Peculiarities of physical and sexual development of girls with autoimmune hepatitis in puberty period

Autoimmune hepatitis (AIH) is a rare immune-mediated chronic disease that, when inadequately treated, leads to progressive liver damage, which in turn leads to cirrhosis, liver failure, or death. Features of physical and sexual development of girls with AIH at puberty are little studied. The objective: to determine the characteristics of physical and sexual development of girls with autoimmune hepatitis in puberty period. Materials and methods. A comprehensive clinical and paraclinical examination of 66 adolescent girls of the group AIH with autoimmune hepatitis and 180 conditionally somatically healthy girls of the control group aged 12-17 years was performed. The examination included clinical and anamnestic data, anthropometry, biochemical examination of liver function, determination of serum autoantibodies, markers of viral hepatitis, ultrasound and elastography of the hepatobiliary system, liver biopsy followed by histological examination of biopsy, assessment. Results. Age-related changes in body length and body weight, chest circumference, waist and hips among girls with AIH were characterized by a significant lag at all stages of pubertal development. In patients with AIH, the onset of pubertal development was manifested by the development of mammary glands to the stage of Mal in 43.94% of girls, the previous appearance of puberty to thelarchein 34.85% of patients, and in 21.21% of patients noted simultaneous puberty and thelarche. Delayed development of sexual characteristics was manifested in 12-, 13- 14-, 15-, 16- and 17-year-old girls with AIH by a decrease in the score of sexual development in all age categories compared to the same indicator in the respective age control groups: respectively 3.21 ± 0.40 vs 4.94 ± 0.37 points, 3.46 ± 1.00 vs 7.91 ± 0.58, 7.03 ± 1.44 vs 11.08 ± 0.25, 7.80 ± 0, 65 vs 11.86, 10.65 ± 0.79 vs 11.98. In the examined girls with AIH during puberty, such disorders of menstrual function were noted as: primary amenorrhea in 7.58% of cases, secondary amenorrhea – in 6.06%, oligomenorrhea – in 27.27%, opsomenorrhea– in 27.27%, juvenile uterine bleeding – in 9.09%, dysmenorrhea – in 31.82%, a combination of various disorders – in 18.18%. Conclusions. The presence of antinuclear antibodies, antibodies to microsomes of the liver and kidneys type 1, antibodies to smooth muscle, disorders of enzymatic, protein-forming, antitoxic, cytolytic activity of the liver in girls with autoimmune hepatitis is accompanied during puberty by a high frequency of abnormalities. formation of inverted puberty, delayed sexual development and delayed onset of menarche for 10-11 months, frequent menstrual disorders

Personified treatment and prevention of sexual developmental disorders in pubertal age girls with diffusive liver diseases

Diffuse liver disease can have a pronounced detrimental effect on the developing reproductive system. Hepatoprotection in gynecological practice is not so much in the choice of drugs that protect or restore the liver, as in the appointment of optimal safe therapy for this category of patients, especially in adolescence. The aim: to study the effectiveness of therapeutic and prophylactic drugs for disorders of the reproductive system in adolescent girls with diffuse liver disease. Material and methods. Under observation for the period 2010-2020 were 486 girls aged 12-17 years, of which 120 - with chronic viral hepatitis (CVH), 120 - with non-alcoholic fatty liver disease (NAFLD), 66 - with autoimmune hepatitis (AIH), 180 - conditionally somatically and gynecologically healthy girls with normal sexual development of the control group. All patients underwent general clinical, hepatological examination, determination of features of neuroendocrine status, sexual development. The author proposed a differentiated method of treatment and prevention measures to restore reproductive health in adolescents with chronic diffuse liver disease, which included the appointment of vitamin D, phytocompositions, vitamin-mineral complexes with myo-inositol, if necessary - hormonal hemostasis. Results. Against the background of improved neuroendocrine status in the examined girls there was a decrease in the number of cases of amenorrhea in the group with CVH from 5.00% to 0.00% (p<0.01), in the group of NAFLD - from 27.50% to 3.33% (OR 11.00 [3.757-32.207]), in the AIH group - from 13.64% to 0.00% (p<0.01); opsomenorrhea - from 24.17% to 2.50% (OR 12.43 [3,670-42,092]), from 67.50% to 7.50% (OR 25.62 [11.750-55.843]) and from 27. 27% to 6.06% (OR 5.81 [1.846-18.304]); oligomenorrhea - from 25.83% to 1.67% (OR 20.55 [4.791-88.152]), from 62.50% to 5.83% (OR 26.91 [11.52-62.83]) and from 27.27% to 4.55% (OR 7.88 [2.192-28.286]); juvenile uterine bleeding - from 18.33% to 1.67% (OR 13.25 [3.039-57.728]), from 10.00% to 0.00% (p<0.01) and from 9.09% to 0.00% (p<0.01); dysmenorrhea - from 38.33% to 12.50% (OR 4.20 [2.181-8.087]), from 14.17% to 5.00% (OR 3.14 [1.191-8.257]) and from 31.82 % to 13.64% (OR 2.96 [1.234-7.078]). Conclusions. The applied personalized treatment-and-prophylactic measures taking into account individual disorders of neuroendocrine status and menstrual health in adolescent girls with diffuse liver diseases are effective and allow to recommend this complex as a means of treatment and prevention of reproductive disorders

Peculiarities of the functional state of the pituitary-gonadal system of the neuroendocrinal regulation in adolescent girl swith auto immune hepatitis

Girls and women make up 75% of patients with autoimmune hepatitis (AIH). The peak incidence of AIH occurs in childhood, when the disease is called juvenile AIH. The objective: to determine the features of the functional state of the pituitary-gonadal system of neuroendocrine regulation in adolescent girls with AIH. Material and methods. During 2010-2020, 66 girls of the main group AIH, patients with AIH, and 180 conditionally somatically and gynecologically healthy girls of the control group K at the age of 12-17 years were under observation. Comprehensive examination included history taking, assessment of sexual development, clinical and biochemical blood tests, determination of autoantibodies, markers of viral hepatitis, ultrasound examination of the abdominal cavity, liver biopsy (in main group). Peripheral serum hormone levels were determined in certain age groups (12, 13, 14, 15, 16 and 17 years): luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin (PRL), thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), estradiol (E2), progesterone (P4), free testosterone (fT). Results. Against the background of disorders of morphofunctional properties of the liver in 12-, 13-, 14- 15-, 16- and 17-year-old girls with AIH noted a significant decrease in the score of sexual development in all age groups compared to the same indicator in the relevant age control groups: 3.21 ± 0.40 vs. 4.94 ± 0.37, 3.46 ± 1.00 vs. 7.91 ± 0.58, 7.03 ± 1.44 vs. 11.08 ± 0.25, 7.80 ± 0.65 vs. 11.86, 10.65 ± 0.79 vs. 11.98 points. The average total level of LH in the Group AIHwas 3.77 ± 0.25 against 4.46 ± 0.10 mIU / ml in group K (p<0.01), FSH – 3.16 ± 0.12 against 4.01 ± 0.08 mIU / ml (p<0.01), PRL– 198.92 ± 6.96 vs. 282.93 ± 8.36 μIU / ml (p<0.01), E2– 124,15 ± 2.39 vs. 437.45 ± 9.59 pmol / ml (p<0.01), P4– 1.49 ± 0.09 vs. 2.78 ± 0.08 nmol / ml (p<0.01 ), fT– 1.96 ± 0.10 vs. 1.16 ± 0.04 nmol / l (p<0.01), TSH – 1.98 ± 0.05 vs. 2.15 ± 0.05 μIU / ml (p<0.03), fT3– 3.50 ± 0.06 vs. 5.46 ± 0.07 pmol / l (p<0.01), fT4– 12.54 ± 0.44 vs. 18.55 ± 0.20 pmol / l (p<0.01). Conclusions. In adolescent girls with AIH on the background of disorders of morphofunctional properties of the liver there is a delayed start of the hypothalamic-pituitary-gonadal system and suppression of hormone-producing function of the pituitary-gonadal link of the neuroendocrine system

The value of the free androgen index depends on the phenotype of polycystic ovary syndrome — a single-centre experience

Introduction: The free androgen index (FAI) values differ among patients with polycystic ovarian syndrome; however, the differences are not fully understood or known. The aim of the study was to evaluate FAI in women with polycystic ovary syndrome (PCOS) in regard to the phenotype of the PCOS and insulin resistance status. Material and methods: Anthropometric, hormonal, and biochemical parameters were assessed in 312 recruited women with PCOS. The FAI values were calculated in the reproductive and metabolic phenotypes of PCOS in groups of insulin resistance status based on the homeostasis model assessment-insulin resistance (HOMA-IR) > 2.0 or fasting insulin (FI) > 10 mmol/L. To test the relationship between individual variables, Spearman’s correlation analysis, the Kolmogorov-Smirnov test, and Student’s t-test were used. Results: The correlation between FAI values and HOMA-IR and FI was 0.42 and 0.47, respectively, in PCOS patients. A two fold higher FAI value was observed in metabolic PCOS phenotype when compared to the reproductive one (8.51 ± 5.56 vs. 4.40 ± 2.45 for HOMA-IR and 8.73 ± 6.09 vs. 4.31 ± 3.39 for FI, respectively; p < 0.05).Conclusions: PCOS patients are not a homogenous group in terms of FAI value. Patients with metabolic PCOS phenotype are characterised by two-fold higher FAI values compared with reproductive PCOS phenotype. Further studies on the metabolic and androgenic status of different types of PCOS phenotypes should be carried out.

Guideline for diagnostic, prevention and treatment of postmenopausal osteoporosis

Background.Postmenopausal osteoporosis (PMO), which is developed due the estrogen deficiency in women after menopause, is the most common type of systemic osteoporosis. The latest Ukrainian recommendation for its management requires revision due to new data from high-quality research performed in recent years. Thepurposewas to develop a guideline on the diagnosis, prevention, and treatment of PMO based on an analytical analysis of modern literary sources in order to improve the awareness of the medical community of Ukraine. Methodology. To develop the guideline, an expert group of 13 leading Ukrainian scientists of various specialties was created who conducted a thorough review of modern literature on this topic, assessed the level of existing evidence using the GRADE system, proposed and voted on 15 recommendations of the guideline. Results. The guideline contains chapters on diagnosis and differential diagnosis of PMO, assessment of the osteoporotic fracture risk, the role of bone turnover markers in the management of PMO, and modern strategies of antiosteoporotic treatment.Conclusions. The Ukrainian guideline on the diagnosis, prevention, and treatment of PMO, which contains 15 main recommendations, created on the basis of a thorough analysis and synthesis of modern literature data, is an important tool for the management of PMO and is recommended by Ukrainian Association of Osteoporosis for use in Ukrainian medical community

Некласична функція вітаміну D – вплив на репродуктивне здоров`я, пубертат та фертильність

In the past few years, there has been growing appreciation for the many roles of vitamin D and its active metabolites in a large number of tissues. Most tissues in the body, not just those participating in the classic action of vitamin D such as bone, kidney and gut, have receptors (VDR) for the active form of vitamin D – 1,25 dihydroxyvitamin D. The recent data on vitamin D from retrospective, prospective observational studies, case-control and experimental studies confirm the essential role of vitamin D in a variety of physiological functions. Last time there has been growing interest in this substance observed in the scientific researches and biomedical literature, due to findings which demonstrate a vitamin D deficiency status in the population. This review is an analysis of the association between the vitamin D and the female and male reproduction and fertility. We highlight the latest findings from medical trials on vitamin D during last years. The aim of this article is to understand how vitamin D affects the female and male fertility. Vitamin D is a hormone which controls nearly 1/3 of human and mice genome, over 200 genes in a human body, including those responsible for cell cycle control: proliferation, differentiation, apoptosis. Apart from basic functions, which are maintaining calcium-phosphoric balance, vitamin D takes active part in process of cell proliferation, epidermal keratinocyte differentiation, immune system stimulation, insulin secretion, brain metabolism, adipocytes function, puberty, reproduction and fertility. The vitamin D receptors (VDR) and vitamin D metabolizing enzymes are found in reproductive tissues of women and men. VDR knockout mice have significant gonadal insufficiency, decreased sperm count and motility, and histological abnormalities of testis, ovary and uterus. Assuming that 30 ng/ml (75 nmol/l) is a lower limit of normal concentration of 25(OH)D3 in serum, the number of people with vitamin D deficit equals about 1 billion worldwide.За останні кілька років дедалі частіше зустрічаються наукові підтвердження впливу вітаміну D та його активних метаболітів на фізіологію різних органів. Доведено, що більшість тканин організму мають відповідні рецептори (VDR) для активної форми вітаміну D – 1,25 дигідроксивітаміну D, і не тільки ті, що беруть участь в класичній дії вітаміну D (кістки, нирки і кишківник). Дані ретроспективних, перспективних, випадок-контроль та експериментальних досліджень підтверджують важливу роль вітаміну D в різних фізіологічних функціях. Протягом останнього часу спостерігається зростаючий інтерес до даної субстанції у наукових дослідженнях та біомедичній літературі у зв’язку з висновками, які демонструють статус дефіциту вітаміну D в популяції. Метою даної статті є аналіз зв’язку вітаміну D з фертильністю та репродуктивною функцією в організмі як жінок, так і чоловіків, з періоду пубертату до зрілого репродуктивного віку. Даний науковий огляд демонструє останні новини медичних досліджень, які підтверджують це. Вітамін D є гормоном, який контролює 1/3 геному людини та миші, понад 200 генів в організмі людини, в тому числі ті, що відповідають за контроль клітинного циклу: проліферацію, диференціювання, апоптоз. Крім основних функцій, таких як підтримка кальційфосфорного балансу, вітамін D бере активну участь у процесі диференціювання кератиноцитів епідермісу, стимуляції імунної системи, секреції інсуліну, метаболізму головного мозку, функції адипоцитів і фертильності. Рецептори для вітаміну D (VDR) і ферменти, що беруть участь в його метаболізмі, знаходяться в тканинах репродуктивних органів обох статей. VDR-нокаутні миші мають значну гонадну недостатність, зниження кількості сперматозоїдів та їх рухливості, гістологічні аномалії яєчка, яєчників та матки. Якщо припустити, що 30 нг/мл (75 нмоль/л) – нижня межа нормальної концентрації 25(OH)D3 в сироватці крові, кількість людей з дефіцитом вітаміну D становить майже 1 млрд у всьому світі

Менархе, пубертат і вітамін D

Puberty is the development process - result of a complex series of molecular and physiological events, culminating in reproductive capability. Gonadotropin-releasing hormone actively released from specialized neurons of the hypothalamus stimulates gonadal activation and triggers physical changes of puberty through initiation of the hormonal cascade. Epidemiologic studies and numerous clinical trials claim that sufficient levels of vitamin D3 are essential for normal physiological growth, development and puberty, by activation of the neurohormonal multisystem in the hypothalamus-pituitary-gonadal axis. Various scientific studies investigate the role of vitamin D3 and its metabolites in specific reproductive disorders of women and men. All these data contribute to intensive research on vitamin D3 and its receptor as a potential factor, affecting the pathogenesis of a numerous diseases, connected with its non-classical function, such as diabetes, obesity, cancer, puberty disorders and infertility. In the last decade, the prevalence of vitamin D3 deficiency has been increasing in many parts of the world, that has caused an increasing number of medical research on the subject. Nevertheless, data on the vitamin D status and its association with puberty in girls are constrained. This paper was written to present different studies on vitamin D3 and its influence on puberty through the regulation of the neurohormonal system during sexual maturityПоловое созревание – это процесс, осуществляющийся в результате сложной серии молекулярных и физиологических явлений, кульминацией которого является способность организма к репродукции. Активное выделение гонадолиберина из специализированных нейронов гипоталамуса начинает каскад гормональных процессов, которые, в свою очередь, приводят к активации гонад и тем самым дают толчок анатомо-физиологическим изменениям организма в период пубертата. Эпидемиологические данные и многочисленные клинические исследования указывают на то, что соответствующий уровень витамина D3 имеет большое значение для нормального физиологического роста, развития и полового созревания, действуя путем активации нейрогормональной мультисистемы в гипоталамо-гипофизарно-гонадной оси. Последние исследования изучают роль витамина D3 и его метаболитов в конкретных нарушениях репродуктивного здоровья женщин и мужчин. Исследование витамина D3 и его рецептора доказали его потенциальное влияние на патогенез многочисленных заболеваний, связанных с классическим действием витамина D3 – таких как сахарный диабет, ожирение, рак и другие. Численность лиц с дефицитом витамина D3 во многих странах мира в последние несколько лет увеличилась, вследствие чего активизировались медицинские исследования по этой теме. Тем не менее, данные о влиянии витамина D3 на процесс полового созревания у девочек остаются недостаточно изученными. Данная статья представляет ряд мировых исследований, описывающих влияние витамина D3 на регуляцию нейрогормональной системы в период полового созреванияСтатеве дозрівання – це процес, що відбувається в результаті складної серії молекулярних і фізіологічних явищ, кульмінацією якого є здатність організму до репродукції. Активне виділення гонадоліберину із спеціалізованих нейронів гіпоталамуса започатковує каскад гормональних процесів, які, в свою чергу, призводять до активації гонад і тим самим дають поштовх анатомо-фізіологічним змінам організму в період пубертату. Епідеміологічні дані та численні клінічні дослідження вказують на те, що відповідний рівень вітаміну D3 має велике значення для нормального фізіологічного росту, розвитку і статевого дозрівання, діючи шляхом активації нейрогормональної мультисистеми в гіпоталамо-гіпофізарно-гонадній осі. Останні дослідження вивчають роль вітаміну D3 і його метаболітів в конкретних порушеннях репродуктивного здоров'я жінок і чоловіків. Дослідження вітаміну D3 і його рецептора довели його потенційний вплив на патогенез численних захворювань, не пов’язаних із класичною дією вітаміну D3 – таких як цукровий діабет, ожиріння, рак та інші. Чисельність осіб із дефіцитом вітаміну D3 в багатьох частинах світу в останні кілька років зросла, через що активізувалися медичні дослідження з цієї теми. Проте дані про вплив вітаміну D3 на процес статевого дозрівання у дівчаток залишаються недостатньо вивченими. Дана стаття представляє ряд світових досліджень, що описують вплив вітаміну D3 на регуляцію нейрогормональної системи в період статевого дозріванн

Endocrine status of adolescent girls with non-alcoholic fatty liver disease and obesity

Along with the increase in the prevalence of childhood obesity, diseases associated with unhealthy morbid obesity, including non-alcoholic fatty liver disease (NAFLD), are also on the rise. How NAFLD affects the hormonal profile in adolescent girls has not been studied enough. Therefore, the aim of this study was to examine the features of the endocrine status of adolescent girls with NAFLD and obesity. Material and methods. From 2010 to 2020, 300 patients aged 12–17 years were monitored, including 120 patients with NAFLD and metabolically unhealthy obesity and 180 conditionally somatically healthy girls with normal sexual development with normal body weight. Clinical examination, biochemical assessment of the functional state of the liver and its morphostructure were performed. Determination of the level of peripheral blood serum hormones was performed by immunochemical method with chemiluminescent detection. Results. Endocrine status of girls with NAFLD and obesity was characterized by an increase in luteinizing hormone (LH) - 9.89 ± 0.18 vs. 5.13 ± 0.08 μIU / ml (p&lt;0.01); follicle-stimulating hormone (FSH) - 5.50 ± 0.16 vs. 5.40 ± 0.07 μIU / ml (p&lt;0.01); the ratio of LH / FSH - 1.91 ± 0.05 vs. 0.98 ± 0.02 (p&lt;0.01); prolactin - 327.73 ± 7.15 vs. 282.93 ± 8.36 μIU / ml (p&lt;0.01); thyroid-stimulating hormone (TSH) - 3.36 ± 0.07 vs. 2.15 ± 0.05 μIU / ml (p&lt;0.01); decrease in estradiol level - 124.15 ± 2.39 vs. 437.45 ± 9.59 pmol / ml (p&lt;0.01); progesterone - 1.49 ± 0.09 vs. 2.78 ± 0.08 nmol / ml (p&lt;0.01); increase in the level of free testosterone - 1.96 ± 0.10 vs. 1.16 ± 0.04 nmol / l (p &lt;0.01); free triiodothyronine - 4.41 ± 0.12 vs. 5.46 ± 0.07 pmol / l (p&lt;0.01); free thyroxine - 14.61 ± 0.41 vs. 18.55 ± 0.20 pmol / l (p&lt;0.01). Conclusions. Endocrine status of girls with NAFLD and unhealthy morbid obesity during puberty is characterized by increased secretion of gonadotropins, prolactin and TSH, decreased levels of estradiol, progesterone, thyroid hormones against the background of a moderate increase of androgens, insulin and insulin resistance.</p

Hormonal profile of pubertal age girls with chronic viral hepatitis

Chronic viral hepatitis (CVH) is more than 70% of the total number of children with chronic hepatitis, and in the population - 0.5%. Adolescents are the most vulnerable group of the population due to the physiological and psychological characteristics of this age. The liver coordinates both adaptive and reproductive processes in the body, and during puberty is the formation of pituitary-gonadal relationships. The aim: to study the features of hormonal homeostasis in adolescent girls with CVH. Materials and methods. We examined 300 girls aged 12-17 years, of which 120 patients with CVH (60 patients with hepatitis B and 60 - with hepatitis C) and 180 relatively healthy patients with physiological sexual development. The diagnosis of CVH was established on the basis of medical history, clinical, virological, biochemical, morphological and instrumental examination. Results. Analysis of the obtained data of the functional state of the liver in the examined patients with CVH revealed disorders of the morphofunctional state of the liver, manifested by cytolysis syndrome, cholestasis, hepatocellular insufficiency and mesenchymal-inflammatory syndrome. In patients with CVH there was a decrease in the production of luteinizing hormone (4.35 ± 0.09 vs. 5.13 ± 0.08 mIU / ml, p&lt;0.01); follicle-stimulating hormone (4.40 ± 0.15 vs. 5.40 ± 0.07 mIU / l, p&lt;0.01); prolactin (215.56 ± 4.76 vs. 282.93 ± 8.36 mIU / ml, p &lt;0.01); progesterone (2.09 ± 0.10 vs. 2.78 ± 0.08 nmol / l, p&lt;0.01) on the background of increasing the average level of estradiol (468.65 ± 21.32 vs. 437.45 ± 9.59 pmol / l, p&lt;0,01) and free testosterone (1,98 ± 0,08 vs. 1,16 ± 0,04 nmol / l, p &lt;0,01). Thyroid status was characterized by a relative decrease in the production of thyroid-stimulating hormone (1.74 ± 0.04 vs. 2.15 ± 0.05 μIU / ml (p&lt;0.01) and an increase in the secretion of free triiodothyronine (9.32 ± 0.09 vs. 5,46 ± 0.07 pmol / l, p&lt;0.01) and free thyroxine (23.35 ± 0.76 vs. 18.55 ± 0.20 pmol / l, p&lt;0.01). chronic infectious process, affects the morphofunctional state of the liver and leads to dysfunction of the hypothalamic-pituitary-ovarian and pituitary-thyroid systems, manifested by pathological changes in the secretion of gonadotropins, prolactin, thyroid-stimulating hormone, sex steroids and hormonal steroids.</p