TX-004HR Improves Sexual Function as Measured by the Female Sexual Function Index in Postmenopausal Women With Vulvar and Vaginal Atrophy: The REJOICE Trial

Introduction: TX-004HR is an investigational, applicator-free, vaginal soft gel capsule containing low-dose solubilized 17 beta-estradiol. The phase 3, randomized, double-blinded, placebo-controlled, multicenter REJOICE trial has shown TX-004HR to be safe and effective for the treatment of moderate to severe dyspareunia in postmenopausal women with vulvar and vaginal atrophy (VVA). Aim: To evaluate the effect of TX-004HR on female sexual dysfunction in postmenopausal women with VVA. Methods: The REJOICE study compared the effects of 12-week treatment with TX-004HR (4, 10, or 25 mu g) with placebo in postmenopausal women (40-75 years old) with VVA and a most bothersome symptom of moderate to severe dyspareunia. Changes in the percentage of superficial and parabasal cells, vaginal pH, and dyspareunia were measured as co-primary end points. Female sexual dysfunction was evaluated as a secondary end point using the Female Sexual Function Index (FSFI) patient self-report inventory. Main Outcome Measures: Changes from baseline to week 12 in total and individual domain FSFI scores for each TX-004HR dose were compared with those for placebo. Results: All three TX-004HR doses increased the baseline total FSFI score after 12 weeks, with 10 mu g (P < .05) and 25 mu g (P = .0019) having a significantly greater effect than placebo. A similar trend was observed for the individual FSFI domains, with 10 and 25 mu g significantly improving baselines scores for pain and lubrication at 12 weeks (P <= .015 for all vs placebo). Changes from baseline to week 12 in arousal (P = .0085) and satisfaction (P = .0073) were significantly greater for TX-004HR 25 mu g vs placebo. All three TX-004HR doses were comparable to placebo in their effect on desire and orgasm. Conclusion: TX-004HR improved FSFI scores in a dose-dependent manner. The observed improvements in sexual function suggest that TX-004HR is a promising treatment option for postmenopausal VVA with a potential added beneficial effect on female sexual dysfunction. Copyright (C) 2016, The Authors. Published by Elsevier Inc. on behalf of the International Society for Sexual Medicine.