Gynoflor Mechanism of Action

Pharmacotherapeutic Group: Gynaecological anti-infectives and antiseptic. ATC Code: G01AX99.
Pharmacology: Pharmacodynamics: Lactobacillus acidophilus is one of the predominant microorganisms of the vaginal flora in healthy women. Lactobacilli are non-pathogenic bacteria and have a protective function in the vagina. It ferments glycogen stored in the vaginal epithelium to lactic acid. The resulting acidic environment (pH 3.8-4.5) provides unfavourable conditions for the colonisation and growth of pathogenic microorganisms, and provides an optimal medium for the proliferation of the Lactobacilli.
In addition to lactic acid, lactobacilli produce hydrogen peroxide and bacteriocins which also inhibit the growth of pathogenic microorganisms.
Estriol is an endogenous estrogenic hormone which has a specific effect on the vagina but not on the endometrium. The purpose of the estriol in Gynoflor is to ensure proliferation and maturation of the vaginal epithelium. A proliferated and matured vaginal epithelium acts as physical barrier and stores glycogen, a nutritional substrate for lactobacilli. In the case of hormonal disorders, more commonly observed at advanced age, the vaginal epithelium is disturbed and the glycogen content is decreased. Vaginal infections can also lead to a damaged vaginal epithelium.
Exogenous estriol, even in very low dose contained in Gynoflor, improves the proliferation and maturation of the epithelium, and thus provides the optimal conditions for the restoration of the vaginal lactobacilli flora.
Disturbance or elimination of the physiological vaginal flora can occur mainly as a result of local or systemic treatment with anti-infective agents, serious general illnesses, improper hygienic measures and vaginal infections. In a non-physiological vaginal environment, the lactobacilli are reduced in number or even absent and the protective function is no longer assured.
The therapeutic concept of Gynoflor is based on the restoration of the vaginal flora through exogenous lactobacilli, and the improved proliferation and maturation of the vaginal epithelium by exogenous estriol, resulting in the re-establishment of the physiological equilibrium of the vaginal flora and the vaginal epithelium.
Lactobacillus acidophilus and estriol exert their actions locally within the vagina.
Lactose, used for manufacturing of the vaginal tablets, can also be fermented to lactic acid by the lactobacilli. Reproduction of the lactobacilli and recolonisation of the vagina by these bacteria does start after the 1st application of Gynoflor.
Pharmacokinetics: As soon as Gynoflor comes into contact with vaginal secretion, the tablet begins to disintegrate, and lactobacilli as well as estriol are released. In vitro experiments have demonstrated that the lactobacilli resume their metabolism and cause a pH reduction within a few hours.
The positive estrogenic effect induced by estriol is also quickly initiated, and the proliferation and maturation status of the vaginal epithelium improves progressively over the course of treatment (6-12 days).
The absorption of estriol from Gynoflor was investigated in healthy, postmenopausal women with atrophic epithelia. After a single intravaginal application of Gynoflor, there was an increase in the plasma concentration of unconjugated estriol (biologically active form) above the basal level and the maximum estriol concentration was reached after 3 hrs. After 8 hrs, the plasma concentration of unconjugated estriol was no longer elevated. However, after the 12th application at the end of the therapy with Gynoflor (once daily), the peak plasma level of unconjugated estriol was not elevated as compared to the basal level.
During the 12-day treatment, no accumulation of estriol was observed. The plasma concentrations observed after repeated application of Gynoflor were within normal range of the endogenous, postmenopausal plasma level of unconjugated estriol.
The plasma concentrations of estrone and estradiol are not affected by estriol therapy, since estriol is their metabolic end-product. Estriol is eliminated rapidly in the urine, primarily in biologically inactive forms (glucuronides, sulphates).
Due to the low dose of estriol (0.03 mg), the local application and the limited duration of treatment (6-12 days), no accumulation of estriol occurs and systemic estrogen effects are very unlikely.
Toxicology: Preclinical Safety Data: Two toxicological aspects must be considered for drugs administered by the vaginal route, the local tolerance and the possibility of systemic toxicity due to absorption of the components.
Lactobacilli are the predominant microorganisms in the healthy human vagina and are regarded as non-pathogenic. For this reason, the introduction of these bacteria into the vagina is not expected to cause any local irritation or epithelial damage.
Results of animal experiments (Wistar rats) have demonstrated that only high doses of estriol can lead to a feminisation of the male foetus.
It should be noted that toxicological data obtained in rodents are of limited value and cannot be extrapolated to man since estriol is specific for humans and does not occur in other mammalian species.
Considering the low dose of estriol in Gynoflor, no acute toxicity is to be expected.