绝经早期女性复发性外阴阴道念珠菌病的综合疗养治疗效果研究

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BACKGROUND

Women in the early postmenopause are particularly susceptible to variability of therapeutic interventions due to age-related and physiological factors [1–4]. These factors contribute to increased adhesion of Candida spp. yeast-like fungi, ultimately resulting in recurrent vulvovaginal candidiasis (RVVC). The treatment of postmenopausal women with RVVC presents specific challenges, is often limited to symptomatic relief, and tends to yield only short-term effects. Conservative management of RVVC in this population necessitates the development of individualized therapeutic and wellness strategies [5–7]. Under current conditions, spa treatment (ST) is considered a reasonable nonpharmacologic approach to comprehensive correction in postmenopausal women with RVVC. The potential benefits of integrated physical ST are attributed to its broad-spectrum effects on endocrine–metabolic processes and hormonal balance, as well as its notable sanogenetic and adaptogenic properties, all of which contribute to the absence of adverse reactions [8–13].

AIM

The work aimed to evaluate the effectiveness of comprehensive ST in early postmenopausal women with the sequelae of RVVC.

METHODS

This study was conducted at the Pyatigorsk Clinic of the North Caucasian Federal Scientific and Clinical Center of the Federal Medical and Biological Agency of Russia in Pyatigorsk and included 108 early postmenopausal women with mild to moderate climacteric symptoms and a history of RVVC previously treated with medication.

Inclusion criteria:

• Early postmenopause (defined as the period beginning one year after the final menstrual period and lasting no more than five years);
• A verified diagnosis of RVVC (≥ 4 recurrences per year), with the latest episode occurring more than two weeks after the last course of drug therapy, and with no detectable pathogens upon arrival at the health resort;
• Signed informed consent for follow-up monitoring and ST.

Non-Inclusion Criteria:

• General or specific contraindications to the selected natural or preformed physical therapy modalities;
• Presence of bacterial vaginosis, ureaplasmosis, mycoplasmosis, or other sexually transmitted infections requiring treatment;
• HIV infection;
• Positive test results for hepatitis C virus or syphilis (Wassermann reaction), or ongoing treatment for these conditions;
• Dermatologic diseases of the external genitalia.

ST methods: all patients were randomly assigned to one of three groups using simple random sampling. In the control group (n=36; group 3), patients received standard therapy for gynecologic conditions, including: therapeutic exercise, 30 minutes per session, 10 sessions per course; general iodine–bromine baths at 36–37 °C for 15 minutes, 8 sessions per course; color rhythm therapy using the ELM-01 Andro-Gin device (Russia) while seated and wearing therapeutic glasses. The device output was set to 1 mW for the first session and 4 mW from the second session onward, with a 2-second switching interval and a frequency of 10 Hz. Blue light was applied to both eyes for 10 minutes per day, totaling 8 sessions per course. In the reference group (n=36; group 2), the patients additionally received local combined peloid therapy: phonophoresis with Tambukan mud (Tambuil) using the Gineton-MM device (Russia). Before the procedure, the vaginal mucosa was cleansed with a furacilin solution; a Cusco vaginal speculum was inserted; then, 2 mL of oil-based Tambuil was administered intravaginally. A disposable VI5 applicator with a waveguide was used for circular insonation of the vaginal mucosa with the following parameters: ultrasound mode pulsed, duty cycle 2:1; ultrasound intensity: 0.1 W/cm²; frequency: 26.5 kHz; vibration amplitude at the waveguide tip: 60–80 μm; distance from the waveguide tip to the insonated surface: ≥ 10 mm; exposure time: 60 s; five sessions were administered on alternate days. In addition, patients received vaginal tampons soaked in oil-based Tambuil: the preparation was applied to a gauze tampon, which was inserted intravaginally once daily for 2 hours; 10 consecutive daily sessions were performed per course. In the main group (n=36; group 1), patients received, in addition to the treatment regimen used in group 2, combined endomassage and magnetic field therapy using the MANTIS MR 991 device (Italy) with the Mini DES applicator. The procedure was performed with the patient lying supine or prone in a special suit. The areas of exposure included the anterior abdominal wall or the L₅–S₁ spinal region. On the device’s touch control panel, the setting “pulsed magnetic fields in stochastic resonance (CMPS SYSTEM)” was selected in simple mode. Intensity was adjusted individually based on the patient’s painless sensory perception. On even-numbered days, sliding horizontal movements were performed with the applicator from the lateral abdominal regions toward the umbilicus, with the patient lying supine — 5 sessions total. On odd-numbered days, the applicator was used to perform slow, alternating vertical upward and downward movements combined with horizontal movements, with the patient lying prone — 5 sessions total. Each session lasted 10 minutes. The total course consisted of 10 sessions.

Criteria for ST effectiveness included: evaluation of vaginal microbiota using the Femoflor-16 test system; assessment of the degree of vaginal atrophy 6 months after completion of ST (post-treatment follow-up period); analysis of psychophysiological testing results based on the well-being, activity, and mood scale [14–16]. Statistical analysis was performed on a JBM PC Pentium IV–2.4 Hz using standard software (Windows XP operating system). Differences were considered statistically significant at p< 0.05. Vaginal microbiota results (i.e., the ratio of pathogenic to total bacterial load) were expressed in decimal logarithmic values.

RESULTS

The overall condition of the women in all three ST program groups remained satisfactory. No negative emotional responses were observed, and daily recorded vital signs were stable. Physiotherapeutic procedures were well tolerated across all groups, regardless of the severity of climacteric syndrome. No cases of intolerance or adverse effects were reported.

As shown in Fig. 1, the regression of total vaginal symptom complaints following ST was most pronounced on day 18 (upon completion of the ST course) in group 1, which received the newly developed treatment regimen. The score decreased from 3.33 to 0.11 points (p< 0.01). In group 2, the score also declined significantly (p< 0.01), from 3.04 to 1.40 points. In group 3, the score decreased from 2.85 to 2.00 points; however, this change was not statistically significant (p > 0.05).

 

Fig. 1. Regression of a set of clinical complaints.

 

Vaginal biocenosis was assessed using the Femoflor-16 test system. The ratio of pathogen count to total bacterial mass was expressed in decimal logarithms. Changes in the vaginal microbiota showed that only in group 1, which received the newly developed therapeutic and preventive ST protocol, the quantitative indicator of total bacterial mass reached 6.71±0.01, and the proportion of lactobacilli was 98.5%, consistent with absolute normocenosis. The relative quantitative indicator of aerobic and anaerobic opportunistic microorganisms was <−3 lg (0.1%), with only Peptostreptococcus spp. reaching −2.55±0.02 lg (0.1–1%), indicating a mildly elevated level. The absolute count of Candida spp. was 2.50±0.01 lg, which was not diagnostically significant. In women of group 2, the quantitative indicator of total bacterial mass was 6.20±0.03, and the proportion of lactobacilli was 96.8%, corresponding to absolute normocenosis. However, several aerobic and anaerobic opportunistic microorganisms were mildly elevated: Peptostreptococcus spp., 1.77±0.01 lg; Streptococcus spp., −1.37±0.02 lg (0.1%–1%); and Enterobacteriaceae spp., −2.01±0.02 lg (0.1%–1%). The absolute count of Candida spp. was 3.30±0.01 lg, which was not diagnostically significant, although some patients reported intermittent vaginal itching. By day 18 of the spa stay, vaginal normocenosis was diagnosed in women of group 1 based on Femoflor-16 testing, whereas women in group 2 demonstrated moderate mixed aerobic–anaerobic dysbiosis, requiring continued pharmacologic therapy at their place of residence. In group 3, which received standard ST, no significant changes in Femoflor-16 parameters were observed.

By day 18 after treatment and at the 6-month follow-up, nearly half of the women in group 1 exhibited vaginal microbiota consistent with absolute normocenosis. At 12 months, the smear type corresponded to an intermediate type, which is typical for healthy women in early postmenopause without subjective complaints or clinical manifestations. In group 2, conditional normocenosis and an intermediate smear type were observed on day 18 and at the 6-month follow-up. However, by 12 months, vaginal dysbiosis developed, characterized by a reduced lactobacillus count and low leukocyte levels. Yeast forms of fungi were identified in 10 women (27.8%). In group 3, only a dysbiotic smear type was recorded throughout the follow-up period. Yeast forms of fungi were found in every second woman at 6 months and in 34 women (94.4%) at 12 months.

As shown in table 1, at baseline, the degree of vaginal atrophy in early postmenopausal women with a history of RVVC corresponded to moderate atrophic changes in the vaginal epithelium, which periodically caused discomfort and interfered with daily activities. By 6 months, positive changes were observed in groups 1 and 2. However, only women in group 1 reported minimal disturbances and mild atrophic changes that did not affect their daily functioning.

 

Table 1. Dynamics of the degree of vaginal atrophy in women after the after-effect period of spa treatment

Period of observation	Group 1 (n = 36)	Group 2 (n = 38)	Group 3 (n = 33)	Statistical significance between groups, p (χ2 test)
Baseline	2.20±0.01	2.30±0.02	2.22±0.02	р1–2 >0.05; р2–3 >0.05; р1–3 >0.05
After 6 months	1.32±0.02	2.10±0.02	2.18±0.02	р1–2=0.0001; р2–3 >0.05; р1–3=0.0001
p (within group), Wilcoxon test baseline — 6 months	0.0001	0.005	0.40

 

Table 2. Dynamics of results of operational assessment of well-being, activity, mood

Period of observation	Group 1 (n = 36)	Group 2 (n = 38)	Group 3 (n = 33)	Statistical significance between groups, p (χ2 test)
Before/after day 18 WELL-BEING	3.36±0.21/ 5.11±0.10*	3.45±0.12/ 4.45±0.12*	3.15±0.20/ 4.16±0.13*	Before: р1–3. р1–3. р2–3 >0.05 Day 18: р1–2 >0.05. р2–3 >0.05. р1–3=0.0001
Before/after day 18 ACTIVITY	2.37±0.13/ 5.23±0.19	2.64±0.15/ 4.88±0.11	2.54±0.10/ 4.65±0.08	Before: р1–3. р1–3. р2–3 >0.05 Day 18: р1–3=0.002. р2–3 >0.05. р1–2 >0.05
Before/after day 18 MOOD	3.36±0.10/ 5.45±0.08	3.21±0.12/ 5.34±0.05	3.29±0.14/ 4.78±0.09	Before: р1–3. р1–3. р2–3 >0.05 Day 18: р1–2=0.005. р1–3=0.005. р2–3=0.005

Note. The numerator is the indicator before treatment, the denominator is the indicator after treatment. *p <0.01 — the significance of the differences between the indicators before and after treatment.

 

The changes in the psychophysiological testing results based on the well-being, activity, and mood scale on day 18 of treatment showed favorable outcomes in all groups of women with RVVC. In group 1, scores for well-being, activity, and mood significantly improved (p < 0.05) by the end of the spa-based treatment, reaching normative values. In group 2, the well-being score was interpreted as favorable but was statistically different from that in group 1. Notably, the difference between groups 1 and 3 was clearly statistically significant.

DISCUSSION

The primary component of the therapeutic program in women from groups 1 and 2 was centrally acting regulatory physiotherapy aimed at improving functional interactions within the higher regulatory centers of the reproductive system. This may be attributed to the influence of physical factors on both local regulatory pathways and central neurohumoral mechanisms [17–20]. Accordingly, the courses of the proposed ST programs used in groups 1 and 2 demonstrated clinical effectiveness in women in early postmenopause with RVVC. The magnitude and duration of the positive effects were more pronounced in group 1. This was associated with the use of physical factors applied to different target areas (general and local), taking into account both general somatic and gynecological complaints. The choice of therapeutic interventions was based on a comprehensive evaluation of overall health status, symptoms of menopausal syndrome, and the condition of the vaginal mucosa at the start of treatment. The effectiveness of the treatment was ensured by age-appropriate, specially developed mitigated therapeutic protocols.

CONCLUSION

The newly developed ST method for early postmenopausal women with RVVC sequelae promotes the restoration of vaginal microbiocenosis, reduces vaginal atrophy, and significantly improves quality of life.

ADDITIONAL INFORMATION

Author contributions. A.E. Bestaeva — collection and statistical processing of material, writing of text; M.V. Ipatova — concept and design of the study, statistical processing of material, writing of text; A.S. Kaisinova — concept and design of the study, writing of text, editing. All authors made a substantial contribution to the conception of the work, acquisition, analysis, interpretation of data for the work, drafting and revising the work, final approval of the version to be published and agree to be accountable for all aspects of the work.

Ethics approval. The study was approved by the local ethics committee of the Pyatigorsk Research Institute of Balneology of the Federal State Budgetary Institution SKFNC FMBA of Russia (protocol N. 4 dated 01/28/2020).

Consent for publication. All study participants voluntarily signed an informed consent form before inclusion in the study. The study protocol is posted at https://skfmba.ru

Funding sources. No funding.

Disclosure of interests. The authors have no relationships, activities or interests for the last three years related with for-profit or not-for-profit third parties whose interests may be affected by the content of the article.

Statement of originality. In creating this work, the authors did not use previously published information (text, illustrations, data).

Data availability statement. The editorial policy regarding data sharing does not apply to this work, and no new data was collected or created.

Generative AI. Generative AI technologies were not used for this article creation.

Provenance and peer-review. This paper was submitted to the journal on an unsolicited basis and reviewed according to the usual procedure. Two external reviewers, a member of the editorial board, and the scientific editor of the publication participated in the review.

作者简介

Angela Е. Bestaeva

North Caucasian Federal Scientific and Clinical Centre

Email: an.beataeva@yandex.ru
ORCID iD: 0009-0004-0371-3302
SPIN 代码: 1156-7981
俄罗斯联邦, Essentuki

Marina V. Ipatova

Academician V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology

Email: mavlip@yandex.ru
ORCID iD: 0000-0003-2094-8571
SPIN 代码: 1006-6969

MD, Dr. Sci. (Medicine)

俄罗斯联邦, Moscow

Agnessa S. Kaisinova

North Caucasian Federal Scientific and Clinical Centre; Pyatigorsk Medical and Pharmaceutical Institute — Volgograd State Medical University

编辑信件的主要联系方式.
Email: zamoms@skfmba.ru
ORCID iD: 0000-0003-1199-3303
SPIN 代码: 6552-9684

MD, Dr. Sci. (Medicine), Professor

俄罗斯联邦, Essentuki; Pyatigorsk

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