Gynecological Endocrinology最新文献

Objective: To compare dydrogesterone versus levonorgestrel-releasing intrauterine system (LNG-IUS) for abnormal uterine bleeding (AUB) management with long-term follow-up and etiology-stratified analysis.

Methods: This single-center retrospective cohort study analyzed reproductive-aged women with International Federation of Gynecology and Obstetrics (FIGO)-classified AUB receiving dydrogesterone (n = 131) or LNG-IUS (n = 118). Propensity score matching balanced baseline covariates between groups (n = 104 pairs). Primary outcomes were bleeding control rates (composite: hemoglobin increase ≥ 1.5 g/dL, ≥ 50% Pictorial Blood Loss Assessment Chart [PBAC] reduction, no rescue interventions) at 3 and 12 months. Secondary outcomes included 24-month recurrence and adverse events (AEs).

Results: LNG-IUS demonstrated superior 3-month bleeding control versus dydrogesterone (82.7% vs. 65.4%; relative risk [RR] 1.26, 95% confidence interval [CI] 1.08-1.48; p = 0.002). At 12 months, bleeding control rates were comparable between groups (78.8% vs. 72.1%; RR 1.09, 95% CI 0.96-1.24; p = 0.17). LNG-IUS significantly reduced 24-month recurrence risk (hazard ratio [HR] 0.48, 95% CI 0.32-0.72; p < 0.001), particularly for structural AUB (HR 0.39, 95% CI 0.24-0.64). Subgroup analysis revealed LNG-IUS superiority in adenomyosis at 12 months (88.2% vs. 60.0%; RR 1.47, 95% CI 1.24-1.74; p < 0.001) but comparable efficacy in nonstructural AUB (76.6% vs. 72.9%; RR 0.95, 95% CI 0.78-1.16; p = 0.63). Dydrogesterone exhibited higher systemic AEs (28.2% vs. 13.6%; p = 0.003), while LNG-IUS had device-related events including expulsion (5.1%).

Conclusion: LNG-IUS offers superior short-term bleeding control and sustained long-term recurrence prevention, especially for structural AUB. Dydrogesterone effectively manages nonstructural etiologies but carries higher systemic adverse event rates. Treatment selection should be etiology-guided, balancing immediate symptom control versus recurrence prevention and individualized safety considerations.

Objective: Uterine peristalsis, which originates from sub-endometrial zone of myometrium, is observed at ultrasonography as a wave-like activity of endometrium. Increased uterine peristalsis is suggested to be related to decreased pregnancy rates in both fresh and frozen embryo transfer cycles. The aim of this study is to compare the effects of two different frozen embryo transfer preparation protocols on the frequency of uterine peristalsis and to evaluate the effect of peristalsis on pregnancy rates.

Methods: In this observational cohort study, 3-min transvaginal ultrasound videos were recorded one hour before embryo transfer in frozen embryo transfer cycles prepared by either artificial hormone treatment or aromatase inhibitor stimulation. Peristalsis frequency was assessed by reviewing videos at triple speed. Consequent pregnancy outcomes were also analyzed.

Results: During the study period of four months, a total of 147 patients with 99 artificial hormone treatments and 48 aromatase inhibitor-stimulated frozen embryo transfer cycles were included. The absence of uterine peristalsis was observed in 27.1% of the aromatase inhibitor-stimulated patients and 23.2% of the artificial hormone-treated patients (p = 0.68). Among those with peristalsis, the frequency was similar between groups (0.95 ± 0.59 and 0.98 ± 0.68 for the aromatase inhibitor-stimulated and artificial hormone treatment protocols, respectively; p = 0.97). Peristalsis presence or frequency was not associated with pregnancy or live birth rates.

Conclusions: In this study, uterine peristalsis frequency at frozen embryo transfer cycles did not differ between endometrial preparation protocols and showed no significant association with pregnancy outcomes. Further randomized studies are warranted.

Premature ovarian insufficiency (POI) is a multifactorial disease characterized by premature depletion of ovarian follicles, leading to impaired ovarian function and increased risk of systemic diseases such as osteoporosis and cardiovascular disease. Although POI significantly impacts women's reproductive health and increases the risk of systemic diseases, little is known about its potential mechanisms, which limits early diagnosis and treatment options. N-acetyltransferase 10 (NAT10), a key regulator of RNA acetylation, plays a crucial role in gene expression, cellular homeostasis, and stress response. This review explores the role of NAT10 in POI, emphasizing its involvement in cell apoptosis, autophagy, ferroptosis, inflammation, oxidative stress, and oocyte maturation disorders. Evidence reveals the dual role of NAT10 in regulating cell damage, balancing protective antioxidant defense and pro-apoptotic/inflammatory pathways depending on the cellular context. Dysregulation of NAT10 suggests its potential utility as a biomarker for early POI diagnosis. Furthermore, NAT10 inhibitors such as Remodelin may reduce ovarian cell damage by modulating apoptosis, inflammation, and oxidative stress. While these findings highlight NAT10 as a promising diagnostic and therapeutic target, challenges remain due to the complexity of its mechanisms and the need for more specific inhibitors. Translating these insights into clinical practice requires integrating molecular and clinical research to refine NAT10-based strategies. This review underscores the pivotal role of NAT10 in the pathophysiology of POI, paving the way for precision medicine and novel therapies targeting NAT10 to address ovarian dysfunction.

After menopause, women have a higher risk of developing metabolic disorders. The discovery of follicle-stimulating hormone (FSH) receptors in extra-ovarian tissues such as the adipose tissue suggests that FSH might influence metabolic processes in postmenopausal women. However, its role remains unclear. To examine the association between serum FSH levels and glucose and lipid metabolism in postmenopausal women. A retrospective analysis was conducted on 82 postmenopausal women (mean age 65.2 ± 8.1 years). Serum levels of FSH, 17β-estradiol (E2), glucose, insulin, HbA1c, total cholesterol, LDL, HDL, and triglycerides were measured. Insulin resistance was calculated using the HOMA-IR index. FSH levels did not significantly differ between women with and without dyslipidemia. However, FSH levels were significantly lower in women with type 2 diabetes (44.3 ± 13.8 IU/mL) compared to those with insulin resistance (60.6 ± 29.4 IU/mL) or normal glucose metabolism (69.4 ± 27.2 IU/mL; p = 0.045). Women in the lowest FSH quartile had higher glucose, insulin, and HOMA-IR values. A significant inverse correlation between FSH and insulin (r = -0.30, p = 0.03) was found, stronger in women more than six years postmenopausal. Serum FSH levels inversely correlate with glucose metabolism disorders in postmenopausal women. These findings suggest a possible role of FSH in glucose metabolism, deserving further study starting from the menopausal transition.

Epidemiological evidence suggests a relationship between frailty and age at menopause. The hormonal fluctuations associated with menopause may contribute to frailty, with androgens being prime candidates due to their anabolic properties. This study aimed to elucidate whether single nucleotide polymorphisms (SNPs) within the androgen receptor (AR) gene are associated with frailty. A cross-sectional study was conducted within the frailty sub-cohort of a population-based sample of community-dwelling postmenopausal women. Two SNPs of the AR gene, selected for their potential to modulate AR functionality, were analyzed. A multinomial ordinal regression model was applied to estimate phenotypic variance. A total of 392 women (mean age: 64.1 years) were included, with a frailty status distribution of 29.6% being frail, 38.5% prefrail, and 31.9% robust, consistent with population-based data for this age group. Neither of the selected AR gene SNPs (rs5919427 and rs2497942) showed a statistically significant association with frailty status. Age, reproductive factors (including number of deliveries and miscarriages), number of comorbidities, and body mass index were independently associated with frailty. Further research is warranted to comprehensively explore the potential role of AR gene variants in frailty susceptibility.

Objective: To evaluate whether hypoxia-preconditioned human umbilical cord mesenchymal stem cells (hUCMSCs) can protect frozen-thawed human ovarian tissue via in vitro co-culture.

Methods: Frozen-thawed ovarian cortical pieces from 10 patients were randomly divided into a control group (no co-culture), N‑MSCs group (normoxia‑preconditioned hUCMSCs co-culture), and H‑MSCs group (hypoxia‑preconditioned hUCMSCs co-culture). Tissues in the co-culture groups were subjected to 48 h indirect Transwell co-culture. Apoptosis was assessed by TUNEL. Metabolic changes in the culture medium were measured, such as glucose consumption and lactate production, and AMH levels were determined. Oxidative stress in ovarian tissue was evaluated by measuring ROS and TAC. RNA-seq was performed, and key pathways were analyzed by GSEA. The protein expression of HIF-1α, VEGFA, GDF9, AKT, and p-AKT was examined by Western blot.

Results: Compared with both the control and N-MSCs groups, co-culture with H‑MSCs significantly reduced follicular atresia and apoptosis, while preserving a greater proportion of resting follicles. The H‑MSCs group presented lower glucose consumption and lactate production and elevated AMH levels in the culture medium. H‑MSCs markedly decreased reactive oxygen species (ROS) and enhanced total antioxidant capacity (TAC). Transcriptomic analysis showed that H‑MSCs induced a distinct gene expression profile characterized by upregulation of the HIF‑1 signaling pathway. H‑MSCs significantly upregulated HIF‑1α, VEGFA, and phosphorylated AKT at the protein level.

Conclusions: This in vitro study showed that co-culture of ovarian tissue with H-MSCs provides stronger protection than N-MSCs. This effect likely involves the HIF-1α/VEGFA pathway, with enhanced pro-angiogenic signaling, reduced apoptosis and oxidative stress, and preservation of the follicular reserve.

Background: Polycystic ovary syndrome (PCOS) is a common endocrine-metabolic disorder affecting up to 18% of reproductive-aged women globally. Women with PCOS exhibit a significantly increased risk of miscarriage, independent of obesity and assisted reproduction variables. The etiology of PCOS-related pregnancy loss is multifactorial. Nevertheless, current clinical interventions target isolated mechanisms and demonstrate limited efficacy in reducing miscarriage rates.

Objective: This review synthesize recent evidence connecting metabolic and immune dysregulation to pregnancy loss in PCOS and evaluate novel therapeutic strategies targeting immunometabolic pathways.

Content: This review first presents an overview of the mechanistic pathways implicated in PCOS-related miscarriage, including endocrine-metabolic dysfunction, immune-inflammatory imbalance, oxidative stress and ferroptosis, vascular and coagulation defects, and uterine-placental abnormalities. Both translational and clinical for interventions with dual metabolic-immune effects are highlighted, such as metformin, antioxidants likeN-acetylcysteine, anti-androgens, and combination regimens including aspirin with low-molecular-weight heparin (LMWH). Agents with mechanistic promise but limited exploration, such as glucagon-like peptide-1 (GLP-1) receptor agonists, selenium nanoparticles, and stem cell-based therapies, are also discussed. Future directions for PCOS pregnancy care are outlined, emphasizing the integration of immunometabolic biomarkers, advanced animal models, and mechanism-informed combination trials.

Conclusion: PCOS-related miscarriage is increasingly recognized as resulting from dysregulation of immune-metabolic crosstalk. Mechanism-based, multidimensional strategies targeting this dual pathology represent a promising paradigm for preventing and managing pregnancy loss in women with PCOS.

Objective: Polycystic ovary syndrome (PCOS) is a common endocrine condition requiring coordinated management across reproductive, metabolic, and psychological domains. This narrative review explores pragmatic strategies that can be applied across levels of care, considering workforce capacity, referral thresholds, and patient access.

Methods: PubMed, Embase, and Ovid were searched (2000-2025) for guidelines, systematic reviews, clinical trials, and qualitative studies. Evidence was synthesised with attention to feasibility in primary versus secondary care.

Results: Menstrual irregularity can usually be managed in primary care with combined oral contraceptives or progestins, with referral for fertility or complex cases. Dermatological symptoms such as hirsutism and acne may require topical or hormonal therapy, with escalation to anti-androgens or dermatology input. Cardiometabolic and glycaemic risk should be screened routinely in general practice, with specialist referral for complex profiles. Emotional wellbeing-including anxiety, depression, eating disorders, and body image concerns-can be screened in primary care using validated questionnaires with onward referral as needed.

Conclusions: Pragmatic PCOS care requires clear delineation between primary and specialist roles, integration of digital tools, and patient-centred education to reduce duplication, improve efficiency, and enhance outcomes.