe that it is essential to determine if the effect of ospemifene on the improvement on sexual function is due to the improvement on the vagina tract or due to its effect on brain function.
Read the detailed description
To evaluate changes from baseline in brain activation patterns, by using functional magnetic resonance imaging (fMRI) techniques and sexual stimuli, in postmenopausal women with moderate to severe vulvovaginal atrophy and FSIAD after 3 months treatment with ospemifene 60mg/day compared to those treated with placebo. fMRI technique allows the study of brain activation by detecting brain blood flow and oxygen level dependent changes induced by neuronal activation.
The brain activation patterns will be defined by the number of voxels that significantly changed their signal intensity during the stimuli presentation compared to the neutral stimuli. Brain connectivity will be evaluated by using the activation map and the atlas of neuroanatomic regions and comparing the number of voxels, its level of significance and the different regions activated.
Brain activation patterns changes (with fMRI) after sexual stimuli (visual or olfactive), in postmenopausal women with moderate to severe VVA and FSIAD after 3 months treatment with ospemifene 60mg/day compared to those treated with placebo.
During the fMRI session, the activation of each brain circuits/pattern is measured by the blood-oxygen level dependent (BOLD) signal and with the Statistical Parametric Mapping method regularly used in fMRI studies to visualize brain activation.
For the longitudinal study, a paired t-test will be used within each group to detect changes in activation over time. The statistical threshold criterion to compare the different activation maps between both groups is p < 0.001 uncorrected with a minimum extent of 10 voxels. Only clusters that survive a p < 0.05 FWE (family wise error) correction for multiple comparisons will be considered statistically significant The region of interests who were mainly observed are: medial occipital gyrus, anterior cingulate cortex, bilateral thalamus, caudate nucleus, left pale globe, cerebellum, left inferior parietal lobe, postcentral gyrus, praecuneus, right medial frontal gyrus and left praecuneus.
A total of 20 consecutive postmenopausal women with moderate to severe VVA and FSIAD with symptomatology will be recruited to participate in the study, 10 of which will be randomised to the ospemifene group (VVA-FSIAD ospemifene group) and 10 will be randomised to the placebo group (VVA-FSIAD placebo group). Additionally, a total of 5 consecutive postmenopausal women with moderate to severe VVA not treated with ospemifene neither with any other VVA treatment and without FSIAD will also be recruited (VVA not treated patients without FSIAD).
- Conditions
- Vulvovaginal Signs and Symptoms, Genitourinary Syndrome of Menopause, Sexual; Disorder, Arousal, Female
- Being tested
- Ospemifene 60 mg, fMRI experiments
- Keywords
- Sexual Disorder, Genitourinary Syndrome of Menopause
- Medical subject headings
- Coitus, Sexual Dysfunction, Physiological
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ospemifene 60 mgDrug
Also called Senshio
Ospemifene vs placebo
fMRI experimentsBehavioural
Participants will see sexually explicit video clips that alternate with non-sexual clips and neutral color projection and b) smell alternate pheromones with clear air and pine aroma.
| Study group | Role | What they receive |
|---|---|---|
| VVA-FSIAD ospemifene group | Active comparator | Women treated with ospemifene 60 mg/day Receives: Drug: Ospemifene 60 mg; Behavioral: fMRI experiments |
| VVA-FSIAD placebo group | Placebo comparator | Women treated with placebo Receives: Behavioral: fMRI experiments |
What is being measured
The primary outcome is the main question the study is designed to answer.
a Activation of each brain circuits
Is measured by the blood-oxygen level dependent (BOLD)
Measured: 3 months
Secondary outcomes (9)
Vaginal pH
vaginal pH measured by ph roll from 1 to 14
Measured: 3 months
Vaginal maturation index
vaginal maturation index meadured by vaginal citology on percentage from 0 to 100 divided in superficial, intermediate and basal cells
Measured: 3 months
Vaginal health index
To describe if there is a correlation between changes in the visual examination of the vagina. using the vaginal health index: from 5 to 25 (min-max).
Measured: 3 months
Female Sexual Function Index
Questionaire from 18 to 90 (min-max).
Measured: 3 months
DSM V evaluation
DSM Criteria
Measured: 3 months
Quality of Life Scale
Questionaire PHQ9 (Patient health questionaire 9) from 0 to 27 (min-max)
Measured: 3 months
Female Sexual Distress Scale
Questionaire FSFI (Female Sexual Function Index) from 18 to 90 (min-max).
Measured: 3 months
Social Functioning Questionnaire
Questionaire SF12 (Physical and Mental Health Composite Scores) from 0 to 12 (min-max)
Measured: 3 months
Patient Health Questionnaire-9
Questionaire from 0 to 9
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Dec 2020
- Study start1 Nov 2021
- Primary completion1 Nov 2022
- Study completion1 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Vulvovaginal Signs and SymptomsStudies of the same condition, open and under way.
- More trials run by Hospital Clinic of BarcelonaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Health services research
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Pilot study, randomised prospective study, triple blind, placebo controlled.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospital Clinic of Barcelona
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Camil Castelo-Branco, Hospital Clinic of Barcelona
- Investigators
- Camil Castelo-Branco, Principal investigator, Hospital Clinic of Barcelona
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04677491
- Sponsor's protocol ID
- 2020-001514-38
- Acronym
- EROS
- Status last verified
- Feb 2022
- First submitted
- 23 Nov 2020
- Last updated
- 15 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Ospemifene on Brain Activation Patterns in Women With Sexual Interest-arousal Disorders
- ClinicalTrials.gov ID
- NCT04677491
- Acronym / sponsor ID
- EROS / 2020-001514-38
- Conditions
- Vulvovaginal Signs and Symptoms, Genitourinary Syndrome of Menopause, Sexual; Disorder, Arousal, Female
- Keywords
- Sexual Disorder, Genitourinary Syndrome of Menopause
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Hospital Clinic of BarcelonaUniversity, hospital or other
- Study start
- 1 Nov 2021 (actual)
- Primary completion
- 1 Nov 2022 (actual)
- Study completion
- 1 Dec 2023 (actual)
- First posted
- 21 Dec 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Ospemifene is the first oral and non-hormonal treatment for moderate or severe vulvo-vaginal atrophy (VVA) in postmenopausal women who are not candidates to treatment with local oestrogens. Its effects are mediated though the regeneration of the proportion of superficial and intermediate cells of the vagina, improving menopausal symptomatology such as dryness and dyspareunia.
Only two studies to date have directly compared brain activation patterns in women with normal sexual function with women complaining with hypoactive sexual desire disorder. Arnow et al. demonstrated that women with normal sexual function showed brain activations in multiple regions different from women with FSIAD. When comparing the two groups, women with normal sexual function showed greater activation of the bilateral entorhinal cortex while women with FSIAD exhibited greater activation of the medial frontal gyrus, right inferior frontal gyrus, and bilateral putamen. The medial frontal gyrus activation has been associated with self-monitoring; thus, it is possible that women with FSIAD allocate more attention to monitoring their response, which may be inhibitory to sexual functioning. The other study was done by Woodard and colleges showing that women with normal sexual function showed significantly differences on cerebral activation in comparison with women with FSIAD.
These differences observed in women with FSIAD could suggest that they may have alterations in activation of limbic and cortical structures responsible for acquiring, encoding, and retrieving memory, the processing and memory of emotional reactions, and areas responsible for heightened attention to one's own physical state.
For this reason the authors believe that it is essential to determine if the effect of ospemifene on the improvement on sexual function is due to the improvement on the vagina tract or due to its effect on brain function.
Detailed description
To evaluate changes from baseline in brain activation patterns, by using functional magnetic resonance imaging (fMRI) techniques and sexual stimuli, in postmenopausal women with moderate to severe vulvovaginal atrophy and FSIAD after 3 months treatment with ospemifene 60mg/day compared to those treated with placebo. fMRI technique allows the study of brain activation by detecting brain blood flow and oxygen level dependent changes induced by neuronal activation.
The brain activation patterns will be defined by the number of voxels that significantly changed their signal intensity during the stimuli presentation compared to the neutral stimuli. Brain connectivity will be evaluated by using the activation map and the atlas of neuroanatomic regions and comparing the number of voxels, its level of significance and the different regions activated.
Brain activation patterns changes (with fMRI) after sexual stimuli (visual or olfactive), in postmenopausal women with moderate to severe VVA and FSIAD after 3 months treatment with ospemifene 60mg/day compared to those treated with placebo.
During the fMRI session, the activation of each brain circuits/pattern is measured by the blood-oxygen level dependent (BOLD) signal and with the Statistical Parametric Mapping method regularly used in fMRI studies to visualize brain activation.
For the longitudinal study, a paired t-test will be used within each group to detect changes in activation over time. The statistical threshold criterion to compare the different activation maps between both groups is p < 0.001 uncorrected with a minimum extent of 10 voxels. Only clusters that survive a p < 0.05 FWE (family wise error) correction for multiple comparisons will be considered statistically significant The region of interests who were mainly observed are: medial occipital gyrus, anterior cingulate cortex, bilateral thalamus, caudate nucleus, left pale globe, cerebellum, left inferior parietal lobe, postcentral gyrus, praecuneus, right medial frontal gyrus and left praecuneus.
A total of 20 consecutive postmenopausal women with moderate to severe VVA and FSIAD with symptomatology will be recruited to participate in the study, 10 of which will be randomised to the ospemifene group (VVA-FSIAD ospemifene group) and 10 will be randomised to the placebo group (VVA-FSIAD placebo group). Additionally, a total of 5 consecutive postmenopausal women with moderate to severe VVA not treated with ospemifene neither with any other VVA treatment and without FSIAD will also be recruited (VVA not treated patients without FSIAD).
Study design
- Primary purpose
- Health services research
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Pilot study, randomised prospective study, triple blind, placebo controlled.
| Arm | Type | Receives |
|---|---|---|
| VVA-FSIAD ospemifene group | Active comparator | Drug: Ospemifene 60 mg, Behavioral: fMRI experimentsWomen treated with ospemifene 60 mg/day |
| VVA-FSIAD placebo group | Placebo comparator | Behavioral: fMRI experimentsWomen treated with placebo |
Who may qualify
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- Women 40 year old or older who have been diagnosed with menopause (either chemical, surgical or natural menopause)
- No menstruation for at least a year.
- Moderate or severe VVA diagnosis (defined by the presence of ≤ 5% of superficial cells and vaginal pH > 5).
- For homogenisation of brain patterns, women had to be right-handed.
- Women should be strictly heterosexual, in a stable relationship of at least 1 year duration (with expectations of remaining with the same relationship), and have had experience viewing sexually explicit images
Key exclusion criteria (16 listed)
- Women with known history of mental illness, history of drug or alcohol abuse.
- Women with VVA treatment (oestrogens or ospemifene) at any time during the last 6 months, and/or laser treatment at any time during the last year.
- Use of medication or herbal preparations at any time during the last 3 months for the purpose of improving sexual performance.
- Women who have received any medication previous to the study inclusion, that may alter or interfere with brain activation patterns (psychoactive drugs).
- Women with history of sexual offenses.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ospemifene 60 mgAlso: SenshioOspemifene vs placebo | Drug | VVA-FSIAD ospemifene group |
| fMRI experimentsParticipants will see sexually explicit video clips that alternate with non-sexual clips and neutral color projection and b) smell alternate pheromones with clear air and pine aroma. | Behavioural | VVA-FSIAD ospemifene group, VVA-FSIAD placebo group |
Primary outcome
a Activation of each brain circuits
Time frame: 3 months
Is measured by the blood-oxygen level dependent (BOLD)
9 secondary outcomes
Vaginal pH
Time frame: 3 months
Vaginal maturation index
Time frame: 3 months
Vaginal health index
Time frame: 3 months
Female Sexual Function Index
Time frame: 3 months
DSM V evaluation
Time frame: 3 months
Quality of Life Scale
Time frame: 3 months
Female Sexual Distress Scale
Time frame: 3 months
Social Functioning Questionnaire
Time frame: 3 months
Patient Health Questionnaire-9
Time frame: 3 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Sep 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Camil Castelo-Branco principal investigator
Hospital Clinic of Barcelona
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Ospemifene 60 mg and fMRI experiments in people with Vulvovaginal Signs and Symptoms and Genitourinary Syndrome of Menopause, run by Hospital Clinic of Barcelona at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
a Activation of each brain circuits (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Sep 2025.