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Section 7. Medical science
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16. Tugusheva F. A., Zubin I. M., Mitrofanova O. V. Oxidative stress and chronic kidney disease: a literature review//Nephrology. - 2007. -Vol. 11, No. 3. - P. 29-47. [In Russian].
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18. Van der Velde M., Matsushita K., Coresh J. et al. Lower estimated glomerular filtration rate and higher albuminuria are associated with all-cause and cardiovascular mortality. A collaborative meta-analysis of high-risk populations cohorts//Kidney Int. - 2011. - Epub ahead of print.
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Shamsutdinova Elvira Faridovna, Republican Specialized Scientific Medical Center of Obstetrics and Gynecology E-mail: mbshakur@mail.ru
Sexual development and biochemical values of hepatic function in dynamics with background various methods of hormonal therapy in adolescent girls with congenital estrogen deficit
Abstract: The results of the performed research confirm the possibility of administration of both 17-beta estradiol and tefestrol in the complex of hormonal therapy for teenager girls with hypo gonadism. Patients with diseases of hepatic-billiary system and its chronic forms in history should prefer tefestrol in combination with didrogesterone Keywords: hypogonadism, female teenagers, hormone replacement therapy.
Disorder of sexual development can be caused by a wide range of pathological states, where, together with various congenital diseases of reproductive system, an important role is played by primary or secondary deficiency of ovarian function. Ovarian deficiency (hypo gonadism) is a pathological state, conditioned by decrease of estrogen level in organism (or weakening of effect in tissue), manifested by underdevelopment of internal and external sexual organs, no secondary sexual traits, and disorder of fertility [1]. We can isolate primary (hyper gonadotropic) hypo gonadism, caused by lesion of ovaries; and secondary (hypo gonadotropic) hypo gonadism, conditioned by decrease of gonadoliberin and\or gonadotropin secretion [3].
In spite of the diversity of clinical forms of estrogen deficiency states in girls today it is generally accepted that hyper gonadotropic and stable hypo gonadotropic hypo gonadism, conditioned by congenital diseases of hypothalamus and pituitary, requires long-term hormonal therapy, the aim of which is compensation of congenital deficit of sexual hormones. At least feminization of appearance and development of secondary sexual traits should be achieved [2].
The therapy with sexual hormones and similar agents in children and teenagers is peculiar, and it is preconditioned by good knowledge of pediatric and adolescent physiology, pharmacology, and pharmacodynamics ofvarious estrogen-containing agents. It is compulsory for optimal choice and success of the therapy. Hormonal therapy started in adolescence requires long term application on
one hand, and following safety rules, on the other. In the modern time in hormonal therapy in teenagers herbal agents are preferred due to softer effect, in comparison with its predecessors — synthetic estrogens. Prescription of these agents lead to significant improvement of psycho-emotional status of teenagers, formation of more complete self-perception of a person, it promotes correction of clinical symptoms of hypo gonadism. The choice of an agent for long-term administration should be done using forms with minimal amount of side-effects [4].
The objective of the research was assessment of the parameters of sexual development and several biochemical values of functional metabolic activity of liver in girls with hypo gonadism together with various methods of compensatory hormonal therapy.
Materials and methods of the research. We examined 42 patients in age groups from 13 to 15 and from 16 to 18 years old with hypo gonadotropic and hyper gonadotropic hypo gonadism, the parameters of sexual development of which had 3 years and more retardation (II-III degree of sexual development retardation). Patients of the 1 group (64 teenagers) administered an agent for traditional hormonal therapy, containing 17-beta-estradiol and didrogesterone (14 tablets, containing 2mg 17-beta-estradiol, 14 tablets containing 2mg of 17-beta-estradiol and 10mg of didrogesterone). Patients of the 2 group (60 teenagers) administered estrogen-like agent tefestrol in combination with 10mg of didrogesterone. All examined patients before and together with the therapy had clinical
Sexual development and biochemical values of hepatic function in dynamics with background various methods...
anthropometering, assessment of the degree of sexual development (assessment of secondary sexual traits with calculation of summary score of sexual development), USD of womb and ovaries. Functional metabolic activity of liver was evaluated according to the definition of ALT, AST, total bilirubin, alkali phosphotase, cholin esterase in blood serum. Laboratory tests were performed using «Bochringer Mannheim» and «Bicon» sets (Germany). The control group involved 20 teenager girls of the similar age with physiologic puberty.
The results and discussion: Analysis of the results obtained after 12 months therapy in compared groups showed that together with the performed therapy alterations of anthropometric parameters had some differences. So, in the 1 therapeutic group average growth in 13-15 years old subgroup was equal to 6.2 cm, and in 16-18 years old group 1.0 cm. Body mass index in the 1 group had no statistically significant changes compared with that value prior to the therapy (Table 1).
Table 1. - Anthropometric parameters before and at the term of the therapy
Parameters Groups A ge
13-15 years old 16-18 years old
Before therapy In 6 mo In 1 year Before therapy In 6 mo In 1 year
Height I 152.1±2.2 154.2±1.8 158.4±1.9* 160.1±1.8 160.2±1.7 161.1±1.6
II 151.2±3.1 153.8±3.4 156.2±3.7 155.7±2.9 157.0±2.9 154.4±2.8
Weight I 43.8±2.0 45.3±2.3 49.3±2.3 47.9±2.0 49.2±2.0 50.2±2.2
II 44.4±1.8 46.9±1.9 49.6±2.6 47.4±1.2 52.1±1.1 53.2±1.0
BMI I 19.0±0.9 19.1±0.97 19.9±1.0 18.8±0.92 19.2±0.92 19.4±0.97
II 19.4±0.6 19.9±0.62 20.3±0.66 19.1±0.6 21.2±0.7* 22.3±0.9**
Bnp I 0.61±1.96 2.68±0.28** 3.95±0.42** 1.25±0.37 3.0±0.33** 3.96±0.38**
II 1.1±0.3 2.5±0.28** 3.7±0.11** 1.6±0.5 2.7±0.6 3.8±0.42**
Note: * — reliability of the data between the values before and after the therapy (* — P<0.05; ** — P<0.01)
In the 2 group with identical growth we revealed reliable increase of BMI in comparison with similar parameter before the therapy, indicating a greater gaining weight rate in the patients administering estrogen-like agent tefestrol.
Summary score of sexual development reflects the degree of secondary sexual traits expression. At the initial application from the total number of the examined patients 92 (72.58%) had Ma0 Ax0 Pb0 formula of sexual development, 21 (16.93%) patients Ma0 Ax1 Pb1, and Mal Ax1 Pb1 eleven (8.87%) patients. Average formula of sexual development in patients in one year, independently of the performed method ofhormonal therapy was Ma2 Ax2 Pb2. Summary score of sexual development in compared groups before the therapy was identical. In the I group it was 0.61±1.96 in 13-15 years old subgroup, and 1.25±0.37 in 16-18 years old subgroup; in the II 13-15 years old subgroup it was equal to 1.1±0.3, and 1.6±0.5 in 16-18 years old group. In one year administration of hormonal therapy the summary score of sexual development in both groups independently of the age was equal and reliably higher than the similar parameters before the therapy (see Table 1).
The greater differences were revealed in ultra sound scanning of ovaries at the time of the therapy in both groups. Patients of the I group had reliably greater sizes ofwomb: width 30.8±1.5mm versus 21.4±1.9mm (p<0.001), length 34.4±1.4mm versus 26.6±1.7mm (p<0.01). In one year the sizes of womb in the patients of the I group were still reliably greater in comparison with similar parameters of the patients of the II group: length 39.8 ±1.2mm and width 36.2±1.2mm versus 32.2±2.1mm (p<0.01) and 27.4±1.7mm
(p<0.001). Reaction similar to menstrual in 48 (75.0%) patients of the I group appeared after 2 cycles of 28-day administration of the agent; in 10 (15.62%) patients after 3 cycles, in 6 (9.37%) after 4 cycles. In the II group of patients administering tefestrol in combination with didrogesteron for 2 cycles reaction similar to menstrual one appeared in 21 (35%) cases; in 21 (35%) after 3 cycles, in 18 (30%) after 4 cycles of administration. Duration of the reaction similar to menstrual in the I group was 4±1 days and 3±1 days in the II.
Tolerance to hormonal agents in both groups was satisfactory. Though in the I group five patients had nausea, two had chloasma on face. In the II group of patients there were no side effects of hormonal therapy.
Before the therapy and in 6 months of the therapy all the examined patients had assessment of functional metabolic activity of liver (Table 2).
Analysis of the obtained data showed that the amount of total bilirubin in both therapeutic groups was in the limits of normal values and did not change within the period of the therapy. The values of alkali phosphotase and cholin esterase demonstrated increase of these values independently of the age with background therapy in the I therapeutic group, and the rise of the absolute value of alkali phosphotase was reliably significant and was equal to 114.8±13.8 versus 154.0±10.1 (p<0.05). The values of ALT and AST in 6 months of the therapy also demonstrated reliably significant increase, but absolute values stayed in the limits of normal figures. In patients of the II group all values stayed unchanged within the whole follow-up period.
Table 2. - Biochemical values of girls with hypo gonadism in comparative aspect
Values Control (n=40) Examined groups
2 group (n=64) 3 group (n=60)
Before therapy In 6 mo Before therapy In 6 mo
ALT 7.5±0.73 5.75±0.97 10.3±3.9* 9.3±1.8 11.0±1.4A
AST 18.1±0.93 11.1±1.72A 18.7±2.4* 19.0±2.1 16.0±0.99
Bilirubin 9.3±0.86 7.3±0.49 7.5±0.55 11.1±0.9 9.8±1.0
Alkali phosphotase 127.4±12.9 114.8±13.8 154.0±10.1* 160.3±27.3 137.8±22.9
Cholin esterase 8166.9±409.2 7714.4±412.9 8732.7±443.3 12329.8±1570.4A 9360.5±426.6
Note: * — reliability of the data between the values before the therapy and in 6 months (P<0.05); A — reliability with control (P<0.05)
