Journal of Endocrinological Investigation最新文献

Background: Effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors on genital cancer risk remains unclear.

Objective: The objective of this study was to investigate the impact of SGLT2 inhibitors/SGLT2 inhibition on genital cancer risk.

Methods: We systematically searched PubMed, Web of Science, EU Clinical Trials Register, and ClinicalTrials.gov for large randomized controlled trials up to June 4, 2025. The Mantel-Haenszel method was applied, with risk ratios (RRs) and 95% confidence intervals (CIs) used for dichotomous outcomes. In the Mendelian randomization study, genetic variants in SLC5A2 served as instrumental variables to investigate the causal relationship between SGLT2 inhibition and genital cancers.

Results: A total of 15 studies (16 trials) involving 101,430 patients were included. SGLT2 inhibitors did not significantly reduce genital cancer risk compared to placebo (RR 1.10; 95% CI 0.93-1.31; P = 0.28; moderate certainty of evidence), with consistent findings across subgroup analyses. No significant effects of SGLT2 inhibitors were observed for cervical, endometrial, ovarian, prostate, uterine, penile, or vulvar cancers. Dapagliflozin potentially increased the risk of male genital cancers (RR 1.31; 95% CI 0.99-1.74; P = 0.06). SGLT2 inhibition significantly reduced testicular [odds ratio (OR) 0.012; 95% CI 0.001-0.220; P = 0.003] and cervical (OR 0.013; 95% CI 0.001-0.122; P = 1.615 × 10 - 4) cancer risks. Pooled results from both discovery and replication cohorts demonstrated that SGLT2 inhibition reduced cervical cancer risk (OR 0.016; 95% CI 0.002-0.116; P < 0.0001).

Conclusion: SGLT2 inhibitors exhibited a neutral overall risk profile for genital cancers, while genetic evidence demonstrated beneficial effects specifically for cervical cancer.

Purpose: To identify clinical and sociodemographic factors that predict follow-up discontinuation and rehospitalisation after multidisciplinary residential rehabilitation for severe obesity, thereby defining high-risk patient profiles and guiding tailored retention strategies.

Methods: We retrospectively followed 1,851 adults with obesity discharged from a multidisciplinary residential programme between 2015 and 2018 (median BMI 42 kg m⁻²). Dropout, defined as more than twelve months without contact, was studied with discrete-time survival models; time to rehospitalisation was analysed with Cox regression.

Results: Within twelve months 1,513 patients (87%) discontinued follow-up. Each five-year increase in age lowered drop-out risk (HR 0.97, 95% CI 0.94-0.99, p = 0.004); diabetes had a similar protective effect (HR 0.89, 0.79-1.00, p = 0.0455). Rehospitalisation occurred in 591 patients (32%). Risk increased with age (5-years increment; HR = 1.05, 95% CI 1.01-1.09, p = 0.0191), baseline BMI (HR = 1.04, 95% CI 1.03-1.05, p < 0.0001), diabetes (HR = 1.22, 95% CI 1.02-1.30, p = 0.0306) and eating disorders (HR = 1.48, 95% CI 1.07-2.05, p = 0.0193).

Discussion: Maintaining the benefits of residential rehabilitation is important. In our cohort, 87% of patients dropped out of follow-up within one year and 32% were readmitted. Two distinct profiles emerged: younger and non-diabetic subjects were prone to dropout, while patients with higher BMI, diabetes, or eating disorders were at higher risk of rehospitalization. Early identification of these groups may suggest flexible, technology-assisted follow-up for working-age patients and integrated metabolic-psychiatric care for complex cases, safeguarding outcomes and optimizing resources.

The sella turcica, a saddle-shaped depression of the sphenoid bone, serves as a critical anatomical structure housing the pituitary gland and holds significant evolutionary, clinical, and anthropological importance. This review traces the evolutionary origins of the sella turcica from early vertebrates through mammalian and primate evolution, emphasizing its role in the stabilization and protection of neuroendocrine functions. Morphological stability of the sella turcica across hominin evolution highlights strong selective pressures on cranial base anatomy, despite broader craniofacial diversification. Anthropologically, the sella turcica provides a durable landmark for craniometric analyses, forensic reconstructions, and paleoanthropological investigations, revealing patterns of sex-based dimorphism, population variation, and disease prevalence. Developmental anomalies such as empty sella syndrome and pituitary hypoplasia illustrate the evolutionary trade-offs between increased encephalization and cranial vulnerability. Integrating historical, paleopathological, and clinical perspectives, this article underscores the sella turcica's significance as a nexus of evolutionary innovation, structural resilience, and biological fragility.

Purpose: Varicocele has been associated with reduced male fertility potential. Treatment modalities for varicocele improve semen parameters, yet more than 50% of cases remain infertile. Varicocele-induced heat and hypoxia stress may cause aberrant epigenetic modifications, possibly leading to abnormal sperm functions. This study aims to investigate the genome-wide sperm DNA methylation alterations in infertile men with clinical varicocele and evaluate the effect of varicocele treatment on methylation and fertility status.

Methods: This study includes 30 healthy fertile men and 50 infertile men with clinical varicocele. Whole genome bisulfite sequencing (WGBS) was employed to identify differentially methylated CpG (DMC) sites in sperm genomic DNA of the infertile men with varicocele compared to the fertile controls. DMCs located within genes associated with spermatogenesis and sperm functions were selected for validation in larger study population by pyrosequencing. Varicocele group were followed up after 3 months of either antioxidant treatment or varicocelectomy, and sperm DNA methylation changes were evaluated. Participants were monitored for 1 to 2 years following treatment to evaluate their fertility status.

Results: From WGBS analysis, a total of 6414 DMCs and 1484 differentially methylated genes (DMGs) were identified. Signalling pathways involved in spermatogenesis process and sperm functions were enriched in the pathway analysis. Selected DMC within gene H2AX was significantly hypermethylated, and CDKN1B and BCR were hypomethylated in varicocele study population. However, after 3 months of varicocele treatment (both modes), notable restoration could only be observed in H2AX and CDKN1B DMCs. 20% of the follow-up patients achieved fertility after varicocele treatment and demonstrated a reversal of DNA methylation alterations.

Conclusion: This study highlights the altered sperm DNA methylation landscape and its possible implications on altered spermatogenesis and sperm function in clinical varicocele cases. It also presents insights into the possibility of restoration of altered DNA methylation levels following varicocele treatment.

Congenital adrenal hyperplasia (CAH) comprises a group of autosomal recessive disorders caused by numerous variants in several genes encoding enzymes involved in adrenal steroidogenesis. While 21-hydroxylase deficit is the most common and well-known form of CAH, accounting for 90%-95% of cases, there are six other forms of CAH, due to mutations in the genes of other key enzymes involved in adrenal steroidogenesis. These forms are less frequent and, consequently, clinician experience is extremely limited. These disorders are 11β-hydroxylase deficiency (11βOHD); 17α-hydroxylase/17,20-lyase deficiency (17OHD); 3β-hydroxysteroid dehydrogenase type 2 deficiency (3ΒHSD2D); P450 oxidoreductase deficiency (PORD); steroidogenic acute regulatory protein (StAR) deficiency, causing congenital lipoid adrenal hyperplasia and cholesterol side-chain cleavage enzyme (P450scc) deficiency. This narrative review therefore focuses on these rarer forms of CAH, providing an update on their clinical presentation, diagnosis, management, and treatment.

Purpose: To characterize, using real-life data, the clinical profile of men undergoing their first bone health evaluation at a tertiary academic center over a 14-year period.

Methods: Retrospective, observational, cross-sectional study including adult men referred to our center between 2007 and 2021 for bone health assessment. Fractures, comorbidities, risk factors for bone loss, and pharmacological treatments were collected.

Results: 536 men were enrolled (147 under 50, 385 over 50). At least one comorbidity associated with bone loss was found in 49.3% of patients, and 43.8% were receiving medications causing bone mineral density (BMD) reduction-mainly corticosteroids and androgen deprivation therapy. The prevalence of osteoporosis, osteopenia, and low BMD for age was 42.3%, 44.8%, and 48.6%, respectively. Osteoporosis-related fractures were found in 216 patients (40.8%), whose 34 men under 50 (15.7%). Up to 17.5% of men with fractures had normal BMD. A total of 181 patients (33.8%) had never received calcium/vitamin D supplementation or bone-active therapy; the prevalence of treatment-naïve patients was 20-23% even among men with fractures or receiving corticosteroids/androgen-deprivation therapy.

Conclusions: Male osteoporosis presents with a high rate of fractures in the real-life clinical practice at a tertiary academic center. The high prevalence of comorbidities associated with bone loss suggests that secondary forms of osteoporosis should be carefully investigated, even in presence of normal BMD. The significant proportion of untreated men-including those with known risk factors or fractures-highlights the urgent need to raise awareness and improve the management of male osteoporosis, especially in primary healthcare.