RU2425641C1 - Method of predicting risk of development of abnormal uterine bleedings in puberty period in teenage girls - Google Patents

Abstract

FIELD: medicine. ^ SUBSTANCE: invention relates to medicine, namely to gynecology, and can be used for prediction of risk of development of abnormal uterine bleedings in puberty period in teenage girls. For this purpose weight is determined (Ves), weight 45 kg and lower is designates as 1, from 46 to 48 kg - as 2, from 49 to 52 kg - as 3, from 53 to 62 kg - as 4; from 62 to 68 kg - as 5; 68 kg and higher- as 6. Height (Rost) is measured, height 154 cm and lower is designated as 1, from 155 to 157 cm - as 2; from 158 to 161 cm - as 3; from 162 to 170 cm - kas 4; from 171 to 173 cm - as 5; from 174 cm and higher - as 6. Pinch test (Proba) is carried out, negative test is designated as 1, positive - as 2. Varga index is determined, norm is designated as 1; moderate body weight reduction as 2; body weight deficit - as 3. In urine concentration of total hydroxyproline is determined in mcmol/l (OGOP); concentration of bound hydroxyproline in mcmol/l (SV-GOP) are determined. In blood concentration of luteinising hormone in mIU/ml (LG); concentration of estradiol in ng/ml (ESTROD); concentration of thyrotropic hormone in ng/ml (TTG); concentration of antibodies to thyroid peroxidase in unit/ml (AT-TPO) are determined. Obtained results of examination are substituted into mathematical prognostic models: Model 1= Ves*9.7489-Rost*2.4950+Proba*2.3133+Index*14.2906-SV-GOP*0.0437+OGOP*0.1088-LG*0.1261+ESTROD*0.2678+TTG*0.8120-AT-TPO*0.0338-47.8720; Model 2 =Ves* 10.3679-Rost*2.5602+Proba*4.4430+Index*16.2118-SV-GOP*0.0730+OGOP*0.1490-LG*0.8682+ESTROD*0.2128+TTG*1.4743-AT-TPO*0.1035-55.7844. From two obtained values the larger one is selected. If larger value is obtained in model 1, low risk of uterine bleedings development is predicted. If larger value is obtained in model 2, high risk is predicted. ^ EFFECT: method ensures increased accuracy of prediction of risk of abnormal uterine bleedings development in puberty period. ^ 2 ex

Description

The present invention relates to medicine, namely to gynecology, and can be used to predict the risk of developing abnormal uterine bleeding during the puberty, also in patients with signs of connective tissue dysplasia (DST) and to monitor patients at risk in dynamics.

According to Article 1 of the UN Convention on the Rights of the Child, WHO recommendations and in accordance with Article 1 of the Federal Law “On Basic Guarantees of the Rights of the Child in the Russian Federation”, which defines a child as a person until he reaches the age of 18 years (of majority), at present in our The country adolescence is indicated by a framework of 10 to 18 years.

The health status of adolescents and the specific features of the adolescent period largely determine the reproductive health of the population in the future. Over the past decade, the number of healthy girls - school graduates - has significantly decreased and amounts to only 6.3%. By the age of 14-17, almost one in ten shows disharmonious development, in 10-12% of adolescent girls, certain gynecological diseases are recorded during examinations (A. Baranov, Medical and demographic situation and children's health of Russia // Sat: Protection reproductive health of the population.Materials of the Second National Assembly February 18-20, 1997 - M. - S.7-10). Over the past decade, there has been a deterioration in the reproductive health of the younger generation, expectant mothers. So, violations of the menstrual cycle are detected in every second (52%) teenage girl (Albitsky V.Yu., 2001).

Oxyproline is one of the main amino acids of collagen, which allows us to consider it a marker that reflects the catabolism of this protein. According to a number of researchers, it has been shown that an increase in the bound hydroxyproline indicates an increased collagen breakdown and is a prognostically significant criterion in assessing the intensity of collagen metabolism. When the synthesis of collagen is slowed down, its level in the urine decreases. In patients with hereditary collagenopathies, there is a significant increase in the amount of oxyproline in daily urine, the severity of which correlates with the severity of the pathological process (Kadurina T.I. 2000).

As emphasizes Uvarova E.V. (2006), today there are many problems in the reproductive health of girls associated with DST, which are manifested by dysmenorrhea, uterine bleeding, hypothalamic syndrome. As the severity of DST increases, the proportion of delayed sexual development and juvenile uterine bleeding increases, which indicates the possible participation of DST in the formation of menstrual dysfunction.

DST is an anomaly of the tissue structure with a decrease in the content of certain types of collagen or a violation of their ratio, which leads to a decrease in the strength of the connective tissue of organs and systems. The consequence of this is a disorder of homeostasis at the tissue, organ and organism levels, which is accompanied by various morphofunctional disorders of the visceral and locomotor systems with a progressive course (Kadurina T.I. 2000).

For girls and women with phenotypic manifestations of DST, a more severe course of varicose veins of the pelvis, a high frequency of complications in childbirth and the postpartum period are characteristic. A number of studies have shown a higher prevalence of neuroendocrine disorders in the form of premenstrual syndrome, algodismenorrhea, ovarian dysfunctions in DST.

Thus, today there remains a steady tendency for a deterioration in the reproductive health of girls, and therefore the problem of studying the causes of this phenomenon, in particular, identifying a connection with a deterioration in the general somatic health of teenage girls, remains urgent. The significance of connective tissue dysplasia in the formation of disorders in the development of the reproductive system of the female body is not well understood today, and this was the subject of our subsequent study.

Abnormal uterine bleeding during the puberty is pathological bleeding caused by deviations of the endometrial rejection process in girls from the first menstruation to 18 years, which occur with a frequency of more than 1 time in 21 days, last more than 7 days and are accompanied by a total blood loss of more than 80 ml (Principles of an interdisciplinary solution to the problem of uterine bleeding in the puberty / E.V. Uvarova [et al.] // Questions of modern pediatrics: a scientific-practical journal / Union of Pediatricians of Russia (M.). - M.: Children’s torus, 2007 - Volume 6, №1 -. 76-79).

There is a method for predicting the risk of developing uterine bleeding in adolescent girls, characterized in that the presence of the following informative risk factors assessed in points: anomalies of labor in the mother of the patient - 1 point, frequent SARS in the girl - 2 points, the patient's infection index is more than 3 - 2 points, chronic stress - 3 points, deviation of the point of sexual development from age standards - 3.5 points, burdened gynecological history of the mother - 3.5 points, chronic diseases of the ENT organs - 3.5 points, disorders the girl’s menstrual cycle - 4 points, calculate the total score, with a score of less than 10, a low risk of uterine bleeding or its relapse is ascertained, with a total of more than 10 they diagnose a high risk of uterine bleeding debut or its relapse (patent RU 2289322, 2006 ) The disadvantage of this method is that most risk factors for uterine bleeding are retrospective. The method does not take into account the physical characteristics of each individual teenage girl.

A known method for predicting the recurrence of juvenile uterine bleeding, which consists in conducting an electroencephalographic study (EEG) during the first episode of the disease, and relapse is predicted when diffuse or dysfunctional changes are detected, and dysfunctional changes in the EEG indicate a more frequent development of relapses (patent RU 2314022, 2008 .).

The prototype of the invention is a method for predicting the risk of developing juvenile uterine bleeding (Avdeeva ON Development of models and algorithms for the diagnosis and treatment of juvenile uterine bleeding. Voronezh. 2005. Abstract of dissertation for the academic degree of candidate of medical sciences). In this model, the dependence of the frequency of development of juvenile bleeding on the age of patients, the age of menarche, the presence of somatic diseases, the number of transmitted infectious diseases, hormonal therapy during pregnancy in the mother, and a burdened premorbid background is studied. This method does not take into account the physical characteristics, hormonal status of teenage girls.

The technical result when using the invention is to increase the accuracy of predicting the risk of developing abnormal uterine bleeding during puberty in adolescent girls.

The proposed method is as follows. An anamnesis is carefully collected from a teenage girl, anthropometric measurements are carried out, hormonal status is studied (determination of luteinizing, thyroid-stimulating hormones, estradiol, antibodies to thyroid peroxidase in the blood) by the method of quantitative enzyme-linked immunosorbent assay according to standard methods (Rational pharmacotherapy in obstetrics and gynecology: Hands. Doctors / V.I. Kulakov, V.N. Serov, P.R. Abakarova, A.G. Antonov, etc. M .: Litter, 2005; 1152 p.). The level of daily excretion of oxyproline is determined by the method of Bergman J., Loxley R., in the modification of A. Kosykh. (Kosykh A.A. Modified method for the determination of oxyproline in urine // Laboratory work. - 1976. - No. 12. - S.715-117). Determine the weight (Ves), while the weight of 45 kg or less is designated as 1, from 46 to 48 kg - as 2, from 49 to 52 kg - as 3, from 53 to 62 kg - as 4; from 62 to 68 kg - as 5; 68 kg and more - like 6; growth (Rost), while the growth of 154 cm and below is designated as 1, from 155 to 157 cm - as 2; from 158 to 161 cm - as 3; from 162 to 170 cm - as 4; from 171 to 173 cm - as 5; from 174 cm and above - as 6; an additional pinch test (Proba) is carried out, with a negative being designated as 1, a positive as 2; determine the Varga index, while the norm is designated as 1; moderate decrease in body weight as 2, body mass deficit as 3; total hydroxyproline concentration (OGOP); the concentration of bound hydroxyproline (SV-GOP); luteinizing hormone (LG) concentration; estradiol concentration (ESTROD); thyroid stimulating hormone (TTG) concentration; the concentration of antibodies to thyroid peroxidase (AT-TPO), the results of the examination are substituted into mathematical prognostic models:

Low risk of development (model 1) = Ves · 9.7489-Rost · 2.4950 + Proba · 2.3133 + Index · 14.2906-SV-GOP · 0.0437 + OGOP · 0.1088-LG · 0.1261 + ESTROD · 0.2678 + TTG · 0.8120-AT-TPO · 0.0338-47.8720,

High risk of development (model 2) = Ves · 10.3679-Rost · 2.5602 + Proba · 4.4430 + Index · 16.2118-SV-GOP · 0.0730 + OGOP · 0.1490-LG · 0.8682 + ESTROD · 0.2128 + TTG · 1.4743-AT-TPO · 0.1035-55.7844,

Where

Ves - weight;

Rost - growth;

Proba - a pinch test;

Index - Varga index;

OGOP — total hydroxyproline concentration (μmol / L);

SV-GOP — concentration of bound hydroxyproline (μmol / L);

LG is the concentration of luteinizing hormone (mMe / ml);

ESTROD - estradiol concentration (ng / ml);

TTG is the concentration of thyroid-stimulating hormone (ng / ml);

AT-TPO - concentration of antibodies to thyroid peroxidase (units / ml).

Of the two values obtained, the larger is chosen, when a larger value is obtained in Model 1, a low risk of uterine bleeding is predicted, and when a larger value is obtained in Model 2, a high risk is predicted.

The application of the developed method makes it possible to predict the risk of abnormal uterine bleeding in the puberty in adolescent girls, taking into account the characteristics of connective tissue, hormonal status and physical development, the method is also acceptable in patients with connective tissue dysplasia and for monitoring patients from risk groups in dynamics.

Discriminant analysis is one of the methods of multivariate statistical analysis. The purpose of discriminant analysis is to classify it on the basis of measuring various characteristics (attributes, parameters) of an object, that is, assign it to one of several groups (classes) in some optimal way, which means either the minimum of the mathematical expectation of losses or the minimum of the probability of false classification. The discriminant analysis was carried out after checking the normality of the distribution (Kolmogorov-Smirnov test), as well as assumptions about the homogeneity of variances and covariances.

Acceptance or rejection of all statistical hypotheses was carried out at a level of ≤0.05, adopted in biomedical research. For all calculations, the Statistica 6.0 program was used. (StatSoft, Inc. (2001). STATISTICA (data analysis software system), version 6. - http://www.statsoft.com.).

A survey of 400 adolescent girls aged 16-18 years. As a dependent variable, we took a variable describing the belonging of teenage girls to one or another group: with abnormal uterine bleeding and without them. At the next stage, only those that revealed a statistically significant effect on the dependent variable were selected from all these variables for discriminant analysis. The results of discriminant analysis were obtained, where the role of independent variables is played by the concentration of bound and total hydroxyproline, luteinizing, thyroid stimulating hormones, estradiol, and antibodies to thyroid peroxidase.

For the resulting model, the statistical significance was at the level of p << 0.00001, which indicates good discrimination and a statistically significant model.

According to the obtained classification functions, according to the results of laboratory studies, a mathematical model for predicting the risk of developing abnormal uterine bleeding of the puberty period in adolescent girls with DST is developed based on the concentration indicators of bound and total hydroxyproline, luteinizing, thyroid stimulating hormones, estradiol, antibodies to thyroid peroxidase; variables were also used: height, weight, pinch test and Varga index. Measurement of height and weight was carried out in accordance with the accepted methodology for the implementation of anthropometric measurements. Using the Varga index, body mass deficiency was determined.

Varga index = body weight (g): height ² (cm) - age (in years) · 100.

The indicator from 1.7 to 1.5 allows you to diagnose a moderate decrease in body weight. An index of 1.5 and below indicates a pronounced deficit in body weight.

Using the “pinch” test (skin capture between the thumb and forefinger in the shoulder area) hemorrhagic manifestations in the form of ecchymoses, petechiae are determined (Kadurina TI 2000).

For the resulting model, p << 0.00001, which also indicates good discrimination and a statistically significant model. The resulting formulas have the following form:

Low risk of development (model 1) = Ves · 9.7489-Rost · 2.4950 + Proba · 2.3133 + Index · 14.2906-SV-GOP · 0.0437 + OGOP · 0.1088-LG · 0.1261 + ESTROD · 0.2678 + TTG · 0.8120-AT-TPO · 0.0338-47.8720,

High risk of development (model 2) = Ves · 10.3679-Rost · 2.5602 + Proba · 4.4430 + Index · 16.2118-SV-GOP · 0.0730 + OGOP · 0.1490-LG · 0.8682 + ESTROD · 0.2128 + TTG · 1.4743-AT-TPO · 0.1035-55.7844,

where Ves (1 - 45 kg and less, 2 - 46-48 kg, 3 - 49-52 kg, 4 - 53-62 kg, 5 - 62-68 kg, 6 - 68 kg and more), Rost (1 - 154 cm and below, 2 - 155-157 cm, 3 - 158-161 cm, 4 - 162-170 cm, 5 - 171-173 cm, 6 - 174 and above), Proba - pinch test (1 - negative, 2 - positive), Index - Varga index (1 - normal, 2 - moderate decrease in body weight, 3 - deficiency of body weight), OGOP - concentration of total hydroxyproline in μmol / L, SV-GOP - concentration of bound hydroxyproline in μmol / L, LG - concentration of luteinizing hormone in mMe / ml, ESTROD - concentration of estradiol in ng / ml, TTG - concentration of thyroid-stimulating hormone in ng / ml, AT-TPO - antibodies to thyroid id peroxidase, concentration in units / ml.

The obtained formulas can be used in the practice of a doctor. The corresponding values obtained in a laboratory study and a survey of a particular patient are substituted into the formula. Using both formulas, two values are deduced, the maximum of which will refer the individual to one of the groups, that is, if the figure obtained in Model 1 is higher than in Model 2, then we can conclude that there is a low risk of developing abnormal uterine bleeding in the studied teenage girls and vice versa. This approach can also be used to monitor patients at risk over time.

The invention is illustrated by the following examples of clinical use of the proposed method.

Example 1

The patient is a teenage girl of 17 years. Weight 63 kg (5). Height 171 cm (5). Varga index = norm (1). A positive pinch test (2). The concentration of total hydroxyproline is 355.1 μmol / L. The concentration of bound hydroxyproline is 323.7 μmol / L. The concentration of luteinizing hormone is 2.5 mIU / ml. The concentration of estradiol is 39 ng / ml. The concentration of thyroid-stimulating hormone is 4.8 ng / ml. Antibodies to thyroid peroxidase 39.9 in units / ml.

Low risk of development (model 1) = 5 · 9.7489-5 · 2.4950 + 2 · 2.3133 + 1 · 14.2906-323.7 · 0.0437 + 355.1 · 0.1088-2.5 · 0.1261 + 39 · 0.2678 + 4.8 · 0.8120-39.9 · 0.0338-47.8720 = 44.4818.

High risk of development (model 2) = 5 · 10.3679-5 · 2.5602 + 2 · 4.4430 + 1 · 16.2118-323.7 · 0.0730 + 355.1 · 0.1490-2.5 · 0.8682 + 39 · 0.2128 + 4.8 · 1.4743-39.9 · 0.1035-55.7844 = 46.7074.

The obtained value indicates a high risk of developing abnormal uterine bleeding in this patient. A year later, the patient complained of acyclic spotting from the genital tract.

Example 2

The patient is a teenage girl of 17 years. Weight 50 kg (3). Height 155 cm (2). Varga index = norm (1). The pinch test is negative (1). The concentration of total hydroxyproline is 286.4 μmol / L. The concentration of bound hydroxyproline is 264.8 μmol / L. The concentration of luteinizing hormone is 2.5 mIU / ml. The concentration of estradiol is 75 ng / ml. The concentration of thyroid-stimulating hormone is 0.9 ng / ml. Antibodies to thyroid peroxidase 10.1 in units / ml.

Low risk of development (model 1) = 3 · 9.7489-2 · 2.4950 + 1 · 2.3133 + 1 · 14.2906-264.8 · 0.0437 + 286.4 · 0.1088-2.5 · 0.1261 + 75 · 0.2678 + 0.9 · 0.8120-10.1 · 0.0338-47.8720 = 32.7363.

High risk of development (model 2) = 3 · 10.3679-2 · 2.5602 + 1 · 4.4430 + 1 · 16.2118-264.8 · 0.0730 + 286.4 · 0.1490-2.5 · 0.8682 + 75 · 0.2128 + 0.9 · 1.4743-10.1 · 0.1035-55.7844 = 28.2679.

The obtained value indicates a low risk of developing abnormal uterine bleeding in this patient.

Using this method allows predicting the likelihood of developing abnormal uterine bleeding in adolescent girls in order to implement measures to prevent this condition.

Claims (1)

A method for predicting the risk of abnormal uterine bleeding during puberty in adolescent girls, characterized in that the parameters are determined by weight (Ves), with a weight of 45 kg or less is designated as 1, from 46 to 48 kg - as 2, from 49 to 52 kg - as 3, from 53 to 62 kg - as 4; from 62 to 68 kg - as 5; 68 kg and more - like 6; growth (Rost), while the growth of 154 cm and below is designated as 1, from 155 to 157 cm - as 2; from 158 to 161 cm - as 3; from 162 to 170 cm - as 4; from 171 to 173 cm - like 5; from 174 cm and above - as 6; a pinch test (Proba) is carried out, with a negative being designated as 1, a positive as 2; determine the Varga index, while the norm is designated as 1; moderate decrease in body weight as 2, body mass deficit as 3; total hydroxyproline concentration (OGOP); the concentration of bound hydroxyproline (SV-GOP); luteinizing hormone (LG) concentration; estradiol concentration (ESTROD); thyroid stimulating hormone (TTG) concentration; the concentration of antibodies to thyroid peroxidase (AT-TPO), the results of the examination are substituted into mathematical prognostic models:
Model 1 = Ves 9.7489-Rost 2.4950 + Proba 2.3133 + Index 14.2906-SV-GOP 0.0437 + OGOP 0.1088-LG 0.1261 + ESTROD 0 2678 + TTG 0.8120-AT-TPO 0.0338-47.8720;
Model 2 = Ves · 10.3679-Rost · 2.5602 + Proba · 4.4430 + Index · 16.2118-SV-GOP · 0.0730 + OGOP · 0.1490-LG · 0.8682 + ESTROD · 0 , 2128 + TTG · 1.4743-AT-TPO · 0.1035-55.7844, where Ves is the weight; Rost - growth; Proba - a pinch test; Index - Varga index; OGOP — total hydroxyproline concentration (μmol / L); SV-GOP — concentration of bound hydroxyproline (μmol / L); LG is the concentration of luteinizing hormone (mMe / ml); ESTROD - estradiol concentration (ng / ml); TTG is the concentration of thyroid-stimulating hormone (ng / ml); AT-TPO - concentration of antibodies to thyroid peroxidase (units / ml); of the two values obtained, choose the larger one, when obtaining a larger value in model 1, a low risk of developing uterine bleeding is predicted, when obtaining a larger value in model 2, a high risk is predicted.