Search Results (4,603)

Background: Uterine fibroids are the most common benign tumors of the female reproductive system and frequently affect women’s health-related quality of life (HRQoL). The increasing use of online surveys in clinical research raises concerns regarding the comparability and reliability of data collected through different recruitment methods. This study aimed to compare the clinical and methodological comparability of data obtained from an online survey and a clinic-based survey assessing symptom severity and HRQoL among women diagnosed with uterine fibroids. Methods: A cross-sectional observational study was conducted among 167 women with confirmed uterine fibroids. The clinic-based cohort included 82 patients recruited in a gynecological outpatient clinic, while the online cohort consisted of 85 women participating through an internet-based survey. Both cohorts were assessed using identical inclusion and exclusion criteria, the same questionnaire structure, and the validated Uterine Fibroid Symptom and Health-Related Quality of Life (UFS-QoL) instrument. Symptom severity scores and HRQoL outcomes were compared descriptively and methodologically. Results: The two independently recruited cohorts showed broadly similar distributions of several demographic characteristics and patient-reported outcomes, although important differences between the source populations should be considered when interpreting these findings. Mean symptom severity scores were 48.55 ± 21.61 in the clinic-based cohort and 46.33 ± 21.40 in the online cohort, while mean HRQoL scores were 57.23 ± 22.81 and 62.50 ± 19.32, respectively. Formal comparisons revealed no significant differences in symptom severity (p = 0.506) or overall HRQoL (p = 0.110). Among the six UFS-QoL domains, only the Concern domain differed significantly between cohorts (p = 0.005), whereas all other domains showed broadly similar distributions. Separate multivariable regression models were fitted for each cohort. Although direct comparison of the models was limited by differences in variable coding, both models identified symptom severity as the strongest independent predictor of HRQoL (β = −0.715 and β = −0.752) and showed similar overall model performance (R² = 0.595 and 0.578). Regression diagnostics confirmed normality of residuals, homoscedasticity, absence of influential outliers, and low variance inflation factors in both datasets. Conclusions: Despite differences in recruitment setting and source population, similar patterns of patient-reported HRQoL and symptom severity were observed across the two independently recruited cohorts. Similarities were observed across overall HRQoL scores, symptom severity measures, and multivariable regression models, suggesting that the relationships between symptom burden and quality of life remained consistent across recruitment methods. Although differences were identified in disease-related concerns and reproductive history, these findings did not substantially alter the overall pattern of results. Taken together, the findings demonstrate that similar patterns of patient-reported HRQoL and symptom severity were observed across two independently recruited cohorts of women with uterine fibroids. These findings support the feasibility of collecting disease-specific patient-reported outcomes within uterine fibroid-specific online communities but should not be interpreted as evidence that online and clinic-based recruitment methods generate equivalent study populations. Full article

Sex- and gender-based immune differences have often been interpreted through a male–female biological binary, overlooking how endocrine signaling dynamically shapes immune function. Gender-affirming hormone therapy (GAHT) offers a unique physiological model to disentangle the effects of sex steroids from chromosomal background and examine immune plasticity in contexts relevant to reproductive health. This hormone-informed framework proposes that estradiol and testosterone regulate immune set-points across innate, adaptive, metabolic, and mucosal compartments. Through genomic and non-genomic signaling via androgen and estrogen receptors (AR, ERα/β), these hormones drive distinct immune outcomes: testosterone dampens type I interferon responses in plasmacytoid dendritic cells and reshapes monocyte inflammatory profiles, while estradiol promotes macrophage polarization and enhances T helper1 (Th1) responses. Hormonal effects are closely coupled to cellular metabolism: androgen signaling acts as a “metabolic brake” on Th17 cells by limiting glutaminolysis, a process reinforced by epigenetic remodeling, and is reflected in shifts in the circulating metabolome, positioning metabolomics as a sensitive tool for monitoring hormone-driven immune adaptation. Regardless, hormones also reshape mucosal barriers and reproductive microbiome composition. GAHT alters vaginal and gut microbial communities and their metabolism, influencing mucosal immunity, local inflammation, and reproductive tract homeostasis, with potential implications for fertility preservation, susceptibility to reproductive tract infections, and long-term genital mucosal health. Collectively, this evidence underscores that human immunity is highly responsive to endocrine context. This review synthesizes evidence linking endocrine trajectories, tissue microenvironments, reproductive biology, and social determinants of health, aiming to advance understanding of immune plasticity and contribute to a more inclusive framework of human immune diversity. Full article

Adolescents with intellectual disabilities are often excluded from mainstream sexual reproductive health education and services. This exclusion is due to stigma and systemic barriers further increasing their vulnerability to exploitation, unintended pregnancies, and limited contraceptive access. Additionally, adolescent childbearing has been linked to an increased risk of long-term health and functional limitations. This study explored contraceptive awareness and decision-making among caregivers of adolescent learners with intellectual disabilities in selected Special Care Centres in Tshwane District Gauteng province. This exploratory, descriptive qualitative research utilised a purposive sampling method to select caregivers from five Special Care Centres to participate in focus group discussions. The sample size was 29 participants. Interviews were audio recorded and transcribed verbatim. Data were analysed using inductive thematic analysis on NVivo15 software and halted after reaching saturation. Intercoder reliability was achieved with consensus agreement among researchers. Three overarching themes, supported by two sub-themes emerged: (1) Caregivers’ understanding of contraception: (1.1) Perceived benefits and disadvantages of contraception; (1.2) Early exposure to contraceptive information. (2) Socio-economic influences on contraceptive decision-making: (2.1) Financial burden; (2.2) Preference for permanent contraceptive method. (3) Negotiating cultural expectations and practical caregiving realities: (3.1) Community acceptance of contraceptive use; (3.2) Willingness to forgo biological grandchildren. Caregivers’ awareness and decisions about contraception reflect not only their health knowledge but also the socio-economic pressures they face and the practical realities that shape choices within their communities. This study recommends disability-inclusive sexual reproductive health education that provides contextually relevant insights for strengthening community-based interventions among adolescents with intellectual disability. Full article

Youth in northern Ghana experience high rates of unintended pregnancy due to limited access to and use of sexual and reproductive healthcare (SRH) services. Peer-led interventions are effective in increasing the youth uptake of SRH services, but limited peer-led interventions have been developed for Ghana. This study explores youth (ages 15–24 years) and clinical provider perspectives on youth SRH to inform the co-design of a peer-led SRH counseling program in northern Ghana. We conducted a qualitative study using semi-structured interviews with 22 SRH providers and 27 youth. We then conducted an inductive thematic analysis and mapped themes onto the COM-B (Capability-Opportunity-Motivation-Behavior) model. Results revealed that youth capability to make informed and confident SRH decisions is constrained by a fragmented information environment. Although access to SRH services is increasing in the region, logistical and privacy barriers limit adolescents’ opportunities to engage in care. Religious and cultural norms stigmatize youth SRH care, though support for contraceptive use is growing among more educated sectors. Youth motivation to use SRH services is driven by a desire for autonomy but undermined by concerns about contraceptive side effects and anticipated stigma. This study supports the co-development of a contextually grounded peer counseling SRH intervention in northern Ghana. Full article

Background: Previous studies have explored the association between ambient ozone (O₃) exposure and gestational diabetes mellitus (GDM). However, little is known about the association of O₃ with different GDM clinical classifications—diet-controlled GDM (GDMA1) and insulin-treated GDM (GDMA2), and whether temperature modifies the associations. Methods: We conducted a retrospective cohort study including 11,491 pregnant women between 2017 and 2023 in Tianjin, China. O₃ exposure levels for each participant were assessed using the Tracking Air Pollution in China dataset. Logistic regression models were employed to analyze the associations of trimester-specific O₃ exposure with GDMA1 and GDMA2. Distributed lag nonlinear model (DLNM) was used to identify potential critical gestational weeks of O₃ exposure. Ambient temperature was categorized using the 10th and 90th percentiles to evaluate the effect modification of extreme temperatures on these associations. Results: No statistically significant association was observed in the fully adjusted trimester-specific models. In the weekly-specific DLNM analyses, we observed 5–12 weeks before pregnancy and 26–28 gestational weeks as sensitive windows where O₃ exposure was weakly associated with elevated GDMA1 risk, and 11–25 gestational weeks for GDMA2. Each 10 μg/m³ increase in O₃ during pregnancy was associated with small increases in the odds of GDMA1 (28 weeks: OR = 1.019, 95% CI: 1.002, 1.035) and GDMA2 (25 weeks: OR = 1.018, 95% CI: 1.002, 1.035). High temperatures appeared to strengthen the observed association between preconception O₃ exposure and GDMA1. Additionally, O₃ exposure during pregnancy may increase the risk of GDMA1 among women aged <35 years, preconception obesity, gestational hypertension, and family history of diabetes. Conclusions: This study suggests possible weak weekly-specific associations between O₃ exposure and GDM classifications and indicates that ambient high temperature may modify the O₃-GDM association. These findings should be interpreted cautiously and require confirmation in future studies. Full article

Background/Objectives: Adolescent pregnancy remains a global public health challenge associated with adverse outcomes for both mothers and newborns. This study aimed to use two instruments and several multivariate techniques to identify a minimal set of variables that reproduces the instrument-based classification of adolescent pregnancy risk, while remaining parsimonious with the original instruments. Methods: A cross-sectional, quantitative methodological study was conducted among Colombian schoolgirls, comprising 160 adolescents in the face-validity phase and 319 in the risk-estimation and modeling phase. The IRENE and REND instruments, originally developed to assess the risk of adolescent pregnancy, underwent cultural adaptation, face validity and content validity. Subsequently, the instruments were administered to estimate the risk. Finally, Factor Analysis and Categorical Principal Component Analysis were applied as exploratory dimensionality reduction techniques to identify the most relevant variables for retention, thereby preserving the parsimony of the original versions. Results: Overall, 80.3% of participants were classified as not at risk, while the remainder were classified as at risk by one or both instruments. The results suggest that variables such as who the adolescent lives with, the age at which the adolescent had their first complete sexual intercourse, and how the adolescent would respond to an unplanned pregnancy are factors associated with the instrument-based risk classification. Subsequently, dimensionality reduction and logistic regression analyses identified a small subset of variables that can be used to reproduce the instrument-based classification of adolescent pregnancy risk. Conclusions: The reduced set of variables reproduced the instrument-based risk classification with high internal accuracy. Because the predictors and the outcome derive from the same instruments, these findings reflect internal reproduction of the instrument classification rather than prediction of an observed pregnancy, and they require external validation. Overall, the reduced and optimized set of variables from the IRENE and REND instruments offers a parsimonious approach that reproduces the instrument-based risk classification and that may support rapid screening once validated in independent adolescent samples. The main limitations are the use of a single institution, the non-probabilistic convenience sample, and the absence of an observed pregnancy outcome. Full article

Background: Gestational anemia represents a major public health challenge in Peru, with a national prevalence ranging from 20% to 27.9%; however, the northern regions remain insufficiently studied. This study aimed to explore the multidimensional structure of clinical and sociodemographic characteristics among pregnant women with gestational anemia treated in northern Peru. Methods: A cross-sectional study was conducted among 70 pregnant women diagnosed with gestational anemia and treated at the Chicama micro-network in the La Libertad region during 2024. Sociodemographic, territorial, reproductive, and nutritional variables were obtained from medical records. Principal Component Analysis for Categorical Data (CATPCA) was applied to identify multidimensional patterns associated with anemia severity. Results: The CATPCA identified a two-dimensional structure explaining 38.47% of the total variance. Dimension 1 (sociodemographic–territorial profile; 22.55%) included health facility (−0.925), educational level (0.887), maternal age (0.878), and district of origin (−0.871). Dimension 2 (reproductive–biological profile; 15.91%) included number of previous pregnancies (0.909), interpregnancy interval (0.909), and body mass index classification (0.589). Multivariate profiles showed that mild anemia (n = 49) was predominantly associated with pregnant women younger than 20 years, lower educational attainment, and rural settings. In contrast, moderate/severe anemia (n = 21) was more frequently associated with women aged 20–35 years, secondary or higher educational attainment, and urban healthcare settings, contrary to the conventional expectation that higher educational attainment acts as a protective factor against anemia. Additionally, mild anemia was associated with multiparity and overweight/obesity, whereas moderate/severe anemia was linked to primiparity and normal BMI. Conclusions: Gestational anemia in northern Peru follows a two-dimensional pattern in which sociodemographic and territorial characteristics showed greater explanatory contribution than reproductive–biological factors. Distinct anemia severity profiles were identified, highlighting the need for context-specific prenatal care strategies and targeted public health interventions. Full article

Background/Objectives: Contemporary endometrial cancer pathology integrates histological and molecular features for risk classification. Endometrioid endometrial carcinoma (EEC) with a squamous cell carcinoma (SCC) component was historically termed adenosquamous carcinoma but later incorporated into the squamous-differentiation subtype of EEC. This reclassification left an evidence gap, and its prognostic significance remains insufficiently defined. We compared clinicopathological aggressiveness and evaluated associations of an SCC component with overall survival (OS) and lymph node (LN) involvement. Methods: We retrospectively analyzed 7590 surgically staged patients from 24 institutions (2000–2019): 7495 pure EEC and 95 EEC with SCC components. Confounding was addressed using overlap weighting (OW), inverse probability of treatment weighting targeting the average treatment effect on the treated (IPTW-ATT), and 1:4 propensity score matching (PSM), each with doubly robust Cox regression. Survival machine-learning models with SHapley Additive exPlanations (SHAP) assessed histological subtype contribution. LN involvement was assessed by OW/IPTW-ATT-weighted logistic regression. Results: EEC with SCC component had higher grade, deeper myometrial invasion, more advanced stage, and worse unadjusted OS (hazard ratio [HR] 7.04; 95% confidence interval [CI] 3.50–14.16; p < 0.001). After adjustment, the OS disadvantage persisted: OW-adjusted HR 3.05 (95% CI, 1.36–6.85; p = 0.007), IPTW-ATT-adjusted HR 3.26 (95% CI, 1.51–7.01; p = 0.003), and PSM-adjusted HR 3.30 (95% CI, 1.24–8.77; p = 0.017). XGBoost-Survival showed stable discrimination (test C-index 0.797 ± 0.057; 5-year AUC 0.787 ± 0.065), and SHAP supported histological subtype as a prominent risk-associated contributor after class-imbalance correction. In contrast, adjusted LN involvement was not increased (OW odds ratio [OR] 1.000, 95% CI 0.505–1.979; p = 1.000; IPTW-ATT OR 1.035, 95% CI 0.527–2.035; p = 0.920). Conclusions: EEC with SCC component was associated with worse OS after adjustment, without an adjusted increase in LN involvement. These findings support explicit morphologic reporting and future validation incorporating systematically recorded molecular testing when available. Full article

Early-onset colorectal cancer is increasing, making reproductive health an increasingly relevant survivorship issue. While immune checkpoint inhibitors have altered the management of deficient mismatch repair/microsatellite instability-high (dMMR/MSI-H) colorectal cancer, their implications for reproductive-age women remain insufficiently defined. We performed a focused narrative review, structured in line with the SANRA framework, to clarify this specific clinical domain. Immunotherapy may reshape female oncofertility counseling through two distinct mechanisms: direct reproductive uncertainty, including established endocrine toxicities and hypothesized, but currently unproven, direct gonadal effects; and indirect pathway-modifying effects, such as the potential avoidance of pelvic radiotherapy or radical surgery in selected patients with locally advanced dMMR/MSI-H rectal cancer. Anatomical organ preservation should not be automatically equated with functional fertility preservation. The key clinical message is that reproductive counseling should not be restricted to historically gonadotoxic chemotherapy. Instead, early multidisciplinary guidance should explicitly distinguish CRC-specific evidence from extrapolated or theoretical concerns, integrate fertility preservation strategies when clinically feasible, and address pelvic and sexual health, contraception, washout, endocrine follow-up, and future pregnancy planning. Until prospective CRC-specific reproductive data become available, immunotherapy should not be presented as either reproductively neutral or fertility-preserving. Full article

Background: The Eastern Cape Province carries the second-highest antenatal HIV prevalence nationally (32.9%), yet province-level longitudinal data on HIV incidence among pregnant and breastfeeding women (PBW) remain limited. This study examined trends in HIV incidence, HIV prevalence, mother-to-child transmission (MTCT), and antiretroviral therapy (ART) coverage among PBW in the Eastern Cape from 2000 to 2023. Methods: A quantitative ecological design was employed using secondary analysis of modelled estimates from the Thembisa Provincial HIV Model, version 4.8. Annual HIV incidence in PBW, HIV prevalence in pregnant women (overall and by five-year maternal age group), MTCT rate, new MTCT cases, and ART coverage were extracted with 95% confidence intervals (CIs) for the Eastern Cape, 2000–2023. Descriptive analysis characterised temporal trends at seven reference years, and formal trend significance was assessed using the Mann–Kendall test and log-linear regression. Results: HIV incidence in PBW declined from 3.8% (95% CI: 3.7–3.9) in 2000 to 1.8% (95% CI: 1.3–2.4) in 2023, a relative reduction of approximately 53%. ART coverage rose from 0% to 71.6%, coinciding with an 88% reduction in MTCT rate from 31.3% to 3.6%. By 2023, the MTCT rate had crossed below the World Health Organization 5% elimination threshold. HIV prevalence among pregnant women remained high at 25.0% despite declining incidence. The age distribution of HIV burden shifted markedly toward older maternal cohorts: prevalence among women aged 40–49 years increased from 9.9% in 2000 to 46.5% in 2023, while prevalence in the 15–24 age group declined substantially. New MTCT cases fell from 9990 in 2000 to 1236 in 2023. Conclusions: Declining HIV incidence in PBW coincided with substantial ART scale-up in the Eastern Cape, while HIV prevalence among pregnant women remained persistently high, a divergence that reflects the accumulating, ART-sustained pool of women living with HIV who survive into older reproductive age rather than a reversal of programmatic progress; this divergence between declining incidence and persistent, ageing prevalence is the central epidemiological finding of this study. Targeted interventions, including age-responsive antenatal protocols and strengthened PMTCT retention, alongside more careful consideration of expanded pre-exposure prophylaxis (PrEP) access, are needed to achieve elimination of mother-to-child transmission. Full article

The first trimester (FT) of pregnancy is characterized by rapid placental growth and differentiation, rendering this period sensitive to maternal metabolic influences. Maternal obesity is associated with chronic low-grade inflammation and altered redox homeostasis with implications in later cardiometabolic risk in offspring, yet its impact on early placental oxidative stress remains unclear. Here, we investigated whether maternal overweight and obesity are associated with oxidative lipid and protein damage and altered expression of antioxidant enzymes and stress signaling pathways. Placental tissue from lean (BMI < 25 kg/m²), overweight (BMI ≥ 25 kg/m²) and obese (BMI ≥ 30 kg/m²) non-smoking women (5–12 weeks’ gestation) was analyzed. Oxidative damage was assessed by immunoblotting for 4-hydroxynonenal and 3-nitrotyrosine, and antioxidant and stress-related transcripts were quantified using targeted mRNA arrays. Explants were exposed to increased oxygen tension or TNF-α to evaluate transcriptional responsiveness. No differences in oxidative lipid or protein modifications were detected between groups. In contrast, overweight and obesity were associated with reduced expression of selected antioxidant enzymes and transcriptional remodeling of MAPK-related genes. These changes correlated with IL6 expression but not with oxidative damage markers. Collectively, maternal overweight and obesity are linked to inflammation-associated transcriptional adaptation in FT placenta without detectable oxidative injury. Full article

The simultaneous occurrence of amphetamine (AMP) and other illicit drugs, such as 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyamphetamine (MDA), butylone (BTL), and 3,4-dimethylmethcathinone (3,4-DMMC), in wastewater and aquatic ecosystems has been frequently reported. These psychoactive substances share similar modes of action and pose a significant threat to freshwater organisms and human health due to their neurotoxicity and physiological harmful effects. The individual adverse effects of AMP and illicit drugs on non-target aquatic organisms have been demonstrated; however, the combined effects of these drugs have been considerably less explored. This study investigated the ecotoxicity of a mixture of these substances at an environmentally relevant concentration (0.1 μg L⁻¹) and at a 10-fold higher concentration (1.0 μg L⁻¹), using the freshwater microcrustacean water flea (Daphnia magna) exposed for 14 days. Several endpoints were evaluated. No significant changes were observed in swimming behavior or reproduction parameters, but some changes were noted for morphophysiological and biochemical endpoints. A significant increase was observed in the organisms’ heart rate and in catalase activity. Overall, the mixture did not induce significant ecotoxicological effects under the tested conditions. Nevertheless, the presence of other contaminants and longer exposure periods in natural environments may increase the ecological risks associated with these psychoactive substances. Full article

Kazakhstan ruminant genomics is expanding through targeted diagnostic testing, SNP-array studies, whole-genome sequencing, runs of homozygosity, candidate-gene analyses, transcriptomic studies and pathogen molecular diagnostics. However, these evidence types differ substantially in their relevance for breeding decisions. This structured narrative review evaluates molecular evidence for inherited disorders, deleterious alleles, disease-resistance loci, reproductive genes and genomic-health indicators in Kazakhstan cattle, sheep and goats. We define actionable evidence as evidence that can directly inform breeding management because it involves a validated pathogenic variant, risk variant or fertility haplotype detected or excluded in breeding-relevant animals or germplasm. Under this definition, cattle currently provide the strongest immediately actionable evidence, mainly because targeted studies have screened validated defects and fertility-related loci in artificial-insemination bulls, imported germplasm or breed-relevant populations. Evidence includes Kazakhstan-associated screening for BLAD (Bovine leukocyte adhesion deficiency), DUMPS (Deficiency of uridine monophosphate synthase), hypotrichosis, OH1-associated achromatopsia, fertility haplotypes and several beef- or dairy-breed recessive defects. In sheep, evidence is broader but less directly actionable, consisting mainly of prion protein gene preparedness, MHC (Major histocompatibility complex)-related immune hypotheses, reproductive candidate loci, runs of homozygosity, genome wide associated data and pathogen-exposure context. In goats, current evidence is mostly population-genomic and adaptation-oriented, while hereditary-disease surveillance and phenotype-linked resistance studies remain sparse. We propose an author-defined staged genomic-health framework that separates validated carrier-screening evidence from candidate genomic signals and international evidence requiring local validation. Priority actions include carrier-aware management of high-impact cattle germplasm, representative prion protein gene and runs of homozygosity baselines in small ruminants, phenotype-first surveillance, biobanking and national genotype–phenotype databases. Full article

Purpose: Severe spermatogenic impairment, including azoospermia, oligozoospermia, asthenozoospermia, and teratozoospermia, represents a major reproductive health concern, yet no validated screening tool exists for early risk stratification in prepubertal boys. We aimed to develop a five-item evidence-based questionnaire and conduct preliminary clinical evaluation to identify prepubertal boys at risk of developing severe spermatogenic impairment. Methods: This retrospective observational study analyzed medical records of 200 male patients aged 18 years who underwent their first semen analysis between 2014 and 2024 at the University of Catania, Italy. Prepubertal risk factor profiles were retrospectively reconstructed by two independent andrologists blinded to semen analysis results across five evidence-based domains: genetic anomalies (0–5 points), cryptorchidism (0–6 points), gonadotoxic cancer therapy (0–7 points), varicocele (0–4 points), and hormonal/endocrine disorders (0–5 points), yielding a total score of 0–27 points. Scoring weights were based on literature evidence and expert consensus. Reliability was assessed using Cronbach’s α (n = 200), test–retest intraclass correlation coefficient (ICC, n = 30, 2-week interval), and inter-rater Cohen’s κ (n = 50). Receiver operating characteristic (ROC) curve analysis identified optimal cut-offs. Semen analysis outcomes were classified according to WHO 2021 criteria. Results: The newly developed questionnaire demonstrated acceptable internal consistency (Cronbach’s α = 0.81), good test–retest reliability (ICC = 0.89, 95% CI 0.84–0.93), and excellent inter-rater reliability (Cohen’s κ = 0.87). Mean questionnaire scores showed a direct progressive correlation with severity of spermatogenic impairment. The highest scores were observed in azoospermia (mean 14), complete asthenozoospermia (13), and complete teratozoospermia (13). ROC curve analysis identified four clinically meaningful cut-offs: ≥6 (AUC = 0.85, 95% CI 0.79–0.91, Youden index = 0.81), ≥7 (AUC = 0.88, 95% CI 0.83–0.93, Youden = 0.80), ≥11 (AUC = 0.91, 95% CI 0.87–0.95, Youden = 0.79), and ≥13 (AUC = 0.94, 95% CI 0.90–0.97, Youden = 0.87). Four risk strata were defined: LOW (0–6), MEDIUM (7–10), HIGH (11–12), and VERY HIGH (≥13 points). Conclusions: The five-item prepubertal risk questionnaire undergoing preliminary clinical evaluation demonstrates strong correlation with subsequent spermatogenic outcomes, enabling early identification of at-risk boys. The four-tier stratification system provides actionable guidance for clinical management and fertility preservation counseling. However, this cohort was enriched for pathological outcomes due to exclusion of subjects with no known risk factors; cut-offs may not apply to general population screening. Multicenter validation studies in unselected populations are warranted. Full article

Endometriosis is a chronic estrogen-dependent condition affecting women of reproductive age and commonly presents with dysmenorrhea, chronic pelvic pain, dyspareunia, and infertility. In a substantial proportion of patients, pain persists despite first-line hormonal treatment, making alternative pharmacologic strategies necessary. GnRH agonists and antagonists act primarily by suppressing ovarian estrogen production and thereby reduce an important hormonal driver of disease activity. Although both classes are effective for pain relief, they differ in onset of action, reversibility, tolerability, and suitability for prolonged use. This narrative review summarizes the current evidence on GnRH-based therapies for endometriosis-associated pain, with particular attention to biological rationale, clinical efficacy, safety, and the role of add-back therapy. Overall, both agonists and antagonists appear to provide clinically significant symptom improvement, especially in women who do not respond adequately to oral contraceptives or progestins. Their clinical use, however, is limited by hypoestrogenic adverse effects such as vasomotor symptoms and bone mineral density loss, which often require monitoring and adjunctive add-back therapy. Oral GnRH antagonists may offer practical advantages in selected patients through rapid action, the absence of a flare effect, and dose-adjustable hormonal suppression, although treatment choice must also consider long-term safety, cost, access, and individual patient characteristics. In summary, GnRH analogues remain useful second-line options, but treatment should be individualized according to symptom severity, previous treatment response, reproductive goals, tolerability, bone health, cost, and availability. Full article