Introduction

Dysmenorrhea is one of the most commonly encountered menstruation disorders at puberty (Siserman et al., 2019; Paşcalău et al., 2021). When appropriate relief is not provided, patients are left incapacitated by dysmenorrhea, as neurohumoral regulation of the menstruation cycle is affected (Mekereș et al., 2017; Gabriela et al., 2020). Possible causes for primary dysmenorrhea are different and include increased prostaglandin secretion, hormonal imbalance, and the psychogenic factor, which is currently one of the most frequent causes of primary dysmenorrhea. Increased excitation of the nociceptive system and underactive hypothalamus cause pain syndrome (Pokrovsky et al., 2002; World Report on Noncommunicable Diseases 2010 Executive Summary, 2011; Sinchikhin et al., 2020; Olson et al., 2021).

The release of prostaglandins contributes to abnormal uterine contractions, which constrict blood vessels and reduce blood flow. The failure to maintain the supply of oxygen to muscle tissue leads to hypoxia; therefore, patients experience painful menstrual cramps, although pelvic pathologies are absent (Rodionova, 2016; Tokhiriyon, 2020; Tutelyan & Nikityuk, 2020; Szabo et al., 2021).

The current most usual treatment for dysmenorrhea includes non-steroidal anti-inflammatory drugs (NSAIDs), which are prostaglandin synthetase inhibitors, and cyclic vitamin therapy. Alternative approaches to relieve dysmenorrhea and to improve the experience of menstruation which are supported by good evidence, but much less frequently prescribed, include using herbal remedies like calendula, cyclodinone, nettle, pink radiola, sage, Chinese lemongrass, Baikal skullcap, remens, ginseng, and aralia. However, when considering using herbal remedies, various side effects have to be taken into account. As the potential risks to the immune and neuroendocrine systems associated with using herbal remedies are not thoroughly researched, further study is required. Currently, nutrition is considered to be important for reducing the severity of primary dysmenorrhea and recent studies of plant-based dietary supplements have demonstrated significant benefits in treating dysmenorrhea (Tokhiriyon, 2019; Bernstein, 2021; Ande, 2022; Hannon & Arslanian, 2023).

Materials and Methods

A new plant-based dietary supplement to help relieve dysmenorrhea was studied. The biochemical and pharmacological studies of the composition of the supplement were conducted, with the following qualitative and quantitative composition developed: Vaccinium macrocarpon (cranberry) extract - 5%, Arctium lappa (burdock root) - 1%, underground and above-ground parts of Comarum palustre (marsh cinquefoil) - 2%; Esobel (natural mineral salt found in Siberian lakes) - 5%; and sorbitol - 87%.

The new plant-based dietary supplement is marketed in a granular form. The active ingredients include such compounds as prostaglandins, fulvic and humic acids, amino acids, mineral salts with potassium, sodium, magnesium, calcium, Cl, So, CO, HCO anions, 4-hydroxyproibetaine, azulene, vitamins as well as phytoncides. Sorbitol is used as a filler. The color of the granules varies from light yellow to dark brown with a sweet taste and a faint smell. The supplement has passed all the required quality assurance tests and is officially registered.

A clinical trial was carried out to assess the supplement's effectiveness in reducing dysmenorrhea symptoms. Sixty participants with dysmenorrhea aged from 14 to 18 were selected for the present study. Before the enrolment, the participants underwent a gynecological examination and a pelvic ultrasound to assess the lower abdomen and pelvis and provided information on the date of their first menarche, the length of their menstrual cycle, underlying medical conditions, etc.

On the first day of their menstrual cycle, the experimental group's participants began taking the supplement, which they were instructed to take three times a day with a spoonful of a plant-based food supplement. Before using the supplement, warm water needs to be added to dissolve it. Following the approach that is typically used, cyclic vitamin treatment was administered. Two weeks of taking one Pentovit pill three times per day, followed by two weeks of taking one Aevit capsule three times per day (both vitamin supplements are made in Russia), were recommended to the experimental group members.

Additionally, the trial group's members underwent 10 sessions of electrotherapy. In the pelvic region, electrode pads were inserted and thoroughly soaked in the 1% solution of the supplement. The treatment for the participants of the control group consisted of vitamin supplements and a placebo.

An extensive questionnaire was used to perform the initial screening. The participants replied to a list of questions about age, weight, smoking and drinking habits, underlying conditions, and their treatment. Vital signs like body temperature, blood pressure, pulse rate, and respiration rate were recorded. Then every participant underwent a physical examination together with bacteriosopic and bacteriologic tests of cervical and vaginal microflora.

The next stage involved electrocardiograms, ultrasound examinations of mammary glands, abdominal organs (pancreas, liver, and gallbladder), and the pelvis with all the data carefully recorded. To measure the heart rate variability, a VNS-Micro vegetotester was used as it provides the opportunity to perform a complex study of the autonomous nervous system. Electroencephalogram scans were performed to evaluate the electrical activity of the brain. Clinical urine tests, full blood count, blood glucose, bilirubin, total protein, creatinine, and liver function tests were carried out. The immune status was analyzed with the help of immunocytochemistry, with the subpopulation composition of lymphocytes examined. Enzyme-linked immunosorbent assay technique was used to assess both pro- and anti-inflammatory responses. A student’s test was applied to analyze the data.

The clinical experiment was conducted at Tomsk Antenatal Clinic No. 4 and the Siberian State Medical University's laboratory complex. The clinical trial was overseen by highly qualified medical professionals, including A.M. Dygai, Doctor of Medical Sciences, professor, and member of the Russian Academy of Sciences, along with L.S. Sotninikova, Professor of Obstetrics and Gynecology at Siberian State Medical University, and N.M. Usynina, Obstetrician-Gynecologist at Tomsk Antenatal Clinic No. 4. The trial conforms in every way to Good Clinical Practice and the Helsinki Declaration.

The present study aims to evaluate the efficacy and safety of a plant-based dietary supplement in treating dysmenorrhea at puberty. The following objectives were set: (a) to study the dynamics of the changes in the brain’s electrical activity and the response of the autonomic nervous system, the morphofunctional state of lymphocytes, and the cell differentiation that occurs when participants are prescribed the dietary supplement and cyclic vitamin therapy and (b) to compare two different treatments of dysmenorrhea. The first treatment is a conventional treatment of dysmenorrhea with cyclic vitamin therapy, and the second treatment is a combination of vitamin therapy and a plant-based dietary supplement.

The objective performance criteria included: (a) the data obtained upon the gynecological examination and the ultrasound examination of the pelvis; (b) the changes in the cellular and humoral mechanisms of immunity, the subpopulation composition of lymphocytes, pro- and anti-inflammatory responses; and (c) the changes in the autonomic nervous system response, the brain’s electrical activity.

The overall health of the subjects and the nature of their complaints were taken into consideration for the subjective performance criteria.

Results and Discussion

According to the clinical trial findings, the tested dietary supplement demonstrated bactericidal, anti-inflammatory, and immune-stimulating effects. In this regard, to assess the effectiveness of the dietary supplement we studied the morphofunctional state of the immune and autonomic nervous systems.

The statistical processing of the data obtained during the trial was carried out to determine the following:

• the influence that the dietary supplement can have when taken in combination with conventionally prescribed medicines;
• the dynamics of different ways of treating dysmenorrhea;
• the differences in the duration of treatment performed with and without the supplement.

The patients in the experimental group had uterine appendages that were within the range of the physiological norm one month following the food supplement prescription, according to information from routine gynecological and ultrasound tests. The uterine appendages of the control group individuals didn't show any improvement in appearance until three months later.

At the same time, the favorable impact that the dietary supplement makes on the autonomic nervous system has been registered. The data obtained indicates that the balance between the systematic and parasympathetic nervous systems has been achieved. The results of cardiovascular tests and the spectral analysis of neurohumoral modulation demonstrated no abnormalities.

To evaluate the mental and emotional state of the participants, we used multidimensional tests. It has been registered that the active ingredients of the dietary supplement block the cascade of reactions that are triggered by the nervous system and inhibit the treatment process.

It is known that anxiety-depressive disorders and dysmenorrhea frequently co-occur with an autonomic dysfunction. The findings of the heart rate variability study demonstrated an imbalance in the functional health of the participants, with an increased activity of the sympathoadrenal system and a decreased activity of the parasympathetic system. These changes harm various aspects of participants’ everyday lives. The complex study of the autonomic nervous system allowed us to evaluate the functional health of the participants and their functional reserves, monitor the treatment, make predictions about the development of dysmenorrhea, and choose the most appropriate ways of treating the condition with neurohumoral regulation taken into account. Tables 1-3 list the data obtained during the study.

Table 1. The immune status

Table 2. Bacterioscopic tests

Table 3. Cardiovascular tests

When the patients were tested before the treatment, severe damage to the parasympathetic division of the autonomic nervous system and moderate damage to the sympathetic division of the autonomic nervous system were registered. Both the parasympathetic and sympathetic divisions had considerable damage, according to studies done following the therapy. Data on the spectrum analysis of neurohumoral regulation done before and after therapy are shown in Tables 4 and 5.

Table 4. The spectrum analysis of neurohumoral regulation before treatment

Table 5. The spectrum analysis of neurohumoral regulation after treatment