Effects of Ospemifene on Brain Activation Patterns in Women With Sexual Interest-arousal Disorders — EROS  

Genitourinary Syndrome of Menopause Clinical Trial

Official title: Effects of Ospemifene on Brain Activation Patterns in Women With Sexual Interest-arousal Disorders

Status Recruiting

Clinical 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. 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.

Clinical Trial 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). ;

Related Conditions & MeSH terms

• Disease
• Genitourinary Syndrome of Menopause
• Sexual; Disorder, Arousal, Female
• Vulvovaginal Signs and Symptoms

• NCT number: NCT04677491
• Study type: Interventional
• Source: Hospital Clinic of Barcelona
• Contact: EDUARD MENSION COLL
• Phone: 626207171
• Email: edmension@gmail.com
• Status: Recruiting
• Phase: Phase 4
• Start date: November 1, 2021
• Completion date: December 1, 2022