Abstract

Introduction: Pelvic varicosity, a subset of pelvic venous incompetence (PVI), is considered a multifactorial, chronic disease with a progressive course. One effective therapeutic approach may be the use of drugs that inhibit oxidative stress (OS) reactions. The aim of this study was to evaluate the effect of an antioxidant complex on the state of the lipid peroxidation system and venous hemodynamic parameters in the treatment of patients with pelvic varicose veins.

Methods: One hundred fifty patients with PVI were divided into two groups of seventy-five each, comparable in basic characteristics. Treatment for both groups included standard therapy with one of the venotropic drugs for 60 days. Additionally, the patients in the second group received an antioxidant complex application (ACA) for 30 days (one course), with a total of three courses over two months. Spectrophotometric and immunoenzymatic research methods were used.

Results: In patients with PVI, the application of an antioxidant complex in combination with baseline venotropic therapy resulted in a statistically significant decrease in levels of LH, CDs, TBARs, and an increase in Catalase, SOD, GPO, GR, GST, and GSH after treatment. Additionally, there was an increase in blood flow velocity in varicose pelvic veins (iliac, ovarian, and arcuate), as well as a decrease in the duration of retrograde discharge to 0.3 cm.

Conclusion: The use of antioxidant drugs (superoxide dismutase, acetyl glutathione, astaxanthin) in combination with venotropic therapy for the treatment of PVI significantly improves the indices of the lipid peroxidation-antioxidant defense system and venous hemodynamics in the pelvic organs of this patient cohort. The advantages of this complex treatment are evident both in comparison with the data before treatment and with the data from patients on venotropic therapy alone.

Introduction

Pelvic varicosity is a distinct subgroup of pelvic venous incompetence (hereinafter referred to as PVI), classified under ICD-10 code I86.2. It is considered a multifactorial, chronic disease with a progressive course (PVI frequency varies widely, from 5 to 80%)1, 2. The primary clinical features of PVI include menstrual disorders, chronic pelvic pain, psycho-emotional disorders, and infertility. These symptoms significantly impair both the work capacity and quality of life of affected female patients3, 4. Typically, PVI progresses chronically and worsens in the absence of adequate treatment4. Most experts link PVI to prolonged exposure to dynamic hypervolemia and hypertension on the venous walls, which underlie the pathological process5, 6. Consequently, there are morphological changes in the venous bed that lead to retrograde blood flow, perfusion disorders, and pelvic phlebohypertension7. However, viewing the pathogenesis of PVI solely through the lens of venous hemodynamic disorders does not fully explain all the mechanisms of disease progression, which hinders the effectiveness of treatment8.

It is believed that conservative treatment should not be considered pathogenetic, as no single drug addresses the morphological basis of the disease or venous congestion in the pelvis, resulting in only a short-term clinical effect when using various pharmacological groups (venotropic, vasoactive, microcirculation-improving drugs, non-steroidal anti-inflammatory drugs)9. The primary role in therapeutic and preventive measures for PVI may be the management of oxidative stress (OS) reactions, which support impaired blood and lymph flow in the pelvis and trigger trophic processes10, 11. The high intensity of OS reactions in PVI is attributed to pelvic venous discirculatory disorders, hypoxemia, and ischemia of organs, which accelerate the formation of toxic lipid peroxidation (LPO) products while simultaneously diminishing their neutralization processes12. As a result, one of the effective therapeutic approaches could be the use of drugs that inhibit OS reactions and regulate antioxidant status13, 14, 15, 16. To date, studies of this nature have not been conducted. Given the foregoing, a comprehensive therapeutic approach to normalize hemodynamics in the pelvic venous system and the disturbed pro- and antioxidant interactions appears very promising. The goal was to evaluate the effect of an antioxidant complex on the state of the lipid peroxidation system and venous hemodynamic parameters in the treatment of patients with pelvic varicose veins.

Materials and Methods Study Design

The study included patients diagnosed with PVI (main group, n=150) who had not received antioxidants, venotonics, angioprotective drugs, or synthetic analogues of female sex hormones (combined oral contraceptives) for the last 6 months. The initial diagnosis was based on ultrasound duplex angioscanning of pelvic veins, and the final diagnosis was confirmed by histological examination of vein biopsy material taken during treatment and diagnostic laparoscopy.

Inclusion Criteria

Inclusion criteria for the main group were as follows: patients aged between 20 and 45 years; clinical symptomatology of complaints indicating persistent dysmenorrhea and/or chronic pelvic pain resistant to non-steroidal anti-inflammatory drugs and antispasmodics; informed consent for inclusion in the study.

Exclusion Criteria

Exclusion criteria included age under 18 or over 45 years; pregnancy and the postpartum period (less than 6 months); concurrent gynecological or other pelvic pathologies; acute inflammatory diseases; severe somatic pathologies; and surgical interventions on pelvic organs in the history (less than 6 months ago).

Patients were divided into two groups of 75 each (groups 1 and 2), comparable by sex, age, presentation of complaints, and degree of PVI severity. Treatment for both groups included standard therapy with one venotropic drug, Detralex 1000 (Diosmin 900 mg + Hesperidin 100 mg, Servier Rus LLC, Russia), prescribed as 500 mg (1/2 tablet) once a day for 60 days. Additionally, group 2 received an antioxidant complex (ACA) for 30 days (1 course), with a frequency of 3 courses in 2 months. ACA included the following drugs: superoxide dismutase (SOD) - 1 capsule (250 mg) twice a day for 30 days with repeated courses at 2 and 4 months; acetyl-glutathione - 1 tablet (100 mg) twice a day for 30 days with repeated courses at 2 and 4 months; astaxanthin - 1 capsule (400 mg) per day for 30 days with repeated courses at 2 and 4 months.

Patient Examination

The examination of the patients included a questionnaire survey, analysis of medical records, collection of anamnesis data, and general and gynecological examinations. The effectiveness of treatment was assessed by analyzing the state of the lipid peroxidation (LPO) - antioxidant defense (AOD) system after treatment, and regional phlebohemodynamics in women with PVI after treatment (peak systolic speed blood flow in the iliac, ovarian, and arcuate veins, and duration of retrograde discharge by the ovarian veins).

Ethics Approval

All women signed informed consent in accordance with the World Medical Association Declaration of Helsinki (1964, 2013 ed.). The Ethics Committee (Scientific Centre for Family Health and Human Reproduction Problems) approved the research (No. 1 dated January 15, 2019).

Biochemical Measurements

To determine the state of pro- and antioxidant systems, blood was collected from the ulnar vein on an empty stomach, following generally accepted methods. Plasma and erythrocyte hemolysates were used as test materials. LPO parameters such as lipid hydroperoxides (LH), conjugated dienes (CDs) were determined by spectrophotometric method, and the level of TBA-reactive products (TBARs) by fluorometric method15. The state of the AOD system was determined by the activity of superoxide dismutase (SOD)15, reduced glutathione (GSH) content15, as well as catalase, glutathione peroxidase (GPO), glutathione reductase (GR), and glutathione-S-transferase (GST) activity using commercial kits by Randox (UK). Measurements were made using the spectrofluorophotometer “Shimadzu RF-1501” and spectrophotometer “Shimadzu RF-1650” (Japan). Enzyme immunoassay was performed on a MultiSkan ELX808 microplate reader (Biotek, USA). The equipment of the Collective Usage Centre “Center for the Development of Progressive Personalized Health Technologies” was used.

Statistical procedure

Statistical analysis of data was performed using Statistica 10.0 programme (Statsoft Inc., USA). The visual-graphical method and the Kolmogorov-Smirnov agreement criteria with the Lilliefors and Shapiro-Wilk correction were used to determine the normality of the distribution of the quantitative features. Due to the fact that the distribution in the studied samples differed from normal, the non-parametric Mann-Whitney test was used. Categorical data were described with absolute values and percentages, quantitative data were described with median (Me) and lower and upper quartiles (Q1; Q3). The critical level of significance was taken as 5% (0.05).

Table 1.

Parameters of the lipid peroxidation system in women with PVI before and after treatment (Me (Q1;Q3))

Parameters Group 1 Group 2 before treatment after treatment before treatment after treatment LH, units 6.25 (6.10 6.41) 6.05 (5.71;6.11) 6.51 (6.38 6.77) 5.22 **, # (5.14;5.43) CDs, μmol/l 2.80 (2.73;2.90) 2.73 (2.60;2.82) 2.79 (2.66 2.94) 2,45 **, # (2.40;2.61) TBARs, μmol/l 4.35 (4.18;4.52) 4.28 * (4.10;4.33) 4.47 (4.30;4.65) 3.90 **, # (3.74 4.02)

Table 2.

Parameters of the AOD system in women with PVI before and after treatment (Me (Q1;Q3))

Parameters Group 1 Group 2 before treatment after treatment before treatment after treatment Catalase, μmol/l 41.66 (40.50;44.21) 37.50 (35.92;41.09) 38.72 (36.50;42.31) 55.74 **, # (46.92;68.09) SOD, units