Gynecological Endocrinology最新文献

Background: The effects of granulose cell (GC) senescence on premature ovarian insufficiency/premature ovarian failure have been extensively examined, the association between GC senescence and ovarian aging remains to be clarified.

Methods: Human and mouse GCs from young/control and old/advanced maternal age (AMA) groups were collected, and GC senescence was determined. The role of the DNMT1-p53 axis in GC senescence during ovarian aging was examined and validated in a KGN cell senescence model.

Results: SA-beta-gal-positive GCs were significantly increased in the AMA group, accompanied by activation of the p53-p21 pathway, which was also found in GCs from aged mice and H₂O₂-induced senescent KGN cells. Pyrosequencing methylation analysis revealed that increased expression of p53 was associated with decreased average methylation levels of CpG sites (-1031, -1019, -1012 and -1008) within the P53 promoter CpG island in senescenct GCs and KGN cells. We further found that decreased DNA-methyltransferase 1 (DNMT1) expression was responsible for the reduced methylation levels of the CpG sites.

Conclusion: Decreased DNMT1 with hypomethylation of the CpG sites within the P53 promoter CpG island in GCs is involved in ovarian aging.

Gestational diabetes mellitus (GDM) affects 9-25% of pregnancies. Undiagnosed or poorly managed GDM is associated with both short- and long-term complications in the fetus and mother. The pathogenesis of GDM is complex and has not yet been fully elucidated. Several biomarkers found in maternal serum have the potential for the early diagnosis of GDM. The aim of this narrative review was to explore novel biomarkers that have not been comprehensively described in previous reviews. We believe these biomarkers may allow for the detection of GDM in the early stages of pregnancy, enabling timely proper treatment and potentially preventing complications for both the mother and the fetus.

Objectives: Premature ovarian insufficiency (POI) is a serious condition that affects women worldwide, In recent years, the number of research publications on POI has increased over the last decades because of the advancement of cutting-edge research in gynecology and the deepening of disciplinary interactions. At the same time, there is a more urgent need to systematically analyze and review existing studies to generalize the research paradigm and disciplinary structure of the field under technological changes.

Materials and methods: We selected the top 100 most cited papers in the Web of Science (WOS) SCI-Expanded database. Knowledge graphs were constructed through the VOS viewer, Cite Space, and Scimago Graphica software, and then relevant information retrieved from the literature was edited using Excel to assess research priorities and trends in the field.

Results: A total of 53 periodicals from 34 different nations and regions published the 100 most-cited publications between 1999 and 2024. The Journal of Clinical Endocrinology & Metabolism published the majority of the papers, while The Lancet had the highest average number of citations per piece. The United States of America produced the highest contribution in terms of publications, with China and France closely trailing after. In terms of total publications, Erasmus MC, Shanghai Jiao Tong University, and Shandong University each contributed the highest number of papers. The main categories were obstetrics and gynecology, endocrinology and metabolism, and reproductive biology. The top five keywords were: failure, women, ANTI-MULLERIAN HORMONE, NATURAL MENOPAUSE, and AGE. The study of HERITAGE AND GENETICS, CARDIOVASCULAR DISEASES, and CELL BIOLOGY AND IMMUNOGENETICS is becoming more and more popular in POI, as shown by cluster analysis.

Conclusions: Bibliometric analysis enables POI researchers to efficiently and visibly pinpoint the cutting-edge areas and focal points of their study. Potential topics of future study may include genetic and molecular biological pathways, cardiovascular pathology, and immunology.

Objective: To evaluate the effects of a combination of carnitines, L-arginine, L-cysteine and myo-inositol on metabolic and reproductive parameters in PCOS overweight/obese patients.

Methods: This was a retrospective study analyzing information of a group of PCOS (n = 25) overweight/obesity patients, not requiring hormonal treatment, selected from the database of the ambulatory clinic of the Gynecological Endocrinology Center at the University of Modena and Reggio Emilia, Modena, Italy. The hormonal profile, routine exams and insulin and C-peptide response to oral glucose tolerance test (OGTT) were evaluated before and after 12 weeks of a daily oral complementary treatment with L-carnitine (500 mg), acetyl-L-carnitine (250 mg), L-arginine (500 mg), L-cysteine (100 mg) and myo-inositol (1 gr). The hepatic insulin extraction index was also calculated.

Results: The mix of complementary substances significantly improved metabolic parameters, homeostatic model assessment for insulin resistance index values and gonadotropin plasma levels. Glucose, C-peptide and insulin response to OGTT was significantly reduced as well as the hepatic insulin extraction index.

Conclusion: The administration of a combination of carnitines, L-arginine, L-cysteine and myoinositol improved gonadotropin plasma levels and insulin sensitivity in overweight/obese PCOS patients and restored hepatic clearance of insulin as demonstrated by the decreased hepatic insulin extraction index.

Purpose: To comprehensively compare and rank hormone therapy for patients with perimenopausal syndrome.

Methods: A comprehensive search was conducted on PubMed, Embase, Cochrane Library, Web of Science, CNKI, VIP, and Wanfang databases from inception to August 20, 2024. The quality of the included randomized controlled trials (RCTs) were measured by the Cochrane risk of bias tool. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) method was applied to grade the quality of evidence in this network meta-analysis. Network plots were depicted to show direct and indirect comparisons of hormone therapy for each outcome. The influences of different hormone therapy on the outcomes were illustrated via forest plots and league tables. Rank probabilities showed the ranking of different administration routes.

Results: Seven studies involving 704 perimenopausal syndrome patients were included. The rank probabilities suggested that oral estradiol (E₂₎ combined with medroxyprogesterone and general health guidance had the highest likelihood to be the optimal therapy for the severity of menopausal syndrome. General health guidance combined with oral E₂ was less likely to have a nausea and vomiting, and breast pain.

Conclusion: Oral E₂ and medroxyprogesterone or general health guidance combined with oral E₂ may be the effective and safe option for the management of perimenopausal syndrome.

Objective: It has been established that male cigarette smoking has a negative effect on the semen quality and that it can induce DNA damage leading to worsening of reproductive outcomes. The aim of our large retrospective study is to determine the influence of male cigarette smoking on assisted reproduction, more specifically in IVF and ICSI outcomes.

Materials and methods: Our study included all consecutive infertile couples (with a nonsmoking female partner) having their first IVF/ICSI cycle. All patients had smoking assessment. Smokers were further classified into mild (1-10 cigarettes/day), moderate (11-20 cigarettes/day) or heavy smokers (>20 cigarettes/day). The primary outcome was live birth rates (LBR).

Results: The overall number of patients analyzed was 4004 and among them 433 (10.8%) were smokers. Baseline characteristics, such as female age and BMI differed significantly between nonsmokers and smokers. The crude analysis showed higher positive hCG and LBR in smokers (positive hCG 28.34% in nonsmokers vs 33.95% in smokers, p = 0.015; LBR 23.55% in nonsmokers vs 28.64% in smokers, p = 0.019) However after adjustment for relevant confounders (female age, BMI, cause of infertility, number of oocytes retrieved, insemination procedure, number of embryos transferred and day of embryo transfer) the smoking status was not significantly associated with fresh LBR (OR = 1.16, CI = 0.92-1.48; p = 0.2). The results were replicated after classification of smoking into mild/moderate/heavy [OR for nonsmokers (reference category) vs. mild vs. moderate vs. heavy= 1, 1.17, 1, 2.99; p = 0.18)].

Conclusion: Male smoking does not seem to impair live birth rates in patients undergoing IVF/ICSI treatment.

Background: Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder associated with chronic low-grade inflammation of the ovary. Sodium glucose co-transporter 2 (SGLT2) inhibitors are a class of antidiabetic drugs that can reduce the weight and hyperglycemia of type 2 diabetes patients. Dapagliflozin is a highly selective, orally active and reversible inhibitor of the human SGLT2. However, the role of dapagliflozin in regulating PCOS remains unclear.

Methods: In this study, 24 six-week-old female Sprague Dawley (SD) rats were randomly divided into control, letrozole, and letrozole + dapagliflozin groups. PCOS model rats were produced by gavage administration of letrozole for 21 days. The intervention was conducted after the gavage administration of dapagliflozin for 14 days to evaluate the estrous cycle and ovarian imaging changes of the rats in each group. We observed changes in the weight, ovarian weight, and ovarian morphology of the rats in each group. Pathological changes in the ovaries were examined by H&E staining, changes in ovarian tissue cell apoptosis were identified using TdT-mediated dUTP Nick-End Labeling (TUNEL) staining, and changes in inflammation-related factors were detected using immunohistochemistry and Western blotting analysis. Network pharmacology was used to predict the inflammatory targets and pathways affected by dapagliflozin in treating PCOS, and the potential interactions between dapagliflozin and inflammation-related target proteins were evaluated through molecular docking.

Results: Our results demonstrated that dapagliflozin treatment significantly improved PCOS symptoms, recovered ovarian morphology and physiological functions, and reduced the apoptosis of ovarian cells after drug intervention. Dapagliflozin treatment also reduced the levels of pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α, indicating its anti-inflammatory properties. Furthermore, network pharmacology identified 26 intersecting target genes relevant to inflammation in PCOS, with subsequent molecular docking simulations revealing strong binding affinities of dapagliflozin to key targets, including AKT1 and TP53.

Conclusions: These findings suggest that dapagliflozin exerts beneficial effects on PCOS by ameliorating ovarian dysfunction and reducing inflammation. Dapagliflozin represents a promising therapeutic candidate for managing PCOS, warranting further clinical investigation to explore its full potential in treating this multifaceted disorder.

Aims: A systematic review and meta-analysis were performed to determine the association of metabolic syndrome (METS) in women with and without overactive bladder (OAB).

Methods: PRISMA guidelines were followed and the protocol was registered at PROSPERO (CRD42024606398). We searched PubMed, Embase, Cochrane Library, and LILACS databases to obtain relevant articles for studies reporting METS outcomes related to OAB published through October 2024. A meta-analysis was performed of available studies using random effect models. Results are reported as mean difference (MD), standardized MD (SMD), or odds ratio (OR) and their 95% confidence interval (CI). Heterogeneity was described with the I² statistic. The quality of studies was assessed using the Newcastle-Ottawa Scale.

Results: Of the 108 non-duplicated retrieved citations, after successive selection, four case-control studies with low or moderate risk of bias reported information about the association of METS in women assessed with the 8-item OAB Symptom Bother Scale. OAB patients displayed higher body mass index (BMI, MD: 3.27, 95% CI: 2.12, 4.43), waist circumference (MD: 7.96, 95% CI: 4.41, 11.52), fasting blood glucose (SMD: 1.26, 95% CI: 0.18, 2.34), triglycerides (SMD: 0.24, 95% CI: 0.01, 0.47), and LDL-cholesterol (SMD: 0.30, 95%CI: 0.06, 0.54) levels. In addition to low HDL-cholesterol levels (SMD: -0.40, 95% CI: -0.74, -0.06) compared to the control group. There were no significant differences in circulating total cholesterol levels and rates of hypertension, hysterectomy, postmenopausal status, and constipation in women with and without OAB.

Conclusion: Women with OAB display associations with age, BMI, waist circumference, and METS factors.

Background: A prolonged release combined oral contraceptive (COC) pill, containing 2 mg dienogest (DNG)/0.02 mg ethinylestradiol (EE) in a 24 + 4 daily dosing regimen has recently been approved in Europe.

Objective: To determine if this COC impacts coagulation and fibrinolytic factors in comparison to an immediate release COC containing 3 mg drospirenone (DRSP)/0.02 mg EE.

Method: Forty-four patients received the novel product, and forty-seven the comparator (immediate release formulation) during nine complete cycles. Coagulation and fibrinolytic parameters were evaluated: activated protein C resistance ratio, Antithrombin III (AT III), C-reactive protein, Factor VII, Factor VIII, and D-Dimer.

Results: Compared to baseline, at the end of the study both groups displayed significantly higher mean values for AT III: 1.06 mg/mL (standard deviation [SD], 95% CI, 0.98-1.15) for the DNG/EE formulation and 1.04 mg/mL (SD 95% CI, 0.96-1.12) for the comparator (p = 0.0006 and p = 0.0009, respectively). D-dimer showed a non-significant slight reduction in the DNG/EE group, from 276.62 ng/mL (SD, 95% CI, 228.92-334.26) before treatment to 243.98 ng/mL (SD, 95% CI, 192.45-309.31) ng/mL after treatment. Contrarily, the comparator displayed a non-significant rise in D-dimer values from 246.46 ng/mL (SD, 95% CI, 205.44-295.66) ng/mL to 275.30 ng/mL (SD, 95% CI 219.21-345.75; p = 0.4520). All other parameters showed no significant differences before and after the treatment for both groups.

Conclusion: The COC 2 mg DNG/0.02 mg EE was not associated with any meaningful changes in the analyzed coagulation and fibrinolytic parameters indicating that a prolonged release formulation does not impact on these factors.

Clinical trial registry: EudraCT: 2019-0018-77-97.

Background: There is no strong evidence demonstrating whether or not aerobic exercise in conjunction with resistance exercise improves metabolic diabetes markers in postmenopausal women.

Objective: To evaluate the effect of aerobic exercise and resistance training on metabolic markers in postmenopausal women with type 2 diabetes mellitus (T2DM) by means of a systematic review and meta-analysis.

Methods: The searches were completed using EMBASE, MEDLINE/PubMed, Scopus and Web of Science databases. This study included non-blinded, single or double-blinded randomized control trials and postmenopausal women diagnosed with T2DM. The imposed intervention was aerobic exercise plus any training protocol to strengthen muscle groups for resistance intervention. The outcomes of interest were the blood glucose levels, insulin secretion, homeostasis model assessment-insulin resistance index (HOMA-IR) and glycated hemoglobin (HbA1c). Risk of Bias tools and GRADE were obligatory.

Results: Three studies were included (83 participants). Exercise intervention ranged between two to four days per week. Compared to the control group, in the group submitted to aerobic exercise + resistance training, no significant change was noted for HbA1c (subtotal = mean difference - 0.35 [95% CI: -0.85, 0.15], p = .17, and heterogeneity = 0%) (GRADE: very low), nevertheless, HOMA-IR index was significantly improved (subtotal = mean difference -0.52 [95% CI: -0.99, -0.05], p = .03, and heterogeneity = 0%) (GRADE: very low).

Conclusion: Despite the very low certainty found in the quality of evidences, our analysis showed that aerobic exercise along with strength exercise seems to improve some metabolic diabetes markers in postmenopausal women with T2DM. There is a need for further studies to support our preliminary findings.