Effects Of Steroids Research Articles

Role of intralesional platelet-rich plasma (PRP) therapy in the treatment of recalcitrant oral ulcers of pemphigus vulgaris

Pemphigus Vulgaris is a chronic, autoimmune vesiculobullous disorder in which 80-90% of patients develop oral lesions and in 60% of cases, oral lesions are the first sign. The platelet-rich concentrate present in autologous platelet-rich plasma (PRP) therapy has a high concentration of growth factors that promote the synthesis of collagen and extracellular matrix. The wound healing property of PRP can be used to treat recalcitrant oral ulcers of pemphigus as it accelerates the healing process, prevents the patients from side effects of steroids, and reduces the pain and discomfort of the patients. To assess the role of intralesional Platelet Rich Plasma (PRP) therapy in the treatment of recalcitrant oral ulcers of pemphigus vulgaris. A total of 15 histo-pathologically proven cases of Pemphigus Vulgaris under treatment, in whom the skin lesions had healed up to 90% but the oral ulcers were still persistent were included in the study. The severity of the ulcers were monitored by calculating the POLIS (Pemphigus Oral Lesion Intensity Score). Autologous intralesional PRP was administered in 3 sittings 7 days apart and the result was evaluated by change in POLIS score after each sitting. The data was analyzed using SPSS IBM version 26.0. Out of the total cases, 12 patients were female and 3 were male. Intralesional PRP was found to accelerate the healing of recalcitrant oral erosions. It was found that POLIS was reduced after every PRP session. The paired t-test was conducted to compare the mean scores of POLIS-0 and POLIS-3. The result indicates a significant difference between the pre-intervention mean score POLIS-0 (M=19, SD=3.25) and post-intervention mean score POLIS-3 (M=6.6, SD=2.97), t(14)=13.33,p<0.001. Intralesional PRP has been found to improve the recalcitrant oral ulcers of pemphigus vulgaris. Hence, it can be a treatment option where oral and topical corticosteroids fail to respond or are contraindicated.

The Effectiveness of Steroids and Antioxidants in the Management of Cisplatin-induced Ototoxicity: A Comprehensive Systematic Review of the Literature and Network Meta-Analysis

Abstract Background: Cisplatin efficacy in cancer therapy is hindered by dose-dependent toxicities, including ototoxicity. Its mechanisms involve cochlear damage and oxidative stress. Gender and age affect susceptibility, with limited treatment options for adults. Objective: To assess the effectiveness of steroids compared to antioxidants (AOs) in preventing and managing cisplatin-induced ototoxicity. Materials and Methods: Data were collected from multiple sources including Medline, CENTRAL, PubMed, and Springer Nature Journals. Adults and pediatrics with the clinical diagnosis of cisplatin-induced ototoxicity, interventional studies (including single-arm studies) were included. Studies with a focus on chemotherapy agents other than cisplatin were excluded. Results: The study encompassed 10 randomized controlled trials spanning 2004–2023 across Canada, Israel, The Netherland, Spain, Turkey, Greece, Italy, and Iran. It aimed to evaluate interventions for preventing cisplatin-induced ototoxicity, including intratympanic injections and oral dietary supplements. Based on the results of this systematic review, thiosulfate-hyaluronate gel showed a 1.3 dB reduction in hearing loss; dexamethasone injections had minimal efficacy; L-N-acetylcysteine (L-NAC) offered significant otoprotection with daily infusion; and transtympanic L-NAC showed no significant benefit. Salicylate usage yielded no decrease in hearing loss. AO dietary supplements showed no difference in results between groups. However, based on the network meta-analysis results, it appears that steroids perform best in reducing cisplatin-induced ototoxicity at higher frequencies (8000 Hz), followed by placebo and then AO. Conclusion: A further molecular and targeted therapy is needed to target the cyto/ototoxic activity and further prevent such deterioration in hearing and promote chemotherapy regime without ototoxic effects.

Androgyny and atypical sensory sensitivity associated with savant ability: a comparison between Klinefelter syndrome and sexual minorities assigned male at birth

IntroductionThe extreme male brain (EMB) theory, a major causal hypothesis of autism (ASD: autism spectrum disorder), attributes excess androgens during early development as one of the causes. While studies have generally followed the EMB theory in females at birth, the co-occurrence of ASD in males at birth has been observed in conditions that are assumed to be associated with reduced androgen action during early development, including Klinefelter syndrome (KS) and sexual minorities. ASD is also associated with atypical sensory sensitivity, synesthesia, and savant syndrome.MethodsIn the present study, we examined adult KS individuals (n = 22), sexual minorities assigned male at birth (n = 66), and control males matched for age and educational background to those with KS [Exploratory analysis (control 1st): n = 36; Reanalysis (control 2nd): n = 583]. Participants completed a self-report questionnaire assessing sensory hypersensitivity/hyposensitivity, savant tendency (developed for the present study), synesthesia, and sexual aspects, including gender identity and sexual orientation.ResultsThe results of the exploratory analysis suggested that individuals with KS exhibited a higher tendency toward sensory hypersensitivity/hyposensitivity than the tendency exhibited by the controls. In the Reanalysis, sexual minorities were more likely to be synesthetes, and in both analyses sexual minorities exhibited a higher savant tendency and sensory hypersensitivity/hyposensitivity than the controls. Moreover, the gender dysphoric state was associated with phenotypes observed in individuals with ASD, such as synesthesia, savant tendency, and sensory hypersensitivity/hyposensitivity.DiscussionThese results suggest a common physiological background among gender dysphoria, synesthesia, savant tendency, and atypical sensory sensitivity. Thus, androgynous features (reduced effects of sex steroids during early development) in males at birth may be partially related to the phenotype commonly observed in individuals with ASD. Based on the present results, we propose that the reduction of sex steroids during early development may lead to atypical neurodevelopment and be involved in the atypicality of external and internal sensory perception, and thus in the atypicality of self-concept integration, through the disruption of oxytocin and the gamma-aminobutyric acid system modulating the neural excitation/inhibition balance.

Effect of steroids on cisplatin-mediated cytotoxicity

Effect of steroids on cisplatin-mediated cytotoxicity

Chronic high-dose testosterone disrupts social cognition and enhances social dominance in male long-Evans rats

While increased aggression is the most consistent behavioral effect of anabolic androgenic steroid (AAS) abuse, its cause remains unclear. AAS may promote aggression by disrupting social behaviors which maintain dominance hierarchies. To model AAS abuse, we treated male rats with chronic high-dose testosterone and tested social recognition, social learning, and competitive and aggressive dominance. Rats received daily injections s.c. of testosterone (7.5 mg/kg) or vehicle (n = 8/group). We tested social recognition by measuring investigation of a novel or familiar stimulus animal, social learning with the social transmission of food preference (STFP) test, aggressive dominance with the tube test, and competitive dominance with a food competition task. For social recognition, testosterone-treated rats did not prefer the novel stimulus rat (72.8 ± 9.3 s) over the familiar rat (68.8 ± 8.0 s, N.S.) rat. In the STFP test, testosterone-treated rats did not show a significant preference for the demonstrated flavor (59.9 ± 9.4 %, N.S.) compared with controls (70.1 ± 5.4 %, p < 0.05). In the tube test, testosterone did not increase the number of rounds won. However, when the testosterone-treated rat won, they were more likely to be lighter than their vehicle-treated opponent, χ2(1,N = 63) = 6.56, p < 0.05, Φ2 = 0.32. In the food competition task, testosterone-treated subjects won more often (48 rounds) than their vehicle-treated partners (15 rounds; p < 0.05). These results suggest that AAS disrupt recognizing and learning from the social hierarchy and increase the likelihood of challenging it. Collectively, these behavioral changes may contribute to AAS-induced aggression.

The molecular mechanisms of steroid hormone effects on cognitive function

ObjectiveThere is a lack of information on the molecular mechanisms by which steroid hormones (testosterone, estrogen, and progesterone) regulate cognitive impairment. Thus, we aimed to identify the protective effects of steroid hormones on cognitive function. MethodsWe analyzed the literature on the molecular mechanisms, biological activities, physicochemical properties, and pharmacokinetics of steroid hormones. ResultsSteroid hormones can protect against cognitive impairment by regulating key genes (INS, TNF, STAT3, ESR1). Specific microRNAs, namely hsa-miR-335-5p, hsa-miR-16-5p, and hsa-miR-26b-5p, along with transcription factors NFKB1, PPARG, NR3C1, GATA2, EGR1, ATF3, and CEBPA, play a significant role in this protective mechanism. The involvement in cognitive processes, regulation of phosphorylation, neuronal apoptosis, and signaling pathways related to Alzheimer's disease significantly influence the protein-protein interaction network underlying these effects. Additionally, steroid hormones exhibit anti-hypercholesterolemic properties, anti-inflammatory activity, antitoxic properties, and function as inhibitors of acetylcholine neuromuscular transmission. They also hold promise as therapeutic agents for the treatment of dementia. Promising therapeutic interventions for cognitive impairment include the use of miRNA sponges targeting hsa-miR-16-5p, along with the administration of capsaicin, minocycline, dopamine, sertraline, and minaprine. The gut microbiota species Lactobacillus amylovorus, Paraprevotella clara, Libanicoccus massiliensis, Prevotella oris, Turicibacter sanguinis, and Dubosiella newyorkensis were identified as significant contributors to cognitive impairment and altered levels of steroid hormones. ConclusionSteroid hormones are promising compounds for improving cognitive function. Further research is needed to validate these findings through focused investigations into apoptosis, regulation of neuronal cell death, miRNA sponges, interactions with gut microbiota, and the potential efficacy of pharmaceutical agents.

REDUCTION OF SCLERAL THICKNESS WITH TOPICAL FLUOROMETHOLONE IN MANAGEMENT OF CHRONIC CENTRAL SEROUS CHORIORETINOPATHY COMPLICATED BY POSTERIOR CYSTOID DEGENERATION

Purpose. To describe the role of topical fluorometholone in the management of eyes with central serous chorioretinopathy (CSCR) complicated by posterior cystoid degeneration (PCD). Methods. Patients with PCD associated with CSCR were prospectively recruited, examined with multimodal imaging and prescribed for topical fluorometholone four times daily. Eyes with macular neovascularization were excluded based on optical coherence tomography angiography. Spectral-domain optical coherence tomography was used to monitor central retinal thickness, subfoveal choroidal thickness, and the thickness of the anterior sclera. Results. Five eyes of four patients were included. Intraretinal and subretinal fluid in all eyes had been unresponsive to all standard treatments, but improved remarkably or completely resolved with limited improvement of visual acuity after a mean of 6.0 ± 2.0 weeks of topical fluorometholone administration. In all cases, significant reduction of scleral thickness was observed with no or mild intraocular pressure rise. Conclusion. Severe cases of CSCR complicated by PCD associated with vision loss may be managed with topical fluorometholone. The positive effects of steroids in CSCR may be mediated by their effects on reduction of the scleral thickness.

Efficacy of Epidural Steroid in Controlling Pain After Unilateral Biportal Endoscopic Discectomy for Single-Level Lumbar Disc Herniation: A Randomized, Double-Blind, Placebo-Controlled Trial.

The effects of epidural steroid (ES) administration following open or minimally invasive surgery lumbar discectomy have been extensively studied. However, no research has investigated the impact of steroids following the unilateral biportal technique endoscopic lumbar discectomy (UBE-D) for lumbar disc herniation. This study aims to evaluate the efficacy of ES administration in controlling postoperative pain and disability scores following UBE-D for single-level lumbar disc herniation. This double-blind, randomized, placebo-controlled trial was conducted between June 2021 and June 2023. Eighty-two patients were assessed, and 60 were eligible and randomized to receive either ES (n = 30) or saline (placebo; n = 30) after UBE-D. The Outcome measures included visual analog scale scores for pain, Oswestry Disability Index scores, morphine consumption over 24 hours, serum C-reactive protein levels, and the occurrence of complications over a 6-month follow-up period. The baseline characteristics were comparable between the 2 groups, with no significant differences observed. Analysis of visual analog scale scores for back and leg pain, as well as Oswestry Disability Index scores, at various postoperative time points (6 hours, 12 hours, 24 hours, 2 weeks, 6 weeks, 3 months, and 6 months), showed no statistically significant differences between the ES and placebo groups (P values ranged from 0.47-0.94). Additionally, no significant differences were found in morphine consumption within the first 24 hours postoperatively (P = 0.85), length of hospital stay (P = 0.36), or C-reactive protein levels at 24 hours and 3 weeks postoperatively (P values ranged from 0.54-0.79) between the 2 groups. Importantly, no postoperative or steroid-related complications were reported in either group within the 6-month follow-up period. ES administration after UBE-D did not significantly reduce postoperative pain, disability scores, or morphine consumption compared with placebo. The findings suggest that routine use of ESs in this context may not provide additional benefits. Clinicians should reconsider the use of epidural steroids as part of standard postoperative management after UBE-D, as the lack of significant improvement in patient outcomes indicates that alternative pain management strategies may be more effective.

Betamethasone Exposure and Neonatal Respiratory Morbidity Among Late Preterm Births by Planned Mode of Delivery and Gestational Age.

To estimate the effect of late preterm antenatal steroids on the risk of respiratory morbidity among subgroups of patients on the basis of the planned mode of delivery and gestational age at presentation. This was a secondary analysis of the ALPS (Antenatal Late Preterm Steroid) Trial, a multicenter trial conducted within the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network of individuals with singleton gestations and without preexisting diabetes who were at high risk for late preterm delivery (34-36 weeks of gestation). We fit binomial regression models to estimate the risk of respiratory morbidity, with and without steroid administration, by gestational age and planned mode of delivery at the time of presentation. We assumed a homogeneous effect of steroids on the log-odds scale, as was reported in the ALPS trial. The primary outcome was neonatal respiratory morbidity, as defined in the ALPS Trial. The analysis included 2,825 patients at risk for late preterm birth. The risk of respiratory morbidity varied significantly by planned mode of delivery (adjusted risk ratio [RR] 1.90, 95% CI, 1.55-2.33 for cesarean delivery vs vaginal delivery) and week of gestation at presentation (adjusted RR 0.56, 95% CI, 0.50-0.63). For those planning cesarean delivery and presenting in the 34th week of gestation, the risk of neonatal respiratory morbidity was 39.4% (95% CI, 30.8-47.9%) without steroids and 32.0% (95% CI, 24.6-39.4%) with steroids. In contrast, for patients presenting in the 36th week and planning vaginal delivery, the risk of neonatal respiratory morbidity was 6.9% (95% CI, 5.2-8.6%) without steroids and 5.6% (95% CI, 4.2-7.0%) with steroids. The absolute risk difference of neonatal respiratory morbidity between those exposed and those unexposed to late preterm antenatal steroids varies considerably by gestational age at presentation and planned mode of delivery. Because only communicating the relative risk reduction of antenatal steroids for respiratory morbidity may lead to an inaccurate perception of benefit, more patient-specific estimates of risk expected with and without treatment may inform shared decision making.

Independent effects of testosterone, estradiol, and sex chromosomes on gene expression in immune cells of trans- and cisgender individuals.

The origins of sex differences in human disease are elusive, in part because of difficulties in separating the effects of sex hormones and sex chromosomes. To separate these variables, we examined gene expression in four groups of trans- or cisgender individuals: XX individuals treated with exogenous testosterone (n=21), XY treated with exogenous estradiol (n=13), untreated XX (n=20), and untreated XY (n=15). We performed single-cell RNA-sequencing of 358,426 peripheral blood mononuclear cells. Across the autosomes, 8 genes responded with a significant change in expression to testosterone, 34 to estradiol, and 32 to sex chromosome complement with no overlap between the groups. No sex-chromosomal genes responded significantly to testosterone or estradiol, but X-linked genes responded to sex chromosome complement in a remarkably stable manner across cell types. Through leveraging a four-state study design, we successfully separated the independent actions of testosterone, estradiol, and sex chromosome complement on genome-wide gene expression in humans.

Case report: Comparative treatment course of generalized lichen nitidus: effectiveness of topical steroids versus maxacalcitol

Lichen nitidus is a chronic skin disease characterized by scattered shiny papules and is common among relatively young individuals. We report a persistent rash covering the body of a 6-year-old boy, unresponsive to prior treatments like moisturizers and topical steroids. Clinical examination revealed small yellow papules predominantly distributed on the trunk, around the eyes, and clustered around the elbow and knee fossa. Histopathological analysis showed a localized infiltrate of lymphocytes and basal epithelial cells, along with giant cells. The overlining rete ridges extended to surround the inflammatory cells, resembling a claw clutching a ball image. Topical treatment with alclometasone dipropionate ointment was more effective compared to maxacalcitol. Remarkably, after about 3 months of treatment, the rash had completely disappeared. We summarized treatments of lichen nitidus in Japan. Maxacalcitol had never been tried. In this report, we demonstrated the effectiveness of the steroid ointment compared to maxacalcitol through the clinical course.

7784 Perspectives Of Anabolic Steroid Users On Steroid Use, Side Effects, And Patient Education

Abstract Disclosure: D.D. Lam: None. M. Potemkin: None. J. Kreutz: None. H. Shah: None. P. Patel: None. P.K. Doyle-Baker: None. Background: Details on first-hand perceived and experienced effects of anabolic steroids (AS) on users are sparse. Furthermore, there is limited information on what type of AS knowledge users possess, irrespective of current published works in AS pharmacology. This study aimed to identify insights of AS users regarding their knowledge and patterns of AS use, commonly experienced side effects, sources used for steroid education, and their unique needs as a population. Study Design: AS users from Calgary, Alberta, Canada of various sexes and ages ≥ 18 were recruited through gyms in Alberta with convenience and snowball sampling techniques. Participant-centered-qualitative research using semi-structured interviews was conducted. Participants discussed their experiences as a user and shared their understanding of AS, details of usage including compounds used, and their commonly experienced or perceived side effects through one-on-one interviews of varying durations. Interviews were coded using NVivo 14 Software prior to thematic analysis. Resulting codes were organized into overarching themes based on researchers' consensus. Results: Seven AS users were confidentially interviewed over Zoom. Several important themes emerged. There existed a wide variety of AS that users have identified, with some of the most commonly mentioned being Anavar, Nolvadex, Testosterone, and Trenbolone. Steroid users frequently identified increased strength with faster recovery from training and better overall appearance as prominent advantages of AS use. Conversely, hair loss, gynecomastia, acne, aggression, erectile dysfunction, altered libido, hypogonadism, infertility, and injection related discomfort were commonly identified disadvantages of AS use. Lastly, individuals using AS report having consulted many different sources to learn about appropriate dosing, techniques, and side effects. These sources ranged from peers, coaches, online forums, social media, and scientific research articles, but rarely included healthcare professionals. Conclusions: This study identified the need for education and research in exploring the impact of AS use. A variety of AS exist on the market, yet information pertaining to the side effect profiles of these AS from a patient’s perspective is lacking and exploration of this topic is warranted. Further investigation as to the impact of user education on their understanding of the risks versus the benefits of AS use must also be conducted. Presentation: 6/1/2024

8483 Changes in kidney hemodynamics during gender-affirming hormone therapy in transgender individuals - findings from the KNIGHT pilot study

Abstract Disclosure: S.A. van Eeghen: None. C. Wiepjes: None. L.L. Pyle: None. M. den Heijer: Research Investigator; Self; Kyowa Kirin. Other; Self; Novartis Pharmaceuticals. P. Bjornstad: Advisory Board Member; Self; AstraZeneca, Bayer, Inc., Boehringer Ingelheim, Novo Nordisk, XORTX. Consulting Fee; Self; AstraZeneca, Bayer, Inc., Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly &amp; Company, LG Chemistry, Horizon Pharma, Novo Nordisk, Sanofi. Research Investigator; Self; AstraZeneca, Merck, Horizon Pharma. Other; Self; Bayer, Inc. D. van Raalte: Consulting Fee; Self; AstraZeneca, Bayer, Inc., Boehringer Ingelheim, Eli Lilly &amp; Company, Merck, Sanofi, MSD. Research Investigator; Self; AstraZeneca, Boehringer Ingelheim, Eli Lilly &amp; Company, Merck, Sanofi, MSD. N.J. Nokoff: Consulting Fee; Self; Neurocrine Biosciences, Inc, Ionis Pharmaceuticals Inc.. Research Investigator; Self; Neurocrine Biosciences, Inc. Other; Self; World Athletics. Background: Studies in transgender individuals have shown that gender-affirming hormone therapy (GAHT) impacts estimated glomerular filtration rate (eGFR). Masculinizing hormone therapy decreases, while feminizing hormone therapy increases eGFR, based on changes in serum creatinine and cystatin C. These substantial changes suggest an effect of sex hormones on kidney hemodynamics. To investigate this, we studied kidney hemodynamic changes before and after 3 months of gender-affirming hormone therapy (GAHT) in transgender individuals. Methods: This prospective observational pilot study assessed kidney hemodynamics in 23 transgender individuals assigned male at birth receiving feminizing hormone therapy and 21 transgender individuals assigned female at birth receiving masculinizing hormone therapy. Feminizing therapy included transdermal (n=16), sublingual (n=5), or oral estradiol (n=2), in combination with an anti-androgen (n=22); intramuscular triptorelin (n=16), spironolactone (n=5) or finasteride (n=1). Masculinizing therapy involved transdermal (n=17) or injected testosterone (n=4). Measures included glomerular filtration rate (GFR; Iohexol clearance), effective renal plasma flow (ERPF; p-aminohippurate clearance), and renal vascular resistance (RVR; mean arterial pressure/renal blood flow). Glomerular hydraulic pressure (PGLO), and afferent/efferent vascular resistance (RA/RE) were estimated by Gomez equations. Linear mixed models compared baseline and three-month measurements. Results: Individuals undergoing feminizing hormone therapy [median age 21 (IQR 19-29) years, BMI median 22.9 (IQR 18.9-30.7) kg/m²] had increased GFR by 2.8 mL/min per 1.73m² (95% CI, 0.01 to 5.6) and a nonsignificant increase in ERPF (+42 mL/min per 1.73m²; 95% CI, -5 to 90). RVR and RA significantly decreased [RVR: -0.007 mmHg/L/min (95% CI, -0.015 to -0.0003), RA: -294 dyn/s per cm5 (5% CI, -568 to -21)], indicating afferent vasodilation. In contrast, individuals receiving masculinizing therapy (median age median 20 (IQR 18-23) years, BMI median 24.2 (IQR 21.1-27.3) kg/m²) showed a slight, nonsignificant decrease in GFR (-2.1 mL/min per 1.73m²; 95% CI, -4.9 to 0.8), with no changes in other kidney hemodynamic parameters. Conclusions: In this cohort of transgender individuals, GFR increased during feminizing hormone therapy, likely due to afferent vasodilatation, while during masculinizing hormone therapy GFR tended to decrease. These findings suggest an influence of sex hormones on kidney hemodynamics, especially during feminizing hormone therapy. Presentation: 6/3/2024

8693 Dexamethasone Increases Bone Mass In Mice

Abstract Disclosure: F. Sultana: None. M.L. Temple: None. S. Kim: None. V. Ryu: None. F. Korkmaz: None. A. Gumerova: None. P. Georgii: None. U. Cheliadinova: None. D. Vasilyeva: None. V. Laurencin: None. R. Witztum: None. O. Barak: None. L. Cullen: None. A.R. Pallapati: None. S. Rojekar: None. J. Gimenez Roig: None. D. Lizneva: None. W. Zhou: None. T. Yuen: None. M. Zaidi: None. Severe osteoporosis and bone fractures are strongly associated with long-term or recurring glucocorticoid use in people. Steroids have traditionally been used as an anti-inflammatory and immunosuppressive agent, and while their use has been widely implicated in causing bone loss by suppressing osteoblastic bone formation, recent data have consistently shown mixed results in mice. It is also important to stress that dexamethasone (DEX) in particular has been used for over three decades in cell cultures to stimulate osteoblast formation. We therefore posit that mechanisms other than direct steroid effects on osteoblasts contribute to bone loss, and that, at least physiologically, steroids stimulate (rather than inhibit) bone formation. Here, we have aimed to clarify the effects of DEX on bone metabolism. We first studied the effects of low and high doses of DEX (1 mg/kg and 10 mg/kg), given daily as intraperitoneal injections to 8-week-old C57BL/6 mice. Micro-CT showed that DEX markedly increased bone microarchitecture, including the bone volume fraction, connectivity density, and trabecular number, while decreasing trabecular spacing in femoral epiphyses compared with vehicle-injected controls. Serum levels of adrenocorticotropic hormone (ACTH) and corticosterone did not change following DEX. These findings suggest that both low and high DEX doses are anabolic to the skeleton. Reaffirming these data, we found that adrenalectomy (with salt replacement) caused a significant decline in bone mineral density. Likewise, Tpit-/- mice, in which ACTH and corticosterone are both reduced, display reduced bone microarchitectural parameters, together with low mineralizing surface and bone formation rates on dynamic histomorphometry, impaired osteoblast formation in Cfu-f cultures, and lowered expression of the osteoblastogenesis genes Bmp2, Ibsp, Runx2 and Sp7. Finally, deleting the glucocorticoid receptor (Gr) specifically in osteoclasts in Acp5-Cre;Grfl/fl mice had no effect on microarchitectural parameters at the spine or proximal tibial metaphysis. However, and importantly, absent GR in the osteoclast, DEX increased bone mass significantly, suggesting that its notable anabolic action was mediated by the osteoblast. Our findings challenge the longstanding premise that steroids directly impact the osteoblast to cause bone loss, and that other mechanisms, such as reduced ACTH levels and/or central effects of DEX, may play a key role. Presentation: 6/1/2024

Menopausal state and rheumatoid arthritis: a systematic review and meta-analysis.

Rheumatoid arthritis (RA) is a chronic inflammatory condition primarily affecting the joints. The higher prevalence of RA among females, combined with the known effects of sex hormones on immune function, has led researchers to investigate the potential relationship between menopausal status and the risk, severity, or progression of RA. This systematic review and meta-analysis aimed to determine the association between menopause and rheumatoid arthritis. In 2023, we conducted a comprehensive search across multiple databases, including Google Scholar, Scopus, PubMed/MEDLINE, Science Direct, Web of Science, EMBASE, Springer, and ProQuest. The search aimed to identify studies exploring the association between menopause and rheumatoid arthritis. Our analysis revealed that post-menopausal women had a higher risk of developing rheumatoid arthritis compared to pre-menopausal women, with an estimated odds ratio of 1.35 (95% CI: 1.04-1.67). Additionally, women who experienced early menopause (defined as onset before age 45) showed significantly higher odds of developing RA, with an odds ratio of 2.97 (95% CI: 1.73-4.22). These findings highlight the importance of considering menopausal status when assessing the risk of RA development in women. The results suggest that post-menopausal women, particularly those who experience early menopause, may be at higher risk for developing RA. Further research in this area could provide valuable insights into potential preventive measures and targeted interventions for high-risk individuals.

Helper T cells: A potential target for sex hormones to ameliorate rheumatoid arthritis? (Review).

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease whose etiology is not fully understood. Defective peripheral immune tolerance and subsequent mis‑differentiation and aberrant infiltration of synovium by various immune cells, especially helper T (Th) cells, play an important role in the development of RA. There are significant sex differences in RA, but the results of studies on the effects of sex hormones on RA have been difficult to standardize and hormone replacement therapy has been limited by the potential for serious side effects. Existing research has amply demonstrated that cellular immune responses are largely determined by sex and that sex hormones play a key role in Th cell responses. Based on the aforementioned background and the plasticity of Th cells, it is reasonable to hypothesize that the action of sex hormones on Th cells will hopefully become a therapeutic target for RA. The present review discussed the role of various Th cell subsets in the pathogenesis of RA and also explored the role of sex hormones on the phenotype and function of these aberrantly regulated immune cells in RA as well as other pathologic effects on RA.

Correlation Between Sex Hormones (Testosterone and Prolactin) and Anti-ds-DNA Antibody Levels in Systemic Lupus Erythematosus Patients: A Gender-Specific Analysis of the Hormonal Influence on Immune Responses.

Background Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that mostly affects women and has a noteworthy gender gap. Although the precise effects of sex hormones on SLE are yet unknown, they may modulate the immune response and affect the severity of the illness. Two important sex hormones that have apossible influence on autoimmune processes are prolactin and testosterone. The objective of this study was to assess the correlation between the levels of different sex hormones (testosterone and prolactin) and anti-double-stranded DNA (anti-ds-DNA) antibody levels in Sudanese anti-ds-DNA-positive SLE patients. Methodology A prospective cross-sectional study was conducted from February to July 2017 at Al-Rayan Specialized Medical Laboratory Complex and Omdurman Military Hospital, Sudan. There were 90 SLE patients who tested positive for anti-ds-DNA. Using commercial kits, serum levels of prolactin, testosterone, and anti-ds-DNA antibodies were tested from blood samples. SPSS version 21 was used for statistical analysis to find relationships between hormone levels and antibody levels. Results In this study of 90 patients with SLE, gender distribution was 14 males (16%) and 76 females (84%). The mean prolactin levels were significantly higher in males (17.99 ng/ml) compared to females (15.73 ng/ml, P < 0.001), and testosterone levels were also significantly higher in males (1.43 ng/ml) than females (0.37 ng/ml, P = 0.001). Although males had slightly higher mean levels of anti-ds-DNA antibodies (4.51) compared to females (4.08), this difference was not statistically significant. The results of correlation analyses indicated a weak and non-significant link between anti-ds-DNA antibody levels and hormone levels, with prolactin's Spearman's rho value of -0.054 (P = 0.616) and testosterone's Spearman's rho value of 0.080 (P = 0.456). Conclusion It was found that prolactin and testosterone levels differ by gender in SLE patients and that these hormones may have an impact on how the condition is managed. But the poor associations with anti-ds-DNA antibody levels suggest that further investigation is required to fully comprehend these intricate interactions.

Gender-specific alteration of steroid metabolism and its impact on viral replication in a mouse model of hepatitis B virus infection

ABSTRACT Hepatitis B virus (HBV) is a sex-specific pathogen that is more severe in males than in females. Sex disparities in HBV infection have been attributed to hormonal differences between males and females. However, whether HBV infection affects the metabolic signatures of steroid hormones and how these influences viral replication remains unclear. In this study, we investigated whether HBV infection alters steroid metabolism and its effects on HBV replication. Serum samples from male and female mice obtained after the hydrodynamic injection of replication-competent HBV plasmids were subjected to quantitative steroid profiling. Serum steroid levels in mice were analyzed using an in vitro metabolism assay with the mouse liver S9 fraction. The alteration of steroids by HBV infection was observed only in male mice, particularly with significant changes in androgens, whereas no significant hormonal changes were observed in female mice. Among the altered steroids, dehydroepiandrosterone (DHEA) levels increased the most in male mice after HBV infection. An in vitro metabolism assay revealed that androgen levels were significantly reduced in HBV-infected male mice. Furthermore, the genes involved in DHEA biosynthesis were significantly upregulated in HBV-infected male mice. Interestingly, reduced dihydrotestosterone in male mice significantly inhibits viral replication by suppressing HBV promoter activity, suggesting a viral strategy to overcome the antiviral effects of steroid hormones in males. Our data demonstrated that HBV infection can cause sex-specific changes in steroid metabolism.

Timed topical dexamethasone eye drops improve mitochondrial function to prevent severe retinopathy of prematurity.

Pathological neovascularization in retinopathy of prematurity (ROP) can cause visual impairment in preterm infants. Current ROP treatments which are not preventative and only address late neovascular ROP, are costly and can lead to severe complications. We showed that topical 0.1% dexamethasone eye drops administered prior to peak neovessel formation prevented neovascularization in five extremely preterm infants at high risk for ROP and suppressed neovascularization by 30% in mouse oxygen-induced retinopathy (OIR) modeling ROP. In contrast, in OIR, topical dexamethasone treatment before any neovessel formation had limited efficacy in preventing later neovascularization, while treatment after peak neovessel formation had a non-statistically significant trend to exacerbating disease. Optimally timed topical dexamethasone suppression of neovascularization in OIR was associated with increased retinal mitochondrial gene expression and decreased inflammatory marker expression, predominantly found in immune cells. Blocking mitochondrial ATP synthetase reversed the inhibitory effect of dexamethasone on neovascularization in OIR. This study provides new insights into topical steroid effects in retinal neovascularization and into mitochondrial function in phase II ROP, and suggests a simple clinical approach to prevent severe ROP.

Corticosteroid-induced Glaucoma: An avoidable blindness

Healthcare professionals frequently advise the use of topical steroid eye drops to manage and control postoperative inflammation following phacoemulsification. Although there are many benefits associated with steroid usage, it is imperative to recognize the potential negative repercussions that may arise. In individuals who respond to steroids, the use of topical steroid drops can lead to an increase in intraocular pressure (IOP). Increase in IOP resulting from the side effects of steroids typically manifests several weeks following the initiation of eye drop therapy. The first documentation of steroid induced glaucoma (SIG) can be traced back to the 1950s on the administration of systemic adrenocorticotropic hormones. The elevation of IOP is a complex issue influenced by various factors, but the primary factor is the increased resistance within the outflow mechanisms of the trabecular meshwork. Out of all the risk factors related to ocular hypertension caused by steroid use, a preexisting glaucoma diagnosis is the most frequently seen. The usage of different routes of steroids administration has been linked to the occurrence of ocular hypertension. The current management approach prioritizes the exploration of steroid-sparing treatment options, discontinuing steroid use, employing medications to lower intraocular pressure, and considering interventional laser and surgical procedures.