Clinical and pathogenetic rationale for the treatment of climacteric syndrome using plasmapheresis

Climacteric syndrome (CS) is a specific clinical symptom complex that develops in some women during the decline of reproductive system function against the background of general age-related involution of the body [Vikhlyaeva E.M., 2006]. Its development complicates the course of the climacteric period, which begins in women at the age of 48–50 years and coincides with the period of their most active social and professional activity [Smetnik V.P., 2006]. The earliest and most typical symptoms of CS are vegetative-vascular disturbances manifesting as hot flashes, sweating, palpitations, dizziness, sleep disorders, and others. The peculiarity of this period is that it is precisely at this time that many diseases arise or become manifest: benign and malignant neoplasms, neuroses, diabetes mellitus, obesity, atherosclerosis, endocrine gland dysfunction, and others [Krymskaya M.L., 1989]. The development of extragenital diseases against the background of general aging of the body leads to disturbances of energy supply and lipid metabolism and to a decrease in the body's resistance to all adverse internal and external factors [Dontsov V.I., 1997]. The absence of timely treatment of climacteric disorders subsequently gives rise to postmenopausal osteoporosis, atherosclerosis, ischemic heart disease, and urogenital disorders, which may lead to loss of working capacity and deterioration of quality of life [Yureneva S.V., 1999; Dobrokhotova Yu.E., 2003].

In connection with the increase in life expectancy, the attention of many researchers has been drawn to the medical problems of women of this age, with corrective therapy occupying a special place — therapy that ensures adaptation of the woman's body to the new metabolic equilibrium after the decline of ovarian function [Vikhlyaeva E.M., 2006].

The treatment and rehabilitation of patients in this group present certain difficulties due to contraindications to drug therapy and its side effects. The high frequency of concomitant somatic diseases, age-related changes in the hemostasis system, and the function of the nervous, cardiovascular, and other body systems at this age determine the need for a comprehensive approach to the management tactics of these complex patients and a rational combination of pharmacological and non-pharmacological treatment methods.

In this connection, the problem of developing new methods of CS therapy aimed at normalizing the function of the aforementioned body systems is highly relevant. These methods should be regarded as a comprehensive system of prevention, therapy, and rehabilitation for women with CS.

At present, special attention is being paid to non-specific non-pharmacological treatment methods that allow influencing disturbances in the activity of adaptive and compensatory-protective mechanisms — effluent methods of action possess such capabilities, and among them the most accessible is plasmapheresis [Gavrilov A.O., 1991; Vorobyev P.A., 1998; Neimark A.I., 2000; Konovalov G.A., 2011].

The therapeutic effect of plasmapheresis (PP) is due to many mechanisms: removal from the bloodstream of toxic and vasoactive substances, autoantibodies, and components of destroyed tissues and cells; enhancement of the functional activity of hematopoietic, stromal, and immunocompetent cells; and improvement of microcirculation.

However, to date this method, despite its advantages and comprehensive action, has not found application in the treatment and rehabilitation of patients with CS. Criteria for selecting patients with this pathology for treatment by effluent methods have not been established. The questions of plasma exsanguination volumes and plasma replacement during PP remain unresolved. The effect of the method on the state of the cardiovascular, nervous, endocrine, and respiratory systems, liver function, and coagulation properties of blood has not been studied. Methods and variants of comprehensive use of PP in the treatment and rehabilitation of these patients have not been developed.

The aim of the present study was the clinical and pathogenetic rationale and evaluation of the efficiency of plasmapheresis application in the treatment of patients with severe and atypical forms of climacteric syndrome.

To achieve this aim, the following objectives were set:

1. To study the physiological mechanisms of plasmapheresis action in experiments modeling pathological states characteristic of the manifestations of climacteric syndrome.

2. To develop indications for plasmapheresis in patients with severe and atypical forms of climacteric syndrome.

3. To clarify the features of the state of the central nervous system, hemostasis system, blood morphology, neuro-endocrine and cardio-respiratory systems, and the main parameters of metabolism in women with severe and atypical forms of climacteric syndrome.

4. To study the effect of plasmapheresis on the state of the central nervous system, hemostasis system, blood morphology, neuro-endocrine and cardio-respiratory systems, and the main parameters of metabolism in women with severe and atypical forms of climacteric syndrome.

5. To establish the effect of plasmapheresis on clinical course and quality of life in women with severe and atypical forms of climacteric syndrome.

6. To determine the clinical efficiency and duration of action of plasmapheresis in the treatment of women with severe and atypical forms of climacteric syndrome.

7. Based on the studies performed, to develop a system of rehabilitation measures using plasmapheresis and to determine the number of procedures and their frequency for the treatment of patients with severe and atypical forms of climacteric syndrome.

In this work, the application of plasmapheresis in patients with severe and atypical climacteric syndrome was pathogenetically justified for the first time, taking into account the state of all systems involved in the pathological process. A comprehensive study of the functional state of the central nervous system, hemostasis system, blood morphology, neuroendocrine and cardio-respiratory systems, and their changes under the influence of plasmapheresis in patients with severe and atypical forms of climacteric syndrome was carried out for the first time. For the first time, an experimental study on aged animals was conducted to investigate the features of compensatory-protective mechanisms when modeling a hypoxic state during plasmapheresis. The principles and methods of performing plasmapheresis for stimulating the compensatory capabilities of patients with severe and atypical forms of climacteric syndrome were scientifically justified. For the first time, the effect of plasmapheresis on self-assessment and quality of life in patients with severe and atypical forms of climacteric syndrome was studied.

Practical significance. Based on the study of disease pathogenesis, principles of treatment and rehabilitation of patients with severe and atypical forms of climacteric syndrome using an effluent method of action — plasmapheresis — were developed. Optimal regimens and variants of plasmapheresis in the treatment of patients with severe and atypical forms of climacteric syndrome were determined. Monitoring of the character of the body's compensatory reactions, carried out based on clinical data, results of peripheral blood tests, and hemostasiograms, allows individual selection of procedure regimens and course duration of plasmapheresis.

A rationale for including plasmapheresis in the therapy of climacteric syndrome in gynecological medical and preventive institutions, both in inpatient and outpatient settings using inexpensive domestic medical equipment, was developed.

1. The anti-hypoxic effect of plasmapheresis, confirmed by the experimental studies performed, contributes to reducing the severity of hypoxic damage and preventing the breakdown of the compensatory system under conditions of a pathological process, which allows its application in the treatment of women with severe and atypical forms of climacteric syndrome.

2. Polysystem disturbances of adaptive-regulatory mechanisms in combination with pathological changes in the state of the hemostasis system, neuro-endocrine and cardiorespiratory systems, and lipid metabolism are indications for plasmapheresis in patients with severe and atypical forms of climacteric syndrome when there are contraindications to drug therapy.

3. The high therapeutic efficiency of plasmapheresis in all patients with severe and atypical forms of climacteric syndrome is due to the combined action of various mechanisms of plasmapheresis: detoxifying, coagulation-correcting, and anti-hypoxic, which lead to normalization of the hemostasis system and microcirculation and improvement of the activity of regulatory neurohumoral systems.

4. Plasmapheresis in women with severe and atypical forms of climacteric syndrome is an effective, pathogenetically justified treatment method that promotes optimal manifestation of the body's adaptive reactions due to its normalizing influence on the state of the main organs and systems involved in the pathological process, which clinically manifests as improvement of general condition and increased quality of life.

The research results and the main recommendations derived from them have been implemented in the educational process and practical work of the Federal State Budgetary Institution "V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology" of the Ministry of Health and Social Development of Russia. Based on the obtained results, methodological recommendations "Effluent treatment methods in obstetrics and gynecology" (1995) were published, and an invention patent "Method for the therapy of climacteric syndrome" No. 2185195 was obtained, registered in the State Register of Inventions of the Russian Federation on July 20, 2002. The developed treatment method was awarded the Government Prize of the Russian Federation in Science and Technology for 2000.

took place on September 5, 2011 at a meeting of the approval commission of the Federal State Budgetary Institution "Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology" of the Ministry of Health and Social Development of Russia. The results of the dissertation work were discussed on July 12, 2010 at an interclinical conference. The materials of the dissertation were presented at seminars for practicing physicians, the VI (1998), VII (1999), VIII (2000), XI (2003), XII (2004), XIV (2006), XV (2007), and XVI (2008) Conferences of the Moscow Society of Hemapheresis, the Conference "Critical States in Obstetrics, Gynecology, and Perinatology" (2003, Moscow), the symposium "Modern Plasma Substitutes: Voluven (HES 130/0.4) — Safety and Efficiency" (2004, Moscow), the meeting of obstetrician-gynecologists of the Khanty-Mansi Autonomous Okrug (2004, Khanty-Mansiysk), the Republican Meeting of Obstetrician-Gynecologists and Pediatricians of the Republic of Bashkortostan (2005, Ufa), the VII Scientific Forum "Mother and Child" (2005, Moscow), the Republican Meeting of Obstetrician-Gynecologists and Neonatologists of the Chuvash Republic (2005, Cheboksary), the Certification Course in Transfusiology (2005, Cheboksary), the Conference "New Medical Technologies in Obstetrics, Gynecology, and Perinatology" (2005, Moscow), the Conference "Modern Views on the Application of Membrane Plasmapheresis in Medicine" (2006, Novosibirsk), the Seminar "Application of Membrane Plasmapheresis in Clinical Practice" (2006, Moscow), the Scientific-Practical Conference "Current Issues of Extracorporeal Therapy" (2007, Moscow), WHO training courses "Rational Use of Blood in Obstetrics and Gynecology" (2006, Kaliningrad), "Clinical Use of Blood" (2007, Sochi), "Rational Use of Blood in Clinical Practice" (2007, Saint Petersburg), the Seminar "Effluent Therapy in Obstetrics and Gynecology" (2007, Moscow), the Scientific-Practical Conference "Current Issues of Using Effluent Therapy Methods in the Treatment of Diseases of Various Etiology" (2007, Kyiv, Ukraine), the Inter-Regional Scientific-Practical Conference "New Medical Technologies in Anesthesiology and Intensive Care" (2007, Voronezh), the Conference "Current Issues of Obstetrics and Gynecology, Anesthesiology and Resuscitation in Obstetrics and Gynecology" (2008, Orenburg), the Scientific-Practical Conference of the Central Federal District of the Russian Federation together with the Moscow Society of Hemapheresis "Current Issues of Hemapheresis, Surgical Hemocorrection, and Dialysis" (2009, Moscow), the Scientific-Practical Conference of Obstetrician-Gynecologists of Stavropol Krai (2009, Stavropol), at the Academic Council of the Center on September 8, 2009, the Scientific-Practical Conference "Effluent Treatment Methods in Medicine" (2010, Vladivostok), the Scientific-Practical Conference of the Central Federal District of the Russian Federation "Current Issues of Renal Replacement Therapy, Hemapheresis, and Transplant Coordination" (2010, Moscow), the Scientific-Practical Conference "Current Issues of Obstetrics and Gynecology" (2010, Ufa), the Scientific-Practical Conference "Plasmapheresis: For and Against. The Aspect of Wide Application in Medical Practice" (2010, Kharkiv, Ukraine), the VI Conference of the Regional Public Organization for the Development of Municipal Healthcare of the Moscow Region "New Biomedical Technologies of Municipal Healthcare of the Moscow Region" (2010, Dubna), the Scientific-Practical Conference "Central Federal District: Innovative Companies — to the Healthcare System" (2011, Dubna), the Round Table "Application of Effluent Therapy Methods in Clinical Practice" (2011, Novosibirsk), and the All-Russian Seminar "Application of Effluent Therapy Methods in Clinical Practice" (2011, Dubna).

consisted in defining the main idea of the study, its planning, developing methods for its execution, and carrying out the collection, processing, and analysis of the material obtained. The author personally participated in performing plasmapheresis sessions in all patients included in the study. The author personally examined 186 patients with severe and atypical forms of climacteric syndrome, filling in individual clinical charts. Diagnostics of self-assessment, quality of life evaluation, as well as analysis of laboratory examination results and statistical processing of the material were personally performed and analyzed by the author.

On the topic of the dissertation, 60 publications have been published in open print, including in 11 journals recommended by the Higher Attestation Commission of the Ministry of Education of the Russian Federation for the publication of dissertation results for the doctoral degree. The materials of this study were included in a work awarded the Government Prize of the Russian Federation. One patent of the Russian Federation No. 2185195 was obtained.

The dissertation consists of an introduction, 4 chapters, conclusions, practical recommendations, and a reference list. The work is written on 259 pages of typewritten text, including 41 tables and 15 figures. The reference list includes 187 domestic and 208 foreign sources.