BACKGROUND: Approximately one in eight women aged 15-49 years seek medical care for infertility. Oxidative stress is a critical factor in female infertility. The Composite Dietary Antioxidant Index (CDAI) is a novel metr...BACKGROUND: Approximately one in eight women aged 15-49 years seek medical care for infertility. Oxidative stress is a critical factor in female infertility. The Composite Dietary Antioxidant Index (CDAI) is a novel metric for assessing overall dietary antioxidant capacity. This study aimed to investigate the association between CDAI, its individual components, and infertility risk. METHODS: A cross-sectional analysis was conducted using 2013-2020 National Health and Nutrition Examination Survey (NHANES) data. The CDAI was calculated based on dietary intake of vitamins A, C, E, zinc, selenium, and carotenoids. Weighted logistic regression models were used to assess associations between CDAI (and its components) and infertility. Restricted cubic spline (RCS) analysis was applied to evaluate potential non-linear relationships. Subgroup and sensitivity analyses were performed to test the robustness of the findings. RESULTS: A negative association between CDAI and infertility was observed (OR = 0.95; 95%CI [0.91-0.99], = 0.014). Stratification by CDAI quartiles showed a consistent decreasing trend in infertility risk (Q4 vs. Q1: OR = 0.52; 95%CI [0.33-0.84], for trend = 0.003). RCS analysis indicated a linear negative relationship between CDAI and infertility ( for non-linear = 0.278). Higher carotenoid intake was inversely associated with infertility risk, whereas intakes of vitamin A and C showed V-shaped, non-linear associations with infertility ( for non-linear < 0.05). These findings remained stable across subgroup and sensitivity analyses. CONCLUSION: CDAI is linearly and inversely associated with the prevalence of female infertility, highlighting the potential importance of antioxidant-rich diets in promoting women's reproductive health.
OBJECTIVE: To assess the potential therapeutic effects of glucose-dependent insulinotropic peptide (GIP) on hyperandrogenism. METHODS: Polycystic ovary syndrome (PCOS) mouse models induced by dehydroepiandrosterone (DHEA...OBJECTIVE: To assess the potential therapeutic effects of glucose-dependent insulinotropic peptide (GIP) on hyperandrogenism. METHODS: Polycystic ovary syndrome (PCOS) mouse models induced by dehydroepiandrosterone (DHEA) were established to evaluate the impact of GIP on androgen synthesis . Additionally, NCI-H295R cells were utilized for studies to investigate the effects of GIP on androgen synthesis using various techniques, including CCK8, flow cytometry, RT‒qPCR, WB, ELISA, and RNA sequencing (RNA-seq). RESULTS: Administration of GIP significantly reduced testosterone secretion in a DHEA-induced PCOS mouse model. Consistent with these findings, GIP treatment decreased testosterone release and downregulated the expression of GIP receptor (GIPR), steroidogenic acute regulatory protein (STAR), cytochrome P450 family 11 subfamily A member 1 (CYP11A1), and cytochrome P450 family 17 subfamily A member 1 (CYP17A1) in NCI-H295R cells. Notably, RNA-seq revealed that was the most significantly downregulated gene upon GIP stimulation. Knockdown of in NCI-H295R cells further decreased testosterone levels in the culture medium, confirming the inhibitory effect of GIP on androgen synthesis. CONCLUSIONS: Our study demonstrated that the administration of GIP reduces androgen synthesis in PCOS mouse models and at the cellular level, suggesting its potential as a novel therapeutic target for managing 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...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.
Polycystic ovarian syndrome (PCOS) is a major endocrine disorder that affects women of reproductive age. This study evaluated global disease burden trends (1990-2021) and projected future trajectories to 2050 to inform p...Polycystic ovarian syndrome (PCOS) is a major endocrine disorder that affects women of reproductive age. This study evaluated global disease burden trends (1990-2021) and projected future trajectories to 2050 to inform public health strategies. Using Global Burden of Disease 2021 data, we analyzed PCOS prevalence, incidence, and disability-adjusted life years (DALYs) and correlations with the sociodemographic index (SDI). Trends were assessed the estimated annual percentage change, and future burden was projected using a Bayesian age-period-cohort model. From 1990 to 2021, global PCOS prevalence among reproductive - age women rose 89.55% to 69.47 million. Incident cases increased 55.90% to 2.30 million, and DALYs surged 87.70% to 607.76 thousand. Regions with rising SDI, particularly South, East, and Southeast Asia, saw the steepest increases in age-standardized rates. The incidence rose most sharply in the 10-19 age group, while the prevalence and DALYs peaked in the 15-49 age group. Projections indicate a continued increase in PCOS burden until 2050. PCOS poses a serious public health challenge, particularly in the medium-SDI regions. This escalating burden underscores the need for targeted interventions, particularly for adolescents and young women, to mitigate its long-term health impacts. Policymakers and clinicians must prioritize PCOS management to address its increasing global prevalence and associated disabilities.
PURPOSE: Pre-eclampsia (PE) is a pregnancy-related disorder for which reliable predictive methods remain limited. METHODS: Data were collected between June 2018 and December 2022. Statistical analyses including Chi-squar...PURPOSE: Pre-eclampsia (PE) is a pregnancy-related disorder for which reliable predictive methods remain limited. METHODS: Data were collected between June 2018 and December 2022. Statistical analyses including Chi-square tests, multivariate logistic regression, and LASSO regression were applied to identify risk factors. RESULTS: A total of 602 pregnant women were included, with 176 diagnosed with PE and 426 without PE. Significant differences between the PE and control groups were observed for high-risk pregnancy history (HRPH), mean arterial pressure (MAP), preeclampsia monitoring system (MP), uterine artery pulsatility index (UtA-PI), placental growth factor (PLGF), thyroid-stimulating hormone (TSH), and 25-hydroxyvitamin D (25-OH). Multivariate logistic regression showed that low 25-OH (OR = 10.24, < 0.001), elevated TSH (OR = 5.13, < 0.001), HRPH (OR = 2.21, = 0.03), high-risk MP (OR = 1.83, = 0.03), UtA-PI > 2.25 (OR = 2.95, < 0.001), and low PLGF (OR = 2.67, < 0.001) were significantly associated with PE, while high MAP showed a non-significant trend (OR = 3.06, = 0.06). ROC analysis indicated that 25-OH had the highest diagnostic efficiency (AUC = 0.719), MAP the lowest (AUC = 0.601), and the combination of 25-OH, TSH, MP, and PLGF achieved the best performance (AUC = 0.843). CONCLUSION: The combination of HRPH, MAP, PLGF, TSH, and 25-OH demonstrated strong predictive power for PE, providing valuable guidance for the prevention and management of PE in clinical practice.
Recent publications have suggested that a novel prolonged-release formulation of ethinylestradiol (EE) 20 µg and dienogest (DNG) 2 mg offers improved bleeding profiles and minimal impact on coagulation. These conclusions...Recent publications have suggested that a novel prolonged-release formulation of ethinylestradiol (EE) 20 µg and dienogest (DNG) 2 mg offers improved bleeding profiles and minimal impact on coagulation. These conclusions, however, are based on incomplete safety assessments and potentially misleading pharmacokinetic assumptions. This critical appraisal highlights several concerns: (1) discrepancies between published and regulatory data on bleeding/spotting rates compared to established EE/DRSP combinations; (2) inappropriate reliance on clotting-time-based activated protein C resistance (APCr) assays that fail to detect contraceptive-induced hypercoagulability; and (3) a strikingly high incidence of venous thromboembolism (VTE) reported in clinical trials of prolonged-release EE/DNG, significantly exceeding rates associated with both traditional EE-based and newer body-identical estrogen-containing contraceptives. Furthermore, these VTE cases are not transparently discussed in the peer-reviewed literature, raising ethical concerns about selective reporting. The pharmacokinetic profile of this formulation does not appear to mitigate estrogenic hepatic effects in a clinically meaningful way. Robust evaluation using validated thrombin generation assays such as the endogenous thrombin potential (ETP)-based APCr test, alongside independent post-marketing studies, is essential before asserting a neutral or favorable safety profile. Until then, claims regarding improved safety remain unsubstantiated.
OBJECTIVE: Is there an association between blastocyst expansion grade and early serum -hCG levels in pregnancies after single euploid embryo transfer? METHODS: This retrospective cohort study included 8394 SEETs performe...OBJECTIVE: Is there an association between blastocyst expansion grade and early serum -hCG levels in pregnancies after single euploid embryo transfer? METHODS: This retrospective cohort study included 8394 SEETs performed at a single center. Blastocysts were categorized as CHBs (= 1677) or PHBs (= 4612) based on their expansion grade. Serum -hCG levels were measured on days 9 and 11 post-transfer. A multivariate logistic regression model adjusted for confounders, including maternal age, ovarian reserve, embryo morphology, year of treatment, and day of biopsy. UNLABELLED: On day 9 post-transfer, the median -hCG level was significantly lower in CHBs (118 mIU/mL, IQR = 129.2) compared to PHBs (133 mIU/mL, IQR = 129.8; < 0.0001). The difference persisted on day 11 post-transfer (CHBs: 290.2 mIU/mL, IQR = 357 vs. PHBs: 327.3 mIU/mL, IQR 358.6; = 0.018). In multivariate regression, CHB status remained significantly associated with lower -hCG on day 9 post-transfer (aOR = 0.998, 95% CI: 0.997-0.999), but not on day 11 post-transfer (aOR = 0.999, 95% CI: 0.999-1.0002). CONCLUSIONS: Completely hatched blastocysts (CHBs) with an expansion grade 6 were associated with lower early serum -hCG levels compared to partially hatched blastocysts (PHBs) with expansion grades 4 and 5. Incorporating expansion grade into prediction models could enhance decision support tools for IVF patients.
OBJECTIVE: Congenital hypogonadotropic hypogonadism (CHH) is a rare condition characterized by incomplete pubertal development, infertility, and gonadotropin-releasing hormone deficiency, associated with mutations in mor...OBJECTIVE: Congenital hypogonadotropic hypogonadism (CHH) is a rare condition characterized by incomplete pubertal development, infertility, and gonadotropin-releasing hormone deficiency, associated with mutations in more than 50 genes. We aimed to conduct an etiological analysis of a CHH Chinese family and summarize the clinical presentations and genetic changes of reported similar cases. METHODS: Whole-exome sequencing (WES) was performed to identify the molecular cause in the proband. In silico tools were employed to analyze the pathogenicity of the variants. Reported cases with similar clinical features and associated genes were summarized by searching through PubMed/MEDLINE using keywords 'FGFR1,' 'CHH,' and 'Kallmann syndrome (KS).' RESULTS: Genetic analysis revealed a novel likely pathogenic deletion mutation in the FGFR1 gene (NM_023110.3: c.263_264del (Val88Alafs*22)) in a Chinese family exhibiting micropenis and underdeveloped testes. A total of 38 cases with CHH or KS have been previously reported. CONCLUSION: This study identified a novel FGFR1 deletion variant responsible for CHH, expanding the known mutational spectrum of FGFR1. Typical manifestations include delayed puberty and diverse presentations. The genotype-phenotype correlation in CHH remains unclear and may involve oligogenic effects and epigenetic regulation.
BACKGROUND: Women during hormonal transitional phases present an increase in mood disturbances. Recently, purified and specific cytoplasmic pollen extract (PureCyTonin®), a natural non-hormonal alternative, has proven to...BACKGROUND: Women during hormonal transitional phases present an increase in mood disturbances. Recently, purified and specific cytoplasmic pollen extract (PureCyTonin®), a natural non-hormonal alternative, has proven to be effective to treat symptoms during perimenopause, and menopause especially vasomotor ones. However, its effects on mood disturbances still need further study. OBJECTIVE: To investigate the potential effects of the pollen extract on dopaminergic and GABAergic systems in order to be proposed as an alternative to treat symptomatic midlife women and other brain-related symptoms. METHOD: experiments were performed to evaluate the effects of pollen extract on dopamine and GABA uptake, as well as GABA and dopamine D receptor binding. RESULTS: Pollen extract inhibited both dopamine and GABA uptake in a concentration-dependent manner (mean IC₅₀ = 79.5 µg/mL and 137 µg/mL, respectively). It also displaced [³H]-muscimol from GABA receptors, suggesting potential allosteric modulation. Contrary to this, pollen extract showed moderate affinity for D receptors (≥1000 µg/mL). These mechanisms might enhance neurotransmitter tone in hormone-sensitive brain regions. CONCLUSION: Purified and specific pollen extract modulates dopaminergic and GABAergic systems and help restore neurochemical balance across hormonal transitions, supporting its non-hormonal beneficial role in managing mood, sleep, and somatic symptoms with a safety profile. There is a need for further research in this regard in the clinical setting.
PURPOSE: To investigate the association between vitamin D receptor (VDR) gene polymorphisms and sub-clinical hypothyroidism (SCH) risk in polycystic ovary syndrome (PCOS) patients. METHODS: Forty-four PCOS patients and 2...PURPOSE: To investigate the association between vitamin D receptor (VDR) gene polymorphisms and sub-clinical hypothyroidism (SCH) risk in polycystic ovary syndrome (PCOS) patients. METHODS: Forty-four PCOS patients and 24 controls were enrolled. VDR gene sequences, lipid profiles, and thyroid function were analyzed, with stratification by SCH status for group comparisons. RESULTS: PCOS patients showed significant differences in fasting glucose, triglycerides, and BMI vs. controls. SCH patients exhibited distinct Apa I genotypes (< 0.05), with the AC genotype rate (76.47%) significantly higher in PCOS + SCH vs. other groups. Unadjusted/adjusted ORs for SCH patients with the AC genotype were 4.2 (95% CI 1.40-13.10), 5.01 (95% CI 1.53-16.38), and 6.25 (95% CI 1.69-23.09). No other polymorphisms were significant. CONCLUSION: This study revealed that the VDR Apa I genotype (AC as a distinct risk factor) was associated with SCH in PCOS patients, suggesting new genetic insights.
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 ana...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 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 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.
Gestational diabetes mellitus (GDM) is a common pregnancy complication with rising incidence and adverse maternal-fetal outcomes. Genetic polymorphisms in folate metabolism genes may influence GDM susceptibility through...Gestational diabetes mellitus (GDM) is a common pregnancy complication with rising incidence and adverse maternal-fetal outcomes. Genetic polymorphisms in folate metabolism genes may influence GDM susceptibility through homocysteine pathway alterations. To investigate the associations between MTHFR (C677T, A1298C) and MTRR (A66G) polymorphisms and GDM risk, including gene‒gene interactions, in Chinese Han pregnant women, this retrospective cohort study analyzed 1312 Chinese Han pregnant women. The MTHFR C677T, A1298C, and MTRR A66G polymorphisms were genotyped using allele-specific PCR. Polymorphism-GDM associations were assessed using logistic regression, adjusting for maternal age, prepregnancy BMI, and folate intake. Gene‒gene interactions were evaluated using multiplicative interaction models. After confounder adjustment, the MTHFR 677TT genotype was associated with GDM (OR 1.89, 95% CI 1.24-2.93) compared to wild-type. The MTRR 66AG and 66GG genotypes were associated with GDM, with ORs of 2.73 (95% CI: 1.93-3.89) and 3.10 (95% CI: 1.72-5.41), respectively. Significant gene‒gene interactions were observed between MTHFR C677T & A1298C (OR 2.22, 95% CI 1.25-4.23 for TT/AA combination) and MTHFR C677T & MTRR A66G (OR 6.06, 95% CI 3.48-14.10 for TT/AG combination), indicating synergistic effects that surpass the expected multiplicative combination of individual polymorphism effects. MTHFR C677T and MTRR A66G polymorphisms independently and interactively increase GDM odds in Chinese Han women, enabling personalized risk prediction and targeted prevention.
In a society whose needs are constantly changing, family planning plays a central role for women, men, and sustainable development. This comprehensive review and position statement summarises the proceedings of a meeting...In a society whose needs are constantly changing, family planning plays a central role for women, men, and sustainable development. This comprehensive review and position statement summarises the proceedings of a meeting on contraception held in Rome in March 2024, supported by major scientific societies in the field. The aim is to inform the medical community about current medical and ethical issues of contraception use. First, the review addresses the complex ethical, religious, and social dimensions of contraceptive use and access; second, it provides a comprehensive analysis of traditional and modern contraceptive methods, discussing their safety and effectiveness; third, it examines current knowledge about male hormonal contraception. When prescribing a contraceptive method, medical indications or contraindications must be integrated to women's religious beliefs, the geopolitical context in which they live, the risk of violence, their need for self-determination and their right to make decisions for themselves. If a partner is involved, the couple's dynamics and shared needs must be considered. Healthcare providers are responsible for providing them with all the information they need to make informed choices, while ensuring individual autonomy. This position statement provides recommendations on how to guide contraceptive choice and identifies knowledge gaps about contraception today.
This study assessed thyroid hormone sensitivity indices (THSI) and their impact on insulin resistance (IR) and dyslipidemia risk in euthyroid individuals with polycystic ovary syndrome (PCOS).A retrospective analysis of...This study assessed thyroid hormone sensitivity indices (THSI) and their impact on insulin resistance (IR) and dyslipidemia risk in euthyroid individuals with polycystic ovary syndrome (PCOS).A retrospective analysis of 226 PCOS patients and 189 healthy euthyroid controls was conducted. Demographic, metabolic, and thyroid function data were collected. Spearman correlation was utilized to assess relationships with THSI and metabolic parameters. The risk of IR and dyslipidemia in relation to THSI was assessed through logistic regression analysis. PCOS patients demonstrated significantly elevated levels of certain THSI, including the FT3/FT4 ratio and TFQI. The risk of IR was found to be increased in relation to higher quartiles of TSHI, TT3RI, TT4RI, TFQI, and TFQI. When controlled for age, BMI, and dyslipidemia, the TFQI group exhibited a threefold higher risk of IR relative to the TFQI group (OR = 3.00; 95% CI: 1.04, 8.64). The elevated risk of dyslipidemia was linked to higher quartiles of TFQI (OR = 3.04; 95% CI: 1.13, 8.19). PCOS individuals with IR or dyslipidemia exhibit impaired central thyroid hormone sensitivity. Furthermore, a heightened susceptibility of IR and dyslipidemia is strongly correlated with impaired central thyroid hormone sensitivity among PCOS individuals.
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 influ...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; = 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, = 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.