DHEA

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.

BACKGROUND: The current knowledge about the efficacy and safety of dietary polyphenol administration in patients with polycystic ovarian syndrome (PCOS) is divergent. OBJECTIVE: To evaluate the pooled efficacy and safety of dietary polyphenol administration in the treatment of patients with PCOS. METHODS: The pubmed, Embase, Scopus, Cochrane Library, and Web of Science databases were searched for randomized controlled trials (RCTs) of dietary polyphenol administration for the treatment of PCOS. English-language RCTs involving adults with PCOS were thoroughly searched in electronic databases from the time of their establishment to May 2024. Random-effects models were used because heterogeneity was derived from differences in intervention materials and study duration, among other confounding factors. The effect sizes of the outcomes in the pooled analysis are expressed as weighted mean differences (WMDs) and 95% confidence intervals (CIs). RESULTS: A total of 15 RCTs involving 934 patients were finally included. Compared with control treatments, dietary polyphenol administration significantly reduced luteinizing hormone (LH) (WMD: -0.85, 95% CI [-1.32 to -0.38], p = 0.00), and prolactin levels (WMD: -3.73, 95% CI [-6.73 to -0.74], p = 0.01). Dietary polyphenol administration significantly reduced insulin levels (WMD: -0.85, 95% CI [-1.32 to -0.38], p = 0.00). Regarding lipid metabolism, dietary polyphenol administration only reduced triglyceride levels (WMD: -8.96, 95% CI [-16.44 to -1.49], p = 0.02). Malondialdehyde (MDA) (WMD: -0.65, 95% CI [-0.68 to -0.62], p = 0.00), tumor necrosis factor (TNF-α) (WMD: -1.39, 95% CI [-2.41 to -0.37], p = 0.01) concentrations were significantly reduced by dietary polyphenol administration. None of the interventions significantly affected weight, body mass index (BMI), waist circumference (WC), homeostatic model-insulin resistance (HOMA-IR), fasting blood sugar (FBS), glycated hemoglobin (HBA1c), follicle-stimulating hormone (FSH), testosterone (T), dehydroepiandrosterone (DHEA), estradiol (E2), anti-Müllerian hormone (AMH), quantitative insulin-sensitivity check index (QUICKI), sex hormone-binding globulin (SHBG), total antioxi

Vitamin D has the potential to therapeutically affect the lipid profile and endocrine parameters of polycystic ovary syndrome (PCOS) patients. However, results from prior studies have been inconsistent. Therefore, we conducted an umbrella meta-analysis of randomized controlled trials (RCTs) to better understand the effectiveness of vitamin D in treating PCOS. We conducted an electronic search across multiple databases, including Embase, PubMed, Web of Science, Cochrane CENTRAL, and Scopus, from their inception to January 2, 2024. Random-effects models were used to perform the umbrella meta-analysis. The analysis included 15 meta-analyses of RCTs. Vitamin D demonstrated a significant reduction in TG levels (SMD = -0.23; 95 % CI: -0.42, -0.04, p = 0.02, and WMD = -8.76, 95 % CI: -11.81, -5.72; p <0.001), TC (SMD = -0.47, 95 % CI: -0.80, -0.13; p = 0.007, and WMD = -8.89, 95 % CI: -13.18, -4.59; p < 0.001), LDL-c (SMD = -0.24, 95 % CI: -0.38, -0.10; p = 0.001, and WMD = -3.83, 95 % CI: -6.49, -1.16; p = 0.005), TT (SMD = -0.15, 95 % CI: -0.29 to -0.01; p = 0.02), and DHEA (WMD: -28.03; 95 % CI: -56.9 to -0.36; p = 0.04). However, no significant effect on HDL-c, insulin, and BMI. The present meta-analysis revealed that vitamin D supplementation might significantly affect TG, TC, LDL-c, DHEA, and TT while it is not effective in improving BMI, HDL-c, and insulin. Vitamin D showed noteworthy effects in preventing lipid profile and enhancing hormonal function in patients with PCOS.

OBJECTIVE: Little evidence exists on the effect of 17beta-estradiol plus norethisterone acetate on all the anthropometric indices. Hence, this systematic review and meta-analysis of Randomized Controlled Trials was conducted to give an evidence-based report on the effect of 17beta-estradiol plus norethisterone acetate on anthropometric indices. METHODS: The literature search was executed in databases including PubMed/Medline, Web of Science, Scopus, Embase, and Google Scholar to recognize clinical trials that examined the influence of 17beta-estradiol plus norethisterone acetate on obesity indices from database inception to Jan 2023. RESULTS: Combined findings were generated from 20 eligible articles. The meta-analysis showed that body weight (Weighted Mean Difference (WMD): -0.47 kg, 95% CI: -1.32, 0.37, p = 0.274), body fat (WMD: 0.16 kg, 95% CI: -1.26, 1.59, p = 0.821), WHR (WMD: 0.001 kg, 95% CI: -0.006, 1.15, p = 0.872), and LBM (WMD: -0.02 kg, 95% CI: -1.19, 1.15, p = 0.970) were not modified in DHEA group compared to the control, but BMI levels were significantly reduced in 17beta-estradiol plus norethisterone acetate group (WMD: -0.15 kg/m2, 95% CI: -0.30, -0.008, p = 0.039). Moreover, based on intervention duration (months), a more significant reduction in BMI was found in trials that were performed on studies with ˃3 months duration (WMD: -0.176 kg/m2) than studies with ≤ 3 months (WMD: 0.05 kg/m2). CONCLUSION: Administration of 17beta-estradiol plus norethisterone acetate for more than 3 months results in a decrease in BMI, which helps to reduce cardiovascular disease risk.

BACKGROUND: Dehydroepiandrosterone (DHEA) may improve the outcomes of patients with poor ovarian response (POR) or diminished ovarian reserve (DOR) undergoing IVF/ICSI. However, the evidence remains inconsistent. This study aimed to investigate the efficacy of DHEA supplementation in patients with POR/DOR undergoing IVF/ICSI. METHODS: PubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI) were searched up to October 2022. RESULTS: A total of 32 studies were retrieved, including 14 RCTs, 11 self-controlled studies and 7 case-controlled studies. In the subgroup analysis of only RCTs, DHEA treatment significantly increased the number of antral follicle count (AFC) (weighted mean difference : WMD 1.18, 95% confidence interval(CI): 0.17 to 2.19, P=0.022), while reduced the level of bFSH (WMD -1.99, 95% CI: -2.52 to -1.46, P<0.001), the need of gonadotropin (Gn) doses (WMD -382.29, 95% CI: -644.82 to -119.76, P=0.004), the days of stimulation (WMD -0.90, 95% CI: -1.34 to -0.47, P <0.001) and miscarriage rate (relative risk : RR 0.46, 95% CI: 0.29 to 0.73, P=0.001). The higher clinical pregnancy and live birth rates were found in the analysis of non-RCTs. However, there were no significant differences in the number of retrieved oocytes, the number of transferred embryos, and the clinical pregnancy and live birth rates in the subgroup analysis of only RCTs. Moreover, meta-regression analyses showed that women with lower basal FSH had more increase in serum FSH levels (b=-0.94, 95% CI: -1.62 to -0.25, P=0.014), and women with higher baseline AMH levels had more increase in serum AMH levels (b=-0.60, 95% CI: -1.15 to -0.06, P=0.035) after DHEA supplementation. In addition, the number of retrieved oocytes was higher in the studies on relatively younger women (b=-0.21, 95% CI: -0.39 to -0.03, P=0.023) and small sample sizes (b=-0.003, 95% CI: -0.006 to -0.0003, P=0.032). CONCLUSIONS: DHEA treatment didn't significantly improve the live birth rate of women with DOR or POR undergoing IVF/ICSI in the subgroup analysis of only RCTs. The higher clinical pregnancy and live birth rates in those non-RCTs should be interpreted with caution because o

BACKGROUND AND OBJECTIVE: Although many trials have evaluated the use of dehydroepiandrosterone to improve outcomes in poor responders undergoing assisted reproductive technology treatment, evidence supporting this approach is controversial. We aimed to conduct a systematic review and meta-analysis of existing published data to further elucidate and supplement the use of Dehydroepiandrosterone (DHEA) to improve the effectiveness of vitro fertilization in patients with diminished ovarian reserve or adverse ovarian reactions. METHODS: PubMed, Embase, Cochrane Library, and the Web of Science databases were searched through December 2020. Oocyte yield, metaphase II oocytes, fertilized oocytes, top-quality embryos, clinical pregnancy rate, ongoing pregnancy rate, and live birth rate were analyzed as relative outcomes. Meta-analysis was performed and fitted to both fixed-effects models and random-effects models. RESULTS: Eight prospective randomized controlled studies, five prospective case-control studies, and three retrospective cohort studies were conducted with a total of 1998 participants. Meta-analyses of these studies showed a significantly higher number of oocytes retrieved (WMD 1.09, 95% CI 0.38 to 1.80), metaphase II oocytes (WMD 0.78, 95% CI 0.16 to 1.40), fertilized oocytes (WMD 0.84, 95% CI 0.42 to 1.26), top-quality embryos (WMD 0.60, 95% CI 0.34 to 0.86), clinical pregnancy rate (RR 1.35, 95% CI 1.13 to 1.61), and ongoing pregnancy rate (RR 1.82, 95% CI 1.34 to 2.46), although there was no difference in live birth rate (RR 1.35, 95% CI 0.94 to 1.94) in the DHEA supplementation groups compared with that in the control groups. CONCLUSION: Oral DHEA supplementation appears to improve some IVF outcomes. On the basis of this limited evidence, we conclude that further studies are required to provide sufficient data.

OBJECTIVE: This study was designed to determine the status of dehydroepiandrosterone (DHEA) in women with anorexia nervosa (AN) and to assess the efficacy of DHEA supplementation as a treatment for bone health in women with AN. METHOD: Studies were retrieved from the PubMed, Embase, Cochrane Library, MEDLINE, and Scopus databases from inception to February 14, 2022. Observational studies that compared serum DHEA levels between women with AN and healthy controls were included for meta-analysis, and randomized controlled trials (RCTs) that evaluated the effects of DHEA supplementation on bone mass were reviewed. RESULTS: Meta-analysis of 15 cross-sectional studies revealed that patients with AN had significantly elevated serum DHEA levels (mean difference (MD) = 311.63 ng/dl; 95% confidence interval (CI), 78.01-545.25) and reduced DHEAS levels (MD = -24.90 μg/dl; 95% CI, -41.72 to -8.07) compared with healthy controls. A systematic review of seven RCTs found that DHEA monotherapy does not improve bone mineral density (BMD) compared with placebo after adjusting for weight gain. While the combination of DHEA and conjugated oral contraceptives has led to increased bone strength and decreased bone loss, the beneficial effect appears to be limited to older adolescents and adults with closed physes. Potential detrimental effects on BMD were identified in younger adolescents with open physes in one study. DISCUSSION: Due to the lack of apparent benefit of DHEA in women with AN and its potential detrimental effect on BMD in young patients with AN, current evidence does not support the use of DHEA. PUBLIC SIGNIFICANCE: This study demonstrates that women with anorexia nervosa have abnormal levels of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS), which have been suggested by previous studies to play a role in the development of low bone density in this condition. However, current evidence does not support the use of DHEA as a treatment to preserve bone health in patients with anorexia nervosa given the lack of clear benefit following its use and also because of a potential detrimental effect on bone mineral density in young patients with anorexia n

BACKGROUND AND AIMS: Dehydroepiandrosterone (DHEA) supplementation has been investigated in patients with altered cortisol levels and is proposed to ameliorate the metabolic profile related to adipose tissue. However, further research is warranted and evidence is no compelling for liver safety. Hence, we aimed to meta-analyse the effects of DHEA supplementation on circulating levels of cortisol, liver enzymes, and adipokines. METHODS: We searched literature published in PubMed, Web of Science, Embase and Scopus, until December 2020. We obtained overall results using the generic inverse of variance method with a random-effects model. RESULTS: Through 10 arms, serum cortisol levels decreased significantly after DHEA supplementation [weighted mean difference (WMD): -53.581 nmol/L, 95% confidence interval (CI): -88.2, -18.9, P = .002], without significant heterogeneity (I2 = 36%, P = .117). In contrast, any significance was noted for adiponectin (WMD: -0.045 µg/mL, 95% CI: -0.56, 0.47; P = .865), leptin (WMD: -2.55 µg/mL, 95% CI: -6.2, 1.06; P = .166), aspartate transaminase (AST) (WMD: -3.7 U/L, 95% CI: -10.35, 2.95; P = .276), and alanine aminotransferase (ALT) (WMD: -1.7 U/L, 95% CI: -3.45, 0.06; P = .058). CONCLUSION: DHEA supplementation decreased circulating cortisol but did not alter adiponectin, leptin, AST, and ALT levels. Hence, DHEA supplementation could be considered as an adjunct in the management of hypercortisolaemia and is safe for the liver. © 2021 John Wiley & Sons Ltd.

Estradiol, an estrogen steroid hormone, serves as the dominant female hormone and its levels fluctuate during lifetime. In women, after the menopause, all estrogens and almost all androgens are locally developed in the peripheral tissues from dehydroepiandrosterone (DHEA). However, the effect of DHEA supplementation on estradiol levels in women is unclear as previously published data has resulted in conflicting findings. Thus, we conducted the present dose-response meta-analysis of randomized controlled trials (RCTs) evaluating the influence of DHEA on estradiol concentrations in women. The PubMed/Medline, Embase, Web of Science and Scopus databases were systematically searched for articles published on this topic until May 10, 2021. No time or language restrictions were applied. The data were expressed as weighted mean differences (WMDs) and 95% confidence intervals (CI), and a P-value of less than 0.05 was considered to be statistically significant. The pooled results were obtained using the generic inverse of variance method with a random effects model. A total of 21 arms, including 1223 participants (case = 610, and control = 613), reported estradiol concentrations as an outcome measure. The overall results demonstrated that estradiol significantly increased following the administration of DHEA (WMD: 7.02 pg/mL, 95% CI: 5.43, 8.62, P = 0.000). The stratified analyses revealed that the elevation of estradiol concentrations was more pronounced in subjects aged ≥60 years old (WMD: 8.56 pg/mL, 95% CI: 6.97, 10.16, I2 = 94%) and in those receiving DHEA supplements for ≥26 weeks (WMD: 7.30 pg/mL, 95% CI: 6.28, 8.32, I2 = 61%). Moreover, estradiol levels increased significantly with DHEA dosages of 50 mg/day (WMD: 7.75 pg/mL, 95% CI: 9.12, 9.39, I2 = 94%) and when DHEA was prescribed to postmenopausal women (WMD: 7.61 pg/mL, 95% CI: 5.97, 9.24, I2 = 93%). This meta-analysis has provided a comprehensive overview of the effects of DHEA administration on circulating estradiol levels, far beyond the available evidence from different RCTs. Subsequent subgroup analyses revealed that postmenopausal women, females aged 60 years and above, those on DHEA dosages of 50 mg/day

BACKGROUND: Hyperandrogenism (HA), inflammation, and oxidative damage play key roles in the pathophysiology of polycystic ovary syndrome (PCOS). Whether vitamin D adjuvant therapy improves hormonal, inflammation, and oxidative damage in PCOS patients has aroused widespread interest, but the results are controversial. To evaluate the effect of vitamin D supplementation on hormonal, oxidative stress, and inflammatory parameters in patients with PCOS. METHODS: A literature search was conducted in Medline, the Cochrane Library, EMBASE, and Web of Science for studies related to PCOS and vitamin D supplementation. All reports of randomized controlled trials (RCTs) published before December 2019 were identified. The fixed-effects model or random-effects model was used to calculate pooled estimates of standardized differences in means (SMD) with 95% confidence intervals (CI). RESULTS: A total of 956 identified studies were retrieved, and eighteen RCTs involving 1,060 participants were ultimately included in the current meta-analysis. The pooled results demonstrated that vitamin D supplementation in patients with PCOS resulted in a significant improvement in serum total testosterone (TT), high sensitivity C-reactive protein (hs-CRP), total antioxidant capacity (TAC), and malondialdehyde (MDA). No significant effect on free testosterone (FT), dehydroepiandrosterone sulfate (DHEA-S), sex hormone-binding globulin (SHBG), free androgen index (FAI), nitric oxide (NO), and total glutathione (GSH) levels was found. Subgroup analysis showed that vitamin D supplementation reduced hs-CRP and MDA irrespective of the treatment course, type of vitamin D intervention, supplementation frequency, and dosage. Twelve weeks of vitamin D supplementation improved TT and TAC while low-dose vitamin D supplementation (≤1,000 IU/day) improved TT and DHEA-S. Vitamin D co-supplementation reduced TT, FT, and DHEA-S, while a daily supplementation regime improved TT, DHEA-S, and TAC in patients with PCOS. CONCLUSIONS: The current meta-analysis demonstrates that vitamin D supplementation in patients with PCOS resulted in an improvement in the levels of TT, hs-CRP, TAC, and MDA, but did not affect FT,

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.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder characterized by insulin resistance, hyperandrogenism, and elevated oxidative stress. The present study aimed to investigate the synergistic therapeutic effects of metformin and curcumin on insulin resistance and oxidative stress in a rat model of PCOS. MATERIALS AND METHODS: Thirty female Sprague-Dawley rats were randomly assigned to blank control (n = 6) and experimental (PCOS) groups (n = 24). The PCOS model was induced through daily subcutaneous injections of dehydroepiandrosterone (DHEA, 60 mg/kg) for 20 days. Subsequently, the experimental group was subdivided into four groups: PCOS-only, PCOS-metformin (300 mg/kg), PCOS-curcumin (50 mg/kg), and PCOS-metformin-curcumin (combined treatment). Treatments were administered daily via oral gavage for another 20 days. Estrous cycles, ovarian morphology, serum sex hormones, insulin resistance, and oxidative stress in ovarian tissues were assessed. RESULTS: Combined treatment with metformin and curcumin significantly restored estrous cyclicity, improved ovarian morphology, reduced serum testosterone and luteinizing hormone levels, decreased LH/FSH ratio, and ameliorated insulin resistance compared to monotherapy groups. Moreover, the combined treatment markedly decreased ovarian oxidative stress markers (ROS and MDA) and enhanced antioxidant enzyme activities (GPx, SOD, GSH), surpassing the effects of either agent alone. CONCLUSION: Combined administration of metformin and curcumin demonstrated synergistic therapeutic effects in PCOS rats by concurrently addressing insulin resistance and oxidative stress. These findings support the clinical potential of this combination as an effective strategy for managing PCOS. Further clinical studies are necessary to validate these promising preclinical findings.

Due to the lack of markers (ER, PR, and HER-2/Neu) for the molecular-targeted therapies triple-negative breast cancer (TNBC) is more challenging than other subtypes of breast cancer. Moreover, the conventional chemotherapeutic agents are still the mainstay of most therapeutic protocols and eventually turn into a refractory drug-resistance , hence, more efficient therapeutic regimens are urgently required. The present study aimed to elucidate the effects of PU-H71 combined with DHEA on triple-negative breast cancer cell line MDA-MB-231 and to assess the synergy using the Chou-Talalay method. The combined therapy controlled the expression of an array of antioxidants and metabolizing enzymes, leading to the induction of oxidative stress which in turn induced apoptotic cell death. Our results indicated that the combined treatment with PU-H71 and DHEA exerts a synergistic anti-tumor effect on MDA-MB-231 triple-negative breast cancer cell line.

The impact of androgens on the thyroid in women is poorly understood. The aim of the present study was to investigate whether vitamin D/dehydroepiandrosterone (DHEA) combination therapy is superior to vitamin D alone in affecting thyroid autoimmunity and hypothalamic-pituitary-thyroid axis activity in young women with autoimmune thyroid disease. The study included 35 euthyroid women with untreated Hashimoto's thyroiditis and reduced sexual drive, allocated to one of two treatment groups. The first group (n = 19) received both vitamin D and DHEA, while the second (n = 16) was treated with only vitamin D. Serum thyroid antibody titres and concentrations of thyrotropin, free thyroid hormones, dehydroepiandrosterone-sulphate (DHEA-S), 25-hydroxyvitamin D, testosterone and estradiol were measured at baseline and 6 months later. Vitamin D administered alone or in combination with DHEA decreased serum titres of thyroid peroxidase and thyroglobulin antibodies, which correlated with baseline antibody titres, baseline 25-hydroxyvitamin D levels and treatment-induced increase in 25-hydroxyvitamin D levels. Apart from a stronger effect on antibody titres, vitamin D/DHEA combination therapy slightly decreased thyrotropin levels, as well as increased DHEA-S and testosterone levels. In this group of women, treatment-induced changes in antibody titres and thyrotropin levels correlated with the impact on DHEA-S and testosterone. The obtained results suggest that vitamin D/DHEA combination therapy may be a better treatment option for euthyroid women with Hashimoto's thyroiditis than vitamin D alone. © 2020 John Wiley & Sons Australia, Ltd.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a complex reproduction and endocrine disorder of women in the reproductive age. Spearmint (Mentha spicata L.) has anti-androgenic activity and flaxseed (Linum usitatissimum L.) contains phytoestrogen and was reported to improve PCOS conditions. This study aimed to evaluate PCOS conditions following administration of a mixture of these two plants. METHODS: Twenty-four rats with regular cycles were randomly divided into four groups as control (C) and treatment-control (TC) received a combination of spearmint extract (SE) + flaxseed extract (FE). PCOS was induced in PCOS and treatment (T) groups by a single intramuscular injection of estradiol valerate. The treatment group received a combination of SE and FE for 30 days, 7 weeks after injection of estradiol valerate. Estrous cycles were monitored for 10 days and in the last day animals were sacrificed, ovaries were collected for the histomorphometric study and the serum levels of progesterone, testosterone, estradiol, and dehydroepiandrosterone (DHEA) were measured. RESULT: Significant rise in progesterone and a decrease in testosterone and estradiol with no significant change of DHEA in the T group, was observed in comparison with the PCOS group (P < 0.05). No significant difference noticed between T and control groups (C &CT) regarding evaluated hormones. A significant increase in primary, pre-antral and antral follicles noticed in the T group compared to the PCOS group. The number of cystic follicles decreased in the T group compared with the PCOS group. Granulosa layer thickness increased while the thickness of theca decreased significantly in the T group compared to the PCOS group (P < 0.05). No significant endocrine or histological differences noticed between C and TC groups. CONCLUSION: A combination of flaxseed and spearmint extract improved the endocrine profile and the histomorphometric features of the ovary in the T group compared to the PCOS group.

The activities of hundreds, perhaps thousands, of metabolites are regulated by human cytosolic sulfotransferases (SULTs) - a 13-member family of disease relevant enzymes that catalyze transfer of the sulfuryl moiety (-SO3) from PAPS (3'-phosphoadenosine 5'-phosphosulfonate) to the hydroxyls and amines of acceptors. SULTs harbor two independent allosteric sites, one of which, the focus of this work, binds non-steroidal anti-inflammatory drugs (NSAIDs). The structure of the first NSAID-binding site - that of SULT1A1 - was elucidated recently and homology modeling suggest that variants of the site are present in all SULT isoforms. The objective of the current study was to assess whether the NSAID-binding site can be used to regulate sulfuryl transfer in humans in an isoform specific manner. Mefenamic acid (Mef) is a potent (Ki 27 nM) NSAID-inhibitor of SULT1A1 - the predominant SULT isoform in small intestine and liver. Acetaminophen (APAP), a SULT1A1 specific substrate, is extensively sulfonated in humans. Dehydroepiandrosterone (DHEA) is specific for SULT2A1, which we show here is insensitive to Mef inhibition. APAP and DHEA sulfonates are readily quantified in urine and thus the effects of Mef on APAP and DHEA sulfonation could be studied non-invasively. Compounds were given orally in a single therapeutic dose to a healthy, adult male human with a typical APAP-metabolite profile. Mef profoundly decreased APAP sulfonation during first pass metabolism and substantially decreased systemic APAP sulfonation without influencing DHEA sulfonation; thus, it appears the NSAID site can be used to control sulfonation in humans in a SULT-isoform specific manner.

Isotretinoin broad effectiveness is limited by its detrimental effect on the Meibomian glands. Androgens have been reported to regulate the Meibomian gland function. Dehydroepiandrosterone (DHEA) is an androgen precursor considered as an efficient and physiological anti-ageing skin agent. This study aimed to investigate the role of the topical DHEA in ameliorating Meibomian gland dysfunction caused by isotretinoin employing different histological and immunohistochemical techniques. Twenty-four adult male albino rats were divided into four equal groups; control group, DHEA-treated group (1% twice daily for 3 months), isotretinoin-treated group (0.5mg/kg/day for 3 months), and both isotretinoin and DHEA-treated group. Meibomian gland specimens were processed for light microscopy. Immunohistochemical study was carried out using antibodies for proliferating cell nuclear antigen (PCNA), androgen receptor (AR) and estrogen receptor-alpha (ER-α). Sections from the isotretinoin-treated group revealed a reduction in the number and size of acini. Thickening and keratinization of the epithelial lining of the ducts were observed. Multiple degenerated acini and casts of acinar cells in the ducts of Meibomian glands were detected. Some dilated congested blood vessels and mononuclear cells were occasionally seen. A significant decrease in PAS reaction and a significant increase in collagen fiber content were detected. Immunohistochemical study revealed a significant increase in immunoexpression of PCNA in basal ductal cells coupled with decreased expression in basal acinar cells. Both AR and ER-α immunoexpression was significantly decreased. Minimal alterations were observed upon concomitant treatment with isotretinoin and DHEA as compared to the control group. Topical DHEA could prove to be beneficial in ameliorating isotretinoin-induced Meibomian gland dysfunction most probably through its androgenic effect.

AIM: A UHPLC-MS/MS assay was developed to quantify urinary dehydroepiandrosterone (DHEA), 7β-hydroxy-DHEA, cortisone and 6β-hydroxycortisone as potential biomarkers to predict CYP3A activity. RESULTS: A sensitive assay at LLOQ of 0.500 ng/ml with good accuracy and precision was developed for the four analytes in human urine. This UHPLC-MS/MS assay was optimized by eliminating nonspecific loss of the analytes in urine, ensuring complete hydrolysis of the conjugates to unconjugated forms and use of the product ions of [M+H-H2O]+ for multiple reaction monitoring detection of DHEA and 7β-hydroxy-DHEA. CONCLUSION: This assay was successfully applied to a pilot clinical study. It is also suitable for future drug-drug interaction studies to continue evaluating the potential of these steroids as biomarkers for CYP3A inhibition and induction.

Endocannabinoids are synthetized as a results of demand from membrane phospholipids. The formation and actions of these lipid mediators depend to a great extent on the prevalence of precursor fatty acid (FA), and can be influenced by diet or supplementation. The purpose of this study was to evaluate the interactive effects of lipopolysaccharide (LPS) and benzo(a)pyrene (BaP) in RAW 264.7 cells supplemented with docosahexaenoic acid (DHA). After LPS and/or BaP treatment in macrophages pre-incubated with DHA, a significant decrease in the amount of fatty acid was observed. The highest content of monounsaturated fatty acids was detected in RAW 264.7 cells co-treated with LPS and BaP. Significant interactions between LPS and BaP co-treatment in terms of endocannabinoid levels were observed in RAW 264.7 cells after DHA supplementation. The highest amount of endocannabinoids was detected in macrophages supplemented with DHA and co-treated with BaP and LPS: arachidonoyl ethanolamine AEA (5.9μg/mL), docosahexaenoyl ethanolamide DHEA (10.6μg/mL) and nervonoyl ethanolamide NEA (16.5μg/mL). The highest expression of cyclooxygenase (COX-2) and cannabinoid receptor 2 (CB2) was noted in macrophages supplemented with DHA and activated with LPS and BaP. Our data suggested a novel, CB2 receptor-dependent, environmental stress reaction in macrophages co-treated with LPS and BaP after supplementation with DHA. Despite the synergistic LPS and BaP action DHA potentiates the anti-inflammatory response in RAW 264.7 cells.

Huntington's disease (HD) is a progressive neurodegenerative disorder with a wide spectrum of cognitive, behavioral and motor abnormalities. The mitochondrial toxin 3-nitropropionic acid (3-NP) effectively induces specific behavioral changes and selective striatal lesions similar to that observed in HD. Some neurosteroids, synthesized in neurons and glial cells, previously showed neuroprotective abilities. 5-Androstene-3β-17β-diol (ADIOL) is a major metabolite of dehydroepiandrosterone (DHEA) with previously reported anti-inflammatory, anti-apoptotic and neuroprotective activities. The neuroprotective potential of ADIOL in HD was not previously investigated. Therefore, the present study investigated the neuroprotective effects of ADIOL against 3-NP-induced behavioral changes, oxidative stress, inflammation and apoptosis. Intraperitoneal administration of 3-NP (20mg/kg) for 4 consecutive days in rats caused significant loss in body weight, reduced prepulse inhibition (PPI) of acoustic startle response, locomotor hypoactivity with altered cortical/striatal histological structure, increased cortical/striatal oxidative stress, inflammation and apoptosis. Administration of ADIOL (25mg/kg, s.c.) for two days before 3-NP significantly attenuated the reduction in body weights and PPI, increased locomotor activity and restored cortical/striatal histological structure nearly to normal. Moreover, it displayed anti-oxidant, anti-inflammatory and anti-apoptotic activities as evidenced by the elevation of cortical and striatal reduced glutathione levels, reductions of cortical and striatal malondialdehyde, striatal tumor necrosis factor alpha and interleukin-6 levels. Only a small number of iNOS and caspase-3 positive cells were detected in sections from rats pretreated with ADIOL. This study suggests a potential neuroprotective role of ADIOL against 3-NP-induced Huntington's disease-like manifestations. Such neuroprotection can be attributed to its anti-oxidant, anti-inflammatory and anti-apoptotic activities.

Comment in Nat Rev Urol. 2015 Mar;12(3):124. doi: 10.1038/nrurol.2015.31. The introduction of enzalutamide and abiraterone has led to improvement in the treatment of metastatic castration-resistant prostate cancer. However, acquired resistance to enzalutamide and abiraterone therapies frequently develops within a short period in many patients. In the present study, we developed enzalutamide-resistant prostate cancer cells in an effort to understand the mechanisms of resistance. Global gene-expression analysis showed that the steroid biosynthesis pathway is activated in enzalutamide-resistant prostate cancer cells. One of the crucial steroidogenic enzymes, AKR1C3, was significantly elevated in enzalutamide-resistant cells. In addition, AKR1C3 is highly expressed in metastatic and recurrent prostate cancer and in enzalutamide-resistant prostate xenograft tumors. LC/MS analysis of the steroid metabolites revealed that androgen precursors such as cholesterol, DHEA and progesterone, as well as androgens are highly upregulated in enzalutamide-resistant prostate cancer cells compared to the parental cells. Knockdown of AKR1C3 expression by shRNA or inhibition of AKR1C3 enzymatic activity by indomethacin resensitized enzalutamide-resistant prostate cancer cells to enzalutamide treatment both in vitro and in vivo. In contrast, overexpression of AKR1C3 confers resistance to enzalutamide. Furthermore, the combination of indomethacin and enzalutamide resulted in significant inhibition of enzalutamide-resistant tumor growth. These results suggest that AKR1C3 activation is a critical resistance mechanism associated with enzalutamide resistance; targeting intracrine androgens and AKR1C3 will overcome enzalutamide resistance and improve survival of advanced prostate cancer patients. ©2015 American Association for Cancer Research.