Despite data showing half of active-duty servicewomen use hormonal contraception, its impact on physical performance during military training remains unclear. This study examined differences in general and military-specific physical performance and bone health changes based on hormonal contraceptive use. 185 female Marine Officer Candidates (MOCs) were grouped by self-reported menstrual/hormonal contraceptive status. Questionnaires, countermovement jumps (CMJ), isometric mid-thigh pull (IMTP), physical fitness tests (PFT), peripheral Quantitative Computed Tomography (pQCT; 4%, 38%, 66% tibia length), and bone biomarkers were assessed at the start and end of the 10-week program. A combat fitness test (CFT) was completed during training. Mixed ANOVAs (group*time) assessed training responses. Among 104 MOCs not using hormonal contraception (Non-Users; age=25[IQR; 22, 27], BMI=23.98±1.98) and 81 MOCs using hormonal contraception (Users; age=24[IQR; 22,26], BMI=23.97±2.19), Users showed no change in CMJ reactive strength index, while Non-Users decreased (interaction p=0.042; Non-Users Δ= -0.03, p<0.001). CMJ jump height was lower in Users than Non-Users (mean difference=-0.02m, p=0.031). CMJ performance decreased overall (all p<0.001); braking and propulsive metrics increased (p≤0.005). PFT total points improved (Δ=6.05 points; p<0.001); total volumetric bone mineral density increased (4% site, Δ=1.37±0.62 mg/ cm3;p=0.029), cortical density decreased (38% site: Δ=-3.04±1.45 mg/ cm3, p=0.038, 66% site: Δ=-2.91±1.35 mg/ cm3, p=0.033); bone formation markers (P1NP: Δ=9.40±1.91 μg/ L; OC Δ=3.42±0.74 ng/ mL; both p<0.001) increased. CFT scores were similar between groups (p≥0.304). Among Non-Users, self-reported menstrual cycle irregularity increased. Users demonstrated minor differences in neuromuscular performance/fatigue, but small in effect. Hormonal contraception use was not meaningfully associated with military outcomes.

Combined oral contraceptives (COCs) have undergone continuous pharmacological evolution since their introduction in the 1960s. The replacement of synthetic ethinyl estradiol (EE) with natural estrogens - estradiol (E2), estradiol valerate (E2V), and estetrol (E4) - represents a significant advancement in improving the tolerability, safety, and acceptability of hormonal contraception.

Background/Objectives: Gallbladder emptying is primarily regulated by postprandial cholecystokinin release. In proteinuric glomerular diseases, renal loss of peptide hormones, hormone-binding proteins, or related regulatory proteins may affect biliary motility. However, gallbladder function has not been adequately investigated in individuals with proteinuric glomerular disease. This study evaluated the association between proteinuria and gallbladder emptying in patients with preserved kidney function and biopsy-proven glomerular disease. Methods: This single-center ultrasonographic case-control study with prospective participant enrollment and data collection included 106 participants: 52 patients with biopsy-proven proteinuric glomerular disease and 54 healthy controls without proteinuria. The proteinuric patient group consisted of individuals diagnosed with primary glomerulonephritis or amyloid A (AA) amyloidosis. Acute kidney injury, estimated glomerular filtration rate <60 mL/min/1.73 m[2], cholelithiasis, liver disease, diabetes mellitus, previous upper gastrointestinal surgery, pregnancy, oral contraceptive use, and recent rapid weight loss were considered exclusion criteria. After an overnight fast of at least 8 h, fasting gallbladder volume was measured by ultrasonography and recorded as baseline volume (V0). Gallbladder volume was measured again 45 min after stimulation with a standardized 40 g chocolate meal and recorded as postprandial volume (V45). Gallbladder volume was calculated using the ellipsoid formula, and gallbladder ejection fraction (GBEF) was calculated as [(V0 - V45)/V0] × 100. GBEF <40% was used as a predefined clinical threshold for impaired gallbladder emptying. In the primary analysis, the association between proteinuria status and GBEF as a continuous outcome was evaluated using a multivariable linear regression model adjusted for age, sex, body mass index, and family history of gallstones. Impaired gallbladder emptying, operationally defined as GBEF <40% for the supportive secondary binary outcome, was examined using multivariable logistic regression model adjusted for the same covariates. Results: Compared with controls, proteinuric patients had significantly higher postprandial gallbladder volume at 45 min: 15,614.04 ± 9148.35 mm[3] versus 10,346.89 ± 5254.17 mm[3] (p = 0.0003). GBEF was significantly lower in the proteinuria group than in healthy controls: 41.76% ± 19.64 versus 53.10% ± 20.22; mean difference, -11.34 percentage points (95% confidence interval, -19.02 to -3.66; p = 0.0042). Impaired gallbladder emptying was more frequently observed in the proteinuria group: 48.1% versus 27.8% (p = 0.031). In unadjusted analysis, the presence of proteinuria was associated with a 2.41-fold increase in the odds of impaired gallbladder emptying. This association remained statistically significant after adjustment for age, sex, and body mass index: adjusted odds ratio, 2.95 (95% confidence interval, 1.17-7.47; p = 0.022). Among proteinuric patients, GBEF did not differ significantly according to nephrotic versus non-nephrotic proteinuria, serum albumin level, serum total protein level, or histopathological diagnostic subgroup. Conclusions: In individuals with preserved kidney function and biopsy-proven glomerular disease, proteinuria was associated with impaired postprandial gallbladder emptying, and this association persisted after multivariable adjustment. These findings suggest that gallbladder dysmotility may represent a potentially relevant functional feature of proteinuric kidney disease; however, its biological basis and clinical consequences remain to be established. Prospective studies incorporating cholecystokinin measurements, duration of proteinuria, and longitudinal clinical follow-up are needed to clarify these issues.

The most common symptom of endometriosis is pain. The pathogenesis of endometriosis-associated pain remains unclear. In this review, we illustrate the pathogenesis of endometriosis-associated pain and the mechanisms of dienogest acts on endometriosis-associated pain, as well as therapeutic applications targeting these processes, by searching the literature in PubMed and Web of Science until May 2026. Abnormal distribution of nerve fibers, central sensitization, imbalance of inflammatory and immune environment, and hypoxic stress contribute to the generation of endometriosis-associated pain. Dienogest, as a fourth-generation selective progesterone receptor agonist, plays a key role in the treatment of endometriosis-associated pain by reducing serum estrogen levels, alleviating inflammatory responses, regulating nerve growth factor, modulating control central nervous system allergies, and influencing the biological processes of endometriotic stromal cells. Moreover, its long-term safety and tolerability are relatively satisfactory according to clinical studies, making it an effective therapeutic agent for endometriosis.

Intravaginal rings (IVRs) are redefining women's health by enabling sustained, localized and user-independent drug delivery that overcomes the limitations of conventional vaginal dosage forms. This review provides a comprehensive perspective on next generation IVR technologies, emphasizing the convergence of biomaterials engineering, advanced manufacturing and clinical translation. We critically discuss how key elastomeric platforms -including ethylene-vinyl acetate, silicones and thermoplastic polyurethanes- govern drug release, mechanical performance and compatibility with the dynamic vaginal microenvironment. Particular focus is placed on the technological evolution of IVR fabrication, from traditional injection molding to disruptive additive manufacturing strategies like three-dimensional (3D) printing and photopolymerizable resin-based systems. These emerging technologies unlock unprecedented opportunities for personalized medicine and sophisticated multi-compartment architectures capable of delivering multiple therapeutics with independently tunable release profiles. In parallel, we examine analytical and regulatory considerations underpinning IVR development, including physicochemical characterization, in vitro release testing and bio-relevant in vivo pharmacokinetic and safety models. Beyond their established role in contraception and hormone replacement, IVRs are rapidly expanding into anti-infective and preventative applications targeting candidiasis, bacterial vaginosis and HIV-1 transmission. In this context, multipurpose prevention technologies (MPTs) are emerging as a transformative strategy capable of simultaneously addressing contraception and sexually transmitted infections within a single long-acting platform. Finally, we discuss the critical challenges that continue to shape the field, including microbiome preservation, user acceptability, regulatory complexity and large-scale manufacturing. Collectively, this review highlights IVRs as a versatile and rapidly evolving drug delivery platform poised to drive the future of personalized and long-acting therapeutics in women's health.

The impacts of chemotherapy exposure on adolescent male osteosarcoma survivors as adults were investigated using a number of physiological parameters, with a focus on chemotherapy, reproduction, and sperm. The Children's Oncology Group (COG) clinical sites (protocol ALTE16C1) of previously collected and stored sperm samples were obtained for this analysis. The epigenetic DNA methylation alterations in sperm were assessed in 176 control adult male patients' sperm, and 183 chemotherapy-exposed osteosarcoma survivors' adult male sperm were provided by COG sites. The current study used a weighted gene co-expression network analysis computational approach that was adopted for use as a weighted epigenetic site correlation network analysis. This analysis identified correlation coefficients between differential DNA methylation regions and other DNA methylation sites with physiological and chemotherapy parameters. Module-trait relationships in the data were determined for epigenetic modules, which highly correlated with sperm parameters, reproductive hormones, and several chemotherapies (e.g. cisplatin). Gene associations of these epigenetic sites were identified and correlated to chemotherapy-associated genes and pathways, as well as reproductive parameters. Observations demonstrate dramatic impacts of adolescent chemotherapy on later adult life sperm epigenetics. Clearly, epigenetics has the potential to mediate the actions of chemotherapy on later life physiology and may potentially impact future generations through epigenetic transgenerational inheritance mechanisms, but this needs further investigation.

Hormonal contraception is used by millions globally, yet side effects remain poorly understood and underrepresented in clinical research and digital health tools. The femtech sector has largely failed to serve marginalised communities, including ethnic minority groups, neurodivergent individuals, and those with lived experience of mental health challenges. This study explored these diverse perspectives through the co-design of T.H.E (The Hormone Effect) app, a digital tool for collecting data on hormonal contraception side effects, to ensure it serves these populations and enables the generation of more diverse and representative datasets.