INTRODUCTION: Recent surveys have indicated that postmenopausal women do continue to have sex, even at advanced age. However, the symptoms of vulvar and vaginal atrophy (VVA) can have a profound impact on sexual functioning and on the relationship with their partner. Ospemifene, a Selective Estrogen Receptor Modulator (SERM) approved for the treatment of moderate to severe symptomatic VVA in post-menopausal women who are not candidates for local vaginal oestrogen therapy in Europe, does not only provide effective relief of VVA symptoms, but has also shown to have a positive effect on sexual function as measured by the Female Sexual Function Index (FSFI). The FSFI is a 19-question questionnaire, measuring sexual function in women in six domains. In this study, women enrolled with either vaginal dryness or dyspareunia as their Most Bothersome Symptom (MBS). We wanted to examine the impact of MBS or sexual activity on the change in FSFI score. AIM: To analyse the impact of the MBS and sexual activity on the change in FSFI score in a clinical trial with ospemifene. METHODS: Post hoc analysis of the populations with dyspareunia and vaginal dryness and also the populations who reported at least one episode of sexual activity during the trial and those that did not report any sexual activity. RESULTS: FSFI data were available of 311 women enrolled in the vaginal dryness stratum and 592 women enrolled in the dyspareunia stratum. 780 Women reported at least one episode of sexual activity during the trial whilst 123 women reported no sexual activity (24.4% in the dryness, 7.9% in the dyspareunia stratum). In the dyspareunia stratum, all domains of the FSFI showed statistically significant improvement vs. placebo in women using ospemifene 60 mg. All women who did not have any sexual activity during the trial showed deterioration in FSFI score. DISCUSSION: The FSFI questionnaire was developed to measure sexual functioning. To derive an unambiguous full scale score, the FSFI is appropriately used only for subjects who have had some level of sexual activity during the measurement period (Rosen et al. J Sex Marit Ther 2000). The improvement in all domains of the FSFI is evident in women with dyspareunia as MBS. Women with no sexual activity during the study attenuate the improvements in FSFI score. Senshio® (ospemifene 60 mg) improves sexual functioning in postmenopausal women with VVA who are sexually active.