Authored by Orazov МR*
Abstract
Introduction: Genitourinary syndrome of menopause (GSM) is a pressing gynecological problem since the condition leads to the deterioration in the quality of life of postmenopausal women.
Objective: compare the efficacy of relief of GSM with intravaginal use of estriol monoproduct and a combination product containing estriol, micronized progesterone and Lactobacillus casei rhamnosus Doderleini.
Materials and Methods: the study enrolled 69 postmenopausal women aged 53.6±2.1 diagnosed with postmenopausal atrophic vaginitis. After screening, the patients were randomized into 2 groups: Group 1 (n=34) used 0.5 mg/day of estriol monoproduct intravaginal for 14 days, followed by a gradual dose reduction based on symptom relief until a maintenance dose was reached (i.e. 1 suppository 2 times a week), Group 2 (n=35) used intravaginal combination product in the form of capsules containing 0.2 mg of estriol, 2.0 mg of micronized progesterone and lyophilized culture of L. casei rhamnosus Doderleini – 341mg (2*107 CFU) (Trioginal, Besins Healthcare SA, Belgium). The product was prescribed to be taken at a dose of 2 capsules intravaginal 1 time/day for 20 days, then 1 capsule/day. Total duration of therapy in both groups was 12 weeks. After the end of therapy, patients were monitored for 12 weeks. To determine the efficacy of the treatment, subjective and objective clinical symptoms of GSM were evaluated using the adapted Nappi RE scale at the study visits. 5-point D. Barlow scale, vaginal pH, Bachmann’s Vaginal Health Index was additionally used. The main software for statistical analysis was the IBM SPSS 22 statistical package.
Results: After 12 weeks of treatment, complaints of dyspareunia resolved completely in 18 (52.9%) patients in Group 1 and 25 (71.5%) in Group 2, p<0.05; 12 weeks after the end of therapy: in 24 (70.6%) patients in Group 1 and in 34 (97.1%) patients in Group 2, p<0.05. Improvement in elasticity after 12 weeks of therapy was observed in 19 (55.9%) and 27 (77.1%) patients of Group 1 and Group 2, respectively (p<0.05); normal epithelial thickness was observed in 26 (76.5%) and 30 (85.7%) patients, respectively (p<0.05). 12 weeks after the end of treatment in Group 1 and Group 2, improvement in elasticity was observed in 22 (64.7%) and 30 (85.7%) patients; normal epithelial thickness was observed in 22 (64.7%) and 27 (77.1%) patients, respectively (p<0.05). For the rest of analysed parameters (D. Barlow scale, pH, Bachmann’s Vaginal Health Index) statistical analysis did not reveal any statistically significant differences between the groups in the dynamics of treatment and follow-up.
Conclusion: Thus, local combination hormone therapy with probiotic support can be an effective treatment option for genitourinary syndrome of menopause since it helps to enhance proliferative processes, improve blood circulation, restore biocenosis and relieve symptoms of coital pain. Compared with local estriol monotherapy, having a comparable effect on the condition of vaginal epithelium, it is significantly more effective for eliminating the symptoms of sexual dysfunction.
Keywords: Genitourinary syndrome of menopause; Vulvo-vaginal atrophy; Local hormone therapy
Introduction
Due to increasingly aging of the population the problem of relieving symptoms caused by age-related changes in the female uro genital tract during menopause remains one of the most pressing problems of the world gynaecology. The widely used terms “uro genital syndrome”, “atrophic vulvovaginitis”, including the diagnosis “postmenopausal atrophic vaginitis” in ICD-X (N95.2) and similar definitions do not reflect the entire scope of modern ideas about the cause, pathogenesis and clinical presentation of the syndrome.
In 2014, the new term “genitourinary syndrome of menopause” (GSM) was introduced into clinical practice to replace the term “vulvovaginal atrophy”, which was commonly accepted earlier and did not fully reflect the essence of the problem. The term GSM emphasizes the many genital, sexual and urinary symptoms associated with the anatomical and functional changes in the vulvovaginal tissues that occur during aging [1].
According to the modern integrative definition, GSM is a complex of symptoms that includes physiological and anatomical changes that occur secondary not only to estrogen deficiency but also other sex steroids in women in the external genitalia, perineum, vagina, urethra and bladder. The use of the new term by all related specialists who deal with the problem of urogenital disorders in women is of high clinical significance since it allows us to consider the complex effect of all sex steroid hormones on the urogenital region [2-4].
According to modern recommendations for menopausal hormone therapy and maintaining the health of older women, local estrogen therapy is the “gold” standard for the treatment of vulvovaginal atrophy. Moreover, local estrogen therapy in low doses is preferable for women with complaints of vaginal dryness or associated discomfort during sexual activity. Vaginal oestrogens are generally more effective for alleviating urogenital symptoms than oral products due to no liver metabolism and a quick vaginal response [5,6]. The modern polyhormonal concept of the pathogenesis of GSM opens up new potential opportunities for studying ways to optimize its traditional local estrogen therapy by additionally prescribing topical forms of products of other sex hormones, for example, a combination of estriol with progesterone, androgens (DHEA), thus turning the hormonal local monotherapy of GSM into hormonal combination local therapy. As is shown in clinical practice, complex hormonal impact gives better results in a shorter time. After local saturation with estriol and progesterone, vaginal colonization with the necessary lactobacilli becomes more favourable, which is necessary to restore normal vaginal micro flora [7,8].
In Russia, in addition to estriol monoproduct, another product is used for intravaginal use in GSM, which is a combination of estriol with micronized progesterone and lactobacillus casei rhamnosus Doderleini (LCR) in vaginal capsules (Trioginal, Besins Healthcare SA, Belgium). The main advantage of the complex product is micronized progesterone in its content with its effects that are not related to the classical role of sexual reproduction. Oestrogens promote the growth and maturation of the vaginal epithelium, as well as the synthesis and accumulation of glycogen, which is a key substrate for the activity of lactobacilli, which must be in the lumen of the vagina in order to be utilized by lactobacilli. The process of release of glycogen from the vaginal epithelium requires participation of progesterone, which contributes to the formation of intermediate layers of vaginal epithelium and its natural desquamation. A similar situation takes place in the hormone-dependent tract of the lower urinary tract, where oestrogens perform the same critical physiological functions for urothelium, ensuring its growth and maturation, synthesis and accumulation of glycogen, as well as synthesis of local immunity factors (immunoglobulin’s) and protective mucopolysaccharides – glycosaminoglycan’s (hyaluronic acid and its sodium and zinc salts, chondroitin sulphate, glycoproteins, mucin) that make up the surface glycocalyx of the bladder mucosa – a powerful natural system of antibacterial and anti-inflammatory protection of the lower urinary tract [9-11]. However, complete natural antibacterial protection of the urothelium of the urethra and bladder in women is impossible without progesterone, which is related to the fact that oestrogens affect the synthesis of glycosaminoglycan’s in urothelium of the bladder, and progesterone affects their release by urothelium out into the lumen of the bladder [12-13]. Moreover, it is important to emphasize non-reproductive effects of micronized progesterone: analgesic – due to suppression of the synthesis of prostaglandins; neuroprotective and neuroreparative – due to selective effect on the receptors of neurotransmitters; regulatory – due to increased synthesis of muscle protein [14].
Thus, modern literature indicates that in order to ensure normal anatomical and functional state of the lower urinary and genital tracts in women, a sufficient level of both estrogen and progesterone is necessary [15-17]. Disorder of the synthesis and release of glycogen secondary to deficiency of sex hormones leads to rapid alkalization of the vagina and the development of dysbiotic processes – a decrease in the number of lactobacilli and an excessive growth of pathogenic and conditionally pathogenic microorganisms [18]. According to the data of Hillier SL, et al. in a detailed analysis of vaginal micro flora of 73 postmenopausal women who did not receive hormonal therapy, 49% had no lactobacilli at all, while in those who had the concentration was 10-100 times lower than in premenopausal women. According to other studies, lactobacilli predominate in the vaginal microflora only in 13% of postmenopausal women not taking hormonal therapy. In postmenopausal women, the most common microorganisms are anaerobic gram-negative bacilli and gram-positive cocci [19]. Thus, the normalization of vaginal microflora is one of the goals of treatment of GSM. Moreover, recently there has been evidence that normalization of vaginal microflora not only reduces the frequency of relapse of urinary tract infections in women in peri- and postmenopausal women, but also contributes to a more rapid relief of GSM symptoms [20-21]. The goal of lactobacilli in products for the treatment of GSM symptoms is to reduce pH and maintain normal biocenosis, preventing colonization of the vagina by pathogenic bacteria.
The goal of this study was to compare the efficacy of the relief of symptoms of genitourinary syndrome of menopause with intravaginal use of estriol monoproduct and a combination product containing estriol, micronized progesterone and Lactobacillus casei rhamnosus Doderleini.
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