Search Results (311)

Background and Objectives: Evidence on the acute effects of caffeine in female team-sport athletes is limited. This study aimed to quantify the acute effects of caffeine on female team-sport athletes across physical performance, sport-specific performance, physiological responses, perceptual responses, and cognitive performance and determine moderators. Methods: PubMed and Web of Science were systematically searched for randomized, placebo-controlled crossover trials of acute, dose-defined caffeine in female team-sport athletes. Effect sizes were expressed as Hedges’ g and synthesized within each domain using a three-level CHE model with CR2 cluster-robust variance estimation and Satterthwaite degrees of freedom; 95% confidence intervals and prediction intervals were reported. Risk of bias (RoB 2), methodological quality (PEDro), and certainty of evidence (GRADE) were assessed. Results: Twenty-six studies were included, comprising 26 randomized, blind, placebo-controlled crossover trials. As a descriptive cross-domain summary, acute caffeine intake showed a small overall effect when all available domains were pooled (Hedges’ g = 0.24, 95% CI 0.13 to 0.35); however, because these domains represent different constructs, domain-specific estimates were considered the primary interpretable findings. For physical performance, caffeine showed a small favorable effect (g = 0.32, 95% CI 0.22 to 0.42), with statistical evidence for repeated sprint ability (g = 0.43), agility or change in direction (g = 0.42), sprint or speed performance (g = 0.39), anaerobic power (g = 0.30), and jumping performance (g = 0.29). For sport-specific performance, the pooled estimate indicated a small favorable effect but did not reach conventional statistical significance (g = 0.36, 95% CI: −0.01 to 0.73). Exploratory sub-indicator analyses, each based on only a few studies, suggested possible favorable directions for sport-specific locomotion or running performance (g = 0.46) and throwing or ball-speed outcomes (g = 0.19), whereas evidence was insufficient for shooting or scoring accuracy. Physiological outcomes were direction-aligned to the value conventionally regarded as favourable for each indicator (i.e., lower heart rate, lactate, and glucose), so that positive values denote the conventionally favourable direction; because the domain aggregates indicators of differing clinical desirability, its pooled value is a descriptive summary only and showed no clear domain-level direction (g = −0.05, 95% CI −0.31 to 0.21). The heart rate submetric showed a statistically detectable difference (g = −0.30), indicating that caffeine increased heart rate, the expected pharmacological response to a stimulant rather than an adverse effect; there were no clear effects on blood lactate or blood glucose. Perceptual responses improved modestly (g = 0.42), largely through reduced rating of perceived exertion (g = 0.35). Cognitive performance, based on only four studies with low degrees of freedom and wide uncertainty, showed a nonsignificant direction (g = 0.37) with no clear evidence for reaction time or cognitive accuracy, and these data should not be interpreted as showing that caffeine improves cognitive performance in female team-sport athletes. Exploratory moderator analyses did not provide statistically reliable evidence of moderation by caffeine dose, timing of intake, formulation or source, sport type, competitive level, habitual caffeine intake, or blinding status. Conclusions: Available evidence most consistently supports small, outcome-specific benefits of acute caffeine for physical performance and reduced perceived exertion. Evidence for sport-specific skills and cognitive outcomes remained uncertain, based on few studies per outcome and not supporting a general benefit. Current data do not support dose-, timing-, formulation-, habitual-intake-, sport-, or population-stratified recommendations. Future trials should be adequately powered, prospectively report menstrual-cycle phase, hormonal-contraceptive use, habitual caffeine intake, and adverse symptoms, and verify the integrity of blinding. Full article

Background: Progesterone is an endogenous pregnancy hormone widely used in reproductive medicine and obstetrics. Its developmental relevance should be interpreted by distinguishing direct molecular plausibility from indirect obstetric effects, including stabilization of the maternal–decidual–placental maternal–decidual–placental environment, cervical stability, and prolongation of gestation. Methods: A focused qualitative narrative review was performed using targeted literature searches and thematic synthesis. This approach was chosen because the available evidence is heterogeneous with respect to indication, formulation, route, dose, timing, comparator group, and offspring follow-up, making quantitative synthesis inappropriate for the present objective. Results: Direct progesterone-related pathways include receptor-mediated signaling, neuroactive metabolites, and biologically plausible epigenetic regulation; however, human evidence for persistent therapy-induced molecular programming remains limited. Indirect pathways are better supported and include decidualization, immune tolerance, placental stabilization, cervical integrity, uterine quiescence, and prevention of prematurity in selected pregnancies. Clinical evidence should be interpreted separately for placebo-controlled trials, untreated pathological cohorts, and observational follow-up studies because underlying maternal conditions may themselves influence offspring outcomes. Potential risk signals also require formulation-specific interpretation, particularly for synthetic progestogens and 17-alpha hydroxyprogesterone caproate, for which long-term observational data and regulatory reassessments have raised concerns regarding efficacy and possible offspring safety signals. Inadvertent exposure to contraceptive progestins during unrecognized pregnancy, including progestin-only preparations and levonorgestrel-releasing intrauterine systems, should be considered separately from therapeutic obstetric progesterone use. Available evidence has not shown a consistent early adverse signal for natural progesterone when used for recognized indications, although long-term offspring data remain limited and cannot be generalized to synthetic progestogens or 17-alpha hydroxyprogesterone caproate. Conclusions: Progesterone-related therapies should be considered indication-specific and formulation-specific rather than interchangeable. Current evidence supports a cautious and comparator-aware interpretation: natural progesterone appears acceptable for recognized clinical indications based on available short-term and early childhood data, but evidence beyond early childhood remains insufficient for broad safety generalizations. Full article

Background: Endometriosis is a chronic inflammatory and estrogen-dependent disease in which oxidative stress, immune dysregulation, and lesion-supportive microenvironmental signaling contribute to lesion development. N-acetylcysteine (NAC), a glutathione-replenishing and redox-modulating agent, has been studied as a possible non-hormonal intervention. Methods: Following preregistration in the Open Science Framework (OSF), we performed a PRISMA-compliant systematic review of studies evaluating NAC in endometriosis-related clinical, in vivo, ex vivo, or in vitro settings. We searched PubMed/MEDLINE, EBSCOhost, and the Bielefeld Academic Search Engine (BASE) from inception to 24 May 2026. Risk of bias was assessed with design-specific instruments. Results: Twenty-two studies were included. Clinical evidence comprised six studies and suggested that the findings vary by clinical context. In non-postoperative settings, NAC was associated with reduced pain, decreased NSAID use, and endometrioma shrinkage or stabilization. In contrast, the only postoperative randomized comparison found no added benefit of NAC over continuous oral contraceptive therapy for recurrence or pain. Fertility-related clinical findings were suggestive but preliminary. Across nonclinical models, NAC reduced proliferation, lesion burden, oxidative stress, inflammatory mediators, and, in selected systems, migration-related behavior. Mechanistic studies linked NAC to modulation of ROS-dependent proliferation, TNF-α, COX-2, MMP-2/-9, autophagy-related signaling, oxidation-sensitive nociception, and partial protection of oocyte and embryo competence under endometriosis-associated oxidative conditions. Conclusions: NAC shows biological plausibility and preclinical activity in endometriosis, but clinical evidence is heterogeneous and methodologically limited. Full article

Meningiomas are the most common central nervous system tumour and are associated with significant morbidity. Mounting evidence implicates the role of exogenous hormones in meningioma development and growth. This has led to increasing pressure on healthcare professionals to understand the risk profile of different hormonal compounds with regards to meningioma incidence and growth. This is particularly relevant when managing patients with pre-existing meningioma tumours or with one or more risk factors for meningioma formation. The aim of this review was to summarise existing evidence from clinical studies (cohort and case–control) concerning the risk of meningioma associated with different types of exogenous hormones and the associated meningioma characteristics. The literature review identified over 30 cohort and case–control studies published between 2003 and 2026. Studies demonstrated a mixed risk profile of broadly defined hormonal replacement therapy and hormonal contraceptives; however, many of these studies did not capture specific information about duration, dose or medication type. Risk associated with synthetic progestin-containing compounds such as depot medroxyprogesterone and desogestrel contraceptives was higher and related to duration of use. Highly potent synthetic progestins including cyproterone acetate (CPA) carried the strongest risk profile and showed a strong association with multiple meningiomas and anterior/middle skull base location. In conclusion, there is strong evidence for a link between meningioma incidence and highly potent synthetic progestins such as CPA, but further evidence is needed regarding menopausal hormone therapy and broadly defined oral contraceptives, as well as the doses and durations that are associated with clinically relevant risk. There is a space for translational research in this area to better understand the molecular basis underlying the relationship between hormones and meningioma growth. Full article

Background: Large Language Models (LLMs) demonstrate promise in medical applications, but their performance in hormonal contraception consultation remains underexplored. Objective: To evaluate the accuracy and comprehensiveness of LLM-generated hormonal contraception counseling compared to evidence-based guidelines. Methods: Ten fictitious clinical case scenarios representing common contraceptive counseling situations were presented to Chat-GPT, Google Gemini, and OpenEvidence. Cases assessed medical eligibility screening, contraindication recognition, drug interactions, side effect management, and emergency contraception guidance. Two board-certified obstetrician–gynecologists independently evaluated the responses based on international clinical guidelines. Results: Across the ten predefined clinical scenarios, all three LLMs achieved high accuracy in identifying contraindications according to Medical Eligibility Criteria (MEC) and provided appropriate alternative contraceptive recommendations. Models demonstrated high proficiency in managing drug interactions, particularly the lamotrigine–estrogen interaction, and provided evidence-based side effect management strategies. However, the communication styles differed. Chat-GPT emphasized structured consultation and shared decision-making, Gemini provided practical action-oriented guidance, and OpenEvidence delivered concise evidence-focused summaries. Conclusions: In this limited set of standardized fictitious cases, the evaluated LLMs generally provided responses that were broadly aligned with selected guideline recommendations. Current LLMs require cautious deployment, given limitations in individualized assessment and health literacy optimization, and are best positioned as complementary educational tools rather than replacements for professional contraceptive counseling. 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

Rodent species belonging to the Arvicanthis genus cause substantial field and postharvest losses in many African countries, where management still relies mainly on lethal control methods. Hormonal fertility control may provide a complementary strategy for reducing rodent population growth. We investigated the antifertility effects of bait containing quinestrol, a synthetic estrogen, levonorgestrel, a synthetic progestogen, and their combination at 10, 50, and 100 ppm in the Nile grass rat (Arvicanthis niloticus). These compounds suppress fertility by disrupting normal reproductive endocrine function. Adult male and female animals were exposed to treated bait under laboratory conditions, and reproductive responses were evaluated through measurements of bait intake, body weight change, reproductive organ weights, sperm count, sperm motility, pregnancy rate, and litter size. Quinestrol and combined treatments significantly reduced male reproductive organ weights and impaired sperm quality. Female reproductive organ weights were generally unaffected, although uterine edema occurred at higher concentrations. Quinestrol at 50 ppm completely inhibited pregnancy in treated females, regardless of the male mating partner. In addition, untreated females paired with treated males exhibited lower pregnancy rates and reduced litter sizes. Our findings demonstrate the potential of hormonal fertility control as a complementary strategy for sustainable rodent pest management in Africa. Future studies should focus on improving bait intake, field evaluation, and determining the duration and reversibility of contraceptive effects. Full article

Background/Objectives: Migraine is a common, disabling neurological disorder disproportionately affecting women during hormonally sensitive phases like menarche, pregnancy, and menopause. Despite awareness of sex-specific risk factors, management remains fragmented and predominantly neurologist-led, with limited coordination. To address these gaps, this project aimed to develop a national expert consensus, endorsed by scientific societies, on multidisciplinary migraine management in women across the lifespan, integrating perspectives from neurology, gynecology, endocrinology, cardiology, and general medicine. Methods: A two-round Delphi survey was conducted among 145 Italian clinicians representing the five specialties. The Scientific Board formulated 50 questions, each consisting of a variable number of statements, covering diagnostic approaches, hormonal therapies, comorbidities, and organizational care pathways. Statements were rated on a nine-point Likert scale, and consensus was defined using pre-specified criteria based on median scores and agreement. Results: Overall, 79 of 145 statements (54%) achieved consensus. High-level agreement emerged on sex-informed diagnostic strategies, including systematic gynecological and endocrinological evaluation and hormonal profiling in women with migraine. Round 2 facilitated consensus on contentious issues, such as avoiding estrogen-containing contraceptives in migraine with aura, individualized thrombotic risk assessment during menopause, and structured interdisciplinary coordination—particularly among neurologists, gynecologists, and general practitioners—during fertility planning and assisted reproduction. Qualitative feedback emphasized the need to update clinical pathways, implement standardized referral models, and strengthen interprofessional communication. However, persistent divergence remained on selected topics, particularly the role of hormonal contraceptives as a first-line approach to migraine management in women of reproductive age, reflecting different priorities between gynecologists and neurologists. Conclusions: This Delphi initiative provides the first national multidisciplinary consensus on migraine management in women in Italy. The findings support the development of sex- and life-stage-specific clinical guidance and integrated care models tailored to the complex needs of women with migraine. Full article

Background/Objective: Anorectal disorders are a common yet underdiagnosed component of pelvic floor dysfunction, particularly among postpartum women. These conditions, including hemorrhoids, anal fissures, and fecal incontinence, are associated with physical discomfort and may negatively affect psychological well-being. Self-esteem has been identified as a potential mediator linking somatic symptoms to mental health outcomes, including depression. We aimed to assess the relationship between anorectal symptoms, self-esteem and the severity of depressive symptoms in a Polish population of postpartum women. Methods: A cross-sectional questionnaire-based study was conducted between June and December 2025, including 120 women aged >18 years, at least 3 months postpartum. Data were collected using online and paper questionnaires. The assessment tools included the Pelvic Floor Distress Inventory—Short Form 20 (PFDI-20), Rosenberg Self-Esteem Scale (RSES), and Beck Depression Inventory (BDI). Statistical analyses included the multiple regression model, logistic regression and Spearman’s rank correlation. Results: The most frequently reported anorectal symptoms included pain (45.83%), bleeding (42.5%), and pruritus (41.7%). The mean PFDI-20 score was 41.15 (SD 31.13). High self-esteem was observed in 55% of participants, whereas depressive symptoms were present in varying degrees of severity, ranging from no depressive symptoms (55.83%), mild (30%) to severe (0.83%). Significant positive correlations were found between pelvic floor dysfunction severity (particularly CRADI-8 and UDI-6 subscales) and depressive symptoms (BDI), while their correlation with self-esteem (RSES) was negative. The strongest positive correlation was observed between the overall PFDI-20 score and depression (r = 0.389). Multiple regression analyses identified anorectal symptoms, parity, hypothyroidism, and pre-pregnancy depression or anxiety as significant predictors of self-esteem. Anorectal symptoms and hormonal contraceptive use were significant predictors of depressive symptom severity. Among women who delivered vaginally, perineal tear was independently associated with greater depressive symptom severity (OR = 1.07, 95% CI: 1.01–1.14, p = 0.019). Conclusions: Postpartum anorectal and pelvic floor dysfunction symptoms are significantly associated with poorer psychological outcomes, including higher depressive symptoms and lower self-esteem. These findings highlight the importance of a multidisciplinary approach with routine psychological screening in postpartum care. Full article

This study aims to determine the effect of an education intervention on female athletes’ menstrual health knowledge, communication, and perceived importance of menstrual cycle tracking, and whether factors such as age, education level, or hormonal contraceptive use influence these outcomes. Three athlete cohorts engaged in two workshops and received targeted handouts. Participants (n = 51) completed surveys before, after, and 3 months following the intervention, which included a menstrual health knowledge assessment and a series of ratings to ascertain perceived knowledge; likelihood that they would discuss menstrual health with teammates, coaches, medical staff, and performance staff; and perceived importance of menstrual cycle tracking. Bayesian generalised linear mixed models and Bayesian linear mixed models were used to understand the effect of time and interactions between time and age, educational level, or hormonal contraceptive use. Actual and perceived knowledge and likelihood to communicate with teammates and performance staff appeared to be higher post-intervention and were retained for at least three months. The importance of menstrual cycle tracking increased from post-intervention to follow-up, while no change in communication with coaches or medical staff was observed. There appeared to be some effect of age, education level, and hormonal contraceptive use on knowledge and communication with medical staff. A menstrual health education intervention could be a practical and effective strategy to promote menstrual health literacy and communication in sport settings. Full article

Spermatogenesis is a highly coordinated biological process in which diploid spermatogonia undergo mitotic expansion, meiotic division, and terminal differentiation into haploid spermatozoa. This process is tightly regulated by intrinsic germ cell programs and extrinsic signals from Sertoli cells within the seminiferous epithelium. Among the signaling pathways governing male germ cell development, all-trans retinoic acid (RA), a bioactive metabolite of vitamin A, has emerged as a master regulator of meiotic initiation and spermatogonial differentiation in mammals. RA functions through nuclear retinoic acid receptors (RARs) and retinoid X receptors (RXRs), which regulate transcriptional networks essential for germ cell progression, including the activation of Stimulated by Retinoic Acid 8 (STRA8), a key determinant of meiotic entry. Intratesticular RA homeostasis is maintained by a balance between synthesis via aldehyde dehydrogenase (ALDH) enzymes and degradation by cytochrome P450 family 26 (CYP26) enzymes, ensuring precise temporal and spatial control of germ cell development. While rodent models have defined core mechanisms of RA signaling, the canine testis provides a valuable comparative and translational system due to its physiological similarity to human spermatogenesis and relevance to reproductive management. Recent studies highlight conserved RA signaling pathways in dogs, including receptor-mediated transcriptional regulation, feedback control of RA metabolism, and post-transcriptional modulation via microRNAs. Importantly, pharmacological manipulation of RA signaling can reversibly disrupt spermatogenesis, supporting its potential applications in non-hormonal male contraception. This review integrates molecular, developmental, pharmacological, and comparative evidence and presents RA signaling as a central regulatory axis of spermatogenesis with important translational applications. Full article

Health, social, and ethical considerations highlight the need for new male contraceptives. Pimozide is an FDA approved drug known to block T-type calcium channels and which shares structural similarities with mibefradil, a proven antagonist of the CatSper channel. In this study, we examined the effect of pimozide on CatSper, a key target for non-hormonal male contraception. Molecular docking and molecular dynamics simulations were carried out to assess how pimozide binds within the channel pore, and binding energies were estimated using MM-GBSA. To determine its impact on sperm function, we evaluated hyperactivation, the acrosome reaction, and CatSper activity. Our computational analyses indicate that pimozide functions as a pore blocker of the CatSper channel. Experimental findings further support this, showing that pimozide inhibits CatSper activity, and impairs hyperactivation and the acrosome reaction in human spermatozoa. Overall, these results identify pimozide as a novel CatSper antagonist and propose a binding mode, offering a basis for the rational design of reversible, non-hormonal male contraceptives that target the CatSper channel. Full article

Background: Menstrual-cycle-associated symptoms and menstrual health conditions are common among female athletes and may influence recovery, perceived readiness, training availability, and athletic performance. However, evidence regarding interventions aimed at managing these symptoms and their functional implications in athletes remains limited and heterogeneous. Objective: The objective of this study is to synthesize the available evidence on pharmacological and non-pharmacological interventions related to menstrual health and menstrual-cycle-associated symptoms in female athletes and to evaluate their impact on performance, recovery, functional capacity, and symptom burden. Materials and Methods: A systematic review with narrative synthesis was conducted following PRISMA 2020 guidelines. Studies evaluating interventions associated with menstrual health or menstrual-cycle-related symptoms in female athletes were included when they reported outcomes related to athletic performance, recovery, functional capacity, or symptom burden. Results: Five studies published between 2023 and 2025 were included. The interventions evaluated included hormonally related strategies involving oral contraceptive timing, recovery interventions such as cryotherapy, mindfulness-based yoga, nutritional supplementation, and pharmacological pain-modulation approaches. However, findings regarding objective athletic performance outcomes were inconsistent, and the included studies showed substantial methodological heterogeneity. Conclusions: The available evidence suggests that certain interventions related to menstrual health may contribute to improvements in symptom burden, perceived recovery, or selected functional outcomes in female athletes. Nevertheless, the current evidence base remains limited, heterogeneous, and insufficient to support strong performance-related recommendations. Further high-quality studies specifically designed in female athlete populations are needed to inform evidence-based sports medicine practice. Full article

Thirty-one U.S. states and the District of Columbia currently authorize pharmacists to prescribe hormonal contraception. Expansion of pharmacist scope of practice into areas such as contraceptive prescribing represents an extension beyond traditional baseline licensure authority. As a result, jurisdictions frequently require additional training to address competency, patient safety, and liability considerations. Because regulation of pharmacy practice occurs at the state level, training requirements vary across jurisdictions. State boards of pharmacy websites and publicly available regulatory materials were reviewed to identify training requirements for pharmacists authorized to prescribe hormonal contraception. Relevant statutes, regulations, and prescribing protocols were examined. Identified requirements were extracted and categorized into thematic groupings based on the level and type of training specified. Most jurisdictions require pharmacists to complete training beyond standard pharmacy education prior to prescribing hormonal contraception. Such requirements are characteristic of newly expanded scope-of-practice authorities, where regulators seek to verify competency and mitigate liability risk. As prescribing activities become more fully incorporated into pharmacy practice acts and professional education, separate training requirements may diminish over time. Full article

Background: Temporomandibular disorders (TMDs) exhibit a marked female predominance, suggesting a potential role for estrogen in their pathophysiology. However, evidence linking estrogen status to TMD remains inconsistent. Objective: To systematically review the association between estrogen-related factors and TMD prevalence and clinical presentation in women. Methods: PubMed, Embase, Scopus, Web of Science, and Google Scholar were searched through September 2025. Observational studies evaluating hormonal contraceptive use, menopausal status, menstrual cycle variation, pregnancy, or estrogen receptor polymorphisms in women with TMD were included. Two reviewers independently performed study selection, data extraction, and risk-of-bias assessment using the Newcastle-Ottawa Scale. Due to substantial heterogeneity, a narrative synthesis was conducted. Results: Seven studies met the inclusion criteria, including six clinical studies involving 2735 participants and one mechanistic supportive study. Moderate-certainty evidence suggested associations between hormonal contraceptive use, menopausal/climacteric status, and increased TMD risk or symptom severity. Additional low-certainty evidence supported associations involving menstrual cycle variation, pregnancy, and estrogen receptor polymorphisms. Conclusions: Current evidence suggests that hormonal factors may influence TMD risk and symptom presentation in women. However, heterogeneity in definitions of hormonal exposure and diagnostic criteria limits definitive conclusions. Further prospective studies using standardized diagnostic protocols and real-time biochemically validated hormonal assessments correlated with clinical symptoms are needed. Full article