Abstract
In order to assess the effectiveness of hypobarotherapy in the correction of clinical, hormonal and cardiovascular disorders, 53 women in the early postmenopausal period (average age 53.8 ± 4.2 years) with menopausal syndrome (group 1) were examined; Group 2 consisted of 36 patients who received complex treatment: hypobaric hypoxic therapy and hormone replacement therapy (HRT). Group 3 included 29 women who received only HRT for 3 months. Patients of groups 2 and 3 were comparable to women of group 1 in terms of age, postmenopausal period and its clinical manifestations. The method of adaptation to hypobaric hypoxia in the Ural-1 pressure chamber was used: 22 three-hour sessions conducted daily at an “altitude” of 3500 m (460 mm Hg).
The influence of this non-drug method, HRT and complex treatment (hypobarotherapy and HRT) on the clinical manifestations of menopausal syndrome, hormonal levels, blood pressure and Doppler echocardiography was assessed. The study revealed the high effectiveness of hypobaric hypoxytherapy in the correction of clinical, hormonal and cardiovascular disorders in women in the early postmenopausal period. There is limited evidence that complementary and alternative therapies improve menopausal symptoms or have the same benefits as hormone replacement therapy (HRT) [6–12]. In women who have absolute contraindications to the use of HRT or have a negative attitude towards it, preference should be given to the so-called alternative methods of treating menopausal disorders.
Study objective and methods
Such means include herbal medicine, homeopathic medicines, and physiotherapeutic methods [5]. Among the methods of non-drug treatment, hypoxic therapy is widely used – a technique for improving the functional state, performance, vitality and quality of life of a sick person through dosed hypoxic effects [4]. Hypoxytherapy is successfully used in the treatment of a number of cardiovascular and endocrine diseases, and pathologies of the nervous system [1]. A positive effect of interval normobaric hypoxic training on the psychoemotional status and hormonal levels in perimenopausal women with menopausal disorders has been revealed [2, 3]. The purpose of the study was to evaluate the effect of hypobaric hypoxic therapy in comparison with HRT on the course of menopausal syndrome, hormonal profile and some indicators of the state of the cardiovascular system in women in early postmenopause.
Material and methods We examined 118 women aged 45–58 years (average age 53.8 ± 4.2 years) with menopausal syndrome as a result of natural menopause. At the time of the examination, the patients were in a period of early postmenopause lasting from 2 to 7 years, the average duration of which was 3.2 ± 1.9 years, the age of menopause was 49.6 ± 1.7 years. All patients were divided into three groups: group 1 – 53 patients, underwent a course of hypobaric hypoxic therapy in the Ural-1 pressure chamber; Group 2 – 36 who received complex treatment, including the use of hypobaric hypoxic therapy and HRT (1 mg 17β-estradiol in combination with 5 mg dydrogesterone).
The patient began taking the drug simultaneously with the start of the course of hypobarotherapy in the Ural-1 pressure chamber and continued for 3 months. Group 3 included 29 patients who received HRT during 3 months of observation. To assess the clinical effectiveness of the therapy, examinations were carried out before the start of treatment, after 1 and 3 months. The method of calculating the modified menopausal index (MMI), proposed in 1959 by N. Kupperman et al., was used. and known in modification by E.V. Uvarova (1962). Each of the individual symptoms was assessed depending on the degree of severity from 0 to 3 points.
The value of the neurovegetative symptom complex up to 10 points corresponds to the absence of clinical manifestations, 10-20 points – a weak degree of severity, 21-30 – a moderate degree, more than 30 – a severe form of the syndrome. Metabolic-endocrine and psycho-emotional disorders were assessed as follows: within 1-7 points – mild severity, 8-14 – moderate severity, more than 14 points – severe form of the disease. The study of the level of hormones: follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E₂), dehydroepiandrosterone sulfate (DHEA sulfate) was carried out by immunoelectrochemiluminescence. Echocardiography was carried out using an Acuson computed-sonography 128 XP/10 p device according to the generally accepted method in B- and M-modes with the following parameters calculated in M-mode using the Teicholz formula: end-systolic and diastolic sizes (ESR and EDR) and volumes (ESR and EDV) of the left ventricle (LV), stroke and cardiac output (SV and MO), ejection fraction (EF), degree of shortening of the anteroposterior dimensions of the left ventricular myocardium in systole (%ΔS), thickness of the interventricular septum (IVS), thickness of the posterior wall of the left ventricle (PLW).
The study of LV diastolic function was carried out using pulsed wave Dopplerography, the following parameters of LV filling were determined: the maximum velocity of early diastolic filling (E), the maximum filling velocity in atrial systole (A), the ratio of these velocities (E/A), the time of isovolumic relaxation, the time of deceleration of the flow of early diastolic filling. Left ventricular myocardial mass (LVMM) was calculated using the formula of R. Devereux (1977). | Hypobaric hypoxytherapy was carried out in a medical vacuum installation – a pressure chamber Ural-1, installed on the basis of the Orenburg Regional Clinical Hospital No. 2, built in accordance with the medical and technical specifications jointly developed by the Research Institute of General Pathology and Pathological Physiology of the USSR Academy of Medical Sciences and the Orenburg Medical Institute.
The course of hypobaric hypoxytherapy consisted of 22 daily three-hour sessions at an “altitude” of 3500 m (460 mm Hg), with the first sessions being carried out with a gradual increase in altitude, starting from 1000 m onwards, adding 500 m daily until the maximum “altitude” (3500 m) was reached. The speed of “ascent” and “descent” was 3-5 m/s. During the treatment process, two main factors affected the patients’ bodies: reduced barometric pressure and reduced oxygen content in the inhaled air. As the patients reached the “plateau” (“altitude” 3500 m), the barometric pressure decreased from 759 ± 1.1 to 467 ± 2.1 mm Hg.
The “plateau” was reached gradually during the first 5 sessions, during which the level of decompression gradually increased and, accordingly, PO₂ in the inhaled air decreased, which was carried out to form a smooth adaptation in order to reduce the number of negative reactions and increase the effectiveness of treatment. Statistical processing of the results was carried out using the Microsoft Excel statistical program in compliance with the recommendations for medical research. The studied quantitative characteristics are presented in the form M ± s, where M is the arithmetic mean, s is its standard deviation.
The significance of differences was assessed using paired and unpaired Student’s t-test.
Differences in values were considered significant at p less than 0.05. To establish the relationship between characteristics, multivariate correlation analysis was used using the Pearson criterion, and the correlation coefficient (r) was calculated. Differences in values and correlations were considered significant at p less than 0.05. Results When assessing MMI, only 12 (10.2%) women had a mild degree of menopausal syndrome, 39 (33%) had a severe degree, and mostly moderate forms predominated (56.8%). The clinical picture in 75.4% (89) of patients was dominated by the neurovegetative form of menopausal syndrome, which was expressed in complaints of hot flashes, increased sweating, palpitations, fluctuations in blood pressure, stabbing pain in the heart, sleep disturbances, and headaches.
Clinical results
The psychoemotional form of menopausal syndrome was identified in 24.6% (29) of patients and was characterized by depression, mood disorders, and decreased libido. Among the diseases of the extragenital system in the women examined, the most common were arterial hypertension (79.7%), obesity (92.4%), and 5 (4.2%) had diabetes mellitus. There was a high level of thyroid diseases – in 41 (34.8%) patients, subclinical hypothyroidism was most often observed – in 22 (18.6%). Osteochondrosis was present in 86.4% of patients, arthrosis – in 34.7%, diseases of the urinary system – in 20.3%. A study of the dependence of the severity of menopausal syndrome on the frequency of extragenital pathology revealed the presence of a direct correlation between them (r=0.75; p less than 0.05).
Thus, in patients with combined extragenital pathology, severe forms of menopausal syndrome occurred significantly more often than in women without general somatic diseases or with one mild disease. As a result of hypobaric hypoxytherapy, pronounced positive results were revealed regarding the clinical manifestations of menopausal syndrome. Patients of the 1st and 2nd groups began to feel an improvement in their well-being during the 1st week of treatment in the Ural-1 pressure chamber; the effect became more pronounced as the number of hypoxic therapy sessions increased. In 14 (26.4%) patients of group 1, improvement in well-being was noted only after completion of the course of treatment in the pressure chamber.
By the end of the course of hypobarotherapy, a clinical effect was observed in 94.3% of patients in group 1. The use of hypobarotherapy, either alone or in combination with HRT, had a positive effect on the most pronounced pathological manifestations of menopausal syndrome, such as hot flashes and sweating, headaches, increased blood pressure (BP), decreased performance, increased fatigue, and depression. In the three observed groups of patients, a significant decrease in MMI indicators was established both in individual groups of complaints and in general. When assessing neurovegetative disorders before treatment, in group 1 the MMI was 29.6 ± 2.1 points, in group 2 – 27.1 ± 3.2 points, in group 3 – 26.6 ± 2.9 points.
As can be seen from table. 1, after 1 month from the start of treatment, there was a decrease in the MMI of neurovegetative disorders by 42.3% (from 29.6 ± 2.1 to 16.8 ± 1.9 points) in the 1st group of patients who underwent a course of hypobarotherapy, and by 47.9% (from 27.1 ± 3.2 to 14.1 ± 1.6 points) in the 2nd group who received complex treatment (hypobarotherapy in combination with HRT). In the 3rd group of patients who received only HRT, there was a decrease in the MMI of neurovegetative disorders by 21.8% (from 26.6 ± 2.9 to 20.8 ± 1.9 points) 1 month after starting the drug.
After 3 months from the start of treatment in the pressure chamber, the MMI of neurovegetative disorders decreased by 54.8% in group 1 (to 13.4 ± 1.6 points), by 61.6% (to 10.4 ± 1.9 points) in group 2. In the group of women receiving HRT, the MMI of neurovegetative disorders decreased by 30.8% (to 18.4 ± 1.4 points) after 3 months. During the course of hypobaric hypoxytherapy in groups 1 and 2, an improvement in the emotional state and normalization of mood were noted. When assessing the MMI of psychoemotional disorders, a progressive decrease was noted in the three examined groups of patients during 3 months of observation, while the most pronounced positive results were revealed in the 2nd group 3 months after the start of treatment in the pressure chamber (a decrease in the MMI of psychoemotional disorders by 59.6%: from 15.1 ± 1.51 to 6.1 ± 1.28 points).
In the 3rd group of women, the MMI of psychoemotional disorders decreased after 1 month by 28.4% (from 16.9 ± 1.34 to 12.1 ± 1.21 points), after 3 months – by 53.3% (to 7.9 ± 0.93 points). The MMI of metabolic and endocrine disorders decreased as much as possible in group 2, which received HRT and underwent treatment in a pressure chamber: after a month, its decrease was detected by 37% (from 8.9 ± 0.89 to 5.6 ± 0.92 points), after 3 months – by 42.7% (to 5.1 ± 0.62 points). In group 1, 3 months from the start of treatment in the pressure chamber, the MMI of metabolic and endocrine disorders was lower than the initial value by 34.9% (decreased from 8.6 ± 0.89 to 5.6 ± 0.82 points).
Hormonal measurements
When assessing the hormonal spectrum of blood in three groups of patients, a significant decrease in the levels of FSH and LH, an increase in estradiol levels was revealed, and in the groups that underwent a course of hypoxic therapy, a significant increase in the level of DHEA sulfate (Table 2). The FSH level decreased in group 1 by 26.8% after 1 month, by 33.1% after 3 months (p less than 0.05). The LH level decreased maximally (by 27.8%) 3 months after the start of treatment (p less than 0.05). The level of estradiol became higher by 15.2% (see Table 2) after 1 month, after 3 months it remained within the same limits (p less than 0.05).
DHEA sulfate was initially relatively low for this age group (72.3 ± 8.6 μg/dL), but as a result of hypoxic therapy, its increase was noted after 1 month by 15.2%, after 3 months – by 17.2%. In the 2nd group of patients who continued treatment with HRT after a course of hypoxic therapy, the FSH level decreased after 1 month by 41.7%, after 3 months – by 54.3%; LH levels decreased by 25.5% after 1 month from the start of treatment and by 47.7% after 3 months. The level of estradiol increased significantly: after 1 month it increased by 47.8%, after 3 months – by 94.5%.
The level of DHEA sulfate increased by 19.3% after 1 month, by 22% after 3 months from the start of observation. In the 3rd group of patients receiving HRT, the FSH level decreased by 31.2 and 46.3% after 1 and 3 months, respectively, and the LH level decreased by 21.7% after 1 month and by 33% after 3 months. The level of estradiol increased in group 3 by 18.6 and 52% after 1 and 3 months, respectively, while the level of DHEA sulfate did not change significantly. Thus, the most pronounced changes in hormonal levels in patients with menopausal syndrome occurred as a result of complex treatment, which included a course of hypoxic therapy and HRT.
Under the influence of hyperbaric hypoxia, patients of the 1st group showed an increase in the level of estradiol and DHEA sulfate and a decrease in the levels of gonadotropic hormones, which is the result of an increase in the production of their own hormones of the ovaries and adrenal glands as a result of hypoxic stimulation. More significant changes in the level of estradiol in groups 2 and 3 are due to the receipt of HRT and, accordingly, a decrease in the level of gonadotropic hormones through a feedback mechanism. A more significant increase in the level of DHEA sulfate as a result of hypobarotherapy in the 1st and 2nd groups of patients, apparently, determined the rapid and pronounced correction of neurovegetative disorders, in contrast to the results of the first 3 months of treatment in patients of the 3rd group who received only HRT.
Cardiovascular measurements
The initial systolic blood pressure (SBP) when measured by auscultation in the examined patients was 138.5 ± 6.2 mm Hg, diastolic blood pressure (DBP) was 88.6 ± 3.4 mm Hg. According to clinical measurements of blood pressure, treatment in a pressure chamber in patients of groups 1 and 2 led to a pronounced hypotensive effect. Indicators of blood pressure dynamics did not have significant differences in groups 1 and 2; the antihypertensive effect was significantly manifested in both groups. During hypobarotherapy, measuring blood pressure after completion of each session revealed a gradual decrease.
In group 1, already from the 8th-9th day of treatment, SBP in patients decreased to 132.3 ± 6.5 mm Hg, DBP – to 83.7 ± 4.5 mm Hg, by the end of the course of barotherapy, respectively, it reached 122.7 ± 6.5 and 81.6 ± 5.8 mm Hg. (p less than 0.05). According to the results of daily blood pressure monitoring, the use of hypoxic therapy, both as a separate type of treatment and in combination with HRT, contributed to a significant decrease in average daily SBP by 12.2%, average daily DBP by 7.9%, and heart rate by 3.8% after 1 month.
After 3 months, the hypotensive effect remained within the specified limits.
In the 3rd group of patients receiving HRT, no significant effect of the HRT drug on blood pressure levels was detected during 3 months of observation. When analyzing the initial echocardiographic data in 69 (58.5%) patients, attention was drawn to the reduced, in contrast to age-related norms, values of such hemodynamic parameters as SV and MO of the heart, EF and the percentage of shortening of the anteroposterior size of the left ventricular myocardium in systole (Table 3). In 47 (39.8%) patients, disturbances in the diastolic function of the left ventricle were revealed, manifested by a decrease in the maximum speed of early filling and the E/A ratio, as well as an increase in the slowdown time of early diastolic filling of the left ventricle, resulting from the deterioration of active relaxation and stretching of the left ventricular myocardium, which indicates the formation of the first type of diastolic dysfunction (see table. 3).
After completing the course of hypobaric hypoxytherapy in patients of groups 1 and 2, left ventricular EDV significantly decreased by 12.1 and 14%, respectively. As a result of hypoxytherapy, there was an increase in EF by 11.4%, and the percentage of shortening of the anteroposterior size of the left ventricular myocardium in systole by 17.4 in the 1st group of patients. In the 2nd group, which received complex treatment, a more pronounced positive dynamics of these indicators was revealed: EF increased by 15.9%, the percentage of shortening of the anteroposterior size of the left ventricular myocardium in systole – by 22.
When monitoring after 3 months, a further improvement in these parameters was noted, indicating optimization of the contractile function of the left ventricular myocardium under the influence of hypobaric hypoxytherapy both immediately after the course and afterwards 2 months after its completion (see table. 3). In the 3rd group, which received only HRT, there was also an improvement in indicators characterizing the systolic function of the left ventricle of the heart, but during 3 months of observation they were not statistically significant. When conducting Doppler echocardiography immediately after completion of the course of hypoxic therapy, a tendency towards normalization of parameters of left ventricular diastolic function in groups 1 and 2 was revealed, but the changes were statistically insignificant.
A pronounced effect of hypobaric exposure appeared 3 months after the start of treatment in the pressure chamber, which led to a significant improvement in parameters characterizing the diastolic function of the left ventricle: an increase in the speed of transmitral blood flow at the beginning of diastole and the ratio of peaks of early and late filling of the left ventricle E/A, a significant decrease in isovolumic time relaxation and early diastolic filling time.
The most pronounced positive changes were detected in group 2, whose patients continued to receive HRT after a course of hypoxic therapy. In the 3rd group receiving HRT, a tendency towards improvement in systolic and diastolic function of the left ventricle of the heart was revealed, but these changes turned out to be statistically unreliable. Thus, the course of hypobaric hypoxytherapy led to a decrease in hemodynamic load and improvement in systolic and diastolic function of the left ventricle. The positive dynamics of Doppler echocardiographic indicators is a consequence of the hypotensive effect of barotherapy, improving myocardial relaxation by reducing myocardial stiffness as a result of normalization of metabolic processes [4, 6].
Thus, the method of hypobaric hypoxytherapy can be used as an independent alternative method for correcting menopausal symptoms in patients during early postmenopause who do not want to use HRT drugs or have contraindications to their use. Conclusions 1. The use of hypobaric hypoxytherapy, both as an independent method and in combination with hormone replacement therapy, leads to a pronounced correction of neurovegetative and psycho-emotional symptoms of menopausal syndrome. 2. A positive effect of hypobarotherapy on the cardiovascular system in women during early postmenopause was noted, manifested by a hypotensive effect and improvement in systolic and diastolic function of the left ventricle of the heart.
3. This non-drug method is especially indicated for patients at risk of developing cardiovascular diseases in postmenopause, with arterial hypertension of the 1st degree (mild) and 2nd degree (moderate) and for the prevention of cardiovascular complications in later life.
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