Search Results (153)

Gestational diabetes mellitus (GDM) is a prevalent metabolic disorder associated with adverse maternal and fetal outcomes. However, current diagnostic strategies have a limited capacity to identify women at risk early in pregnancy. In this longitudinal prospective pilot study, 200 pregnant Mexican women were recruited at 11–14 weeks and underwent follow-up throughout pregnancy. Of these, 34 women (19 with GDM and 15 with normal glucose tolerance [NGT]) completed follow-up and were included in the final analyses. Most withdrawals were due to logistical constraints, although the reduced final sample size should be considered when interpreting generalizability. Nine serum proteins (ADIPOQ, AFM, FABP4, IGFBP-5, PAPP-A, PAPP-A2, RBP4, RETN, SHBG) were measured simultaneously using an antibody array and subsequently validated by ELISA. FABP4 showed the greatest increase in the first trimester (4.9-fold, p = 0.0105) and the highest apparent discriminative performance (AUC = 0.91), which declined in the second and third trimesters. Exploratory, hypothesis-generating multivariable analyses suggested a stronger association when FABP4 was combined with gravidity and serum triglycerides (AUC up to 0.97). Overall, FABP4 emerged as a promising candidate biomarker for early GDM detection in Mexican women; however, these findings are preliminary and require validation in larger, independent cohorts to support early risk stratification. Full article

Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with insulin resistance and metabolic disturbances. Sex hormone-binding globulin (SHBG) is closely linked to metabolic regulation and has been shown to differ between individuals with and without MASLD. Objective: This study aimed to investigate the associations between SHBG and MASLD and their relationships with insulin resistance, body mass index (BMI), age, and sex in a combined male–female cohort. Patients and Methods: We studied 98 men and 54 women with MASLD and 74 men and 55 women without MASLD (aged 25–64 years). Participants underwent abdominal ultrasonography and fasting blood sampling, including measurements of glucose, liver enzymes, lipids, insulin, SHBG, estradiol, and testosterone. Results: SHBG levels were lower in individuals with MASLD than in controls, with a more pronounced reduction in women. MASLD status was associated with an approximately 10 nmol/L lower SHBG concentration (p < 0.0001; gender × MASLD interaction p = 0.0462). Higher estradiol levels were associated with higher SHBG concentrations (p = 0.0009), although this association differed by sex (gender × log-estradiol interaction p = 0.0147). Older age and higher total cholesterol levels were associated with higher SHBG levels, whereas higher triglyceride levels were associated with lower SHBG levels. Conclusions: SHBG showed significant associations with MASLD and with key metabolic and hormonal factors, including BMI, age, and sex. Inclusion of both men and women extends prior male-only research and provides a broader characterisation of sex-specific associations in MASLD. Full article

Background and Objectives: Cut-off points for the triglyceride-glucose-body mass index (TyG-BMI) and the triglyceride-glucose-waist circumference index (TyG-WC) have been established for the assessment of insulin resistance (IR) only in the population of Asian women with polycystic ovary syndrome (PCOS). Therefore, the present study aimed to estimate the cut-off value for these indices discriminating the IR based on the homeostatic model assessment for insulin resistance (HOMA-IR) and sex hormone binding globulin (SHBG) levels established previously in Caucasian women with PCOS. Material and Methods: The medical records of 264 selected young adults (18–40 y.o.) Caucasian women with PCOS were the source of parameters: age, body weight, height, waist circumference, glucose, insulin, triglyceride, and SHBG levels, used for calculation of TyG-BMI and TyG-WC indices. The cut-off values for TyG-BMI and TyG-WC indices were calculated using receiver operating characteristic curve analysis. Results: The study group included 68 overweight (25.8%) and 62 overweight (23.4%) women. The empirical optimal cut-off values for TyG-BMI and TyG-WC indices corresponding to HOMA-IR values ≥ 2.1 were 233 and 735 [area under the curve (AUC) 85.1% and 86.7%, accuracy 0.814 and 0.784, sensitivity 66.3% and 67.3%, specificity 90.4% and 84.9%, PPV 80.2% and 72.5%, NPV 82.0% and 81.5%], respectively. The empirical optimal cut-off values for TyG-BMI and TyG-WC indices corresponding to SHBG levels < 41.5 nmol/L were 230 and 734 (AUC 79.5% and 77.1%, accuracy 0.735 and 0.723, Se 57.4% and 57.4%, Sp 87.3% and 85.2%, PPV 79.5% and 76.9%, NPV 70.4% and 69.9%), respectively. Conclusions: The cut-offs for the TyG-BMI and TyG-WC indices discriminating IR in young Caucasian women with PCOS were similar regardless of whether they are based on HOMA-IR values or SHBG levels. Full article

Objectives: Polycystic ovary syndrome (PCOS) is a heterogeneous disorder with diverse pathogenetic mechanisms and clinical manifestations. Phenotype D PCOS is characterized by oligomenorrhoea and polycystic ovaries without hyperandrogenism. Altered adipokine profiles may contribute to reproductive and metabolic disturbances. Chemerin is an adipokine involved in inflammatory and metabolic processes. It remains unclear whether altered chemerin levels in PCOS reflect metabolic dysfunction alone or are directly associated with hyperandrogenism. The aim of this study was to compare serum chemerin levels in women with normoandrogenic PCOS and a control group. Methods: This cross-sectional preliminary study included 49 women with phenotype D PCOS and 40 healthy, age- and body mass index (BMI)-matched controls. Anthropometric, biochemical, hormonal parameters, and serum chemerin concentrations were assessed. Results: Serum chemerin concentrations did not differ significantly between the groups. In the PCOS group, the 95% confidence interval ranged from 198.61 to 234.37, while in the controls, it ranged from 187.13 to 216.21. In women with PCOS, chemerin showed significant positive correlations with weight, BMI, waist and hip circumference, total adipose tissue, and both gynoid and android fat content. Positive correlations were also observed with highly sensitive C-reactive protein (hs-CRP), insulin, glucose, triglycerides, and Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), and a negative correlation was found with high-density lipoprotein (HDL) cholesterol. Chemerin was weakly negatively correlated with sex hormone binding globulin (SHBG) and positively correlated with the free androgen index (FAI). In the control group, chemerin correlated positively with CRP, insulin, triglycerides, total and gynoid adipose tissue, and negatively correlated with HDL cholesterol and SHBG. Conclusions Although chemerin levels did not differ from controls, chemerin was associated with metabolic and inflammatory markers in both groups. These findings should be considered preliminary due to the limited sample size. Chemerin may reflect metabolic and inflammatory status rather than hyperandrogenism in normoandrogenic PCOS. Full article

Background: Recently, based on HOMA-IR, we estimated empirical optimal cut-off values for SHBG levels of ≤41.5 nmol/L in women with PCOS. Other proposed markers of insulin resistance include triglyceride and glucose levels, and anthropometric measurements. Therefore, our current study aimed to analyze its consistency with the cut-off values that discriminate insulin resistance based on the TyG, TyG-BMI, and TyG-WC indices in women with PCOS. Methods: Age, body weight, height, waist circumference, glucose, insulin, triglyceride, and SHBG levels were retrieved from the medical records of 264 Caucasian women diagnosed with PCOS. The TyG, TyG-BMI, and TyG-WC indices were calculated. The mean meta-cut-off SHBG level was calculated using receiver-operating characteristic (ROC) analysis combined with diagnostic test accuracy meta-analysis. Results: The mean meta-cut-off value for SHBG levels for the assessment of insulin resistance was less than 43.1 (95% CI: 37.0–49.2) nmol/L. The pooled sensitivity and specificity of SHBG levels for the assessment of insulin resistance were 74.7% and 66.9%, respectively. The pooled mean prevalence of insulin resistance based on all indices was 36.1% (95% CI: 33.5–38.7%) with a standard deviation of 18.7% and positive predictive value (PPV) of 52.8% (95% CI: 12.2–87.5%) and the negative predictive value (NPV) of 80.2% (95% CI: 45.1–97.7%). Conclusions: Our study confirms the usefulness of SHBG level as a marker of insulin resistance in Caucasian women with PCOS. A value below 43 nmol/L, with high sensitivity and specificity, enables the detection of insulin resistance and a high risk of prediabetes, prompting close monitoring of liver function. Full article

Endometriosis is a hormone-dependent disease, in the pathophysiology of which sex hormones (androgens, estrogens, etc.) are involved. The level of bioactive androgens/estrogens (in the free state) in the organism largely depends on sex hormone-binding globulin (SHBG), which binds/transports a significant portion of the androgens/estrogens of the body and, due to this, changes the amount of these hormones in a free state (bioactive), which may be important in the development of endometriosis. The study was devoted to identifying the link between the genetic determinants (single nucleotide polymorphisms [SNPs]) of SHBG (according to predating genome-wide associative studies [GWAS]) and the risk of endometriosis in the Caucasian women of Russia. The study was accomplished on a total sample of 1368 women (395 endometriosis; 973 endometriosis free [controls]). Nine loci with an impact on SHBG level in predating GWAS have been examined. The search for associations of these loci with endometriosis was carried out: both their independent effects and interlocus interactions with an in silico interpretation of the functionality/pathways in which endometriosis-related loci and strongly linked SNPs were involved have been evaluated. Polymorphic locus rs440837 (A > G) ZBTB10 correlated with endometriosis development (recessive genetic model): the SHBG-raising genotype GG rs440837 (A > G) ZBTB10 serves as a risk factor for the disease formation; its presence in the genotype almost doubles the risk of endometriosis (OR = 1.91; 95%CI = 1.13–2.98; p_perm = 0.024; power = 81.13%). The SHBG-impacts of 7 SNPs from 9 analyzed loci such as rs17496332 (A > G) PRMT6, rs780093 (C > T) GCKR, rs10454142 (T > C) PPP1R21, rs3779195 (T > A) BAIAP2L1, rs440837 (A > G) ZBTB10, rs7910927 (G > T) JMJD1C, and rs8023580 (T > C) NR2F2 interacting with each other have been endometriosis-associated. Endometriosis-causal SNP rs440837 (A > G) ZBTB10 and 5 proxy SNPs determine the DNA interaction in the region of 3 genes (RP11-48B3.3, RP11-48B3.4, ZBTB10) with 22 transcription factors and, due to this, affect the processes of development of the endocrine system, gene transcription regulation, TGF-beta signaling pathway, regulation of cell proliferation/differentiation, etc. In conclusion, the results of this study showed the endometriosis risk effect of the SHBG-impact polymorphic variants. Full article

Background/Objectives: Chronic endometritis (CE) is a well-known risk factor for recurrent implantation failure. However, the traditional approach to CE diagnosis has several drawbacks. On the other hand, there is a lot of evidence that some clinical, instrumental, and/or laboratory parameters of patients are associated with CE. The aim of this study is to build a CE prediction model using machine learning tools based on low-invasive pathological features. Methods: The data of 108 women (44 with and 64 without CE) from a multicenter perspective cross-sectional study was included in this study. Basic characteristics, reproductive history, laboratory and ultrasound indicators, and immunohistochemistry results were collected. Binary feature selection was performed using forward stepwise selection with logistic regression as the evaluation criterion. For each feature configuration, a gradient-boosting model was trained on decision trees with a binary logistic loss function. The models were evaluated and compared on test data using standard metrics. Results: We built five comparable predictive models for CE. The models yielded the following AUCs (95% CI): Model 1 (seven indicators)—0.704 (0.5170, 0.8907), Model 2 (seven indicators)—0.673 (0.4716, 0.8745), Model 3 (nine indicators)—0.677 (0.4916, 0.8622), Model 4 (five indicators)—0.758 (0.5913, 0.9241), and Model 5 (five indicators)—0.769 (0.5913, 0.9241). Models 2 and 5 have the better recall and precision values, but the differences were not significant. SHAP values indicated that serum adiponectin level (Model 2) and SHBG (Model 5) had the greatest association with CE risks. Conclusions: Models 2 and 5 show the most promising potential for clinical application, as they demonstrate superior recall and precision metrics and require assessment of only 5–7 risk markers (with only a few being non-routine) for their implementation. Full article

Vitamin D plays a key role in immune modulation, cell proliferation, and hormone regulation. Dysregulated testosterone may contribute to breast cancer progression. We investigated whether long-term vitamin D supplementation affects serum testosterone levels in breast cancer survivors. Complete data at baseline, 12, and 24 months were derived from 253 women with early-stage breast cancer participating in the DEDiCa trial and randomized to receive either a high-dose vitamin D to maintain serum 25(OH)D at 60 ng/mL (group A) or a standard dose to maintain serum levels at 30 ng/mL (group B). Serum 25(OH)D levels significantly increased in both groups (p < 0.001). No significant changes in testosterone concentrations were observed between treatment groups over the 24 month treatment period (A: 0.125 to 0.140 ng/mL; B: 0.162 to 0.193 ng/mL; p = 0.682). Baseline serum testosterone levels emerged as the most significant predictor of testosterone trajectories, possibly modulated by hormone-suppressive therapy. These results are reassuring that vitamin D supplementation did not adversely affect testosterone levels in this population of breast cancer survivors and may partially concur with a healthy lifestyle to equilibrate testosterone levels. Full article

Positioned at the intersection of sex medicine and endocrinology, metabolic dysfunction-associated steatotic liver disease (MASLD) is often managed by specialists who may not be fully familiar with the complex roles of sex hormones in its pathogenesis and clinical course. To address this gap, we review the molecular actions of testosterone, estradiol, and progesterone on liver functions, as well as the role of sex-hormone binding globulin (SHBG) in MASLD histogenesis, highlighting disparities by sex as well as reproductive status. We also discuss how sex hormones influence fatty acid metabolism, gut dysbiosis, mitochondrial activity, gluco-lipidic homeostasis, lipotoxicity, inflammation, and MASLD-related liver tumorigenesis. Furthermore, we examine observational studies on associations between endogenous and exogenous sex hormones and SHBG with MASLD, with attention to hypogonadism in either sex or polycystic ovary syndrome. We summarize the role of sex hormones in modulating MASLD risk across life stages such as menopause, breastfeeding, and lactation. Lastly, we review the hepatic effects of hormone replacement therapy (HRT) on MASLD in both sexes, prospects, and safety of HRT and contraceptives among individuals with chronic liver disease. In conclusion, sex hormones play significant roles in MASLD pathobiology, underscoring the importance of sex-specific approaches in clinical practice and research. Full article

The main goal of this study was to consider the role of obesity/overweight as a potential modifier of associations between gene single nucleotide polymorphisms (SNPs) affecting the sex hormone-binding globulin level (SHBG_level) and uterine myoma (UM). In the two women cohorts differentiated by body mass index (BMI) (BMI ≥ 25, n = 782 [379 UM/403 control] and BMI < 25, n = 760 [190 UM/570 control]), the association of genome-wide association studies (GWAS)-correlated SHBG_level-tied nine loci with UM was studied by method logistic regression with a subsequent in-depth evaluation of the functionality of UM-causal loci and their strongly linked variants. BMI-conditioned differences in the associations of SHBG_level-tied loci with UM were revealed: in the BMI < 25 group, a variant rs17496332 (A/G) PRMT6 was UM-correlated (OR = 0.70; p_perm = 0.024), and in the BMI ≥ 25 cohort, a SNP rs3779195 (T/A) BAIAP2L1 was UM-associated (OR = 1.53; p_perm = 0.019). Both the UM-causal loci and their proxy SNPs have pronounced probable functionality in the organism as a whole, as well as in the liver (the SHBG synthesis place), adipose tissue, uterus, etc., thereby influencing significant processes for UM biology such as regulation of the gene transcription, embryogenesis/development, cell proliferation/differentiation/apoptosis, metabolism, lipid exchange, etc. In conclusion, the results of our work demonstrated, for the first time, the essential role of obesity/overweight as a meaningful modifier of associations between SHBG_level-tied polymorphisms and UM. Full article

Background/Objectives: Polycystic ovary syndrome (PCOS) is the most common endocrinopathy experienced by females. Diagnosis of PCOS is established when at least two of the following are present: hyperandrogenism, oligo-anovulation, and/or polycystic ovaries. Conservative treatment for PCOS includes dietary modifications and physical activity. The purpose of this scoping review was to evaluate the efficacy of a ketogenic diet in improving biochemical measures and reducing the severity of PCOS symptoms. Methods: CINAHL, PubMed, and Google Scholar databases were searched to find research published in peer-reviewed journals between 2019 and 2025. An article was included in this scoping review if the study assessed the effectiveness of a ketogenic diet on improving the signs and symptoms in patients with PCOS. Results: Eight studies met the inclusion criteria. Weight loss was achieved by subjects who adopted a very low-calorie ketogenic diet (VLCKD), low-calorie ketogenic diet (LCKD), classic ketogenic diet (CKD), or a Mediterranean eucaloric ketogenic diet (KEMEPHY). Patients with PCOS who consumed a ketogenic diet experienced improved biochemical measures, including androgen levels, lipid levels, HOMA-IR, blood glucose, insulin, LH/FSH ratio, DHEAS, SHBG, AFC, and AMH. A ketogenic diet was also associated with improvements in menstruation, fertility, and OHSS. Conclusions: Adopting a short-term ketogenic diet may have positive health benefits for patients with PCOS. Full article

Background/Objectives: Increased dehydroepiandrosterone sulfate (DHEAS) is used as a diagnostic marker of hyperandrogenism in women with polycystic ovary syndrome (PCOS). The mechanisms of adrenal hyperandrogenism in PCOS include hyperinsulinism as a potential stimulator, but results of studies associating insulinemia with DHEAS in PCOS are conflicting. The objective of this study was to evaluate the factors associated with DHEAS levels in PCOS, focusing on insulinemia. Methods: We performed a cross-sectional retrospective study in a total of 257 patients with PCOS (Rotterdam criteria) evaluated in our tertiary center of endocrinology. Clinical and biochemical parameters included body mass index (BMI), serum DHEAS, total testosterone and sex hormone-binding globulin (SHBG), insulin and glycaemia at fasting and 2 h during the oral glucose tolerance test (OGTT), and homeostasis model assessment for insulin resistance (HOMA-IR) was calculated. Results: The comparative analysis of PCOS divided into DHEAS tertiles revealed that patients in the upper tertile were younger (p < 0.05) and had higher 2 h insulin in the OGTT (p < 0.05) than the lower tertile, while fasting insulin and HOMA-IR were not different. DHEAS correlated negatively with age (r = −0.146, p < 0.05) and positively with 2 h insulinemia (r = 0.246, p < 0.001), while fasting insulin and HOMA-IR did not correlate with DHEAS in all PCOS. In stepwise linear regression models, 2 h insulin remained a positive independent predictor for DHEAS only in non-obese PCOS (p < 0.0001). Conclusions: Our data indicate a positive association between stimulated insulin and DHEAS in PCOS. Two-hour insulin in OGTT was an independent predictor of DHEAS in non-obese PCOS, suggesting that DHEAS might be a reliable marker for the stimulatory insulin effect on adrenal steroidogenesis in non-obese PCOS patients. Full article

Background: Asprosin is a relatively recently discovered glucogenic adipokine secreted during fasting that plays an important role in various biochemical processes in the body, including those connected with obesity and insulin resistance. The aim of this exploratory study was to investigate the associations between selected hormonal, anthropometric, and lifestyle-related parameters and serum asprosin concentration. As studies concerning fertility and asprosin have so far been limited to men or women with PCOS, its role in the general female population remains largely unexplored. The direction of this exploration was thus pointed toward possible connections with female fertility. Methods: The case-control study group included 56 women of reproductive age (25–42 years), who were patients of the Reproductive Health Clinic and the Clinic of Endocrinology, Diabetology, and Internal Medicine of the Medical University of Białystok, Poland. The levels of selected hormones, including anti-Müllerian hormone (AMH), estradiol, sex hormone-binding globulin (SHBG), and testosterone, body composition parameters, and a lifestyle parameter—night fasting duration—were assessed to test their associations with serum asprosin concentration. Results: A weak negative correlation was found between AMH level and serum asprosin concentration, suggesting a potential link between asprosin and ovarian reserve. Furthermore, a moderate positive correlation was found between the percentage of total body water (TBW) and serum asprosin concentration. No significant associations were observed between the levels of the other tested hormones and serum asprosin concentration, or between body composition parameters or night fasting duration and serum asprosin concentration. The multivariate model designed in the study shows that AMH, TBW, and night fasting duration explain 23.4% of asprosin variability. Conclusions: Although the nature of the study is exploratory, the findings indicate that the role of asprosin in the female population—particularly its role in fertility—requires further research. Not only is the number of available studies on asprosin insufficient, but the results of this study partly contradict what is known about the hormone from previous studies, which were largely performed with male cohorts. In addition, the results of this study suggest that asprosin may indeed be involved in mechanisms related to female fertility, particularly those connected with ovarian reserve. Nevertheless, studies performed in larger, more homogeneous populations are necessary to confirm the role of asprosin in women, including its association with female fertility. Full article

Background/Objectives: The effect of metformin on the secretory function of thyrotropic cells is sex-dependent. The current study aimed to investigate whether the impact of this drug on activity of the hypothalamic–pituitary–thyroid axis in women is impacted by the androgen status of patients. Methods: The study population included 48 levothyroxine-naïve reproductive-aged women with subclinical hypothyroidism and prediabetes receiving 3.0 g of metformin daily. Women with (n = 24) and without (n = 24) polycystic ovary syndrome were matched for age, insulin sensitivity, TSH, and reasons for thyroid hypofunction. Circulating levels of glucose, glycated hemoglobin, insulin, TSH, thyroid hormones, gonadotropins, androgens, estradiol, SHBG, prolactin, ACTH, and IGF-1 were measured before metformin treatment and six months later. Results: At entry, women with and without polycystic ovary syndrome differed in LH, LH/FSH ratio, androgens, and estradiol. The decrease in TSH, fasting glucose and glycated hemoglobin, and the improvement in insulin sensitivity were less pronounced in women with than in women without polycystic ovary syndrome. In each group, there were no differences in the impact on TSH and thyroid hormones between patients with subclinical hypothyroidism of autoimmune and non-autoimmune origin. The changes in TSH inversely correlated with total testosterone and free androgen index. Only in women with coexisting polycystic ovary syndrome, did metformin slightly reduce LH, LH/FSH ratio, testosterone, and free androgen index. Conclusions: The results suggest that concurrent polycystic ovary syndrome attenuates metformin action on TSH secretion, which can be explained by increased androgen production. Moreover, the drug seems to alleviate PCOS-associated changes in the activity of the reproductive axis. Full article

Background: Chronic stress in childhood and adolescence leads to excessive cortisol secretion, adipokines production and obesity with all the negative mental and physical effects on the health of individuals and adulthood. Objectives: The aim of the present non-randomized controlled trial was to investigate the effect of a stress management protocol with diaphragmatic breathing (DB) and physiotherapy exercise on stress, body composition, cardiorespiratory and metabolic markers of children and adolescents with morbid obesity. Methods: The study included 31 children and adolescents (5–18 years old) with morbid obesity (22 in the intervention arm and 9 controls). All participants completed anxiety questionnaires and a self-perception scale. Forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), blood pressure (BP) and SpO₂ were measured. Fasting glucose, uric acid, triglycerides, HbA1c, (AST/SGOT), (ALT/SGPT), HDL, LDL, insulin, ACTH, cortisol, HOMA-IR, 17-OH, S-DHEA, SHBG were assessed, and anthropometric measurements were also performed. Results: In the intervention group, 4 months after the treatment, an improvement was noted in the BMI, BMI z-score, waist-to-height ratio, FEV1, SpO₂, pulse and systolic BP. HDL increased, ALT/SGPT and insulin resistance improved. Positive changes were observed in temporary and permanent stress and self-esteem of children in the intervention group, including anxiety, self-perception, physical appearance, etc. Conclusions: A combined exercise and DB protocol has a positive effect on stress, by improving body composition, reducing insulin resistance, and ameliorating physical and mental health and quality of life of pediatric patients with morbid obesity. Full article