Search Results (1,016)

Background: Polycystic ovary syndrome (PCOS) is a leading cause of anovulatory infertility and a frequent indication for in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). Multivariable regression estimates adjusted associations, whereas association rule mining (ARM) can describe frequently co-occurring attributes; however, ARM outputs are unadjusted and may be sensitive to analytic specification. Objectives: We used ARM alongside multivariable logistic regression and internal robustness analyses to describe combinations of clinical and treatment-related variables that co-occurred with clinical pregnancy failure among women with PCOS undergoing IVF/ICSI. Methods: We retrospectively analyzed 733 deidentified patients with PCOS from the Reproductive Hospital of Guangxi. The original one-hot-encoded analytic file was linked to a supplemental clinical record file containing continuous age, BMI, infertility duration, anti-Müllerian hormone, total gonadotropin dose, fertilization method, embryo-transfer day, number of embryos transferred, and embryo score. Embryo quality was derived from D3 cleavage-stage and blastocyst morphology records. Multivariable logistic regression was used to estimate adjusted associations. ARM results were assessed using Fisher’s exact test, Benjamini–Hochberg false discovery rate (FDR) correction, 1000 bootstrap resamples, fivefold cross-validation, and threshold/cutoff sensitivity analyses. Results: In the multivariable model (n = 730), age remained associated with clinical pregnancy failure (adjusted odds ratio [aOR] = 1.04 per year, 95% CI 1.00–1.08, p = 0.031), whereas BMI was not independently associated with failure (aOR = 1.00 per kg/m², 95% CI 0.96–1.05, p = 0.860). Transfer of two embryos (aOR = 0.55, 95% CI 0.35–0.85, p = 0.008), D5 blastocyst transfer (aOR = 0.49, 95% CI 0.32–0.75, p = 0.001), and transfer of at least one high-quality embryo (aOR = 0.63, 95% CI 0.43–0.93, p = 0.020) were associated with lower odds of failure. Under the primary host-factor specification, age > 35 years + BMI ≥ 24 kg/m² + pelvic adhesion defined 48 patients, 30 of whom had clinical pregnancy failure (support = 0.07; confidence = 0.63; lift = 1.38; FDR q = 0.098). In the secondary treatment-inclusive analysis, infertility duration > 5 years + no high-quality embryo transferred defined 43 patients with 30 failures (support = 0.06; confidence = 0.70; lift = 1.54; FDR q = 0.026). Lift represents the subgroup failure proportion divided by the overall failure proportion and is not an adjusted risk ratio. The rule composition and the number of FDR-supported rules changed under alternative cutoffs and confidence thresholds. Conclusions: ARM described transparent but specification-sensitive co-occurrence profiles that complement, rather than compete with, regression. Treatment-inclusive profiles combine baseline and downstream cycle characteristics and are therefore especially exploratory. These findings require prospective multicenter validation before any clinical decision-support use. Full article

Background/Objectives: Polyendocrine metabolic ovarian syndrome (PMOS) is a complex endocrine–metabolic disorder of multifactorial etiology, driven by interactions among hyperandrogenism, metabolic dysfunction, oxidative stress, and chronic low-grade inflammation that interact to promote reproductive dysfunction and increase risk of cardiometabolic complications. Although the combination of letrozole and high-fat diet (LET + HFD) represents a widely used experimental approach for inducing a PMOS-like phenotype in rats, its multisystem pathophysiological features remain incompletely characterized. The present study aimed to characterize reproductive, cardiometabolic, hormonal, inflammatory, oxidative, and morphometric alterations associated with a LET + HFD-induced PMOS-like phenotype in rats. Methods: PMOS-like model was induced in rats over a 21-day period of orally administered letrozole combined with a high-fat diet. Results: Body weight gain was higher, while uterine weight was lower in the PMOS group compared with controls. Metabolic parameters suggested insulin resistance, while hormonal profiling revealed increased total testosterone and LH levels, accompanied by reduced FSH, estradiol, and progesterone levels. Elevated triglycerides and reduced HDL levels were also observed in the PMOS group. Morphometric analysis revealed numerous atretic and large thin-walled cystic follicles in the ovaries, accompanied by thinning of the uterine luminal and glandular epithelium, stromal layer, and hypoplasia of endometrial glands. Both the longitudinal diameter and cross-sectional area of cardiomyocytes were increased in the PMOS group, together with nuclear hypertrophy and enhanced myocardial collagen deposition. In addition, altered oxidative stress markers, including increased lipid peroxidation and reduced glutathione levels, were observed, whereas IL-6, IL-1β, and IL-23 were not significantly altered. Conclusions: The LET + HFD model reproduces key reproductive and cardiometabolic features of PMOS, extending beyond reproductive dysfunction to involve oxidative and structural alterations in multiple organs. These findings support its use for investigating PMOS pathophysiology and evaluating potential preventive and therapeutic strategies. Full article

The estrobolome, defined as the collection of gut microbial genes encoding enzymes that metabolize estrogens and, by extension, the taxa that harbor them, has emerged as a central node of the new concept of “microbial endocrinology” within the gut–vagina axis. By regulating enterohepatic recirculation of conjugated estrogens, the estrobolome may modulate systemic estrogen availability and thereby may influence the estrogen-dependent biology of gynecological organs and tissues, including ovaries, endometrium, and the vaginal mucosa with its Lactobacillus-dominated ecosystem. In this narrative review, we synthesize current evidence on how gut microbial β-glucuronidases, sulfatases, and related enzymes shape circulating estrogen pools and, in turn, gynecological health. We outline the enzymatic and taxonomic architecture of the estrobolome, describe its major ecological determinants, and integrate these with mechanisms of the gut–vagina axis. We then examine how estrobolome function varies across a woman’s lifespan and how these dynamics intersect with vaginal health, dysbiosis, and conditions such as recurrent vaginitis, endometriosis, and polycystic ovary syndrome. We also review emerging strategies that may modulate the estrobolome as a microbial endocrine organ and discuss their potential downstream effects on gynecological health. Finally, we highlight major research gaps, particularly the need for causal, longitudinal, multi-omics studies explicitly linking estrobolome activity, systemic estrogens, and gynecological outcomes. Overall, available data support a mechanistically plausible but incompletely defined role for the estrobolome as a key microbial endocrine player in the gut–vagina axis and point toward microbiome-informed strategies to preserve and restore gynecological health across a woman’s lifespan. Full article

Oocyte quality is the primary determinant of success in assisted reproductive technologies (ART), and mitochondrial dysfunction is increasingly recognized as a central mediator of poor oocyte competence across advanced maternal age, recurrent implantation failure, polycystic ovary syndrome, endometriosis, and obesity. Chemical interventions improve the mitochondrial microenvironment but cannot restore depleted mitochondrial mass, while heterologous mitochondrial replacement remains constrained by ethical, legal, and biological limitations. This review examines the biological basis for mitochondrial intervention in oocytes, evaluates chemical and cellular therapeutic approaches, and assesses the evidence for autologous Adipose Stem Cell-derived Mitochondria ENergy Transfer (ASCENT). Mitochondria govern oocyte ATP production, calcium-mediated meiotic integrity, and redox homeostasis, and their disruption contributes to aneuploidy, fertilization failure, and embryonic arrest. Among cellular interventions, autologous adipose-derived stem cell mitochondrial transplantation offers minimally invasive tissue accessibility, morphological compatibility with oocyte mitochondria, robust membrane potential, and a preclinically validated Mito-ICSI delivery platform. Notably, ASCENT is currently the only autologous approach for which safety across three consecutive offspring generations has been reported in a mammalian model, with primary maternal origin of offspring mtDNA confirmed. Together, preclinical efficacy, transgenerational safety, and human proof-of-concept support progression toward a rigorously designed clinical trial, while ASC-derived mitochondria hold broader relevance in regenerative medicine. Full article

Background: Polycystic ovary syndrome (PCOS) is a complex endocrine disorder that affects women of reproductive age, often associated with metabolic issues, causing infertility. Although it is common, the cause of PCOS remains unknown, and early diagnosis is challenging. MicroRNAs (miRNAs) serve as post-transcriptional regulators of gene expression, play a significant role in PCOS development, and have emerged as biomarkers for reproductive and metabolic disorders. However, research on miRNA signatures in the Indian population is limited. This pilot exploratory study aims to compare the candidate differentially expressed miRNAs (DE miRNAs) in serum samples from individuals with and without PCOS using high-throughput miRNA sequencing. Methods: In the study, patients with PCOS and age-matched controls were included; small RNAs were isolated from their serum, libraries were prepared, and the libraries were analyzed by next-generation sequencing. Bioinformatics analysis, including miRBase annotation, differential expression analysis, target prediction, GO/KEGG enrichment, and hub gene network analysis, was performed. Results: A total of 967 miRNAs were identified, with seven showing differential expression (log2FC > 1, p < 0.05). Among these, six miRNAs of hsa-miR-219a-2-3p, hsa-mir-384, hsa-miR-149-5p, hsa-miR-3182, hsa-miR-3960, and hsa-miR-4508 were upregulated, whereas hsa-mir-139 was downregulated. Functional enrichment and hub gene analyses identified key targets, including TP53, FOXO1, HIF1A, and HDAC1, that are crucial to the cell cycle, insulin signaling, and hypoxia. Conclusions: These preliminary findings identify candidate serum miRNA signatures in Indian women that may be associated with PCOS’s reproductive and metabolic issues. These pilot study results suggest potential miRNAs and their target pathway links with PCOS that need validation in larger cohorts for diagnostic or therapeutic applications. Full article

Background/Objectives: Letrozole combined with intrauterine insemination (IUI) is a common first-line treatment for unexplained and anovulatory infertility; however, the optimal dominant follicle size at human chorionic gonadotrophin (hCG) triggering remains uncertain. We evaluated associations of follicle size with biochemical pregnancy, clinical pregnancy, and live birth. Methods: This retrospective cohort included 596 letrozole–IUI cycles from 454 women aged <40 years treated between May 2024 and August 2025. Cycles were grouped by dominant follicle diameter at trigger (17.0–18.9, 19.0–21.0, and >21.0 mm). Mixed-effects logistic regression accounted for repeated cycles. Results: Biochemical pregnancy, clinical pregnancy, and live-birth rates differed across groups and were highest at 19.0–21.0 mm; live-birth rates were 3.4%, 15.1%, and 8.6%, respectively (p = 0.008). Compared with 17.0–18.9 mm, the 19.0–21.0 mm group had higher adjusted odds of clinical pregnancy (aOR 5.58, 95% CI 1.31–23.84; p = 0.020) and live birth (aOR 15.15, 95% CI 1.74–131.95; p = 0.014), although both estimates were imprecise. Adjusted live-birth probabilities were 3.5%, 16.1%, and 9.1%, respectively. The direction of the live-birth association was preserved in the single-cycle sensitivity analysis (aOR 3.85, 95% CI 1.22–12.13; p = 0.021). Continuous linear and quadratic follicle-diameter models were not significant. Conclusions: The 19.0–21.0 mm category was associated with higher reproductive outcome rates, including live birth; however, the observational design, sparse events, wide confidence intervals, and null continuous analyses preclude defining an optimal trigger threshold. These findings are hypothesis-generating and require prospective multicenter confirmation. Full article

Obesity is a multifactorial condition that profoundly affects female reproductive health through endocrine, metabolic, and inflammatory mechanisms that disrupt the hypothalamic–pituitary–gonadal (HPG) axis. Women with obesity frequently develop menstrual irregularities, anovulation, amenorrhea, infertility, polycystic ovary syndrome (PCOS), impaired endometrial receptivity, and adverse pregnancy outcomes. Central obesity and insulin resistance contribute to hyperinsulinemia, reduced sex hormone-binding globulin (SHBG) levels, hyperandrogenism, altered gonadotropin secretion, and impaired folliculogenesis, while adipokines such as leptin and chronic inflammation further impair ovarian steroidogenesis and ovulatory function. Obesity-related oxidative stress and lipotoxicity also negatively affect oocyte quality, embryo development, implantation, and assisted reproductive technology outcomes, increasing the risk of gestational diabetes, preeclampsia, miscarriage, and preterm birth. This review evaluates the therapeutic potential of pharmacological weight-loss therapies in obesity-associated female reproductive dysfunction. A comprehensive literature review was conducted using various databases, focusing on anti-obesity pharmacotherapy on obesity, infertility and fertility in reproductive-aged women. Evidence suggests that several FDA-approved and off-label anti-obesity agents, including orlistat, liraglutide, semaglutide, phentermine/topiramate, bupropion/naltrexone, metformin, exenatide, and tirzepatide, may improve reproductive outcomes primarily indirectly through weight reduction and metabolic improvement. GLP-1 receptor agonists, particularly liraglutide, semaglutide, and exenatide, appear especially promising, demonstrating beneficial effects on insulin sensitivity, menstrual regularity, ovulation, androgen levels, and pregnancy rates in women with PCOS. Tirzepatide, a dual GLP-1/GIP receptor agonist, has shown potent weight-loss and metabolic effects with potential indirect fertility benefits. Metformin improves insulin sensitivity and is widely used in PCOS to regulate androgen levels and restore ovulation, although its effects on pregnancy and live birth rates remain controversial. However, evidence for several agents remains limited, and concerns persist regarding reproductive safety during pregnancy. Overall, anti-obesity pharmacotherapy may represent an important adjunctive strategy for improving reproductive and metabolic health in women with obesity, although larger randomized clinical trials are still required. Full article

Women with polycystic ovary syndrome (PCOS) have a substantially increased risk of endometrial cancer (EC), yet the biological mechanisms underpinning this association, to support future prevention and therapeutics, remain incompletely understood. Insulin-like growth factor (IGF)-associated signaling has been implicated, but existing evidence is conflicting. In this pilot translational study, serum IGF1 and IGFBP-3 were measured in women with PCOS (n = 12 for IGF1 and n = 6 for IGFBP-3) and controls (n = 24 for IGF1 and n = 7 for IGFBP-3). Pooled serum, stratified by IGF bioactivity, was applied to human EC cells to further assess effects on cell viability, cell cycle distribution, and downstream signaling. Computational analysis of publicly available endometrial cancer datasets was used to contextualize experimental findings. Serum IGF1 and IGFBP-3 levels did not differ significantly between PCOS and control groups. However, pooled PCOS serum was associated with increased EC cell viability, altered cell cycle progression and PI3K/AKT/mTOR signaling compared with control serum in this exploratory model. Pharmacological inhibition of IGF1R partially attenuated these effects, suggesting that IGF-associated pathways may contribute but are unlikely to act in isolation. In silico analysis identified frequent alterations in PI3K/AKT/mTOR-related genes in EC, consistent with pathway-level vulnerability rather than IGF1-specific dependence. These findings suggest that PCOS serum contains factors that are associated with increased EC cell viability and altered signaling pathways with partial involvement of IGF signaling; however, these findings should be interpreted cautiously given the exploratory pooled-serum design, small subgroup sizes, and use of a single EC cell line. However, multiple metabolic and hormonal pathways are likely to contribute. Larger, better-controlled studies incorporating insulin, sex steroids, and multiple EC models are required before causal inferences can be made. Full article

Melatonin has evolved from its classical role as a pineal-derived circadian regulator to a molecule increasingly recognized for its mitochondrial and cytoprotective functions. This review examines the molecular mechanisms and translational implications of melatonin within a mitochondria-centered framework, with particular emphasis on reproductive medicine. Available evidence suggests that melatonin may influence mitochondrial quality control (MQC) through multiple interconnected processes, including ROS regulation, mitochondrial dynamics, mitophagy, biogenesis, and mitochondrial inflammatory signaling. In mitochondria, melatonin can attenuate electron transport chain-derived oxidative stress through direct radical-scavenging reactions, antioxidant metabolite formation, and indirect activation of endogenous antioxidant systems. Experimental studies further suggest that melatonin may modulate Drp1-mediated fission, OPA1- and Mfn1/2-associated fusion, PINK1/Parkin-mediated mitophagy, and SIRT1/PGC-1α-related mitochondrial biogenesis. In reproductive medicine, melatonin has been investigated as a potential adjunctive strategy in assisted reproductive technology, endometriosis, and polycystic ovary syndrome. However, clinical evidence remains heterogeneous, and most human studies have evaluated reproductive or biochemical outcomes rather than direct MQC-related biomarkers. Therefore, although melatonin represents a promising mitochondria-targeted adjunct, standardized dosing strategies, tissue-level pharmacodynamic assessment, and validated mitochondrial biomarkers are needed to determine whether these mechanisms translate into reproducible clinical benefit. Full article

Semaglutide and tirzepatide, glucagon-like peptide-1 (GLP-1) and dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonists, respectively, have revolutionized the management of type 2 diabetes mellitus and obesity. Beyond their established metabolic indications, emerging preclinical and clinical evidence suggests these incretin-based therapies exert pleiotropic effects across multiple organ systems through mechanisms extending beyond glycemic control and weight reduction. This comprehensive review synthesizes current evidence for unconventional applications of semaglutide and tirzepatide across five distinct therapeutic domains: oncology, psychiatry and addiction medicine, orthopedics, aesthetic medicine, and human reproduction. In oncology, both agents demonstrate antitumor activity primarily through immune and metabolic reprogramming rather than direct cytotoxicity, with promising signals in pancreatic, thyroid, breast, and colorectal cancers. In psychiatry, modulation of mesolimbic dopamine reward pathways and GABAergic neurotransmission underlies robust preclinical and observational evidence for reducing alcohol use disorder, substance use, and binge-eating behaviors. Orthopedic applications include clinically meaningful improvements in knee osteoarthritis pain and function, though bone health signals remain mixed. Aesthetic medicine faces the dual challenge of managing GLP-1 receptor agonist-associated facial volume loss while exploring therapeutic potential in inflammatory dermatoses. In reproductive medicine, metabolic improvements translate to benefits in polycystic ovary syndrome and male fertility, though periconception safety concerns persist. Across all domains, evidence derives predominantly from preclinical models, observational cohorts, and pharmacoepidemiologic studies, with randomized controlled trials remaining limited. This review critically evaluates mechanisms, efficacy signals, safety considerations, and research priorities for each application domain, providing a roadmap for translating unconventional uses of semaglutide and tirzepatide into evidence-based clinical practice. Full article

Background: Gestational diabetes mellitus (GDM) and polycystic ovary syndrome (PCOS) are clinically distinct disorders that share important metabolic features. This Perspective proposes a non-causal intergenerational framework linking maternal PCOS-related metabolic vulnerability, susceptibility to GDM, intrauterine metabolic exposure, and later reproductive-metabolic risk in female offspring. Methods: A narrative synthesis of evidence from reproductive endocrinology, obstetrics, diabetology, developmental biology, and public health was undertaken. The strength of evidence supporting individual components of the proposed continuum was qualitatively appraised. Separately, aggregated surveillance data from Belgrade for 2015–2024 were used as a registry-based illustration of ICD-10 O24.4-coded GDM diagnoses. No formal time-series analysis, causal modeling, or forecasting was performed. Results: Evidence was strongest for the increased risk of GDM among women with PCOS and for the association between intrauterine exposure to maternal diabetes and later offspring metabolic susceptibility. Evidence linking maternal PCOS with offspring metabolic vulnerability was less definitive, while direct evidence that GDM exposure leads to clinically diagnosed PCOS in female offspring remained weak and indirect. Registry-recorded GDM rates varied across years, but this variability may reflect differences in screening, diagnostic criteria, coding, reporting completeness, and healthcare access rather than true changes in prevalence. Conclusions: The proposed GDM–PCOS continuum is a hypothesis-generating and probabilistic framework, not an established causal pathway. Its clinical value lies in connecting prevention opportunities before conception, during pregnancy, after delivery, and across the life course. Longitudinal maternal–offspring studies are required to test the proposed relationships. Full article

Polycystic ovary syndrome (PCOS), newly named as Polyendocrine Metabolic Ovarian Syndrome (PMOS) is the most common endocrinopathy affecting women of reproductive age, which often leads to infertility due to anovulation and poor oocyte quality. Poor oocyte quality is a major reason for women’s infertility in humans and a barrier to efficient assisted reproduction technology (ART) treatment. Supplementation of melatonin, a free radical scavenger, has been reported to show satisfactory results in women undergoing ART. This review investigates whether the endogenous melatonin or supplementation of melatonin impact on oocyte/embryo quality and pregnancy rate in PCOS patients undergoing ART treatment. Articles published between 2010 and 2025 were reviewed to perform a comprehensive search on observational studies and clinical trials that evaluated the use of melatonin in PCOS patients undergoing in vitro fertilization (IVF) or intrauterine insemination (IUI) or intracytoplasmic sperm injection (ICSI). The databases searched included PubMed, Google Scholar, Science Direct, and Cochrane Library. This systematic review indicates that the group that received melatonin had significantly higher clinical pregnancy probabilities than the control group. Similarly, the melatonin administration significantly enhanced the endometrium thickness (p < 0.001) and the chemical pregnancy rate (30% versus 18%, p = 0.012). Additionally, in comparison to the control group that received metformin alone, the group that received melatonin (3 mg) significantly increased the proportion of top-quality embryos (40.3% vs. 29.9%; p < 0.001). According to this systematic review, melatonin significantly improves endometrial thickness, mature oocytes, high-quality embryos, and pregnancy rates, all of which improve ART outcomes in PCOS patients. Because of its safety, affordability, and efficacy, it is a useful supplement to ART procedures. The most popular and well-tolerated dosage is still 3 mg per day, despite variations in research. Full article

Background: The aim of this study was to evaluate the clinical and diagnostic utility of metabolic and systemic inflammatory marker indices in adolescent patients with polycystic ovary syndrome (PCOS). Methods: This retrospective case–control study included 63 adolescent girls diagnosed with PCOS, based on the strict presence of both menstrual irregularity and hyperandrogenism, and 63 healthy controls matched for age and body mass index (BMI). Fasting blood glucose (FBG), fasting insulin (FI), and lipid profiles were measured. Metabolic indices, including the Triglyceride-Glucose (TyG) index, Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), and Metabolic Score for Insulin Resistance (METS-IR), as well as systemic inflammatory indices (Systemic Immune-Inflammation Index (SII), Systemic Inflammation Response Index (SIRI), and the Aggregate Index of Systemic Inflammation (AISI)), were calculated. The diagnostic performance of these markers was evaluated using Receiver Operating Characteristic (ROC) curves and binary logistic regression analyses. Results: No statistically significant difference was observed between the PCOS and control groups in terms of age and BMI (p > 0.05). FBG levels (p = 0.001) and the TyG index (p = 0.028) were found to be significantly higher in the PCOS group. However, no significant differences were observed between the groups in terms of other metabolic indices (HOMA-IR, METS-IR) and systemic inflammatory markers (SII, SIRI, AISI). In the ROC analysis, only the TyG index demonstrated statistically significant but weak discriminatory power for PCOS (AUC = 0.614; 95% CI: 0.515–0.712; p = 0.028). Furthermore, binary logistic regression analysis revealed that the TyG index was not an independent predictor of PCOS after adjustment. Conclusions: While early metabolic signals such as elevated FBG and TyG index were detected, the evaluated systemic inflammatory indices did not demonstrate significant differences. However, the weak discriminatory capacity of the TyG index and the failure of other composite indices restrict their clinical utility. Therefore, these biomarkers cannot be recommended as reliable standalone diagnostic tools in adolescent PCOS. Full article

Background/Objectives: Relatively little is known about how the aberrations in cardiometabolic health linked with polyendocrine metabolic ovarian syndrome (PMOS, formally called polycystic ovary syndrome or PCOS) persist beyond the menopause transition. The study aim was to explore and contrast cardiometabolic health indicators in postmenopausal women with PMOS with postmenopausal women without PMOS. This study employed a cross-sectional analysis; comparisons between groups were completed with a two-tailed t-test. Methods: Postmenopausal females with a self-reported history of PMOS/PCOS (n = 10; 58.0 ± 5.1y; P) and without a self-reported history of PMOS/PCOS diagnosis (56.5 ± 3.6 n = 19; y; CON) completed a study visit to assess indicators of cardiometabolic health, including anthropometric measurements, body composition, sex hormones, fasting blood lipids, glucose, insulin, and glycosylated hemoglobin. Medical diagnosis of PMOS, menstrual health history, medication usage, and quality-of-life indicators were self-reported. Results: Postmenopausal women with PMOS had a significantly higher BMI (CON vs. PMOS: 25.8 ± 5.3 kg/m² vs. 29.0 ± 3.1 kg/m², p < 0.045), ratio of trunk fat to appendicular fat mass (CON vs. PMOS, 1.20 ± 0.39 vs. 1.40 ± 0.21; p = 0.041), and tended to have a higher waist-to-hip ratio (p = 0.089). Circulating sex hormones, glucose, and insulin were not significantly different between the two groups (p > 0.05). However, women with PMOS tended to report a higher number of prescription medications (n = 9; p = 0.058), with all PMOS participants reporting at least one prescription medication, while 36.8% of CON participants reported no prescription medications. Conclusions: These preliminary findings suggest that postmenopausal women with a self-reported history of PMOS may have greater central fat distribution and higher prescription medication use than controls. Larger, more diverse studies with confirmed PMOS diagnosis and detailed medication indication data are needed before clinical conclusions can be drawn. Full article

Background and Clinical Significance: Cantú syndrome (OMIM #239850) is a rare autosomal dominant disorder caused by gain-of-function variants in ABCC9 or KCNJ8, which encode subunits of the ATP-sensitive potassium (K_ATP) channel. Its characteristic features—generalized hypertrichosis, coarse facial appearance, skeletal abnormalities, and cardiovascular involvement—may be overlooked when other major comorbidities dominate the clinical picture. Case Presentation: A 29-year-old Taiwanese woman, born prematurely and complicated by neonatal hydrocephalus with subdural hemorrhage requiring ventriculoperitoneal shunt placement, had been followed since infancy under a working diagnosis of cerebral palsy with left hemiparesis and borderline-to-mild intellectual disability. Over the ensuing years, additional features gradually emerged, including generalized hypertrichosis with thick scalp and body hair, coarse facial features, bilateral hallux valgus, mild thoracic scoliosis, polycystic ovaries, mild aortic regurgitation, recurrent hemoptysis associated with abnormal pulmonary vasculature, and iron-deficiency anemia. Earlier genetic investigations—including chromosome analysis (46,XX), array comparative genomic hybridization (array-CGH; 2013), and a trio-based next-generation sequencing study performed under a national rare disease research initiative (2019)—were unrevealing. Whole-genome sequencing performed in December 2025 identified a heterozygous ABCC9 variant (NM_020297.4:c.4174A>G, p.(Ile1392Val)), initially classified as a variant of uncertain significance. Parental Sanger sequencing confirmed the variant to be de novo, and reclassification according to ACMG/AMP criteria supported a likely pathogenic interpretation. Re-evaluation of the patient’s phenotype demonstrated findings consistent with Cantú syndrome. Conclusions: This case illustrates how Cantú syndrome may remain unrecognized for years when a prominent neurological comorbidity—perinatally acquired hydrocephalus and presumed cerebral palsy—dominates the clinical narrative. We report a previously undescribed de novo ABCC9 missense variant (c.4174A>G, p.(Ile1392Val)), thereby expanding the mutational spectrum associated with Cantú syndrome. This case also highlights the practical value of resequencing and periodic reanalysis using updated next-generation sequencing platforms in patients with long-standing undiagnosed disease, even after prior negative genetic testing. Full article