Treatment of vaginal atrophy with estriol and lactobacilli combination: a clinical review

Figures & data

Figure 1. Dual mechanism of action of 0.03 mg estriol/Lactobacillus acidophilus (0.03 mg-E3/L) combination^5,7,66.

Figure 2. Transformation of various estrogen types^40,41.

Table 1. Overview of main publications with 0.03 mg estriol (E3)–Lactobacillus acidophilus KS400 combination (0.03 mg-E3/L) relating to the treatment of vaginal atrophy.

Publication	Design	Patients	Intervention	Outcome
Kaiser et al. 2000^72	Pharmacokinetic, open, monocentric, multiple-dose	8 menopausal volunteers aged 57–65	0.03 mg-E3/L, 1 tablet per day for 12 days	VMI improved substantially, plasma concentrations of E3 remained at same level, no accumulation
Kanne & Jenny, 1991^16	Double-blind, active- and placebo-controlled, randomized, parallel-group, dose-finding	15 women with atrophic vaginitis aged 51–65	0.03 mg-E3/L, 2 tablets per day for 6 days or E3 0.5 mg + lactobacilli or lactobacilli	No significant difference between test medication (0.03 mg E3) and active control (0.5 mg E3)
Feiks & Grünberger, 1991^73	Double-blind, randomized, active-controlled, parallel groups	48 women with atrophic vaginitis aged 49–69	0.03 mg-E3/L, 1 tablet per day for 12 days and E3 0.5 mg 1 ovule per day for 12 days	No significant difference between 0.03 mg-E3/L and 0.5 mg E3
Jaisamrarn et al. 2013^61	Double-blind, randomized, placebo-controlled, parallel groups	83 women with symptomatic vaginal atrophy	0.03 mg-E3/L, 1 tablet per day for 12 days +12 weeks’ maintenance therapy 1 tablet twice a week	Significant improvement or disappearance of clinical signs and symptoms, normalization of VMI and LBG compared to placebo. Only a few local adverse reactions
Donders et al. 2014^53	Pharmacokinetic, open, monocentric, multiple-dose	16 BC survivors under AI therapy suffering from severe symptomatic vaginal atrophy	0.03 mg-E3/L, 1 tablet daily for 28 days + maintenance therapy of 3 tablets weekly for 8 weeks	Serum E3 transiently increased after first application. After 4 weeks, serum E3 levels increased in only 50% of women. The product was well tolerated
Buchholz et al. 2015^75	Pharmacokinetic, open, monocentric, multiple-dose	16 BC survivors under AI therapy suffering from severe symptomatic vaginal atrophy	0.03 mg-E3/L, 1 tablet daily for 28 days + maintenance therapy of 3 tablets weekly for 8 weeks	Vaginal atrophy resolved or improved. All vaginal flora markers of vaginal microflora and epithelial vaginal cell quality improved dramatically
Donders et al. 2015^76	Pharmacokinetic, open, monocentric, multiple-dose	16 BC survivors under AI therapy suffering from severe symptomatic vaginal atrophy	0.03 mg-E3/L, 1 tablet daily for 28 days + maintenance therapy of 3 tablets weekly for 8 weeks	Sexually active increased from 19% to 63% (44% intercourse). The sexual questionnaire highlighted trend for improved sexuality parameters
Capobianco et al. 2014^59	Prospective randomized, parallel groups	136 postmenopausal women with urogenital aging	Group I: triple therapy 0.03 mg-E3/L per day for 2 weeks and two ovules once a week for 6 months + pelvic rehabilitation; Group II: one intravaginal estriol 1.0 mg ovule similar regimen + pelvic rehabilitation	Symptoms and signs of urogenital atrophy improved in both groups. Therapy with 0.03 mg-E3/L was more effective for urogenital aging in postmenopausal women due to synergic action

AI, aromatase inhibitor; BC, breast cancer; LBG, lactobacillary grade; VMI, vaginal epithelium maturation index.

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