Vaginal hormone-free moisturising cream is not inferior to an estriol cream for treating symptoms of vulvovaginal atrophy: Prospective, randomised study

Abstract

This prospective, open-label, multicentre, multinational, randomised trial investigated the non-inferiority of treatment with a vaginal hormone-free moisturising cream compared to a vaginal estriol (0.1%) cream in a panel of post-menopausal women suffering from symptoms of vulvovaginal dryness in a parallel group design. In total, 172 post-menopausal women were randomly allocated to either one of the two treatments, each administered for 43 days. The primary endpoint was the total severity score of subjective symptoms (dryness, itching, burning and pain unrelated to sexual intercourse) of the respective treatment period. Secondary endpoints were severity of single subjective symptoms (including dyspareunia if sexually active), impairment of daily life, Vaginal Health Index, as well as assessment of safety. In both groups, women treated with hormone-free moisturising cream and those treated with estriol cream, total severity score improved significantly compared to baseline by 5.0 (from 6.1 to 1.1) and by 5.4 (from 6.0 to 0.6), respectively, after 43 days of treatment (p < 0.0001). One-sided test of baseline differences (for a clinically relevant difference Δ = 1.5) confirmed the hormone-free moisturising cream to be non-inferior to the estriol cream. Severity of dyspareunia as well as impairment of daily life due to subjective symptoms, significantly improved for both treatment groups (p<0.0001). Subgroup analysis of women with mild or moderate impairment of daily life at baseline caused by "vaginal dryness" symptoms benefited from both creams, while women with severe impairment showed a significantly greater benefit from the estriol cream (p = 0.0032). Both treatments were well tolerated with no serious adverse events occurring. This study provides clinical evidence that a hormone-free vaginal moisturising cream cannot only improve vaginal dryness compared to an 0.1% estriol cream but also can relieve dyspareunia as well as improve woman's impairment of daily life, justifying its use as a first choice for mild or moderate vulvovaginal dryness symptoms.

Fig 1. CONSORT flow diagram.

Disposition of patients. SP, Safety Population; ITT, Intention-To-Treat Population; PP, Per Protocol Population.

Fig 2. Mean of Total Severity Score (TSS) over time.

Mean of TSS (sum score of the single subjective symptom parameters: dryness, itching, burning and pain unrelated to sexual intercourse) over time until Day 43. Scale of TSS: 0 = no complaints to 16 = very severe complaints. Values represent Mean ± SEM. Number of patients (PP): Hormone-free moisturizing cream n = 80; Estriol cream n = 71.

Fig 3. Vulvovaginal subjective symptoms at baseline.

Percentage of patients suffering from at least mild subjective symptoms or free of symptoms. Number of patients (PP): Hormone-free moisturizing cream n = 80; Estriol cream n = 71.

Fig 4. Vulvovaginal subjective symptoms at the end of the treatment.

Percentage of treated patients with improvement of their individual subjective symptoms at the end of the treatment (Day 43). Number of patients (PP): Hormone-free moisturizing cream n = 80; Estriol cream n = 71.

Fig 5. Dyspareunia severity.

Percentage of patients for the assessment of dyspareunia severity (if sexually active). The total number of patients refers to sexually active patients at Day 1/ Day 43: Hormone-free moisturizing cream n = 64/57; Estriol cream n = 42/37. Scale severity score for dyspareunia: 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe.

Fig 6. Comparison of the impairment of daily life due to each of the subjective symptoms (AUC).

Values represent Mean ± 95% CI. Not significant (n.s.). *Due to different baseline values, an ANCOVA using the baseline value as covariate was performed. The result demonstrated no significant difference at Day 43 between treatments.

Fig 7. Overall impairment of daily life due to the condition "vaginal dryness".

Number of patients (PP) with mild/moderate/severe “vaginal dryness” in each treatment group: Hormone-free moisturizing cream n = 20/24/32; Estriol cream n = 19/30/21. Mean ± 95% CI of the AUC value. Not significant, p > 0.05.

Fig 8. Objective assessment of vaginal findings.

Improvement of all Vaginal Health Index criteria (objective assessment of vaginal findings) and significant differences in favor of the estriol cream. Number of patients (PP): Hormone-free moisturizing cream n = 74; Estriol cream n = 69. Mean AUC values ± 95% CI. Mann-Whitney-Wilcoxon tests were applied to evaluate any differences in the effect of the treatments (statistically significant, p < 0.001).