Indication
Blissel (Estriol 50 micrograms/g Vaginal Gel) is indicated for local treatment of vaginal dryness in post-menopausal women with vaginal atrophy. The gel vehicle employed is highly hydrating, clear, aqueous, and strongly mucoadhesive. Blissel is administered (using a dose-marked applicator) once daily for 3 weeks, then twice weekly for maintenance treatment.1
  • An innovative, strongly hydrating
    mucoadhesive, clear gel for the local
    treatment of vaginal atrophy
  • Ultra-low concentration of estriol
    (0.005% w/w estriol)
The clinical efficacy of Blissel has been evaluated in the following clinical studies:
The therapeutic effect of a new ultra-low concentration estriol gel formulation (0.005% estriol vaginal gel) on symptoms and signs of post-menopausal vaginal atrophy: results from a pivotal phase III study.2
In a double-blind placebo-controlled trial, 167 post-menopausal women with vaginal atrophy were randomised to receive either 1g of vaginal gel containing 50 microgram estriol or 1g of placebo (vehicle) gel, daily for 3 weeks and then twice weekly for a further 9 weeks.

After 12 weeks of treatment, women receiving estriol gel (n=114) showed significant
improvements in the maturation value of vaginal epithelium (the primary endpoint – see Figure 4) and vaginal pH (see Figure 5) compared with those receiving placebo (n=53; p < 0.001 for both endpoints). There were also significant improvements in signs of vaginal atrophy such as fragility, dryness and pallor of the mucosa and flattening of folds.

For patient-reported symptoms, assessed as
secondary endpoints, statistical significance versus placebo was reached for vaginal dryness after 12 weeks of treatment, but not for dyspareunia, vaginal pruritus, burning or dysuria. Nevertheless, the mean global symptom score at week 12 was significantly lower in women treated with estriol than in those who received placebo (p=0.02).

In total 88.2% of estriol-treated patients reported improvement, or resolution, of vaginal dryness compared with 66.7% of patients who received placebo (p=0.001). The authors highlighted the hydrating properties of the gel vehicle, which was used (without the active ingredient) as the study placebo and could have contributed to the lack of significance achieved for some of the patient reported endpoints.

Figure 4. Vaginal Maturation Value (MV) at baseline and at weeks 3 and 12 (p<0.001)
Overall, 73.6% of patients in the estriol group considered the gel's effectiveness as excellent or good, compared with 43.1% of those in the placebo group. Opinion on aspects related to the product itself (leakage, cleanliness, and ease of administration) was, as expected, more balanced with 87.7% (estriol) and 84.3% (placebo) considering these special features as excellent or good - see Figure 6.

Treatment-related adverse events were similar in the two groups.

Figure 5. Vaginal pH at baseline and weeks 3 and 12 (p<0.001)
Figure 6. Final evaluation of the acceptability of therapy as expressed by patients at the final visit
Quality of life and sexual function of naturally post-menopausal women on an ultra-low concentration estriol vaginal gel3
Post-menopausal women with vulvovaginal atrophy symptoms and sexual disorders were enrolled in a case control study. Sixty-eight women were treated with vaginal gel (containing 50 mcg of estriol) daily for 3 weeks and then twice weekly up to 12 weeks.
Determination of vaginal maturation index, vaginal pH, and assessment of vaginal atrophy symptoms were carried out. QoL, sexual function, and distress were also investigated. Changes between baseline and week 12 were assessed.
Figure 7. Vaginal pH of postmenopausal women before and after 12 weeks Blissel treatment
After 12 weeks treatment, women on estriol vaginal gel had a significant increase in vaginal maturation index and improvement of vaginal pH (see Figure 7) compared with baseline (p < 0.05) and there were significant improvements from baseline in somatic aspects of quality of life (p < 0.05) and sexual health- see Table 2.
Table 2. Comparison between baseline and 12th week follow-up Female Sexual Function Scale (FSFS)
References

1. Blissel SmPC (Accessed February 2022)

2. Cano, A. et. al. 2012 ‘The therapeutic effect of a new ultra-low concentration estriol gel formulation (0.005% estriol vaginal gel) on symptoms and signs of postmenopausal vaginal atrophy: results from a pivotal phase Ⅲ study’, The North American Menopause Society, Volume 19, No.10, 1130-9

3. Caruso, S. et. al. 2016 ‘Quality of life and sexual function of naturally postmenopausal women on an ultralow-concentration estriol vaginal gel’, The North American Menopause Society. Volume 23, No.1, 47-54