Estetrol for the Treatment of Female Sexual Arousal Disorder in Postmenopausal Women

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.