DHEA (25mg)

PURPOSE OF REVIEW: To systematically examine the available literature on circulating biomarkers of performance resilience in a military environment, with the goal of identifying the most promising circulating biomarkers. RECENT FINDINGS: The construct 'resilience' is hypothesized to play an important role in increasing Special Operations Forces' and other military personnel's capacity for withstanding exposure to various military-specific stressors. However, objectively measuring resilience is challenging. Some of the most important and well-studied circulating biomarkers that affect military-specific resilience are cortisol, dehydroepiandrosterone (sulfate) [DHEA(S)], noradrenaline, serotonin, neuropeptide-Y (NPY) and brain-derived neurotrophic factor. Despite growing evidence, the available knowledge is yet to be summarized and reviewed while considering the intensity and duration of military-specific stressors, military experience, and methodological differences between studies. Cortisol, Insulin-like growth factor-1 (IGF-1), NPY and DHEA(S) provide a physiological window into military-specific resilience. In general, individuals who exhibit a pronounced but controlled biomarker response to an acute stressor, combined with a quick recovery to baseline, demonstrate physiological flexibility that is associated with greater military-specific resilience. Future research will need to determine relative thresholds for the acute stressor-related change in circulating biomarkers and relative timing to stressor, to correctly interpret 'a pronounced but controlled biomarker response' and 'quick recovery to baseline'. © 2026. The Author(s).

BACKGROUND: Major Depressive Disorder (MDD) represents a major global health issue with complex and partially characterised biological foundations. In addition to the recognised hypothalamic-pituitary-adrenal (HPA) axis in stress response, there exists evidence for hypothalamic-pituitary-thyroid/gonadal (HPT/G) axis dysregulation in MDD. Addressing the prior research inconsistencies, this meta-analysis provides quantitative syntheses of evidence regarding endocrine changes in MDD. METHOD: Cross-sectional studies of endogenous levels in drug-free MDD and healthy controls were included. Standardised difference in means (Hedge's g) using a random-effects model was computed. Heterogeneity (Q-statistic, I2 index), publication bias (Egger's test, funnel plots), and robustness (sensitivity) were examined. Clinical and demographic factors were assessed in subgroup analyses. RESULTS: MDD patients exhibited significantly elevated cortisol levels across all measured time points (Hedges' g = 0.41 to 0.75, all p < 0.01). ACTH, β-endorphin, and norepinephrine levels were also significantly elevated, indicating HPA axis hyperactivity. Conversely, HPT axis hormones like FT3, T3, and TSH were reduced (Hedges' g = -0.32 to -0.59, all p < 0.05). HPG axis changes included decreased LH in women (Hedges' g = -0.43, p = 0.02) and elevated estradiol in men (Hedges' g = 1.51, p = 0.02). Subgroup analyses showed a diurnal cortisol rise correlating with depression severity. DHEA-S reduction was more pronounced in males. Melancholic depression was associated with elevated β-endorphin, while atypical depression was linked to increased leptin and TSH. CONCLUSION: This meta-analysis highlights alterations across the HPA/HPT/HPG axes in MDD patients. More studies focusing on these hormonal markers within specific MDD subtypes are warranted to clarify their mechanistic roles and provide stronger evidence of their association with this heterogeneous disorder.

OBJECTIVE: Evaluate the adjuvant effects of oral nutritional supplements including vitamins, coenzyme Q10, and dehydroepiandrosterone (DHEA) on fertility in patients with diminished ovarian reserve (DOR). METHODS: We conducted a generalized explore of 9 databases established as of September 1, 2024. Mainly studing and analyzing outcomes including serum follicle stimulating hormone (FSH) levels, anti Mullerian hormone (AMH) levels, antral follicle count (AFC), retrieved oocytes, and clinical pregnancy rate with the methodology of a systematic review and meta-analysis. The inclusion quality of each experiment was evaluated through the Newcastle Ottawa Scale (NOS). RESULTS: The meta-analysis consisted of 16 studies with 2773 participants. A review of existing evidence suggested that oral nutritional supplements, including vitamins, coenzyme Q10, and DHEA, could significantly lower FSH levels (SMD = -0.67, 95% CI [-0.94, -0.40], p < 0.0001), rise AMH levels (SMD = 0.35, 95% CI [0.02, 0.69], p = 0.04), AFC counts (MD = 0.99, 95% CI [0.28, 1.69], p = 0.006), retrieved oocyte counts (MD = 0.88, 95% CI [0.54, 1.23], p < 0.0001), and clinical pregnancy rate (OR = 1.70, 95% CI = [1.35, 2.13], p < 0.0001). Oral nutritional supplements for more than 2 months have a better effect on lowering FSH levels, raising AMH levels, and oocyte numbers (p < 0.05). In addition, we found that the use of coenzyme Q10 alone was more effective than the use of DHEA alone through subgroup analysis. There was a remarkable correlation (p < 0.05) between the use of both nutritional supplements and the decrease of FSH, as well as the increase of AMH, AFC, and oocytes retrieved. We used sensitivity analysis to conclude that our summary results are robust. CONCLUSIONS: Oral nutritional supplements, including vitamins, coenzyme Q10, and DHEA may be a simple and relatively low-risk treatment option to assist in improving fertility in women with DOR. REGISTRATION NUMBER: CRD42024580831.

Autism Spectrum Disorder (ASD) is a heterogeneous neurodevelopmental condition characterized by underdeveloped social cognition, along with restricted interests and repetitive behaviors. ASD manifests through a range of genetic, environmental, and psychosocial factors, which influence brain development and lead to maladaptive social and behavioral processes. While early diagnosis is common, ASD traits can develop and express themselves through various stages of childhood, driven by dynamic changes in cognitive and social abilities in relation to stressors and challenges. A recent study reports genomic and psychological evidence for two different age-related trajectories of autism development, one early, and one later and near the time of adrenarche and middle childhood, around ages 7 - 10. Given that middle childhood represents a key period for the development of social cognition including complex theory of mind and peer relationships, that adrenarche mediates the origin and social adaptations of middle childhood, and that social challenges increase with its onset, we hypothesize that autism onset, expression and diagnoses during this period may involve alterations to adrenarche, and to its endocrinological and neurological bases. Adrenarche involves onset and increase in secretion of the androgens dehydroepiandrosterone (DHEA) and its sulfate (DHEAS). A series of systematic reviews was conducted to evaluate the hypothesis that DHEA or DHEAS levels are associated with ASD, autism spectrum traits, or aspects of brain development relevant to autism. The reviews showed that: (1) higher DHEA demonstrated evidence of positive associations with aspects of internalizing and externalizing, including social anxiety, with especially notable effects in girls, and (2) higher DHEA showed evidence of association with ASD diagnoses overall, as also indicated by a recent meta-analysis. These findings provide initial support for the hypothesis that alterations to the social adaptations associated with adrenarche, and DHEA levels in middle childhood may underlie a subtype of autism with diagnosis during this developmental period.

BACKGROUND: Polycystic Ovary Syndrome (PCOS) is a prevalent endocrine disorder characterized by excess body weight, hyperandrogenism, hyperglycemia, and insulin resistance often resulting in hirsutism and infertility. Dietary strategies have been shown to ameliorate metabolic disturbances, hormonal imbalances, and inflammation associated with PCOS. Recent evidence indicates that intermittent fasting (IF) could effectively enhance health outcomes and regulate circadian rhythm; however, its impact on PCOS remain unclear. OBJECTIVE: Therefore, this systematic review and meta-analysis aims to examine the effect of IF on women diagnosed with PCOS. METHODS: Comprehensive research was conducted across three major databases including PubMed, Scopus, and Web of Science without date restrictions. Meta-analysis was performed using Cochrane Review Manager Version 5.4 software. RESULTS: Five studies fulfilled the inclusion criteria. IF significantly reduced body weight (MD = -4.25 kg, 95% CI: -7.71, -0.79; p = 0.02), BMI (MD = -2.05 kg/m2, 95% CI: -3.26, -0.85; p = 0.0008), fasting blood glucose (FBG; MD = -2.86 mg/dL, 95% CI: -4.83, -0.89; p = 0.004), fasting blood insulin (FBI; MD = -3.17 μU/mL, 95% CI: -5.18, -1.16; p = 0.002), insulin resistance (HOMA-IR; MD = -0.94, 95% CI: -1.39, -0.50; p < 0.0001), triglycerides (TG; MD = -40.71 mg/dL, 95% CI: -61.53, -19.90; p = 0.0001), dehydroepiandrosterone sulfate (DHEA-S; MD = -33.21 μg/dL, 95% CI: -57.29, -9.13; p = 0.007), free androgen index (FAI; MD = -1.61%, 95% CI: -2.76, -0.45; p = 0.006), and C-reactive protein (CRP; MD = -2.00 mg/L, 95% CI: -3.15, -0.85; p = 0.006), while increasing sex hormone-binding globulin (SHBG; SMD = 0.50, 95% CI: 0.22, 0.77; p = 0.004). No significant changes were observed in waist-to-hip ratio (WHR), total cholesterol (TC), LDL, HDL, total testosterone (TT), or anti-Mullerian hormone (AMH). CONCLUSIONS: IF represents a promising strategy for improving weight and metabolic, hormonal, and inflammatory profiles in women with PCOS. However, the existing evidence remains preliminary, necessitating further robust studies to substantiate these findings.

BACKGROUND: Bilateral oophorectomy has a significant effect on changes in hormone levels in postmenopausal women. This meta-analysis aimed to evaluate the effects of bilateral oophorectomy on estradiol, testosterone, androstenedione, dehydroepiandrosterone sulfate (DHEAS), dehydroepiandrosterone (DHEA), sex hormone-binding globulin (SHBG), and estrone levels. METHOD: We conducted a search for studies on focused ultrasound for cervical high-grade squamous intraepithelial lesions in PubMed, EMBASE, Web of Science, and Cochrane Library databases. This review included 7 studies related to bilateral ovariectomy or retention in postmenopausal women. Using Stata software version 12.0, we applied the random effect model, fixed effect model, and subgroup analysis to evaluate the change of different hormones. RESULTS: After bilateral ovariectomy, estradiol levels decreased significantly (standardized mean difference [SMD] = -0.26, 95% confidence interval [CI] [-0.50, -0.02], P = .031). The overall analysis did not show significant differences (SMD = -0.10, 95% CI [-0.46, 0.26], P = .585), although significant differences were observed between subgroups (P = .025). Testosterone levels also decreased significantly after bilateral ovariectomy (SMD = -0.58, 95% CI [-0.86, -0.31], P < .001). The overall analysis indicated a significant difference between the 2 groups (SMD = -0.35, 95% CI [-0.63, -0.07], P = .014). DHEA levels decreased significantly after bilateral ovariectomy (SMD = -0.51, 95% CI [-0.93, -0.10], P = .015). In contrast, the hormone levels of androstenedione, DHEAS, SHBG, and estrone did not show significant differences between the 2 groups: androstenedione (SMD = -0.04, P = .682), DHEAS (SMD = -0.07, P = .489), SHBG (SMD = -0.02, P = .781), and estrone (SMD = -0.04, P = .587). CONCLUSIONS: The present meta-analysis showed that bilateral ovariectomy had a significant effect on both estrogen and androgen levels in postmenopausal women, especially estradiol, testosterone, and DHEA. In contrast, the changes in androstenedione, DHEAS, SHBG, and estrone were not obvious. The findings of this study underscore the importance of monitoring hormone levels in postmenopau

BACKGROUND: While abundant research suggests a sex-specific role of endogenous sex steroid hormones in chronic diseases, research on mortality remains inconclusive. We quantified the sex-specific associations of endogenous sex steroid hormones, including total testosterone (TT), free testosterone, bioavailable testosterone, estradiol, dehydroepiandrosterone (DHEA), and DHEA sulfate (DHEAS), and sex hormone-binding globulin (SHBG) with risk of all-cause and cause-specific mortality in the general population. METHODS: Embase, Medline, Web of Science, and Cochrane Central were searched and population-based cohort studies investigating the association of interest were included. The risk of bias was assessed using the ROBINS-E tool. The certainty of evidence was evaluated using the GRADE framework. Pooled hazard ratios (HRs) and 95% CI were calculated using a random effects model for the top vs bottom tertile of sex hormones and risk of mortality. RESULTS: The systematic review included 53 publications with 359 047 participants. A significant association was observed between higher level of TT and risk of all-cause mortality (HR [95% CI]: 0.89 [0.83-0.97], n = 19 studies) in men, while no association was found in women. Dose-response analysis suggested a significant U-shaped association between TT and all-cause mortality in men and a J-shaped association in women. Higher SHBG level was significantly associated with higher risk of all-cause mortality in women (1.25 [1.13-1.39], n = 3) and no association was observed in men. Additionally, higher DHEAS levels were associated with lower risk of all-cause mortality in men (0.72 [0.57-0.91], n = 6) and no association was observed in women. CONCLUSION: This meta-analysis reveals a dose-response link between endogenous sex steroid hormones and mortality, highlighting the need for sex-specific studies on hormone modulation's impact on mortality and longevity. © The Author(s) 2025. Published by Oxford University Press on behalf of the Endocrine Society.

Erratum in PLoS One. 2026 Jul 7;21(7):e0353341. doi: 10.1371/journal.pone.0353341. Tactical athletes must maintain high levels of physical and cognitive readiness to handle the rigorous demands of their roles. They frequently encounter acute stressors like sleep deprivation, muscle fatigue, dehydration, and harsh environmental conditions, which can impair their readiness and increase the risk of mission failure. Given the challenging conditions these athletes face, there is a vital need for non-invasive, rapidly deployable point-of-care assessments to effectively measure the impact of these stressors on their operational readiness. Salivary biomarkers are promising in this regard, as they reflect physiological changes due to stress. This systematic review aims to investigate salivary markers as potential indicators for readiness, specifically focusing on their sensitivity to acute stressors like sleep deprivation, dehydration, environmental factors, and muscle fatigue. A search was conducted using the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines (PROSPERO; registration #: CRD42022370388). The primary inclusion criteria were the use of a quantitative analysis to assess salivary biomarkers changes in response to acute stressors. Risk of bias and methodological quality were evaluated with the modified Downs and Black checklist. Hormonal salivary biomarkers were the most commonly studied biomarkers. Muscle damage and fatigue were the most frequently studied acute stressors, followed by sleep deprivation, multiple stressors, dehydration, and environmental. Biomarkers such as creatine kinase, aspartate aminotransferase, uric acid, cortisol, testosterone, and the testosterone to cortisol ratio were indicative of muscle damage. Dehydration influenced osmolality, total protein, flow rate, and chloride ion concentrations. Sleep deprivation affected proteins, peptides, and alpha-amylase levels. Environmental stressors, such as hypoxia and cold temperatures, altered cortisol, pH, dehydroepiandrosterone-sulfate (DHEA-s), and salivary IgA levels. The current body of research highlights that various salivary biomarkers react to acute s

BACKGROUND: The positive effects of dehydroepiandrosterone (DHEA) on oocyte and embryo quality improvement are often concerned. While the results on DHEA-induced endometrial improvement are controversial. OBJECTIVE: To evaluate whether DHEA intervention improved endometrial function and reproductive outcomes during in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles and to thus provide clinical recommendations. DATA SOURCES: PubMed, Cochrane Library, EMBASE and Web of Science from database inception to 31 July 2024, without language restrictions. The references of conference proceedings and websites on clinical trials were manually checked. STUDY DESIGN: Systematic review and meta-analysis. STUDY ELIGIBILITY CRITERIA: Parallel-controlled randomized controlled trials (RCTs) design; women underwent IVF/ICSI, patients in the experimental group received adminstration with DHEA, whereas the control group received with or without placebo; and the outcomes included reproductive or endometrial function. STUDY APPRAISAL AND SYNTHESIS METHODS: RCTs evaluating the effects of DHEA on IVF/ICSI outcomes were included. Risk of bias and quality of evidence (QoE) were assessed according to the Cochrane Collaboration's tool and the Grading of Recommendations Assessment, Development and Evaluation system. Odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals (CIs) were assessed by random-effects or fixed-effects models. Subgroup and meta-regression analyses were used to find sources of heterogeneity. Trial sequential analysis was used to judge the stability of the outcomes. Trial sequential analysis was used in order to control for random errors. RESULTS: A total of 16 trials included 1973 women. DHEA treatment significantly increased endometrial thickness (MD = 0.93, CI: 0.27 to 1.60; low QoE), which helped improve clinical pregnancy rate (CPR) (OR = 1.34, 95% CI: 1.08 to 1.67; low QoE). DHEA administration also increased the quality of oocyte and embryo [including the number of oocytes retrieved (MD = 0.73, CI: 0.36 to 1.10; low QoE), oocytes fertilized (MD = 0.48, CI: 0.10 to 0.87; low QoE), transferred embryos (MD = 0.27, CI: 0.09 to

OBJECTIVE: To systematically evaluate the effectiveness of non-pharmacological interventions (NPIs), including electroacupuncture, exercise, diet, and lifestyle changes, in reducing androgen levels in women with polycystic ovary syndrome (PCOS) through a systematic review and network meta-analysis. METHODS: Comprehensive searches were conducted in PubMed, Embase, Cochrane Library, Web of Science, CNKI, and Wanfang up to June 2024. Randomized controlled trials (RCTs) comparing NPIs with other NPIs or placebo treatments in adult women with PCOS were included. Study selection was independently performed by three authors. Quality assessment followed PRISMA guidelines using the Cochrane RoB2 tool. The confidence of evidence was examined using Confidence in Network Meta-Analysis (CINeMA). Traditional meta-analysis of continuous variables was conducted using Stata 17.0 software with a random-effects model, reporting effect sizes as standardized mean differences (SMD) and weighted mean differences (WMD). Network meta-analysis (NMA) was used to synthesize data, with network diagrams illustrating comparisons between NPIs. We assessed the consistency of the results, performed sensitivity analyses, and examined publication bias to evaluate the influence of individual studies. Furthermore, subgroup analysis and network meta-regression analysis were conducted to explore potential sources of heterogeneity. RESULTS: The review included 21 studies with 1,196 participants, with meta-analysis focusing on 17 studies involving 1,013 participants. NPIs significantly reduced serum testosterone (SMD = -0.57; 95% CI: -0.86 to -0.29, p < 0.01), A4 (SMD = -1.37; 95% CI: -2.63 to -0.12, p = 0.03), and mFG score (WMD = -0.81; 95% CI: -1.26 to -0.37, p < 0.01). Notably, the reduction in testosterone levels achieved with NPIs met the Minimum Clinically Important Difference (MCID) of 12.47 ng/dL (WMD = -12.57; 95% CI: -18.92 to -6.23; p < 0.01), affirming the clinical relevance of these reductions. No significant effects were observed on Free Androgen Index (FAI), Sex Hormone-Binding Globulin (SHBG), Dehydroepiandrosterone (DHEA), DHEA Sulfate (DHEAS), Free Testosterone (FT), or Dihydrotestost

OBJECTIVES: The primary objective was to evaluate the efficacy of vaginal dehydroepiandrosterone (DHEA) and estradiol (E2) on dyspareunia, a symptom of vulvovaginal atrophy (VVA) in postmenopausal women. STUDY DESIGN: In an open-label, randomized controlled trial, 172 naturally postmenopausal women with a mean age of 62.4 ± 5.7 years and moderate or severe dyspareunia caused by VVA, received DHEA (6.5 mg pessaries) or E2 (10 μg vaginal tablets) daily for 4 weeks and then twice-weekly up to 12 weeks. Symptoms and signs of VVA were assessed at baseline, week 4 and 12 of treatment. MAIN OUTCOME MEASURES: The primary outcome was the proportion of patients in each treatment group achieving an improvement of 1 point or more in dyspareunia score on a 4-point scale (none, mild, moderate, severe). Secondary outcomes included other symptoms and objective signs of VVA. RESULTS: Women in both groups had improved in dyspareunia by week 12 (DHEA 92% and E2 82%), with a tendency of significant difference between the groups (OR 2.87, 95% CI 1.00-8.25; p = 0.051). For those with severe dyspareunia at baseline there was higher odds of improvement in the DHEA group than in the E2 group (OR 3.4, 95% CI 1.07-10.5). Vaginal pH, maturity index, and total score for clinical signs of atrophy improved more in the E2 group than in the DHEA group. CONCLUSION: Vaginal DHEA tended to improve dyspareunia more than E2 and was superior in alleviating severe dyspareunia in postmenopausal women. On the other hand, vaginal E2 was superior in improving clinical subjective and objective signs of VVA. CLINICALTRIAL: gov registration number NCT05586711.

BACKGROUND: This study aimed to illustrate the effect of garlic supplementation on metabolic syndrome (MetS) components in women with polycystic ovary syndrome (PCOS). METHODS: From 2020 to 2021, a randomized controlled clinical trial was conducted on 97 women with PCOS and MetS. Participants were randomly assigned to receive either garlic tablets (500 mg containing 2-3 mg allicin; n = 49) or placebo tablets (n = 48) twice daily for 8 weeks. The study assessed changes in MetS indices, quality of life (QoL), and sexual function before and after the intervention. RESULTS: After 8 weeks, the garlic group showed significant reductions in fasting blood sugar (FBS) by 10.5% (from 107.2 to 95.9 mg/dL; P < 0.001), triglycerides (TG) by 17.8% (P = 0.002), low-density lipoprotein cholesterol (LDL-C) by 14.2% (P < 0.001), total cholesterol (TC) by 12.6% (P < 0.001), and C-reactive protein (CRP) by 24.7% (P < 0.001), compared to the placebo group. A significant increase in sex hormone-binding globulin (SHBG) levels was also observed (18.3%; P = 0.005). Systolic and diastolic blood pressure decreased significantly by 5.2% and 6.1%, respectively (P < 0.001 and P = 0.001), and both weight and body mass index (BMI) were significantly reduced (P < 0.01). However, the waist-to-hip ratio (WHR) did not change significantly (P = 0.86). Notable improvements were also observed in all six domains of the Female Sexual Function Index (FSFI)- desire, arousal, lubrication, orgasm, satisfaction, and pain (P < 0.05 for all). Moreover, significant enhancements were recorded in all domains of the Modified Polycystic Ovary Syndrome Health-Related Quality of Life Questionnaire (MPCOSQ), including hirsutism, acne, weight, infertility, menstrual, and emotional disturbances (P < 0.001 for all). The study's limitations include a relatively short follow-up period, lack of strict dietary control, and the omission of some relevant hormonal assays (e.g., androstenedione, DHEA, and DHEAS) due to budgetary constraints. CONCLUSIONS: The results suggest that garlic supplementation may be an effective strategy for managing MetS markers in women with PCOS. TRIAL REGISTRATION: IRCT20150905023897N4, Registratio

BACKGROUND: Transcutaneous trigeminal nerve stimulation (tTNS) and transcutaneous auricular vagal nerve stimulation (tVNS) are neurostimulation methods that have recently gained attention for their potential to modify the response to stress. However, current understanding of the effects of tVNS and tTNS on autonomic nervous system (ANS) activity in healthy individuals is limited. Therefore, this study compared the effect of tTNS and tVNS on the biochemical markers of ANS activity after an acute stress test in a cohort of young healthy adults. MATERIALS AND METHODS: Participants aged 18 to 45 years were randomized to tTNS, tVNS, or sham stimulation conditions. Participants received 20 minutes of neurostimulation/sham and then completed the Trier Social Stress Test (TSST). Cortisol, sulfated dehydroepiandrosterone (DHEA-s), insulin-like growth factor-1 (IGF-I), prolactin, norepinephrine (NE), γ-aminobutyric acid (GABA), and brain-derived neurotrophic factor were measured prestimulation and then again 0, 15, 30, and 60 minutes after TSST. RESULTS: The TSST induced a stress response by increasing levels of cortisol, DHEA-s, prolactin, IGF-I, and NE relative to baseline. Neither tTNS nor tVNS caused significant changes in stress biomarker concentrations compared with sham, except for norepinephrine (NE). NE levels were significantly higher in participants receiving tTNS than in those receiving tVNS at both 15 minutes (p < 0.01) and 30 minutes (p < 0.02) after the TSST. In addition, NE was elevated in the tTNS group compared with sham at 15 minutes after stress (p < 0.01). CONCLUSION: In this study, although tVNS and tTNS did not appear to influence biochemical markers of stress generally, tTNS was uniquely associated with elevations in NE. These findings provide evidence that tTNS may influence arousal under conditions of stress. Published by Elsevier Inc.

Memory consolidation is enhanced by post-encoding stress via cortisol, although the role of dehydroepiandrosterone (DHEA) remains uncertain. This study investigated the effect of the Maastricht Acute Stress Test (MAST) on psychological and hormonal (salivary cortisol and DHEA) responses and performance on a virtual reality object-location memory (OLM) task. The association between hormonal reactivity and OLM task performance was also investigated. Fifty-four participants aged 18-23 were randomly assigned to a stress group (n = 30) and a control group (n = 24). Participants completed an encoding trial of the OLM task and the MAST/control procedure in an acquisition session. A retrieval session 24 h later included verbal object and visual location recognition tests, as well as an object-context binding (OCB) trial. Results showed that the stress group reported significantly higher state anxiety and negative affect after the MAST, perceived as more stressful, painful, and unpleasant. This group also exhibited a significant increase in cortisol and DHEA levels in response to the MAST. Controlling for age, participants in the stress condition made fewer errors in recognising semantically unrelated objects and tended to complete the OCB trial in a shorter time. In addition, no associations were found between cortisol or DHEA reactivity and memory performance in either the stress group or the control group. Our data indicate that post-encoding stress enhances consolidation; however, no association was found between hormonal reactivity and this process, suggesting that these endocrine responses do not directly support the observed improvement in memory consolidation.

Background: Steroid hormone dysregulations have frequently been implicated in posttraumatic stress disorder (PTSD) pathogenesis. However, the translation into naturalistic clinical settings as markers of symptomatology and treatment success remains complex. Particularly, there is little longitudinal data on steroid secretion over the course of interventions.Objective: This study examined the potential of long-term steroid hormone secretion assessed in hair as diagnostic and intervention-related biomarkers among medicated, multimorbid inpatients with PTSD.Method: As part of a secondary analysis of a randomised controlled trial, 54 female inpatients with a primary diagnosis of PTSD received standardised treatment and provided hair samples at pre-treatment, post-treatment, and 3-month follow-up. Cortisol, cortisone, and dehydroepiandrosterone (DHEA) were determined, alongside clinical assessments.Results: Cross-sectional results showed a negative association of pre-treatment DHEA with anxiety symptoms and a trend-level association with lifetime trauma exposure. While inpatients improved in PTSD symptomatology during treatment, neither pre-treatment steroids, nor treatment-induced steroid changes predicted PTSD symptoms at post-treatment or 3-month follow-up.Conclusion: The study highlights the challenges of establishing biomarkers in naturalistic clinical populations. While the association of attenuated DHEA with anxiety symptoms warrants further exploration, our data points towards the potential necessity of patient sub-sample selection to understand, and in the long run clinically target, the endocrine mechanisms in PTSD. Plain Language Summary: Hair steroids (Cortisol, Cortisone, DHEA) were assessed in inpatients with PTSD.Lower pre-treatment DHEA levels were associated with greater anxiety symptoms.Hair steroids did not predict treatment response at hospital discharge or 3-month follow-up. Antecedentes: Las desregulaciones en las hormonas esteroideas han sido frecuentemente asociadas a la patogénesis del trastorno de estrés postraumático (TEPT). Sin embargo, resulta complejo plasmarlo en entornos clínicos naturales como marcadores de sintomatología y éxito en

26. Nutr J. 2024 Dec 2;23(1):152. doi: 10.1186/s12937-024-01056-7. The effects of portfolio moderate-carbohydrate and ketogenic diets on anthropometric indices, metabolic status, and hormonal levels in overweight or obese women with polycystic ovary syndrome: a randomized controlled trial. Shari

Low back pain is a common health problem. In this study, we investigated the effects of yoga, physical therapy (PT), and home exercise (HE) on pain perception, function, stress, and quality of life in chronic low back pain (cLBP). We randomly assigned 54 participants to three distinct treatment groups: (a) a physical therapy group (PT) who received spinal stabilization exercises (SSE) combined with local heat and transcutaneous electrical stimulation; (b) a home exercise group (HE) who received SSE as part of the home program; and (c) a yoga group who received yoga exercises. The primary outcome measures were a Visual Analog Scale (VAS) for measuring pain, and the Oswestry Disability Index (ODI) to measure function. Secondary outcome measures were the Tampa Kinesiophobia Scale (TKS), Central Sensitization Inventory (CSI), pain sensitivity (L3 and deltoid R/L PPTs), Spielberger State-Trait Anxiety Inventory (STAI), plasma cortisol and DHEA-S levels, Transversus Abdominis (TrA) muscle activation, and the Nottingham Health Profile (NHP). Assessments were conducted before and after a six-week intervention period. All three groups demonstrated improvements in pain on the VAS, function on the ODI, pain sensitivity on the L3 and deltoid R/L PPTs, CSI, anxiety on the STAI, TrA muscle activation, and quality of life on the NHP (p < .05). The PT group exhibited a more pronounced improvement on the ODI score (p < .05) than the other groups. Cortisol levels only decreased in the PT group (p < .05). The exercises did not impact DHEA-S and NHP-S parameters. Thus, all interventions resulted in decreased stress, pain intensity, pain sensitivity, central sensitization, and improved function and quality of life; there was no singularly superior approach between interventions. These findings will aid in tailoring treatment programs for managing cLBP according to individual needs.

BACKGROUND: Low physical activity among older adults is related to adverse health outcomes such as depression and loneliness, poor physical function and increased risk of falls. This study was designed to increase physical activity through a digital, group-based, physical activity and music intervention and to examine its effectiveness on social, mental and physical health outcomes. METHODS: Participants were 34 older adults (65 years +) recruited across four care homes in Scotland to a pilot study. Surveys were administered at baseline and post-intervention, comprising measures of fear of falling, depression and anxiety, loneliness, sleep satisfaction and quality of life. A battery of physical function tests and saliva sampling for cortisol and dehydroepiandrosterone hormone analysis were also conducted at each time point. Additionally, process evaluation measures (recruitment, intervention fidelity, attendance, retention rates and safety) were monitored. The intervention comprised 12 weeks of three prescribed digital sessions per week: movement and music (n = 2) and music-only (n = 1), delivered by an activity coordinator in the care home. Post-intervention interviews with staff and participants were conducted to gain qualitative data on the acceptability of the intervention. RESULTS: An average of 88% of prescribed sessions were delivered. Pre- to post-intervention intention-to-treat analysis across all participants revealed significant improvements in anxiety, salivary DHEA, fear of falling and loneliness. There were no significant improvements in health-related quality of life, perceived stress, sleep satisfaction or physical function tests, including handgrip strength. Qualitative analysis highlighted benefits of and barriers to the programme. CONCLUSIONS: The digital movement and music intervention was deemed acceptable and delivered with moderate fidelity, justifying progression to a full-scale trial. Although a proper control group would have yielded more confident causal relationships, preliminary psychosocial and biological effects were evident from this trial. To show significant improvements in physical function, it is likely that a bigger sample si

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive age and the most common cause of infertility due to anovulation. PCOS in adolescents is concerning. Nigella sativa is effective in improving gonadotropins and sex hormones. The current study was designed to investigate the effect of Nigella sativa supplementation on PCOS symptoms and their severity in adolescents. METHODS: The current randomized clinical trial was conducted on 114 adolescents with PCOS who were referred to gynecologist offices and clinics in Gonabad, Iran from March 2022 to March 2023. Participants were randomly allocated to the intervention (Nigella sativa 1000 mg/day) and control (10 mg/day medroxyprogesterone from the 14th day of the cycle for 10 nights) groups. The study duration was 16 weeks. Ovarian volume (measured by ultrasound), anthropometric and blood pressure; serum testosterone, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEA-S), luteinizing hormone (LH), hirsutism severity (Ferriman-Gallwey score) levels were evaluated before and after the study. RESULTS: Data from 103 participants (control group = 53, intervention group = 50) were analyzed. The mean age of participants was 17.0 (Interquartile range [IQR]:2.0). The mean difference in hirsutism score changes (p < 0.001), right (p = 0.002), and left (p = 0.010) ovarian volume, serum LH (p < 0.001) and testosterone (p = 0.001) were significantly higher in the intervention group compared to the control group. The frequency of oligomenorrhea, menometrorrhagia, and amenorrhea, were significantly reduced after the study in the intervention group compared to the control group (ps < 0.001). CONCLUSIONS: Short-term Nigella sativa supplementation may be effective in reducing ovarian volume and improving hormonal balance, and menstrual irregularities in adolescents with PCOS. Further research and long-term studies are warranted to validate the potential therapeutic effects of Nigella sativa in adolescents with PCOS. IRCT REGISTRATION NUMBER: IRCT20221017056209N1 Registration date: 2022-11-22. © 2024. The Author(s).

Update of medRxiv. 2024 May 15:2024.05.15.24307415. doi: 10.1101/2024.05.15.24307415. This study examined the effects of time restricted eating (TRE) on sex hormones in males and females, versus daily calorie restriction (CR). Adults with obesity (n = 90) were randomized to 1 of 3 groups for 12-months: 8-h TRE (eating only between 12:00 to 8:00 pm, with no calorie counting); CR (25% energy restriction daily); or control. Body weight decreased (P < 0.01) in the TRE and CR groups, relative to controls, in males, premenopausal females, and postmenopausal females, by month 12. Total testosterone, dehydroepiandrosterone (DHEA), and sex hormone binding globulin (SHBG) levels did not change over time, or between groups, in males, premenopausal females, and postmenopausal females. Estradiol, estrone, and progesterone were only measured in postmenopausal females, and remained unchanged. These findings suggest that TRE produces significant weight loss but does not impact circulating sex hormone levels in males and females with obesity over 12 months, relative to CR and controls. © 2024. The Author(s), under exclusive licence to Springer Nature Limited.

Background: Polycystic ovary syndrome (PCOS) is a complex endocrine-metabolic disorder characterized by interconnected dysregulation of steroidogenesis and insulin signaling. Multi-target therapeutic strategies are increasingly needed to address its heterogeneous pathophysiology. Methods: An integrative approach combining transcriptomic analysis of GSE137684, including stratification of normoandrogenic and hyperandrogenic PCOS subtypes to capture androgen-related heterogeneity, network pharmacology, molecular docking, and in vitro validation was employed. Principal component analysis (PCA), differential expression analysis, and enrichment analyses were used to identify candidate genes and pathways. Molecular docking evaluated interactions between phytochemicals from Cinnamomum burmannii and Myristica fragrans and key PCOS targets. Functional validation was performed in insulin-resistant 3T3-L1 adipocytes and DHEA-induced KGN cells, assessing cell viability, lipid accumulation, glucose uptake, gene expression, and hormone levels. Results: PCA revealed partial separation between PCOS and the control samples, with PC1 and PC2 explaining 44.8% and 12.5% of variance, respectively. No genes remained significant after multiple testing correction; however, nominally significant candidates (p < 0.01) highlighted pathways related to steroidogenesis and metabolic regulation. Network analysis identified key hub genes including CYP17A1, CYP19A1, AKT1, ESR1, and MAPK1. Molecular docking demonstrated strong binding affinities, with top compounds showing binding energies up to -11.4 kcal/mol (CYP17A1) and -10.9 kcal/mol (AKT1). In vitro, cell viability remained above 80% across all tested concentrations, indicating low cytotoxicity. Treatment significantly reduced lipid accumulation and enhanced glucose uptake in insulin-resistant 3T3-L1 cells (p < 0.05). Additionally, expression of AKT1 and MAPK1 was significantly restored (p < 0.05). In KGN cells, testosterone levels were significantly decreased while the estradiol levels increased (p < 0.05), accompanied by the downregulation of CYP17A1 and upregulation of CYP19A1 (p < 0.05). The combination treatment exhibited more consiste

Idiopathic pulmonary fibrosis (IPF) is a severe progressive lung disease with limited treatment options. Dehydroepiandrosterone (DHEA), an endogenous steroid hormone, possesses anti-inflammatory and anti-fibrotic properties, but its mechanism of action in pulmonary fibrosis (PF) remains incompletely understood. This study aimed to investigate whether DHEA alleviates PF by modulating macrophage-driven inflammatory responses. An in vitro model of PF was established using conditioned medium from LPS-stimulated, PMA-differentiated THP-1 macrophages to treat MRC-5 pulmonary fibroblasts. DHEA pretreatment (5-20 μM) was applied to macrophages, and the TLR4-specific inhibitor TAK-242 was used for mechanistic validation. Inflammatory cytokines were measured by ELISA, protein expression of TLR4/NF-κB/NLRP3 cascade components and extracellular matrix markers (α-SMA, Collagen I) by Western blotting, and cell proliferation by CCK-8 and flow cytometry. DHEA significantly reduced LPS-induced secretion of TNF-α, IL-6, IL-1β, and IL-18 from macrophages. It downregulated TLR4 expression, inhibited NF-κB phosphorylation, and suppressed NLRP3 inflammasome activation (NLRP3, ASC, Caspase-1). Furthermore, DHEA treatment of macrophages prevented their conditioned medium from inducing abnormal proliferation of MRC-5 cells and reduced α-SMA and Collagen I expression in these fibroblasts, similar to the effects of TAK-242. In conclusion, DHEA alleviates inflammatory responses and in vitro pulmonary fibrosis by blocking the TLR4/NF-κB/NLRP3 signaling cascade in macrophages, providing a new mechanistic basis for its potential therapeutic application in PF.

Immune checkpoint blockade (ICB) unleashes antitumor immunity but frequently provokes enduring endocrine toxicities. We hypothesize that ICB accelerates adrenal aging by establishing chronic low-level inflammation within the adrenal cortex, with targeting vulnerability of the zona reticularis. Integrating a recently published human multiorgan aging proteome atlas and primate adrenal aging study with survivorship data after ICB therapy, we propose a testable signaling cascade: ICB-amplified interferon gamma (IFNγ)/ tumor necrosis factor (TNF)/ interleukin-1 signaling activates nuclear factor kappa B (NF-κB)/signal transducer and activator of transcription 1 (STAT1), suppressing sterol regulatory element-binding protein 2 (SREBP2)-low-density lipoprotein receptor (LDLR)-mediated cholesterol uptake; concurrent mitochondrial/endoplasmic reticulum stress drives proteome-transcriptome decoupling, loss of cytochrome b5 type A (CYB5A), and impaired cytochrome P450 family 17 subfamily A member 1 (CYP17A1) 17,20-lyase activity; inflammatory transcriptional repression of sulfotransferase family 2A member 1 (SULT2A1) with proteostasis decay reduces dehydroepiandrosterone (DHEA) sulfation. The net result is a persistent fall in DHEA/DHEA sulfate (DHEAS) with comparatively preserved cortisol-mirroring natural adrenal aging. We advocate prospective measurement of DHEAS, DHEA, adrenocorticotropic hormone (ACTH), and cortisol at baseline, during therapy, end of therapy, and 6-24 months post-therapy; if early DHEAS decline is confirmed, targeted interventions including DHEA replacement or glucocorticoid receptor antagonism warrant evaluation. This framework reframes certain endocrine immune-related adverse events as "accelerated organ aging," with implications for risk stratification, toxicity prevention, and survivorship care. © Author(s) (or their employer(s)) 2026. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder that severely impacts female fertility. The natural dihydrochalcone trilobatin (TLB) has shown potential in managing metabolic diseases; however, its therapeutic effect on PCOS and the underlying mechanisms remain unexplored. PURPOSE: To investigate the therapeutic potential of TLB for PCOS and to elucidate the mechanistic basis, focusing on glycolytic metabolism and mitochondrial function in granulosa cells (GCs). METHODS: A dehydroepiandrosterone (DHEA) -induced PCOS rat model was established and treated with two different doses of TLB or metformin.Therapeutic effects were assessed based on estrous cyclicity, ovarian morphology, serum hormone levels, and the HOMA-IR index. Key targets were identified through integrated metabolomics and bioinformatics analyses. The mechanism was further validated in vitro using dihydrotestosterone (DHT)-induced primary rat GCs, combined with molecular docking, cellular thermal shift assay (CETSA), drug affinity responsive target stability (DARTS) assay, co-immunoprecipitation (CO-IP), and Seahorse metabolic analysis. RESULTS: TLB administration alleviated estrous cycle disruption, improved ovarian morphology, and normalized serum testosterone, luteinizing hormone, and HOMA-IR index in PCOS rats. Metabolomics and bioinformatics analyses identified SIRT2 as a primary target of TLB. Mechanistically, TLB targets SIRT2, promoting the deacetylation of pyruvate kinase M2 (PKM2) at the K305 site. This deacetylation enhanced PKM2 tetramerization and enzymatic activity, thereby ameliorating the glycolytic imbalance in GCs, as evidenced by reduced pyruvate accumulation and restored lactate production. Furthermore, TLB, via the SIRT2/PKM2 axis, improved mitochondrial function, supported by the recovery of ATP production, mitochondrial membrane potential, and mitochondrial permeability transition pore integrity, ultimately suppressing GC apoptosis. CONCLUSION: Our findings demonstrate that TLB alleviates ovarian PCOS phenotypes by targeting SIRT2 to promote PKM2 deacetylation at K305, which effectively corrects glycolytic flux and restores mitochondrial function

Primary dysmenorrhea (PD), a prevalent gynecological disorder, is fundamentally driven by chronic uterine inflammation, leading to severe lower abdominal pain and recurrent cramping. Given the known anti-inflammatory properties of Puerarin (Pue) and Dehydroepiandrosterone (DHEA), we investigated their individual and combined therapeutic effects on PD using an estradiol benzoate/oxytocin-induced mouse model. Our findings revealed that both Pue and DHEA alleviated PD symptoms, as evidenced by reduced writhing frequency, prolonged inter-writhe intervals, diminished uterine edema, lower uterine PGF2α/PGE2 ratio, decreased levels of inflammatory cytokines, and downregulated endometrial cyclooxygenase-2 (COX-2) expression. Notably, co-administration of Pue and DHEA produced superior therapeutic efficacy. Mechanistically, this combination more effectively reversed the pathological upregulation of Hsp90ab1 and the heightened phosphorylation of p38 and JNK in the PD uterus. However, lentiviral overexpression of Hsp90ab1 significantly attenuated the therapeutic benefits conferred by Pue and DHEA. Collectively, these results demonstrated that the synergistic action of Pue and DHEA represents a potent therapeutic strategy for PD, primarily through suppression of the Hsp90ab1/p38/JNK signaling and subsequent mitigation of uterine inflammation, offering a promising avenue for clinical intervention.

OBJECTIVE: The beneficial effect of Vitex agnus-castus on the female endocrine system has been reported. This study examines the impact of Vitex extract (VE) on the serum anti-Mullerian hormone (AMH), sex hormones, and P450 arom, AMH, and CTRP6 gene expression in the ovaries of a rat model of PCOS. MATERIALS AND METHODS: Thirty-two rats with regular estrous cycles were enrolled as controls, polycystic ovary syndrome (PCOS), and two treatment groups. PCOS was induced by estradiol valerate. The treatment groups (T1 &T2) received VE (150 or 200 mg/kg body weight, respectively) for 30 days following PCOS induction. Serum and left ovary were used to assess hormone levels and P450 arom, AMH, and CTRP6 gene expression. RESULTS: In the T2 group, a significant decrease in estradiol (E2, testosterone, and AMH levels (p=0.028) was observed with no significant change in DHEA (p=0.967) in comparison with the PCOS group. AMH in the serum was significantly higher in the PCOS group than in all the other groups (p=0.021). The level of progesterone was not considerably changed between treatments and the PCOS group (p=0.11). The expression of P450 arom in the T2 group was significantly higher than the PCOS group (p=0.003) and had no significant difference from the control (p=0.200). The expression of AMH (p=0.003) and CTRP6 was significantly (p=0.0001) higher in the ovaries of the PCOS group compared to other groups, and consumption of the extract improved the evaluated parameters significantly. CONCLUSION: The endocrine profile and gene expression were improved in the rat ovary following administration of VE, and therefore, the therapeutic effect of VE may be expected in PCOS.

BACKGROUND: Although hair cortisol is an established index of long-term cumulative cortisol output, associations with chronic stress have been inconsistent, potentially due to heterogeneous and temporally misaligned stress assessments. Here, we integrate detailed lifetime stressor measures and ecological momentary assessments (EMA) to examine associations with hair cortisol and the cortisol/DHEA ratio. METHODS: Two methodologically aligned studies were conducted. Study I (N = 79; cross-sectional) assessed self-reported cumulative lifetime stressor exposure using the Stress and Adversity Inventory (STRAIN), distinguishing early-life and adulthood stressor exposure. Study II (N = 86; two time points, three months apart) additionally assessed recent stress using the three-month STRAIN and repeated EMA. Hair hormone concentrations were quantified in proximal 3 cm segments via LC-MS/MS. RESULTS: In Study I, neither early-life nor adulthood stressor exposure were associated with hair cortisol. In Study II, greater severity of adulthood stressor exposure was related to elevated hair cortisol concentrations, stable across time points and robust to covariate adjustment. Early-life and recent stress measures were not related to hair cortisol. Across both studies, the hair cortisol/DHEA ratio showed no consistent associations with any stress dimension. CONCLUSIONS: Our findings provide partial support for a positive association between self-reported adulthood stressor exposure and hair cortisol. However, the absence of consistent effects across both studies, despite substantial methodological overlap, echoes the heterogeneity reported in prior research. Potential reasons are discussed. Future research should address the complexity of individual stress exposure, incorporate hair cortisol into multimethod HPA axis assessments, and advance methodological standardization. © 2026 The Authors.

Depression and anxiety symptoms surge during adolescence, particularly in females, yet the biological mechanisms underlying this vulnerability remain poorly understood. Although estrogen has traditionally been emphasized, androgens such as dehydroepiandrosterone (DHEA) and testosterone may represent distinct pathways to affective symptom risk. The present study examined whether increases in testosterone predict internalizing symptoms in adolescent females by examining hormonal and physical aspects of pubertal development and testing whether testosterone effects persist beyond estradiol and observable maturation. Using data from 5476 females (ages 9-13) in the Adolescent Brain Cognitive Development Study, we analyzed annual salivary DHEA, testosterone, and estradiol alongside caregiver-reported pubertal development and youth-reported internalizing symptoms. Latent change score models captured developmental dynamics: univariate models characterized growth trajectories, bivariate coupling models tested directional hormonal influences, and the final model evaluated whether testosterone and pubertal development changes predicted internalizing symptoms, controlling for estradiol, age, and assay covariates. Testosterone increased gradually across early adolescence, whereas DHEA showed accelerating, nonlinear growth. Increases in testosterone predicted higher internalizing symptoms between ages 10 and 12 (b = 0.041, 95% CI [0.007, 0.076]; b = 0.075, 95% CI [0.009, 0.142]). Observable pubertal development was negatively associated with internalizing symptoms at one assessment. Estradiol predicted subsequent pubertal development and showed concurrent associations with internalizing symptoms at two assessments but did not explain the testosterone-internalizing link. Increases in testosterone predicted internalizing symptoms after accounting for observable maturation and estradiol, identifying a specific vulnerability window between ages 10-12 with implications for early identification and timing of preventive interventions. Published by Elsevier Ltd.

OBJECTIVES: To evaluate the effect of androgens on retinal microvasculature in prepubertal girls with isolated premature pubarche (PP) with optical coherence tomography (OCT) and OCT angiography (OCTA). METHODS: Eighty-six prepubertal, non-obese girls with isolated PP with normal birth weight and 86 age-matched control girls were evaluated. Retinal microvascular structures in the macular and optic disc regions were examined using OCT and OCTA. Data from subjects with isolated PP were compared with data from healthy controls. Correlations between dehydroepiandrosterone sulfate (DHEA-S), androstenedione (AS), testosterone, 17-hydroxyprogesterone (17-OHP) levels, bone age, pubertal stage as well as OCT and OCTA parameters were evaluated. RESULTS: The inferior retinal nerve fiber layer (RNFL) thickness in the isolated PP group was significantly higher than the control group (p=0.007). A statistically significant increase in the vessel density (VD) was observed in temporal quadrant of the superficial capillary plexus (SCP) and inferior quadrant of the deep capillary plexus (DCP) in the isolated PP group compared with the control group (p<0.05). There were significant positive correlations between DHEAS, AS, testosterone levels and RNFL, macula-disk regions's OCTA parameters (p<0.05). CONCLUSIONS: In the isolated PP patients, thickening of RNFL and increased VD in the macula and optic disc region were recognized under the effect of androgens compared to the control group. In these patients, early microvascular changes can be detected noninvasively by means of OCT and OCTA. These findings suggest a potential link between androgen exposure and retinal microvascular alterations; however, further studies are needed to explore their clinical implications. © 2026 Walter de Gruyter GmbH, Berlin/Boston.

STUDY DESIGN: Systematic review. OBJECTIVE: To synthesize human and animal evidence on the potential neuroprotective effects of sex hormones in women with spinal cord injury (SCI) and in female animal models, with the aim of comparing findings across experimental and clinical studies and identifying gaps in clinical research. METHODS: EMBASE, Medline, Cochrane CENTRAL, and Web of Science were searched from inception to August 22, 2025, without language restrictions. Two reviewers independently performed study screening, data extraction, and risk of bias assessment. RESULTS: Of 2832 screened records, 26 studies were included (23 preclinical and 3 clinical). Human evidence was scarce and primarily addressed functional recovery after acute SCI, as well as cardiovascular risk factors and bone outcomes in small cohorts of pre- and postmenopausal women with chronic SCI. Preclinical studies consistently demonstrated broad neuroprotective effects of estradiol across multiple outcomes. Inhibition of estrogen synthesis with letrozole was associated with impaired motor recovery, while the presence of intact ovaries was linked to improved sensory outcomes, supporting a protective role of endogenous estrogens. Evidence for progesterone and dehydroepiandrosterone (DHEA) was mixed, although DHEA showed promising effects in two of three studies, including improved motor and sensory recovery and tissue preservation. CONCLUSION: This review highlights the therapeutic potential of sex hormones in SCI recovery while also revealing substantial gaps in human research. Future studies should investigate endogenous hormone profiles and hormone-based interventions during the acute and subacute phases of SCI to guide therapeutic development and bridge the gap between animal models and clinical practice. © 2026. The Author(s), under exclusive licence to International Spinal Cord Society.