Endocrines, Volume 6, Issue 1 (March 2025) – 13 articles

Introduction: Early-life neurological and inflammatory disorders significantly affect long-term cognitive, social, and emotional development. The ‘Developmental Origins of Health and Disease’ hypothesis states that an adverse intrauterine environment may predispose offspring to chronic health conditions due to altered growth and development. Factors measured in umbilical cord blood can provide information about the status of the in utero environment during development. Evidence indicates that umbilical cord blood adipokines, namely leptin and adiponectin, may influence fetal programming and could be useful in predicting offspring health outcomes. Leptin and adiponectin are crucial in energy homeostasis, immune response, and placental function, and some studies suggest that altered concentrations may increase the risk of developing inflammatory and neurological disorders in later life. Further, limited studies have demonstrated sex-specific differences in adipokine concentrations and disease risk. Conclusions: Understanding the role of umbilical cord blood adipokines in fetal programming could offer new insights into early risk prediction and intervention strategies, promoting better health outcomes for children at risk of neurological and inflammatory diseases due to an adverse maternal environment during pregnancy. Full article

Background/Objectives: Dienogest 0.5 mg tablets (DNG0.5) taken twice daily (1 mg/day) are more effective than cyclic low-dose estrogen/progestin/combined oral contraceptive (LEP/COC) in ameliorating dysmenorrhea pain and are recommended for dysmenorrhea treatment in Japan. However, their efficacy has not been directly compared with continuous LEP/COC regimens. Here, we evaluated the effectiveness of DNG0.5 compared to Yazflex^® (YZF), a continuous LEP, in treating dysmenorrhea. Methods: The efficacy of DNG0.5 in treating dysmenorrhea was compared retrospectively with that of Yazflex, the longest continuously administered LEP/COC available in Japan. Results: The improvement rates of dysmenorrhea scores at 3 and 6 months post-treatment were 59.1% and 66.4% in the LEP group (n = 113) and 88.1% and 96.4% in the DNG0.5 group (n = 125), respectively. The complete resolution rate of dysmenorrhea at 6 months was 88.0% in the DNG0.5 group and 23.9% in the LEP group. These findings indicate that DNG0.5 was significantly more effective than LEP (p < 0.01). DNG0.5 exerted an early pain-suppressing effect, which continued to increase thereafter. Furthermore, the presence of endometrial polyps, uterine fibroids, or adenomyosis, which are risk factors for irregular genital bleeding, was examined. Among these, endometrial polyps were particularly more likely to cause bleeding and potentially reduce the effect of DNG0.5; however, even with these three risk factors, DNG0.5 was more effective than LEP in reducing pain. Conclusions: Dienogest was more effective than LEP in managing dysmenorrhea, even at a dosage of 0.5 mg twice daily. However, factors affecting irregular vaginal bleeding should be considered when prescribing DNG0.5. Full article

Stress responses enable vertebrates to adapt to environmental challenges while maintaining homeostasis. Zebrafish larvae are a valuable model for studying stress regulation due to their genetic accessibility and rapid development. This review examines the integration of zebrafish larvae with water vortex protocols to investigate hypothalamic–pituitary–interrenal (HPI) axis functionality during early development, advancing stress research while adhering to the 3Rs principle. Key publications are reviewed to discuss the potential of water vortices in zebrafish larvae for studying stress responses. These purely physical stressors exploit the innate positive rheotropism of developing zebrafish, offering precise control over timing and strength while avoiding confounding factors associated with chemical or biological interventions. The approach enables reproducible assessments of stress responses. The reviewed publications show advances in understanding cortisol response dynamics, glucocorticoid feedback, and early-life stress-induced changes in HPI axis function. Key findings include detailed cortisol patterns after acute stress, rapid glucocorticoid receptor-mediated feedback regulating cortisol levels, developmental shifts in HPI axis sensitivity, and reduced cortisol reactivity following early-life challenge (ELC). Vortex-driven ELC affects cortisol regulation, neuropeptide expression in the nucleus preopticus, and stress-related gene transcription. Combining zebrafish larvae and vortex protocols provides a robust and innovative platform for investigating stress biology. This approach leverages active, demanding behaviour to study stress mechanisms under controlled conditions, yielding insights with broad applications across vertebrate models while supporting the 3Rs principle. Future studies can build on these findings to address unresolved questions in stress regulation and enhance our understanding of adaptive physiological mechanisms. Full article

A balanced diet and regular physical activity are essential for maintaining musculoskeletal health. Key nutrients such as calcium, vitamin D, and protein are especially important for preventing falls and fractures. While the benefits of these nutrients are well-established, other dietary components have not been studied as extensively. For instance, vegetables, which are rich in nutrients vital for muscle and bone health, play a crucial role in preventing falls and fractures. Over recent decades, a great emphasis has been given to the combinations of nutrients and foods in dietary patterns that may have synergistic or antagonistic effects. Despite the challenges in researching the impact of nutrition and physical activity on musculoskeletal health due to the extensive heterogeneity of the results, healthcare professionals should continue to promote healthy eating and regular physical activity, and these principles should be emphasized in public health initiatives. Ultimately, a sufficient and balanced diet, abundant in plant-based foods and low in processed or discretionary foods, along with consistent physical activity, remains the most effective strategy for the prevention of musculoskeletal issues. This article aims to review the updated literature of recent years on the links between nutrition and physical activity with bone and skeletal muscle health. Full article

Background/Objectives: In contrast to endochondral bone healing, the process of intramembranous bone regeneration is poorly understood. This limits our ability to repair and regenerate the craniofacial skeleton to either correct deformity or optimally heal tissues following injury. While there are several preclinical models of intramembranous regeneration within the craniofacial skeleton, some are not load bearing and others are technically challenging. The goal of this pilot study is therefore to describe a simple method for induction of cortical defects within the mandible that does not involve compounding injury to the surrounding tissues. Methods: Single cortex defects were generated in the mandible body of 8-week-old male and female mice. The extent of bone regeneration within the defect was characterized at days 0, 3, 14, and 28 following defect generation via micro-computed tomography and histology. Conclusions: Observed healing was predictable and reproducible and resulted in intramembranous bone formation. This model will help aid the understanding of intramembranous bone healing in load bearing bones (e.g., mandible) within the craniofacial skeleton Full article

Background/Objectives: Primary aldosteronism (PA) is associated with a higher cardiovascular disease (CVD) risk than essential hypertension (EH) and is mainly driven by the excess of aldosterone production. Studies suggest a relationship between aldosterone and parathormone (PTH) homeostasis. Excessive PTH levels seem to also be associated with CVD. The impact of PTH levels on CVD in PA patients has not been totally elucidated. We evaluated the associations of PTH levels and hyperparathyroidism with CVD in patients with PA and EH. Methods: A cross-sectional study of a group of 67 patients was carried out, with 35 patients with PA and a control group of 32 patients with EH. We looked at the presence of CVD and data on the factors associated with its presence were collected and analyzed. A binary logistic regression was performed to assess multivariate relationships. Results: PA patients had higher PTH levels compared to the EH group (64 ± 42 vs. 39 ± 13 pg/mL, p = 0.004). Significative differences in PTH levels were observed according to the grade of hypertension in PA patients. Both hyperparathyroidism and CVD were found at higher rates in patients with PA. Patients with CVD exhibited significantly higher PAC values than patients without it (41.4 ± 18 vs. 21.4 ± 12 ng/dL, p < 0.001). Patients with hyperparathyroidism had higher rates of CVD than patients without it (58 vs. 24%, p = 0.018). Patients with PA and hyperparathyroidism manifested a higher rate of CVD than patients without this combination. A logistic regression showed an independent association of PAC and hyperparathyroidism with the presence of CVD in the total cohort. Conclusions: Hyperparathyroidism is associated with a higher probability of CVD both in PA and EH. The presence of hyperparathyroidism in PA seems to exacerbate the risk of CVD, with higher PTH levels associated with higher grades of hypertension in this cohort. Full article

Alex Vermeulen (1927–2023) was a leading Belgian endocrinologist whose name will forever remain linked to testosterone and androgen metabolism. As a dedicated scientist and clinician, he made seminal contributions to endocrinology throughout his career. These included the development of chromatography and radioimmunoassays of steroid hormones. His work also focused on the biological significance and metabolism of corticosteroids and androgens, and he defined key concepts in the role of steroid hormones in the human menstrual cycle, pregnancy, and menopause. His love for math, endocrinology, and problem-solving led to a formula for the estimation of free testosterone in serum, which has not been improved upon to date and is still in use worldwide. He contributed to enhancing our understanding of the role that male sex hormones may play in a variety of clinical problems in endocrinology, including bone health, type 2 diabetes, and, especially, endocrine function in aging males. Alex Vermeulen literally was “a giant in endocrinology”. Beyond his scientific contributions, Vermeulen was a wise and engaging mentor, a Renaissance man, and an aficionado of the finer things in life. He owned an eclectic choice of modern artworks, all of which he bequeathed to the Ghent Museum of Fine Arts, thus significantly enhancing the museum’s art patrimony. Full article

Gestational diabetes mellitus (GDM) is a prevalent condition impacting approximately 14% of pregnancies globally, posing significant health risks to mother and child. This review explores the role of diet, physical activity (PA), and sedentary behavior (SB) in preventing and managing GDM. Consumption of fish, fruits, vegetables, and legumes, and adherence to healthy dietary patterns, like the Mediterranean diet, are linked to lower GDM risk. Higher levels of PA and structured exercise consistently show protective effects against GDM, enhancing glucose metabolism and insulin sensitivity. Conversely, SB is a risk factor for GDM; prolonged sedentary periods detrimentally affect glucose regulation. The review emphasizes the need for a combined approach integrating healthy dietary habits, regular PA, and reduced SB to mitigate GDM risk effectively. Future research should prioritize standardized assessment methods and personalized lifestyle interventions to optimize GDM prevention strategies, ultimately informing public health guidelines and clinical recommendations for healthier pregnancies and better long-term outcomes. Full article

The endocrine system relies on complex cell signaling and epigenetic processes to adjust to the body’s needs. However, stressors such as climate change and heat can disrupt the endocrine system. This study aims to collect and systematically review evidence from publications exploring how climate change impacts endocrine laboratory parameters. The review process included developing research questions, defining inclusion and exclusion criteria, conducting database searches, screening and selecting relevant publications, collecting and analyzing data, interpreting the findings, and drawing conclusions. This review identified multiple endocrine parameters linked to climate change and the mechanisms by which various stressors disrupt endocrine function. Climate change, especially heat stress, affects the production and levels of key hormones. The mechanisms underlying the disruption of key hormones are also explored in this paper. This review provides a clear overview of how climate change influences endocrine parameters and outlines the processes underlying stress-triggered endocrine disruption. Full article

Background: Lipocalin 2 (LCN2), also known as neutrophil gelatinase-associated lipocalin, is a 25 kDa protein involved in immune defense, inflammation, and metabolism. Results: LCN2 is widely expressed across various tissues, including immune cells, bone, adipose tissue, liver, kidneys, lung, spleen, and epithelial cells, and exhibits sex- and fat depot-specific expression patterns. Structurally, LCN2 contains a hydrophobic lipid-binding pocket and glycosylation sites, enabling it to interact with diverse ligands and form dimers. In innate immunity, LCN2 plays a critical role by sequestering iron-laden siderophores, thereby restricting bacterial growth. Beyond its role in infection control, LCN2 is implicated in metabolic inflammation and diseases such as obesity and diabetes. Recent research has highlighted a pivotal role for LCN2 in mitochondrial phospholipid metabolism and mitochondrial function. In metabolic diseases and mitochondrial metabolism, LCN2 appears to display paradoxical effects. While some studies link it to improved insulin sensitivity, glucose regulation, and mitochondrial function, others associate it with insulin resistance, obesity, and mitochondrial dysfunction. These inconsistencies may arise from differences in experimental conditions and study populations. Conclusions: This review provides an up-to-date summary of LCN2’s multifaceted roles in obesity, diabetes, energy balance, and mitochondrial function, emphasizing its context-dependent effects. LCN2 appears to have dual roles, exerting both protective and detrimental outcomes depending on the physiological or pathological context, sex, cell types, and experimental conditions. Further research is necessary to unravel its complex functions and resolve conflicting findings, particularly in metabolic disorders. Full article

Background: Type 2 Diabetes (T2D) is increasingly becoming a critical healthcare priority globally. Medical interventions are primary strategies for managing diabetes, but more recently, diet/nutrition therapy, including the use of functional food products such as cinnamon and/or cinnamon products, has garnered considerable attention. The focus of this systematic review and meta-analysis is to examine whether cinnamon improves blood glucose parameters, body mass index, and inflammatory markers in people with T2DM. Method: PRISMA and PICOS frameworks were used for the review. EBSCOhost was used to search for relevant literature in health science research databases, while EMBASE and reference lists were used to access other relevant articles. Results: For systematic review and meta-analysis, 14 and 12 studies, respectively, were included (five from Iran, two each from the USA and India, and one each from the UK, China, Germany, Portugal, and Iraq). All participants had T2DM with ages ranging from ≥30–65 years. The effect of cinnamon on glycaemic control and other parameters did not follow a regular pattern. Effect on HbA1c (nine studies and 605 participants; MD of −0.07 (95% CI, −0.13, −0.01, p = 0.02), postprandial blood glucose (PBG) and BMI showed significant (p < 0.05) reductions. However, cinnamon exhibited no significant (p > 0.05) impact on FBG (MD of −1.73 (95% CI, −3.98, 0.52, p = 0.13), CRP, TNF-α, and IL-6 in people with T2D; neither did the sensitivity test reveal any change in relation to these parameters. Conclusions: Cinnamon or cinnamon extracts/products are significantly effective in diabetes management through reduction in HbA1c, PBG, and BMI. Full article

Background: Osteoporosis is common in transplant recipients, and fracture risk is high. Standard treatment is with anti-resorptive medications. Despite high fracture rates, there are limited data on the use of anabolic bone therapies in transplant recipients. Aim: To evaluate skeletal outcomes after treatment with romosozumab for 12 months in heart and lung transplant recipients. Methods: Retrospective analysis of transplant recipients who completed 12 months of romosozumab treatment at a single centre. Results: Six transplant recipients completed 12 months of romosozumab treatment, commenced after a median of 3 years post transplant (range 2–20). Four patients (66%) were still receiving prednisolone treatment at the time of starting romosozumab. All patients had a history of fracture and had previously received anti-resorptive therapy (4 with zoledronate, 2 with denosumab for >2 years). Following completion of romosozumab treatment, all patients were consolidated with zoledronate or denosumab. Bone mineral density (BMD) was measured prior to and after completion of romosozumab treatment. The median baseline lumbar spine (LS) T-score was −2.3 SD (range −3.1 to +0.9) and total femur T-score was −2.2 SD (range −2.9 to −1.6). Most (5/6) patients experienced an increase in BMD at the LS (median change +7.1%). Most (5/6) patients did not experience clinically significant change in total femur BMD, apart from one patient who experienced a 9% gain. Three patients (50%) experienced subsequent fractures during (1/3) or after completing (2/3) romosozumab treatment. Conclusions: These cases demonstrate severe osteoporosis in transplant recipients. Most patients in our case series had improvement in LS BMD following romosozumab treatment, yet new fractures still occurred during follow-up. The appropriate use of romosozumab in heart and lung transplant patients with osteoporosis requires further study. Full article

Objective: The effect of testosterone on the development of cardiovascular disease (CVD) is of interest due to the higher risk of CVD in men. This study aims to examine the impact of testosterone depletion and supplementation on atherosclerosis progression in normoglycemic and hyperglycemic mouse models. Methods: Male apolipoprotein E-deficient (ApoE^−/−) and hyperglycemic (insulin deficient) ApoE^−/−Ins2^+/Akita mice were fed a standard chow diet and were either castrated or subjected to sham operations at 5 weeks of age. At 8 and 16 weeks of age, subsets of these mice were implanted subcutaneously with a silastic tube containing either 40 µL of dihydrotestosterone (DHT, 25 mg/mL) or sesame oil as a vehicle control. Survival was monitored and all remaining mice were sacrificed at 24 weeks of age. Blood, heart, and aortic samples were collected for analysis. Metabolic parameters were evaluated, and atherosclerotic lesion volumes were measured at the aortic sinus and in en face whole aorta mounts. Results: Castration significantly promoted atherosclerosis in normoglycemic mice, with a 3.0-fold increase (p < 0.05) at the aortic sinus and a 3.5-fold increase (p < 0.05) in en face aortas. However, in hyperglycemic mice, castration attenuated atherosclerosis in en face aortas. Supplementation with exogenous DHT led to increased atherosclerosis in hyperglycemic mice and was associated with significant cardiac-related mortality in 21–24-week-old hyperglycemic mice. Conclusions: In this mouse model, while testosterone/DHT may offer cardioprotective benefits under normoglycemic conditions, it appears to exert substantial harmful effects, such as promoting atherosclerosis and increasing the risk of myocardial infarction, in hyperglycemic conditions. Full article