Search Results (16)

Traumatic brain injury (TBI) in childhood is a major global health concern and a leading cause of morbidity and mortality in the pediatric population. Its incidence is rising worldwide, with early childhood and adolescence representing the most vulnerable age groups. Beyond acute neurological injury, post-traumatic endocrine dysfunction has emerged as an underrecognized but clinically significant sequela, with potential long-term consequences for growth, puberty, metabolism, and overall quality of life. The hypothalamic–pituitary axis (HPA) is uniquely vulnerable due to its anatomical and vascular characteristics, making pituitary cells—particularly somatotrophs and gonadotrophs—susceptible to ischemic, traumatic, and inflammatory damage. Reported prevalence of post-TBI pituitary dysfunction in children ranges from 5 to 57%, reflecting a deep heterogeneity in injury severity, diagnostic methods, and timing of evaluations. Growth hormone deficiency (GHD) is the most frequently reported abnormality, with presentations varying from transient to persistent forms. Gonadal axis disturbances, including hypogonadotropic hypogonadism and, less commonly, central precocious puberty, highlight the impact of TBI on pubertal development. Adrenal dysfunctions, though less frequent, may be life-threatening if unrecognized, while posterior pituitary disorders, such as diabetes insipidus, usually revealed acutely, are often transient. Importantly, many endocrine sequelae manifest months to years after the initial trauma, complicating a timely diagnosis. Current evidence underscores the need for structured, longitudinal endocrine surveillance after pediatric TBI, with baseline and follow-up assessments at defined intervals. Early recognition and intervention, including hormone replacement when appropriate, may improve neurocognitive recovery and overall rehabilitation outcomes. Future multicenter studies and standardized screening protocols should be considered essential to clarify incidence, natural history, and optimal management strategies for post-traumatic endocrine dysfunction in children. Full article

Testosterone is a hormone that plays a crucial role in men, maintaining muscle mass and bone density and regulating sexual function. This hormone is associated with the inhibition of obesity and the prevention of obesity-related diseases, such as type 2 diabetes, impaired glucose tolerance, dyslipidemia, hypertension, coronary artery disease, and non-alcoholic fatty liver disease. Obesity has a complex effect on testosterone production and metabolism. Chronic inflammation and hormones associated with obesity cause dysfunction of the hypothalamic-pituitary-gonadal axis, leading to reduced testosterone production. Studies have demonstrated that blood testosterone levels decrease in obese men, suggesting a reciprocal interaction between decreased testosterone and obesity. Additionally, decreased testosterone levels are closely associated with aging. The natural decline in testosterone levels with age can lead to visceral obesity, thus increasing the risk of type 2 diabetes and other chronic metabolic diseases. In many countries, the population is aging, and the importance of testosterone replacement therapy (TRT) for aging men with low testosterone is increasing. Recent studies have expanded our understanding of TRT, highlighting its potential benefits in obese individuals, its interaction with gut microbiota, and the influence of racial differences and genetic polymorphisms on treatment efficacy. This review provides a comprehensive overview of the physiological mechanisms linking obesity and testosterone, current therapeutic approaches including TRT, and emerging research directions that may inform personalized treatment strategies. Full article

Sex-related differences in the structure and function of the adrenal cortex in mature rats are well recognized, largely driven by the action of sex hormones on the hypothalamic–pituitary–adrenal axis (HPA). By replacing testosterone or estradiol in gonadectomized rats, we aimed to elucidate the regulation of micro RNA (miRNA) profiles by sex hormones and their role in physiological adrenal function, providing new insights into gene expression modulation in the adrenal gland. This paper focuses on the description of miRNA profiles using the microarray technique. In our study, we observed significant sex differences in miRNA and mRNA expression levels. These differences are as follows: miRNA expression profiles Male C vs. Female C-0 down, 25 up-regulated, while mRNA profiles were 43 down and 27 up-regulated. Moreover, we observed the most significant differences in miRNA profiles between orchiectomized male rats supplemented with testosterone (ORX + T) and ovariectomized female rats treated with estradiol (OVX + E). Furthermore, we described changes in target gene expression and biological processes regulated by miRNAs. The processes most differentially expressed between the ORX + T and OVX + E groups are those related to the metabolism and synthesis of sterol compounds, the positive and negative regulation of metabolic processes in cells, e.g., cholesterol metabolism, response to various external factors, e.g., hormones, regulation of processes related to cell motility. We also identified several miRNAs, such as miR-370, miR-377, and miR-503, that exhibited interesting changes in their expression after testosterone or estradiol replacement. These results contribute to a deeper understanding of adrenal physiology. Full article

Chronic pain, pain that lasts beyond three months, is a common finding in the elderly. It is often due to musculoskeletal conditions but can be precipitated by other factors as well. While physiological systems decline with aging, chronic pain is influenced by changes in hormone profiles as men and women enter into andropause and menopause, respectively. Research on gonadal hormones is limited, especially when it comes to their relationship with chronic pain. Women tend to experience less pain with aging compared to their premenopausal years, and this is partially explained by the fact that estrogen enhances pain sensitivity and its decline during menopause decreases it. However, hormone replacement therapy (HRT) seems to increase pain tolerance post-menopause. There is some evidence that testosterone plays a protective factor in pain perception. Men on the other hand, have higher pain tolerance as testosterone is considered to be a protective factor. With aging and decreasing testosterone, older men tend to be less tolerant to pain. This paper explores how hormonal changes with aging impact pain perception in both men and women, highlighting several pain conditions influenced by hormones. Although research remains limited, the potential of HRT as a treatment for common pain conditions is examined. Full article

Numerous studies have explored alternative protein sources to fishmeal (FM) to enhance fish diets, yet limited research exists on their effects on maturation. This study assessed the impact of replacing FM with soy protein concentrate (SPC) supplemented with lysine and methionine on growth and gonadal development in olive flounder (Paralichthys olivaceus). Three diets were tested: a control (Con) diet with 60% FM and two diets replacing FM with 25% (LF1) and 50% (LF2) SPC. Fish were fed to apparent satiation twice daily for 12 months. Growth performance and feed intake were not significantly different between groups. However, the gonadosomatic index varied with diet. Muscle composition and amino acid levels were similar across treatments, though n-3 fatty acids were higher in Con. Spermatogonia was increased, and spermatogenesis was impaired in SPC groups. At 12 months, oocytes in Con diets had absorbed yolk globules, whereas this was absent in SPC groups. Growth-related genes in the brain (growth hormones and insulin-like growth factor) were increased with higher SPC, while follicle-stimulating and luteinizing hormones decreased. Estrogen receptor α levels were elevated in SPC groups. Vitellogenin gene expression in gonads was highest in Con, while liver expression peaked in LF2. The expression of digestive enzymes, chymotrypsin2, and trypsin2 was highest in LF2, while lipase genes were lower. In summary, up to 50% FM replacement with SPC, with amino acid supplementation, supported growth performance and muscle composition without adverse effects on growth in olive flounder but influenced gonadal development. Full article

Background: The incidence of colorectal cancer (CRC) is increasing in the population under 50 years of age, with more than 10% of cases occurring in young adults. Fertility preservation counseling has therefore received increased attention in this younger patient population. The treatment of CRC is often based on multimodal therapies, including surgery, radiotherapy, chemotherapy, and, more recently, immunotherapy, which makes it difficult to estimate the expected effect of treatment on fertility. We, therefore, systematically analyzed the published literature on the gonadotoxic effects of CRC treatments to better advise patients on the risk of infertility and the need for fertility preservation measures. This systematic review and meta-analysis are part of the FertiTOX project, which aims to reduce the data gap regarding the gonadotoxicity of oncological therapies. Objectives: The aim of this review and meta-analysis is to evaluate the potential impact of CRC therapies on gonadal function to allow more accurate counseling regarding the risk of clinically relevant gonadotoxicity and the need for fertility preservation measures before oncological treatment. Materials and Methods: A systematic literature search was conducted in Medline, Embase, the Cochrane database of systematic reviews, and CENTRAL in March 2024. A total of 22 out of 4420 studies were included in the review. Outcomes were defined as clinically relevant gonadotoxicity, indicated by elevated follicle-stimulating hormone (FSH) and/or undetectable anti-Müllerian hormone (AMH) levels and/or the need for hormone replacement therapy in women and azoo-/oligozoospermia and/or low inhibin B levels in men. Studies with fewer than nine patients were excluded from the meta-analysis. Results: The qualitative analysis included 22 studies with 1634 subjects (775 women, 859 men). Treatment consisted of active surveillance after surgery (37.7%), chemotherapy (12.7%), radiation (0.2%), or radiochemotherapy (53.9%). In 0.5%, the therapy was not clearly described. The meta-analysis included ten studies and showed an overall prevalence of clinically relevant gonadotoxicity of 23% (95% CI: 13–37%). In women, the prevalence was 27% (95% CI: 11–54%), and in men, 18% (95% CI: 13–26%). A subanalysis by type of CRC was only possible for rectal cancer, with a prevalence of relevant gonadotoxicity of 39% (95% CI: 20–64%). In patients undergoing chemotherapy exclusively, the prevalence was 4% (95% CI: 2–10%). In those receiving only radiotherapy, the prevalence was 23% (95% CI: 10–44%); in contrast, it reached 68% (95% CI: 40–87%) in patients who received radiochemotherapy. Conclusions: This first meta-analysis of the clinically relevant gonadotoxicity of CRC therapies provides a basis for counseling on the risk of infertility and the need for fertility preservation measures. Despite the low prevalence of gonadotoxicity in cases receiving chemotherapy alone, fertility preservation is still recommended due to the uncertainty of subsequent therapy and the lack of large longitudinal data on individual treatment effects. Further prospective studies are needed to investigate the impact of CRC treatment on gonadal function and estimate the effect of new treatment modalities, such as immunotherapies. Full article

Background: Male patients with congenital hypogonadotropic hypogonadism (CHH) have impaired postnatal activation of the hypothalamic–pituitary–gonadal axis that occurs during mini-puberty. The aim of this study was to report our experience using gonadotropin replacement therapy for mini-puberty in male infants with CHH and to establish treatment recommendations. Methods: The patients included in this retrospective case series (n = 9) were diagnosed in the postnatal period due to micropenis, with two being accompanied by cryptorchidism and four with other associated hormonal deficits. All patients started treatment with gonadotropins early after diagnosis, between 2 weeks and 5 months of age, with a schedule of discontinuous injections with subcutaneous human chorionic gonadotropin (62.5–500 IU) two times per week and recombinant follicle-stimulating hormone-alpha (37.5–75 IU) three times per week. Results: The data from our study show an early response, ranging from almost undetectable levels of testosterone at diagnosis to elevated levels after starting treatment, as well as a positive clinical response with increases in testicular volume and penis size in all cases without requiring complementary treatment with testosterone esters and without adverse effects. Conclusions: Our results show that gonadotropin replacement therapy is a well-tolerated and effective treatment for testicular and penile problems in male patients with CHH. Full article

Gonadal steroids exert different effects on the central nervous system (CNS), such as preserving neuronal function and promoting neuronal survival. Estradiol, progesterone, and testosterone reduce neuronal loss in the CNS in animal models of neurodegeneration. However, hormone replacement therapy has been associated with higher rates of endometrial, prostate, and breast cancer. Tibolone (TIB), the metabolites of which show estrogenic and progestogenic effects, is an alternative to reduce this risk. However, the impact of TIB on memory and learning, as well as on choline acetyltransferase (ChAT) and tryptophan hydroxylase (TPH) levels in the hippocampus of aging males, is unknown. We administered TIB to aged C57BL/6J male mice at different doses (0.01 or 1.0 mg/kg per day for 12 weeks) and evaluated its effects on memory and learning and the content of ChAT and TPH. We assessed memory and learning with object recognition and elevated T-maze tasks. Additionally, we determined ChAT and TPH protein levels in the hippocampus by Western blotting. TIB administration increased the percentage of time spent on the novel object in the object recognition task. In addition, the latency of leaving the enclosed arm increased in both TIB groups, suggesting an improvement in fear-based learning. We also observed decreased ChAT content in the group treated with the 0.01 mg/kg TIB dose. In the case of TPH, no changes were observed with either TIB dose. These results show that long-term TIB administration improves memory without affecting locomotor activity and modulates cholinergic but not serotonergic systems in the hippocampus of aged male mice. Full article

Van Wyk–Grumbach syndrome (VWGS) refers to the development of peripheral precocious puberty, long-standing hypothyroidism, and gonadal masses; when not diagnosed, an unnecessary gonadectomy may be performed. Herein, we present a case of a 10-year-old girl with Down’s syndrome, short stature, and vitiligo who presented to our hospital with vaginal bleeding and a palpable pelvic mass. Upon ultrasound and topographical examination, bilateral ovarian masses with negative tumor markers were detected. After bilateral gonadectomy, endocrine studies revealed profound hypothyroidism and peripheral puberty that led to the VWGS syndrome diagnosis (TSH 367.3 mUI/mL, isolated menstruation, indetectable LH, and elevated estradiol). Levothyroxine treatment improved obesity and short stature, and sexual hormone replacement began at 13 years of age. The literature on Van Wyk–Grumbach syndrome shows that it presents most often in women, and classic hypothyroidism symptoms always precede the diagnosis. Approximately 11% of patients have Down’s syndrome, sometimes tumor markers are elevated, and some develop severe symptoms (myopathy, short stature, mental delay, ascites, pericardial effusion, Cullen’s sign, pituitary hyperplasia, and severe anemia) that respond to levothyroxine treatment. Conclusions: Children with peripheral precocious puberty and gonadal masses must be studied for hypothyroidism before any radical decision is made. Full article

A complete gonadal dysgenesis (CGD) with 46,XY karyotype is known as the Swyer syndrome and belongs to the group of 46,XY differences of sex development (DSD). The main problem in patients with Swyer syndrome is the delayed puberty and primary amenorrhea. Moreover, intrabdominal dysgenetic gonads in the patient with genetic material of a Y chromosome may conduce to the development of gonadal tumors, such as gonadoblastoma or germinoma. The management of such patients is based on preventive excision of dysgenetic gonads and long-term hormonal replacement therapy. Sporadic cases are considered more common than familial cases. This paper presents two siblings with Swyer syndrome in whom gonadoblastoma was found. A thorough review of familial CGD with 46,XY DSD in the literature from the last 15 years suggests that the risk of gonadal tumors could be increased in familial compared to sporadic cases (66.6% vs. 15–45%, respectively). Full article

Complete Androgen Insensitivity Syndrome (CAIS) is a rare genetic condition by mutations in the androgen receptor (AR) gene resulting in target issue resistance to androgens and a female phenotype in genetically male individuals. A 16-year-old phenotypically female individual presented to our clinic with primary amenorrhea. Her clinical evaluation showed normal female external genitalia, Tanner III breast development and sparse pubic and axillary hair (Tanner stage II). Hormonal assessment revealed increased concentrations of Luteinizing Hormone (LH), Testosterone and Antimüllerian Hormone (AMH). Image studies detected no uterus or gonads, but a blind vagina and the karyotype was 46, XY. These findings suggested the diagnosis of CAIS, and genetic testing of the AR gene revealed a rare pathogenic mutation of cytosine to adenine (c.2612C>A) replacing alanine with glutamic acid at position 871 (p.Ala871Glu) in the AR, previously described once in two adult sisters. The patient underwent gonadectomy and received hormonal replacement therapy. This study expands the AR mutation database and shows the complexity and the importance of prompt diagnosis, proper management, and follow-up for CAIS patients, underlining the need for standardized protocols. Full article

Androgens are an important and diverse group of steroid hormone molecular species. They play varied functional roles, such as the control of metabolic energy fate and partition, the maintenance of skeletal and body protein and integrity and the development of brain capabilities and behavioral setup (including those factors defining maleness). In addition, androgens are the precursors of estrogens, with which they share an extensive control of the reproductive mechanisms (in both sexes). In this review, the types of androgens, their functions and signaling are tabulated and described, including some less-known functions. The close interrelationship between corticosteroids and androgens is also analyzed, centered in the adrenal cortex, together with the main feedback control systems of the hypothalamic–hypophysis–gonads axis, and its modulation by the metabolic environment, sex, age and health. Testosterone (T) is singled out because of its high synthesis rate and turnover, but also because age-related hypogonadism is a key signal for the biologically planned early obsolescence of men, and the delayed onset of a faster rate of functional losses in women after menopause. The close collaboration of T with estradiol (E2) active in the maintenance of body metabolic systems is also presented Their parallel insufficiency has been directly related to the ravages of senescence and the metabolic syndrome constellation of disorders. The clinical use of T to correct hypoandrogenism helps maintain the functionality of core metabolism, limiting excess fat deposition, sarcopenia and cognoscitive frailty (part of these effects are due to the E2 generated from T). The effectiveness of using lipophilic T esters for T replacement treatments is analyzed in depth, and the main problems derived from their application are discussed. Full article

Beta-thalassemia (BTH), a recessively inherited haemoglobin (Hb) disorder, causes iron overload (IO), extra-medullary haematopoiesis and bone marrow expansion with major clinical impact. The main objective of this review is to address endocrine components (including aspects of reproductive health as fertility potential and pregnancy outcome) in major beta-thalassemia patients, a complex panel known as thalassemic endocrine disease (TED). We included English, full-text articles based on PubMed research (January 2017–June 2022). TED includes hypogonadism (hypoGn), anomalies of GH/IGF1 axes with growth retardation, hypothyroidism (hypoT), hypoparathyroidism (hypoPT), glucose profile anomalies, adrenal insufficiency, reduced bone mineral density (BMD), and deterioration of microarchitecture with increased fracture risk (FR). The prevalence of each ED varies with population, criteria of definition, etc. At least one out of every three to four children below the age of 12 y have one ED. ED correlates with ferritin and poor compliance to therapy, but not all studies agree. Up to 86% of the adult population is affected by an ED. Age is a positive linear predictor for ED. Low IGF1 is found in 95% of the population with GH deficiency (GHD), but also in 93.6% of persons without GHD. HypoT is mostly pituitary-related; it is not clinically manifested in the majority of cases, hence the importance of TSH/FT4 screening. HypoT is found at any age, with the prevalence varying between 8.3% and 30%. Non-compliance to chelation increases the risk of hypoT, yet not all studies confirmed the correlation with chelation history (reversible hypoT under chelation is reported). The pitfalls of TSH interpretation due to hypophyseal IO should be taken into consideration. HypoPT prevalence varies from 6.66% (below the age of 12) to a maximum of 40% (depending on the study). Serum ferritin might act as a stimulator of FGF23. Associated hypocalcaemia transitions from asymptomatic to severe manifestations. HypoPT is mostly found in association with growth retardation and hypoGn. TED-associated adrenal dysfunction is typically mild; an index of suspicion should be considered due to potential life-threatening complications. Periodic check-up by ACTH stimulation test is advised. Adrenal insufficiency/hypocortisolism status is the rarest ED (but some reported a prevalence of up to one third of patients). Significantly, many studies did not routinely perform a dynamic test. Atypical EM sites might be found in adrenals, mimicking an incidentaloma. Between 7.5–10% of children with major BTH have DM; screening starts by the age of 10, and ferritin correlated with glycaemia. Larger studies found DM in up to 34%of cases. Many studies do not take into consideration IGF, IGT, or do not routinely include OGTT. Glucose anomalies are time dependent. Emerging new markers represent promising alternatives, such as insulin secretion-sensitivity index-2. The pitfalls of glucose profile interpretation include the levels of HbA1c and the particular risk of gestational DM. Thalassemia bone disease (TBD) is related to hypoGn-related osteoporosis, renal function anomalies, DM, GHD, malnutrition, chronic hypoxia-induced calcium malabsorption, and transplant-associated protocols. Low BMD was identified in both paediatric and adult population; the prevalence of osteoporosis/TBD in major BTH patients varies; the highest rate is 40–72% depending on age, studied parameters, DXA evaluation and corrections, and screening thoracic–lumbar spine X-ray. Lower TBS and abnormal dynamics of bone turnover markers are reported. The largest cohorts on transfusion-dependent BTH identified the prevalence of hypoGn to be between 44.5% and 82%. Ferritin positively correlates with pubertal delay, and negatively with pituitary volume. Some authors appreciate hypoGn as the most frequent ED below the age of 15. Long-term untreated hypoGn induces a high cardiovascular risk and increased FR. Hormonal replacement therapy is necessary in addition to specific BTH therapy. Infertility underlines TED-related hormonal elements (primary and secondary hypoGn) and IO-induced gonadal toxicity. Males with BTH are at risk of infertility due to germ cell loss. IO induces an excessive amount of free radicals which impair the quality of sperm, iron being a local catalyser of ROS. Adequate chelation might improve fertility issues. Due to the advances in current therapies, the reproductive health of females with major BTH is improving; a low level of statistical significance reflects the pregnancy status in major BTH (limited data on spontaneous pregnancies and growing evidence of the induction of ovulation/assisted reproductive techniques). Pregnancy outcome also depends on TED approach, including factors such as DM control, adequate replacement of hypoT and hypoPT, and vitamin D supplementation for bone health. Asymptomatic TED elements such as subclinical hypothyroidism or IFG/IGT might become overt during pregnancy. Endocrine glands are particularly sensitive to iron deposits, hence TED includes a complicated puzzle of EDs which massively impacts on the overall picture, including the quality of life in major BTH. The BTH prognostic has registered progress in the last decades due to modern therapy, but the medical and social burden remains elevated. Genetic counselling represents a major step in approaching TH individuals, including as part of the pre-conception assessment. A multidisciplinary surveillance team is mandatory. Full article

Many adrenocortical diseases are more prevalent in women than in men, but the reasons underlying this sex bias are still unknown. Recent studies involving gonadectomy and sex hormone replacement experiments in mice have shed some light onto the molecular basis of sexual dimorphism in the adrenal cortex. Indeed, it has been shown that gonadal hormones influence many aspects of adrenal physiology, ranging from stem cell-dependent tissue turnover to steroidogenesis and X-zone dynamics. This article reviews current knowledge on adrenal cortex sexual dimorphism and the potential mechanisms underlying sex hormone influence of adrenal homeostasis. Both topics are expected to contribute to personalized and novel therapeutic approaches in the future. Full article

Bisphenol A (BPA), which is widely used for manufacturing polycarbonate plastics and epoxy resins, has been banned from use in plastic baby bottles because of concerns regarding endocrine disruption. Substances with similar chemical structures have been used as BPA alternatives; however, limited information is available on their toxic effects. In the present study, we reviewed the endocrine disrupting potential in the gonad and thyroid endocrine system in zebrafish after exposure to BPA and its alternatives (i.e., bisphenol AF, bisphenol C, bisphenol F, bisphenol S, bisphenol SIP, and bisphenol Z). Most BPA alternatives disturbed the endocrine system by altering the levels of genes and hormones involved in reproduction, development, and growth in zebrafish. Changes in gene expression related to steroidogenesis and sex hormone production were more prevalent in males than in females. Vitellogenin, an egg yolk precursor produced in females, was also detected in males, confirming that it could induce estrogenicity. Exposure to bisphenols in the parental generation induced a decrease in the hatchability associated with offspring generation. In zebrafish exposed to bisphenols, significant decreases in thyroxine concentrations and increases in thyroid-stimulating hormone concentrations were commonly observed. Alternative compounds used to replace a chemical of concern are believed to be less toxic than the original compound; however, several BPA alternatives appear to have similar or greater effects on the endocrine system in zebrafish. Since endocrine systems interact with each other, further studies are needed to assess the primary target of BPA alternatives among the endocrine axes. Full article