Hormonal Disbalance Research Articles

Semi-Automated MicroCT Analysis of Bone Anatomy and Mineralization in Mouse Models.

The skeletal system mirrors several processes in the vertebrate body that impact developmental malfunctions, hormonal disbalance, malfunction of calcium metabolism and turn over, and inflammation processes such as arthrosis. X-ray micro computed tomography is a useful tool for 3D in situ evaluation of the skeletal system in a time-related manner, but results depend highly on resolution. Here, we provide the methodological background for a graduated evaluation from whole-body analysis of skeletal morphology and mineralization to high-resolution analysis of femoral and vertebral microstructure. We combine an expert-based evaluation with a machine-learning-based computational approach, including pre-setup analytical task lists. © 2024 Wiley Periodicals LLC. Basic Protocol 1: In vivo microCT scanning and skeletal analysis in mice Basic Protocol 2: Ex vivo high-resolution microCT scanning and microstructural analysis of the femur and L4 vertebra.

Innovation and Challenges in Male Contraception

The unwanted cases of pregnancy have increased resulting in improper family planning and cases of depression or stillbirth. The decision regarding reproduction is shared equivalently by men and women. Although the contraception methods result in effectiveness, they have more complications than effective results. Hormonal disbalance and endometriosis are a few such examples. Contraception for males is limited, yet has more effective results and fewer complications. The development of male contraception is vastly researched over the past few decades. Various hormonal and non-hormonal methods are being developed to provide better contraception with minimum or no disadvantage. The basic advantage of developing a male contraceptive includes its availability, low cost, no side effects, and ease of use.

Causes of Infertility in Women with Diabetes: Literature Review

Diabetes Mellitus (DM) is a serious chronic disease, resulting from long-term hyperglycemia can lead to various complications. Complications of DM are associated with changes occurring in blood vessels and nerve fibers. Diabetes can affect a woman's reproductive function and lead to infertility. Decreased fertility in women with DM can be caused by various factors related to this disease. To date, the final mechanisms of reduced reproductive function in these women have not been fully elucidated, but it is known that the leading role belongs to chronic hyperglycemia. Purpose: Based on these literature sources, to investigate the possible causes of infertility in women with diabetes. Object: reduced fertility in women as a result of diabetes. Research methods: a review of literary sources. Results: There are quite a few causes of infertility and reduced fertility in women with DM, these include complications of diabetes (diabetic polyneuropathy); insulin resistance and, as a result, polycystic ovary syndrome; obesity; autoimmune and genetic factors; disorders of the menstrual cycle and hormone balance; low quality of egg cells due to oxidative stress and the formation of glycation products; reduction of cervical mucus due to hormonal disbalance, dehydration and inflammatory processes of the genital organs; psychogenic factors (phobias, fear of childbirth, future changes both in the body and in life). Conclusions: Based on the study of literary data, it can be said that the main causes of infertility in women with DM are caused by chronic hyperglycemia, and as a result, the development of pathological conditions that lead to disorders in the reproductive system. In addition, the causes of infertility in women with DM include disorders of the menstrual cycle and hormone balance, polycystic ovary syndrome, obesity, and autoimmune and genetic mechanisms. Taking this into account, glycemic control, prevention and treatment of diabetes complications, lifestyle modification, nutrition, and psychological health support are necessary.

Perinatal pathology for women with reproductive losses in anamnesis

Perinatal aspects of miscarriage, despite progress in the study of pathogenetic mechanisms, continue to be leading in modern obstetrics. The presence of even one case of miscarriage in a woman’s anamnesis negatively affects her further reproductive function, affects the course and outcome of the next pregnancy, and even pre-pregnancy correction of detected disorders does not always allow to achieve the desired result - the birth of a healthy child. The issues of prediction, prevention, and prevention of perinatal complications require a clear understanding of the mechanism of influence of the threat of spontaneous abortion and premature birth on the fetus. Placental dysfunction can have serious consequences during pregnancy, affecting both mother and baby. Therefore, it is very important to study the relationship between potential risk groups, such as women with a history of recurrent pregnancy loss, and placental dysfunction. Perinatal pathology for women with reproductive losses in anamnesis. Based on the germination of a pathogeny of unmaturing of pregnancy and violations of placenta dysfunction, previous abortions in anamnesis can be related to the enhanced able risk of violations of placenta dysfunction. Comparing primiparous women, in which there were abortions in anamnesis, to the control group of women giving birth, can bring the overvalue of risks, as for the primiparous women of violation of placenta dysfunction more widespread, than for women giving birth. It is set that the most closely-coupled interface from preeclampsia was observed for patients with premature births of <37 weeks of gestation, but not in those, who gave in a term. Found out the theenhanceable risk of preeclampsia at the repeated losses of pregnancy, but only at the presence of an anamnesis of auxiliary genesial technologies. Other research it was not succeeded to find out the higher risk of preeclampsia for women with repeated loss of pregnancy, that it is possible to explain the small population and absence of a clear determination of the sequence of abortions. The repeated loss of pregnancy is a studied not enough problem, which causes serious disturbance in pair which try to create a family. Separate patients can have isolated infertility, repeated spontaneous abortions, or repeated losses in the ІІ and ІІІ trimesters. However much epidemiology information testify to strong intercommunication between these unfavorable results. The set reasons for the repeated loss of pregnancy include a hormonal disbalance, anomalies oogenesis highway, genetic or chromosomal anomalies, psychosocial, autoimmune diseases, and, possibly, immunological incompatibility of mother and fetus.

The Main Theories on the Pathogenesis of Endometriosis.

Endometriosis is a complex disease, which is defined by abnormal growth of endometrial tissue outside the uterus. It affects about 10% of women of reproductive age all over the world. Endometriosis causes symptoms that notably worsen patient's well-being-such as severe pelvic pain, dysfunction of the organs of pelvic cavity, infertility and secondary mental issues. The diagnosis of endometriosis is quite often delayed because of nonspecific manifestations. Since the disease was defined, several different pathogenetic pathways have been considered, including retrograde menstruation, benign metastasis, immune dysregulation, coelomic metaplasia, hormonal disbalance, involvement of stem cells and alterations in epigenetic regulation, but the true pathogenesis of endometriosis remains poorly understood. The knowledge of the exact mechanism of the origin and progression of this disease is significant for the appropriate treatment. Therefore, this review reports the main pathogenetic theories of endometriosis based on current studies.

Proteins and proteases of Prader-Willi syndrome: a comprehensive review and perspectives.

Prader–Willi Syndrome (PWS) is a rare complex genetic disease that is associated with pathological disorders that include endocrine disruption, developmental, neurological, and physical problems as well as intellectual, and behavioral dysfunction. In early stage, PWS is characterized by respiratory distress, hypotonia, and poor sucking ability, causing feeding concern and poor weight gain. Additional features of the disease evolve over time. These include hyperphagia, obesity, developmental, cognitive delay, skin picking, high pain threshold, short stature, growth hormone deficiency, hypogonadism, strabismus, scoliosis, joint laxity, or hip dysplasia. The disease is associated with a shortened life expectancy. There is no cure for PWS, although interventions are available for symptoms management. PWS is caused by genetic defects in chromosome 15q11.2-q13, and categorized into three groups, namely Paternal deletion, Maternal uniparental disomy, and Imprinting defect. PWS is confirmed through genetic testing and DNA-methylation analysis. Studies revealed that at least two key proteins namely MAGEL-2 and NECDIN along with two proteases PCSK1 and PCSK2 are linked to PWS. Herein, we summarize our current understanding and knowledge about the role of these proteins and enzymes in various biological processes associated with PWS. The review also describes how loss and/or impairment of functional activity of these macromolecules can lead to hormonal disbalance by promoting degradation of secretory granules and via inhibition of proteolytic maturation of precursor-proteins. The present review will draw attention of researchers, scientists, and academicians engaged in PWS study and will help to identify potential targets and molecular pathways for PWS intervention and treatment.

CHEK2p.I157T Mutation Is Associated with Increased Risk of Adult-Type Ovarian Granulosa Cell Tumors.

Simple SummaryGranulosa cell tumors of the ovary represent a distinct subset of ovarian cancers typically characterized by hormonal disbalance, slow disease progression, and late recurrence years after surgical removal of the primary tumor. Risk factors associated with development of these rare tumors have not yet been established. In this study, we identified an association between increased risk of developing adult-type granulosa cell tumors (AGCTs) and a specific germline mutation in the CHEK2 gene. Our findings further support the relevance of this deleterious mutation in the increased risk of various cancer types, and opens a new avenue that can be exploited for future development of CHEK2-targeted preventive and therapeutic interventions directed at AGCTs.Pathogenic germline mutations c.1100delC and p.I157T in the CHEK2 gene have been associated with increased risk of breast, colon, kidney, prostate, and thyroid cancers; however, no associations have yet been identified between these two most common European founder mutations of the CHEK2 gene and ovarian cancers of any type. Our review of 78 female heterozygous carriers of these mutations (age > 18 years) found strikingly higher proportion of adult-type granulosa cell tumors of the ovary (AGCTs) among ovarian cancers that developed in these women (~36%) compared to women from the general population (1.3%). Based on this finding, we performed a cross-sectional study that included 93 cases previously diagnosed with granulosa cell tumors, refined and validated their AGCT diagnosis through an IHC study, determined their status for the two CHEK2 mutations, and compared the prevalence of these mutations in the AGCT cases and reference populations. The prevalence ratios for the p.I157T mutation in the AGCT group relative to the global (PR = 26.52; CI95: 12.55–56.03) and European non-Finnish populations (PR = 24.55; CI95: 11.60–51.97) support an association between the CHEK2p.I157T mutation and AGCTs. These rare gynecologic tumors have not been previously associated with known risk factors and genetic predispositions. Furthermore, our results support the importance of the determination of the FOXL2p.C134W somatic mutation for accurate diagnosis of AGCTs and suggest a combination of IHC markers that can serve as a surrogate diagnostic marker to infer the mutational status of this FOXL2 allele.

A Case of Secondary Hypogonadism with Increased Risk of Fractures in a 57-year-old Male Patient on Methadone Maintenance Therapy

Oral maintenance opioid agonists have an important role in the management of heroin addiction and chronic pain. Methadone is one of the most popular and effective treatments for opioid dependence, however many patients following methadone’s clinics can develop a few metabolic and sexual side effects. Methadone can induce a few hormonal disbalance over time, including hypogonadotropic hypogonadism with sexual dysfunction, muscle weakness, and decreased bone mass density. Most of the side effects are dose-related especially when methadone is above 100 mg daily. Low levels of testosterone increase the risk of erectile dysfunction, loss of libido, sexual unsatisfaction, osteopenia, and osteoporosis, giving a poor quality of life in patients on methadone maintenance therapy. We present a case of a 57 -year-old male patient complaining about erectile dysfunction and loss of libido secondary to central hypogonadism induced by methadone with decreased bone density. The purpose of this case report is to bring these patients to the primary care world and improve their management with a multidisciplinary team including primary care, endocrinologists, and psychologists. Physicians should be aware of opioid-induced endocrinopathies and address properly with early sex hormones work up, bone density screening, and encourage methadone tapering every visit.

Association of Poland Syndrome and hypertrichosis in pubertal girl - Case report

Poland syndrome (PS) is a rare congenital malformation, most commonly characterized by absence of chest wall muscles on one side of the body. It may be accompanied with other deformities of the extremities. We present the case of a 10-year-old girl with Poland syndrome and hypertrichosis of the back of the trunk and extremities. The clinical examination did not reveal the etiology of the syndrome, such as familial predisposition or some event that led to interrupted blood flow during the early embionic growth. The pregnancy was concieved with in vitro fertilization (IVF); triplets were born and our patient is one of these three girls. The hypertrychosis appeared at 8 years of life, without evidence of previous familial occurance, medications or hormonal disbalance. Other malformations that were found were: a mild form of kyphoscoliosis and mitral valve prolapse. The child was evaluated using a multidisciplinary approach, with further follow-up planned with surgical correction of the chest wall and breast augmentation.

МЕДИЧНІ АСПЕКТИ СУРОГАТНОГО МАТЕРИНСТВА

Surrogacy is associated with a wide range of factors that increase maternal and perinatal risks. The use of in vitro fertilization and embryo transfer technologies determines the higher frequency of multiple pregnancies that enhances the risk of cesarean section, premature birth, low body weight in newborns, etc. in case of surrogacy. Genetic differences and immunogenetic reactions increase the risk of pre-eclampsia, placental pathology, abortion, intrauterine growth retardation. Hormonal disbalance under the effect of adverse factors during surrogate pregnancy may initiate prenatal reprogramming of morphogenesis through epigenetic mechanisms. This can affect the organogenesis and predispose to susceptibility to various diseases. Psychological factors and emotional link between a surrogate mother and a fetus are associated with increased levels of hormones of stress-releasing systems, which affect the formation of neurohumoral systems of the fetus and can modulate its mental development.

Mitochondrial Dysfunction and Chronic Inflammation in Polycystic Ovary Syndrome.

Polycystic ovarian syndrome (PCOS) is the most common endocrine–metabolic disorder affecting a vast population worldwide; it is linked with anovulation, mitochondrial dysfunctions and hormonal disbalance. Mutations in mtDNA have been identified in PCOS patients and likely play an important role in PCOS aetiology and pathogenesis; however, their causative role in PCOS development requires further investigation. As a low-grade chronic inflammation disease, PCOS patients have permanently elevated levels of inflammatory markers (TNF-α, CRP, IL-6, IL-8, IL-18). In this review, we summarise recent data regarding the role of mtDNA mutations and mitochondrial malfunctions in PCOS pathogenesis. Furthermore, we discuss recent papers dedicated to the identification of novel biomarkers for early PCOS diagnosis. Finally, traditional and new mitochondria-targeted treatments are discussed. This review intends to emphasise the key role of oxidative stress and chronic inflammation in PCOS pathogenesis; however, the exact molecular mechanism is mostly unknown and requires further investigation.

Doxorubicin induces cytotoxicity and miR-132 expression in granulosa cells

Doxorubicin (DOX) is one of the most commonly used drugs for the treatment of childhood cancers, including leukemia and lymphomas. Despite the high survival rate, female leukemia survivors are at higher risk of ovarian failure and infertility later in life. Treatment with chemotherapeutic drugs like DOX is associated with damage in ovarian follicles, but the affectation grade of granulosa cells remains unclear. To assess and avoid the possible side-effects of DOX, early biomarkers of ovarian injury and chemotherapy-induced ovarian toxicity should be identified. MicroRNAs (miRNAs) have emerged in recent years as a promising new class of biomarkers for drug-induced tissue toxicity. In this study, the effects of DOX on cell viability, steroidogenesis, and miRNA expression were studied in primary granulosa cells (GCs) and in two cellular models (COV434 and KGN cells). We report that compared to other chemotherapeutic drugs, DOX treatment is more detrimental to granulosa cells as observed by decrease of cell viability. Treatment with DOX changes the expression of the aromatase gene (CYP19A1) and the secretion of 17β-estradiol (E2) in a cell-specific manner. miR-132−3p is dose-dependently increased by DOX in all cellular models. In absence of DOX, miR-132−3p overexpression in COV434 cells has no effect on E2 secretion or CYP19A1 expression. Altogether, these findings contribute to understanding the hormonal disbalance caused by DOX in human ovarian cells and suggest miR-132 as a putative sensor to predict DOX-induced ovarian toxicity.

КУЛЬТУРА ЗОВНІШНЬОГО ОСВІТЛЕННЯ. ПРОБЛЕМА СВІТОВОГО ЗАБРУДНЕННЯ НАВКОЛИШНЬОГО СЕРЕДОВИЩА

КУЛЬТУРА ЗОВНІШНЬОГО ОСВІТЛЕННЯ. ПРОБЛЕМА СВІТОВОГО ЗАБРУДНЕННЯ НАВКОЛИШНЬОГО СЕРЕДОВИЩА

47, XYY Syndrome and its Association with Male Infertility: Case Report

47, XYY syndrome is one of the most common sex chromosomal anomaly found in humans after Klinfelter syndrome (47, XXY). It is frequently associated with infertility in males. This syndrome has an extra Y chromosome (XYY) due to non-disjunction of the Y chromosome in paternal meiotic II. The presence of an extra Y chromosome causes hormonal disbalance in the gonads that responsible for abnormal function of human chorionic gonadotropin. In our case of infertile men with severe oligozoospermia that also confirm by conventional cytogenetic analysis of the peripheral blood lymphocytes revealed the constitutional karyotype of 47, XYY. This report is likely to be helpful for counselling and early management of such infertile males.

Expression of voltage-operated calcium channel subunit CAV1.2. in human mesenchymal stem cells during chondrogenic differentiation

Purpose: There is emerging evidence that hypertension is a comorbidity in many osteoarthritis (OA) patients and is mechanistically linked to the progression of OA due to age, obesity, hormonal disbalance etc. A group of cardiovascular drugs, such as nifedipine, are well known voltage-operated calcium channel (VOCC) inhibitors, which prevent high pressure in blood vessels in people struggling with hypertension.VOCCs are crucial for intracellular ion intake, leading the cells to a chain of metabolic reactions, while VOCC subunit CaV1.2.

Prevalence of metastases within the hypothalamic-pituitary area in patients with brain metastases

AimTo quantify the prevalence of brain metastases involving the hypothalamic-pituitary (HT-P) area.IntroductionCognitive impairment and fatigue are common side effects of whole brain irradiation (WBI) comprising the quality of life (QoL) for survivors. While the former is related to radiation-induced hippocampal injury, the latter could be secondary to hormonal disbalance as a consequence of radiation of the HT-P area. Thus, sparing both regions from higher irradiation doses could reduce these sequelae.MethodsT1 contrast medium enhanced magnetic resonance imaging (MRI) scans of 865 patients with brain metastases (4,280 metastases) were reviewed. HT-P area was individually contoured with a margin of 5 mm in order to evaluate the prevalence of brain metastases in this region.ResultsInvolvement of the hypothalamic region was found in 26 patients (involvement rate of 3% for patients and 1% for metastases), involvement of the pituitary gland in 9 patients (1% for patients and < 1% for metastases). Binary logistical regression analysis revealed the presence of > 10 brain metastases as the only factor associated with hypothalamic involvement while no distinct factor was associated with an involvement of the pituitary gland.ConclusionThe low prevalence of metastases within the HT-P area in patients with brain metastases calls for further studies examining whether sparing of this region might improve patients QoL.

The effect of hormonal disbalance on the aging rate change in the patients with arterial hypertension and comorbid endocrinopathies

Due to the growing number of patients with age-related diseases, the aim of the study was to investigate in the changes of aging rate (AR) in patients with comorbid course of arterial hypertension (H), type 2 diabetes mellitus (T2DM) and subclinical hypothyroidism (SH) and to study the features of these changes depending on hormonal imbalance. 118 patients (63 women and 55 men, average age — 53.6±4.3 years) were divided into 3 groups: group 1 (n=37) with isolated H; group 2 (n=42) — with H and T2DM; group 3 (n=39) — with H, T2DM and SH. The investigation program included: measurement of anthropometric parameters (blood pressure, height, body weight (BW), body mass index (BMI)), carbohydrate and thyroid metabolism using standard methods, biological age (BA) by V.P. Voitenko et al. Statistical processing was performed using the Statistica for Windows 8.0 software package. When evaluating AR, physiological aging was found in 8 patients (21.6%) of group 1, in 4 (9.5%) patients of group 2 and 3 (7.7%) of patients in group 3. In the overwhelming majority of the examined patients, premature aging (PA) was noted, however, the acceleration of PA between patients of groups 2 and 3 was not differ significantly (p&gt;0.05). The increase in AR in group 2 patients was accompanied by an increase in BA by 7.2 years, in 3 group patients — by 7.3 years compared with their chronological age. A correlation analysis revealed a positive relationship between BMI and coefficient of aging rate (CAR) (r=0.679; p&lt;0.05); BMI and BA (r=0.562; p&lt;0.05) and CAR and the TSH level (r=0.050; p=0.388) in the 3rd group. Thus, the presence of hypertension and comorbid endocrinopathies — T2DM and SH significantly increases the AR and when assessing the effect of endocrine disorders, the presence of T2DM is more important than SH.

Polycystic ovary syndrome (PCOS) and genetic predisposition: A review article.

Polycystic ovary syndrome (PCOS) is a heterogeneous condition which is related to an endocrine reproductive disorder of females. It affects females of 18–44 age. The persistent hormonal disbalance leads to the complexities such as numerous cysts, an irregular menstrual cycle that ultimately leads to infertility among females. Many candidate genes have been identified to be one of the causes of PCOS. Different studies have been carried out to find the genetic correlation of PCOS. It is essential to carry out such studies that identify the clear cause of PCOS and its genetic association and hormonal disbalance. This review has highlighted different genes and their correlation with PCOS that leads to hormonal disbalance. Yet not in-depth but an attempt to study the genetic predisposition of PCOS.

Neuroendocrine and immune disequilibrium as a probable link between metabolic syndrome and carcinogenesis

Numerous investigations prove a higher incidence of carcinogenesis in metabolic syndrome (MetS). They indicate the important role of obesity, elevated inflammatory biomarkers, hyperinsulinemia, hyperglycemia, and dyslipidemia as well. Elevated plasma insulin and free insulin-like growth factor-1 (IGF-1) levels stimulate cell proliferation. The present publication considers the role of neuroendocrine and immune disequilibrium in MetS as a reason for transition to carcinogenesis. It emphasizes the role of hormonal disbalance, i.e. hyperleptinemia, hyperinsulinemia, hypercortisolemia, hypercatecholaminemia, hyperestrogenemia and hyperandrogenemia in MetS. It is presumed that these important components modify cellular microenvironment towards carcinogenesis. The interactions between neurotrophins, leptin, and mast cells and the alterations in the hypothalamo-hypophyseal-adrenal axis in MetS are discussed. It is assumed that they are the consequence of inflammatory distress followed by hormonal and immune disbalance at a central level as well as of enlarged adipose tissue and changed adipocyte microenvironment leading, finally, to carcinogenesis.

The possible role of stress induced hormonal disbalance in the patophysiology of insulin resistane in lean individuals

Insulin resistance (IR) is a common denominator of metabolic and hemodynamic disorders simultaneously present in one person and responsible for elevated risk of developing type 2 diabetes (T2DM) and cardiovascular incidents. According to the latest research, IR is present in 25–45% of the general population. Therefore, the mechanism of its development is in the center of scientific and professional interest. Established or acquired factors, or combinations thereof, which disturb any step of the physiological insulin action mechanism: its binding to the cellular receptor, through the complex cascade of intracellular signaling pathways might cause IR. Although the adiposity and its underlying risk factors are considered to be the primary cause of IR, it is present in a great porportion in lean individuals as well.There are insights of the possible role of psychological factors: exposure to stress and deprssion to IR development, although the mechanism of this relationship has not been comperhensively studied. Data driven from cell cultures and experimental animal models suggest that there is an elevated level of counter-regulatory insulin hormones: growth hormone, prolactin and cortisol due to acute stress exposure. However, the relationship between these psychological disorders with the hyperreactivity of the axis of the hypothalamic–pituitaryadrenal axis as the underlying mechanism in the patophysiology of IR in lean individuals has not been systematically investigated. Based on the aforementioned, we hypothesise that this mechanism would be responsible for the formation of IR, and consequently, T2DM in lean individuals.The possible effect of the amount of stress in conjunction with the serum concentration of growth hormone, cortisol, prolactin and dehydroepiandrostendone to the abnormal 5-h oral glucose tollerance test results could contribute to the primary prevention of diabetes and its complications.