Zinc (Testosterone)

Orexin-A and orexin-B, originally discovered as hypothalamic neuropeptides, have been detected in extra-hypothalamic tissues together with their receptors (OX1R and OX2R) since the early 2000s. This systematic review is the first to comprehensively synthesize evidence on the autocrine/paracrine effects of locally produced orexin across extra-hypothalamic tissues. Following PRISMA 2020 guidelines, a systematic search was conducted in PubMed, Web of Science Core Collection, Cochrane Central Register of Controlled Trials, and Google Scholar. Eligible studies were original, full-text, peer-reviewed articles reporting primary data on prepro-orexin/orexin peptide and/or OX1R/OX2R expression in non-neuronal extra-hypothalamic tissues, with evidence of co-expression within the same cell/tissue or functional effects reasonably attributable to locally produced orexin. From the 10 eligible studies, autocrine orexinergic signaling was functionally demonstrated in the adrenal gland (steroidogenesis via Gq/PLC/IP3/Ca2+), male reproductive tract (testosterone secretion), adipose tissue (lipolysis/thermogenesis), heart (myocardial protection via PI3K/Akt/eNOS), pancreas (glucose-regulated insulin/glucagon modulation), and liver (lipogenesis via ERK1/2). OX1R primarily activates the Gq/PLC/IP3/Ca2+ pathway, resulting in ERK1/2 and p38 MAPK signaling (promoting secretion and proliferation), while OX2R couples to Gs/Gi, modulating cAMP and PI3K/Akt (favoring cytoprotection and anti-apoptosis). Autocrine orexinergic signaling constitutes a legitimate, compartment-autonomous regulatory mechanism in peripheral tissues, enabling rapid, tissue-specific responses insulated from central fluctuations. © 2026 The Author(s). Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.

OBJECTIVE: To evaluate the effects of oral vitamin D supplementation on semen parameters, reproductive hormones and fertility outcomes in infertile men. METHODS: We searched PubMed, Cochrane Library, Web of Science, Scopus and Embase for studies published within the last 10 years. Randomized controlled trials (RCTs) and observational studies evaluating oral vitamin D supplementation in infertile men and reporting semen parameters, reproductive hormones and/or fertility outcomes were included. Risk of bias was assessed using RoB 2.0 (RCTs) and ROBINS-I (observational studies). RESULTS: Eleven studies (eight RCTs and three observational studies; n = 1,168) were included. Vitamin D supplementation was associated with small but statistically significant improvements in semen volume, sperm concentration, progressive motility and serum testosterone. No significant effects were observed on clinical pregnancy or live birth. Reporting of adverse events was limited; no vitamin D-related serious adverse events were reported. CONCLUSIONS: Vitamin D supplementation may improve selected semen parameters and testosterone levels in infertile men, particularly progressive sperm motility. However, current evidence does not demonstrate improved clinical fertility outcomes, and higher doses (>4,000 IU/day) do not appear to confer additional benefits. Larger, well-designed trials with standardized fertility endpoints are needed to confirm clinical efficacy. ©2026 Zhang et al.

Although sex differences in spatial cognition have been widely studied, the extent to which men and women differ in their use of egocentric and allocentric spatial strategies remains unclear. This systematic review summarizes findings from 21 studies published between 2014 and 2024 that examined sex differences in spatial strategy use throughout development, adulthood, and aging. Studies were identified through searches of Scopus, Web of Science, PubMed, and PsycINFO, in accordance with PRISMA guidelines. Eligible articles examined egocentric and allocentric spatial strategies in humans and reported results by sex. Results demonstrated male advantages in allocentric strategy, as observed in thirteen studies involving children, young adults, and older adults. Men also outperformed women in several navigation outcomes, including target retrieval, route efficiency, and directional accuracy. Evidence for a female advantage in egocentric strategies was limited and inconsistent. Seven studies reported no sex differences, particularly those using small-scale, familiar, or less immersive tasks. This suggests that methodological factors and task demands strongly influence the observed effects. Age also influenced outcomes. Male advantages in allocentric strategies emerged in early childhood. Older women showed relatively preserved egocentric abilities, but greater decline in allocentric tasks. Men showed stronger hippocampal-parietal connectivity supporting allocentric processing, while women exhibited enhanced fronto-temporal connectivity. Hormonal studies highlight the context-dependent effects of testosterone and estrogen. These findings indicate that sex differences in spatial strategies are highly sensitive to task complexity, environmental familiarity, cognitive load, and individual factors. These findings emphasize the necessity of integrative models that consider developmental, neurobiological, and sociocultural contributors.

BACKGROUND: Obesity has become a major global public health challenge, closely associated not only with metabolic and cardiovascular disorders but also with male sexual dysfunction. Emerging evidence suggests that bariatric surgery may improve sexual function in obese men by enhancing hormonal balance, reducing visceral adiposity, and restoring endothelial function. However, existing studies show strong heterogeneity in design, surgical approaches, and sample sizes, underscoring the need for an updated systematic review and meta-analysis. OBJECTIVE: To systematically evaluate and meta-analyze the effects of bariatric surgery on sexual function and related hormonal levels in obese men. METHODS: PubMed, Web of Science, Embase, and the Cochrane Library were systematically searched for relevant studies published up to June 2025. A random-effects model was applied to pool effect sizes, and heterogeneity was assessed using the I² statistic. Changes in International Index of Erectile Function (IIEF) scores and hormone levels before and after surgery were evaluated. Subgroup analyses, sensitivity analyses, and publication bias assessments were conducted, with all analyses performed using Stata 17.0. RESULTS: A total of 21 studies involving 695 participants were included. Pooled analyses showed significant improvements in both IIEF-5 and IIEF-15 total scores after surgery (MD = 6.45 and 9.03, respectively; p < 0.001), indicating overall enhancement in sexual function. Domain-specific results demonstrated significant improvements in erectile function, orgasmic function, sexual desire, intercourse satisfaction, and overall satisfaction, with erectile function showing the greatest improvement (SMD = 0.76); however, differences between domains were not statistically significant. Regarding hormonal outcomes, total testosterone increased significantly after surgery (MD = 8.21, p < 0.001), whereas free testosterone showed no significant change. Body mass index (BMI) decreased markedly (MD = -13.86, p < 0.001). Subgroup analyses consistently supported the beneficial effects of surgery. Sensitivity analyses confirmed the robustness of the results, and Egger's test indicated no si

BACKGROUND: Accentuated eccentric loading (AEL) is a resistance training (RT) method applying greater eccentric- than concentric-phase load to intensify the training stimulus; however, despite its common use, a comprehensive and quantitative review remains lacking. OBJECTIVE: The aim was to compare acute responses and chronic adaptations between AEL and constant-load RT, and examine whether effects vary by AEL protocol (submaximal, maximal, supramaximal). METHODS: PubMed, Web of Science, Embase, and EBSCO were searched from inception through July 3, 2024; eligible English-language studies were included. Pooled and subgroup meta-analyses were performed using random-effects models. RESULTS: Forty-nine studies involving 773 participants were included. Although considerable variance exists in certain outcomes, our estimated effects suggest that, compared to constant-load RT, AEL results in (1) similar acute responses in loads lifted during the concentric phase (standardized mean difference [SMD] = - 0.16; p = 0.48), mechanical performance at submaximal loads during the concentric phase (SMD = - 0.07; p = 0.37), countermovement jump height both immediately (SMD = - 0.06; p = 0.86) and delayed (SMD = - 0.23; p = 0.44) post-intervention, maximal voluntary isometric force immediately post-intervention (SMD = 0.03; p = 0.89), blood lactate concentration during the intervention (SMD = - 0.06; p = 0.78), testosterone concentration immediately post-intervention (SMD = 0.68; p = 0.15), creatine kinase concentration both immediately (SMD = 0.09; p = 0.72) and delayed (SMD = 0.14; p = 0.48) post-intervention, cortisol concentration immediately post-intervention (SMD = 0.39; p = 0.05), heart rate during the intervention (SMD = 1.18; p = 0.07), acute muscle swelling immediately post-intervention (SMD = 0.26; p = 0.42), muscle electrical activity during the concentric phase (SMD = - 0.01; p = 0.90), and muscle soreness both immediately (SMD = 0.28; p = 0.30) and delayed (SMD = 0.18; p = 0.28) post-intervention; (2) greater acute responses in blood lactate concentration immediately post-intervention (SMD = 0.44; p = 0.03), growth hormone concentration immediately post-intervention

OBJECTIVE: To systematically evaluate the effect of short-term androgen therapy on final adult height in boys with constitutional delay of growth and puberty (CDGP). METHODS: Original studies investigating androgen therapy in children with CDGP and reporting final adult height as an outcome were retrieved from PubMed, Embase, Web of Science, and SpringerLink. The search period extended from database inception to September 2025. EndNote 20.0 was used for duplicate removal, and study quality was assessed using the Newcastle-Ottawa Scale (NOS). Literature screening, data extraction, and quality assessment were independently conducted by two researchers, with discrepancies resolved through consultation with a third researcher. Meta-analysis was performed using R 4.5.2 and Review Manager 5.4.1. RESULTS: A total of 13 eligible retrospective cohort studies involving 803 patients were included. Sensitivity analyses demonstrated good robustness of the pooled results, and Egger's tests indicated no significant publication bias (P1 = 0.0794, P2 = 0.3982). Meta-analysis showed that, compared with untreated controls, androgen therapy-including testosterone and oxandrolone-significantly increased measured final adult height [MD = 1.78 cm, 95% CI (0.47, 3.08), P = 0.0076] and significantly improved final height Z-scores [MD = 0.24, 95% CI (0.07, 0.41), P = 0.0057]. Subgroup analyses revealed that the low-dose regimen yielded the most favorable effect [MD = 1.88 cm, 95% CI (0.63, 3.12), P = 0.003], whereas the medium-dose [MD = 1.17 cm, 95% CI (-0.90, 3.25), P = 0.268] and high-dose regimens [MD = 1.68 cm, 95% CI (-5.07, 8.42), P = 0.626] showed no statistically significant benefit. Short-course therapy was associated with greater improvement in final adult height compared with long-course therapy [MD = 2.70 cm, 95% CI (1.30, 4.09), P < 0.001]. In addition, testosterone demonstrated superior efficacy compared with oxandrolone [MD = 2.64 cm, 95% CI (1.44, 3.80), P < 0.001]. CONCLUSION: Short-term androgen therapy can improve final adult height in boys with CDGP, with low-dose, short-course testosterone regimens appearing to be the most favorable option. Given the limited number

PURPOSE: This systematic review aimed to summarize evidence on continuous testosterone therapy during ovarian stimulation in trans masculine individuals. METHODS: A search of Medline, EMBASE, Cochrane, PubMed, CINAHL, Web of Science, and ClinicalTrials.gov was conducted through October 2024 in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies reporting ovarian stimulation on continuous testosterone therapy were included. The Joanna Briggs Institute Checklist for Case Reports was used to assess risk of bias, and descriptive statistics and qualitative synthesis were conducted. RESULTS: The review included six articles involving eight patients. Median age at oocyte cryopreservation was 27 years (range 20-34), and median age at initiation of testosterone was 24 (range 18-27). An antagonist protocol was used for seven patients. Letrozole was given to three patients during their cycle. Oocytes were cryopreserved for four patients, embryos were cryopreserved at the time of stimulation for two patients, and two patients created embryos from cryopreserved oocytes. The median number of oocytes retrieved from seven patients was 20 (range 13-56), and the median number of oocytes cryopreserved from six patients was 22.5 (range 9-30). To date, three embryo transfers (two frozen and one fresh) have been reported, all resulting in live births. CONCLUSION: Live births, oocyte and embryo cryopreservation, are possible across a range of stimulation protocols under testosterone exposure. As trans masculine patients report gender dysphoria with the fertility preservation process, these case reports present an opportunity for reconsideration of current practices and propose a paradigm shift in fertility care for transgender individuals.

BACKGROUND: The negative impact of obesity on male fertility and sexual health is well-established. Although metabolic and bariatric surgery (MBS) offers a powerful solution for severe obesity, its impact on the male androgens, semen quality, and sexual function are not yet fully understood. METHODS: A comprehensive systematic search of the literature was conducted in PubMed, Embase, the Cochrane Library, and Web of Science for relevant studies published up to July 2024. Data about reproductive hormones, semen parameters, and sexual function in men with obesity undergoing bariatric surgery was extracted. For data synthesis, weighted mean differences (WMDs) and their 95% confidence intervals (CIs) were calculated using random- or fixed-effects models, as appropriate. RESULTS: Fifty-nine studies with 60 arms were included in our meta-analysis. Metabolic and bariatric surgery indicated elevated levels of total testosterone (TT) (WMD: 5.46 nmol/L, p < 0.001; WMD: 6.58 nmol/L, p < 0.001; and WMD: 8.02 nmol/L, p < 0.001), sex hormone-binding globulin (SHBG) (WMD: 14.56 nmol/L, p < 0.001; WMD: 18.08 nmol/L, p < 0.001; and WMD: 23.64 nmol/L, p < 0.001), international index of erectile function (IIEF) (WMD: 9.36, p < 0.001), and diminished levels of PRL (WMD: -76.48 mIU/L, p = 0.003) at all intervals. Moreover, increased levels of free testosterone (FT) at 6-9 month (WMD: 66.61 nmol/L, p < 0.001), and >12 months (WMD: 78.94 nmol/L; p < 0.001) were observed pos-operative state among obese men. Also, decreased levels of estradiol (E2) at 6-9 month (WMD: -14.52 nmol/L, p = 0.005), and ≥12 months (WMD: -11.63 nmol/L; p < 0.001) was seen after bariatric surgery. CONCLUSION: Overally, this meta-analysis illustrated that bariatric surgery improves the hormonal profile and sexual function in obese men profoundly. These findings introduce bariatric surgery as an effective therapeutic strategy for weight loss management and male reproductive health improvement.

INTRODUCTION: Male infertility is a rising problem globally with male factors contributing up to 50% of all couple infertility cases. The sperm quality decline raises serious concerns regarding future population sustainability and male reproductive health. Adipose-derived mesenchymal stem cell (AdMSC) secretome, defined as a cell-free product comprising paracrine factors secreted by these cells, has emerged as a promising cell-free regenerative therapy for testicular injury, offering advantages of accessibility and therapeutic potential. This systematic review aimed to evaluate the effectiveness of AdMSC secretome in chemically induced testicular injury models. METHODS: A systematic literature search was conducted across four electronic databases (PubMed, Google Scholar, OVID and Cochrane) covering publications from 2015 to 2025. Preclinical studies investigating the therapeutic effects of AdMSC secretome in murine models of chemically induced testicular injury were included. RESULTS: Three preclinical studies utilizing male murine models were analysed. Testicular injury was induced using busulfan, doxorubicin or acrylamide. AdMSC secretome was administered via intra-testicular injection (n=2) and intravenous injection (n=1). All studies demonstrated partial regeneration of seminiferous tubule in secretome-treated groups compared with controls. Two studies reported reduced cellular apoptosis using TUNEL assay and acridine orange staining. An increase in Leydig cell numbers was observed following secretome treatment, while Sertoli cells remained unchanged. One study identified vascular endothelial growth factor (VEGF) as a key paracrine mediator, with anti-VEGF intervention abolishing the therapeutic effect. Testosterone levels were consistently higher in secretome-treated groups compared to those receiving AdMSC transplantation. CONCLUSIONS: AdMSC secretome demonstrates therapeutic potential in chemically-induced testicular injury by promoting seminiferous tubule regeneration, reducing apoptosis, and enhancing Leydig cell recovery, with VEGF playing a critical mechanistic role. These findings support the potential AdMSC secretome as a cell-free regenerative appr

Background/Objectives: Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder characterized by reproductive and metabolic dysfunction. Vitamin D deficiency is common in women with PCOS and is linked to adverse metabolic and reproductive outcomes. However, the role of vitamin D supplementation in managing PCOS remains unclear due to the heterogeneous evidence available. This systematic review aimed to synthesize both observational and interventional studies to assess the association between vitamin D levels and PCOS, focusing on prevalence, metabolic outcomes, and reproductive parameters. Methods: A comprehensive search of PubMed, Web of Science, Scopus, and Embase was conducted in October 2025, identifying studies published between January 2000 and October 2025. Eligible studies included observational studies and randomized controlled trials (RCTs) evaluating serum 25-hydroxyvitamin D [25(OH)D] levels and/or the effects of vitamin D supplementation in women with PCOS. Studies were included if they used recognized diagnostic criteria for PCOS or sufficient diagnostic details to confirm the condition. Two reviewers independently performed screening, data extraction, and quality assessment according to PRISMA 2020 guidelines. Results: Eleven studies (nine RCTs, two observational) encompassing 1063 women with PCOS met the inclusion criteria. Observational studies demonstrated inverse associations between serum 25(OH)D levels and insulin resistance, body mass index (BMI), and leptin, but not with total testosterone. RCTs showed modest and inconsistent improvements in insulin sensitivity, with effects more apparent in some trials enrolling vitamin D-deficient women. Reproductive benefits (cycle regularity/ovulation) were observed only in selected trials, generally with small samples and short follow-up. Conclusions: Vitamin D deficiency is common in women with PCOS and correlates with metabolic and reproductive dysfunction. While vitamin D supplementation shows variable effects, it should not be considered a stand-alone therapy for PCOS. Correction of deficiency may complement existing treatments, but evidence remains insufficient to support routine vitami

BACKGROUND: This study investigated whether triple therapy with human chorionic gonadotropin (hCG), follicle-stimulating hormone(FSH) and testosterone(T) in congenital hypogonadotropic hypogonadism(CHH) promoted more timely virilization, aiding psychosocial development while reducing hCG requirements, offering a balanced approach to long-term management. METHODS: An open-label randomized controlled trial (1:1:1) was conducted in adult males with CHH. Group A received triple therapy, Group B received combined hCG and FSH from the outset, and Group C received hCG monotherapy followed by combined FSH and hCG. Initial doses comprised hCG 2,000 IU twice weekly, FSH 75 IU thrice weekly and intramuscular testosterone(T) 100 mg every two weeks. Group A titrated hCG to achieve AMH of 7.4ng/ml; Groups B and C aimed for T normalization. Primary outcomes were hCG/FSH doses required for spermatogenesis induction and the time to spermatogenesis. RESULTS: Forty-five CHH males (mean age 25.8 ± 6.1years) were randomized. Spermatogenesis was achieved in 84.6% of group A participants compared with 69.2% and 75% in groups B and C, respectively(p=0.648). Median hCG dose at spermatogenesis was 7500IU/week in group A and 9000IU/week in groups B and C(p=0.016). The time to spermatogenesis was comparable (Groups A/B:12 months; Group C:15 months;p=0.345). Group A participants achieved an AMH of 3.5(2.31-5.38)ng/ml, comparable to the other groups(p=0.962). Predictors of spermatogenesis included USGmTV cut-off of 1.97ml (sensitivity-86.2%,specificity-62.5%), hCG dose of 9,000 IU/week (sensitivity-79.3%,specificity-87.5%) and an Inh B cut-off of 66.8 pg/ml(sensitivity-92.6%,specificity-100%). CONCLUSIONS: Triple therapy provided a better quality of life without compromising spermatogenesis. The AMH and Inh B provided an effective means of monitoring. CLINICAL TRIAL REGISTRATION: www.ctri.nic.in, identifier CTRI/2022/05/042795.

TESTOPEAK™ (KGC08EA; Korea Ginseng Corporation, Daejeon, Korea) has been developed to improve the symptoms of andropause. This 8-week, randomized, double-blind, parallel-group, placebo-controlled study was conducted to assess its efficacy and safety in improving the symptoms of andropause in Korean men. The eligible subjects were randomized either to the trial group or the control group, followed by an 8-week treatment period. The subjects of the trial group (n = 48) and those of the control group (n = 48) were orally given a tablet of TESTOPEAK™ and its matching placebo, respectively, at a dose of 500 mg/day once daily in the morning within 30 min after meal during an 8-week treatment period. Efficacy outcome measures include differences in changes in the Aging Male's Symptoms (AMS) scores, the Androgen Deficiency in Aging Male (ADAM) scores, the International Index of Erectile Function (IIEF) scores, hormone biomarker levels, lipid biomarker levels and body compositions at 8 weeks from baseline between the two treatment arms. Incidences of adverse events (AEs) served as safety outcome measures. There were significant differences in changes in the AMS scores, the ADAM scores, the IIEF scores, total testosterone, free testosterone and sex hormone binding globulin (SHBG) levels, total cholesterol, high-density lipoprotein (HDL) cholesterol and low-density lipoprotein (LDL) cholesterol levels and triglyceride levels and visceral and total fat area at 8 weeks from baseline between the two groups (p < .05). Moreover, there were no cases of AEs in each treatment group. TESTOPEAK™ is an effective, safe natural compound in alleviating symptoms of andropause in middle-aged or elderly men.

BACKGROUND: Transdermal estradiol (tE2) is an alternative to luteinizing hormone-releasing hormone (LHRH) agonists as androgen-deprivation therapy in patients with prostate cancer. With tE2, testosterone is suppressed, and the side effects of estrogen depletion due to LHRH agonists and the thromboembolic side effects of oral estrogen are mitigated. METHODS: In this phase 3, noninferiority, randomized trial, we assigned men with locally advanced (M0 and N0 or N+) prostate cancer to receive tE2 patches (100 μg of estradiol every 24 hours) or LHRH agonists. The primary outcome was 3-year metastasis-free survival. The noninferiority margin was 4 percentage points; this corresponded to a target hazard ratio of 1.31, as derived from the observed 3-year metastasis-free survival in the LHRH agonist group. Secondary outcomes included castrate levels of testosterone (<1.7 nmol per liter), overall survival, and safety. RESULTS: Between 2007 and 2022, we recruited 1360 patients at 75 U.K. centers. The median age of the patients was 72 years (interquartile range, 68 to 77); 85% had a T3 tumor stage and 65% an N0 nodal stage. Observed 3-year metastasis-free survival was 87.1% with tE2 and 85.9% with LHRH agonists (hazard ratio for confirmed metastasis or death, 0.96; upper limit of the one-sided 95% confidence interval [CI], 1.11, which met the criterion for noninferiority). Among patients continuing the assigned treatment, castrate levels of testosterone were sustained during the first year after randomization in 85% in each group. Observed 5-year overall survival was 81.1% with tE2 and 79.2% with LHRH agonists (hazard ratio for death, 0.90; 95% CI, 0.75 to 1.07). During treatment, hot flashes occurred in 44% of the patients who received tE2 and 89% of those who received LHRH agonists (grade ≥2 events, 8% and 37%, respectively) and gynecomastia in 85% and 42% (grade ≥2 events, 37% and 9%). CONCLUSIONS: In patients with locally advanced prostate cancer, tE2 was noninferior to LHRH agonists for 3-year metastasis-free survival, with a lower incidence of hot flashes but a higher incidence of gynecomastia. (Funded by Cancer Research U.K. and the U.K. Research Institute Medical Re

Severe diet- and exercise-induced energy deficit (SED) suppresses androgen production in healthy men, altering metabolism and driving muscle loss. The gut microbiota modulates host metabolism, yet the community's response to SED and any role of androgen hormones are unclear. Herein, healthy, physically active men were randomized to receive 200 mg/wk testosterone enanthate (n = 24) or placebo (n = 26) during a 28-day residential intervention that restricted energy intake and increased energy expenditure inducing a ∼2,000 kcal/day SED. Multiomic analyses revealed altered gut microbiota composition, reduced fecal short-chain fatty acids (SCFA), and shifts in bacterial metabolic pathways toward lipid utilization and mucin degradation during SED, suggesting adverse effects of SED on gut microbiota metabolic functions. Testosterone administration preserved certain SCFA-producing taxa and bioenergetic pathways without fully counteracting the effects of SED indicating a limited but potentially important interplay between androgen status and the gut microbiota under conditions of SED.NEW & NOTEWORTHY This study is the first to demonstrate that testosterone administration partially preserves gut microbiota composition and metabolic function during severe energy deficit in healthy men. Using a multiomic approach, we show that testosterone modulates short-chain fatty acid-producing taxa and microbial pathways linked to host energy metabolism. These findings reveal a novel role for androgens in shaping host-microbiome interactions during catabolic stress and may inform strategies to maintain metabolic resilience.

BACKGROUND: Female sexual dysfunction (FSD) among females with hypertension (HTN) is frequently overlooked, with a reported prevalence of 42.1%. OBJECTIVES: We aimed to determine the impact of beta-blockers (BBs), angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs), and thiazides on sexual function in hypertensive females. METHODS: A prospective randomized controlled trial enrolled 125 female participants. Group (1) included 25 normotensive females serving as the controls. Groups (2) and (3) consisted of 50 controlled and uncontrolled hypertensive patients who received BBs, respectively. Groups (4) and (5) consisted of 50 patients with controlled and uncontrolled HTN who received ACIs/ARBs, respectively. Each group consisted of patients who received one tablet daily of ramipril 2.5 mg for one month, while the other half received one tablet daily of valsartan (VAL) 80 mg for the same duration. After one month, the subjects were transitioned to a daily regimen of one tablet of ramipril 2.5 mg combined with hydrochlorothiazide 12.5 mg, as well as one tablet of VAL 80 mg with hydrochlorothiazide 12.5 mg for two months, respectively. RESULTS: Controlled and uncontrolled hypertensive patients receiving ACEIs/ARBs, as well as controlled hypertensive patients receiving BBs, demonstrated a significant decrease in serum total testosterone and free testosterone levels, accompanied by a significant increase in estradiol after 3 months. Furthermore, controlled and uncontrolled hypertensive patients receiving ACEI/ARBs showed significant increases in all female sexual function (FSF) domains and total FSF scores after 3 months. Consistently, controlled hypertensive patients receiving BBs showed significant improvements across all domains of the validated Arabic version of the female sexual function index (ArFSFI) and the total score, comparable to the ACEI/ARB groups, except for pain. Conversely, uncontrolled hypertensive patients receiving BBs demonstrated significant increases in scores for desire and arousal and orgasm and satisfaction after 3 months. After three months, there was a significant reduction in the GAD-7 scores among all hyperten

We investigated the effects of electroacupuncture on hormonal and metabolic characteristics in women with obesity-related polycystic ovary syndrome (PCOS). In this randomized controlled study, 120 patients were assigned to either an electroacupuncture group or a sham acupuncture group (60 per group) and treated three times weekly for 16 weeks. Hormonal profiles, metabolic parameters, inflammatory markers, ovarian morphology, and clinical outcomes were evaluated before and after intervention. Compared with sham treatment, electroacupuncture significantly reduced luteinizing hormone, LH/FSH ratio, testosterone, and anti-Müllerian hormone levels, while increasing sex hormone-binding globulin and progesterone. Metabolic improvements included reductions in triglycerides, LDL cholesterol, uric acid, fasting insulin, HOMA-IR, total cholesterol, and fasting plasma glucose, along with increased HDL cholesterol and vitamin D levels. Inflammatory markers (CRP, IL-6, TNF-α, WBC, C3, and C4) were also significantly decreased. Clinically, electroacupuncture improved ovulation rate and quality of life, and reduced hirsutism, ovarian volume, and antral follicle count. These findings suggest that electroacupuncture may serve as an effective adjunct therapy for endocrine and metabolic dysfunction in PCOS. Publisher: Nous avons étudié les effets de l’électroacupuncture sur les caractéristiques hormonales et métaboliques chez des femmes atteintes d’un syndrome des ovaires polykystiques (SOPK) associé à l’obésité. Dans cette étude randomisée contrôlée, 120 patientes ont été réparties en un groupe recevant une électroacupuncture ou un groupe témoin recevant une acupuncture simulée (60 patientes par groupe), avec trois séances par semaine pendant 16 semaines. Les profils hormonaux, les paramètres métaboliques, les marqueurs inflammatoires, la morphologie ovarienne ainsi que les résultats cliniques ont été évalués avant et après l’intervention. Comparativement au groupe témoin, l’électroacupuncture a significativement réduit les taux d’hormone lutéinisante, le rapport LH/FSH, la testostérone et l’hormone anti-müllérienne, tout en augmentant les concentrations de globuline liant les ho

BACKGROUND: Low muscle mass and reduced muscle strength are prevalent among adults, particularly in the aging population, and are associated with an increased risk of sarcopenia-related complications. Pennisetum purpureum Schumach is a plant known for its antioxidant properties, but its effects on muscle strength and function in adults with low muscle mass remain unexplored. In this study, we investigated the effects of Pennisetum purpureum Schumach supplementation on liver and kidney function, hormonal markers, anthropometric measurements, and physical performance in adults with low muscle mass. METHODS: A 12-week randomized, double-blind, placebo-controlled trial was conducted with 35 participants with low muscle mass and reduced muscle strength. The experimental group received 300 mg of Pennisetum purpureum Schumach extract three times daily, while the placebo group received a placebo. Assessments included grip strength, muscle mass, liver and kidney function, and a 10-meter walk test at baseline, 8 weeks, and 12 weeks. RESULTS: The experimental group showed a significant increase in grip strength (p < 0.05) after 8 and 12 weeks compared to baseline. No significant changes in muscle mass or performance in the 10-meter walk test were observed. Liver and kidney function remained unaffected in both groups. CONCLUSION: Pennisetum purpureum Schumach supplementation was associated with an increase in grip strength after 8 and 12 weeks. No definitive effects were identified for muscle mass, walking performance, liver or kidney function, or hormonal markers. Observationally, some variability in testosterone levels was noted among male participants; however, the study lacked the design and statistical power necessary to determine hormonal effects. These findings suggest that the supplementation may be safe and potentially useful, although larger and parameter-comprehensive trials are required to verify physiological mechanisms and confirm efficacy. © The author(s).

OBJECTIVES: Facial hair development is a crucial aspect of gender affirmation for transgender men. Despite testosterone therapy, incomplete facial hair growth remains a common concern. This randomized, double-blind, placebo-controlled trial evaluated topical 3% minoxidil for facial hair enhancement in 69 transgender men on stable gender-affirming hormone therapy (GAHT). METHODS: This randomized, double-blind, placebo-controlled trial enrolled 69 transgender men on stable GAHT, registered on the Thai Clinical Trials Registry (TCTR20220205004). Participants were randomized 1:1 to receive topical 3% minoxidil or vehicle placebo twice daily for 12 weeks. Primary outcomes were changes in hair density and diameter assessed via videodermoscopy. Secondary outcomes included modified Ferriman-Gallwey Score (mFGS), Dermatology Life Quality Index (DLQI), and patient satisfaction. RESULTS: The minoxidil group (n = 34) demonstrated significant improvements versus placebo (n = 35) in beard density (11.16 vs. 0.08 hairs/cm2, p = 0.01), beard diameter (5.37 vs. -0.33 μm, p = 0.01), mustache density (18.45 vs. 1.74 hairs/cm2, p = 0.003), and mustache diameter (4.83 vs. 1.31 μm, p = 0.008). Physician and patient-assessed mFGS showed significant improvements with minoxidil (p < 0.05). Quality of life improved markedly (median DLQI: 5 to 1.5 vs. 4 to 3, p < 0.05), with higher patient satisfaction scores (8.16 vs. 5.36, p < 0.001). Adverse events were minimal and comparable between groups. CONCLUSIONS: Topical 3% minoxidil represents an effective, safe, and well-tolerated adjunctive treatment for facial hair enhancement in transgender men receiving GAHT.

PURPOSE: This randomized controlled trial aimed to evaluate the impact of intermittent fasting (IF) during resistance training (RT) on body composition, muscular strength, and the testosterone:cortisol ratio in obese males. METHODS: Twenty obese males (aged 20-30, BMI 30-36 kg/m2) were selected from eligible volunteers and randomly assigned to control (regular diet) and IF (4:3 IF) groups. All subjects participated in RT 3 days/week for 8 weeks. Forty-eight hours before and after the protocol, blood sampling and anthropometric measurements were done in a fasting state, and data were analyzed at a significance level of p < 0.05. RESULTS: The IF/RT group lost twofold more weight and fat, had higher arm and chest measurements, and had less waist circumference than the C/RT group. The testosterone levels and muscle strength improved with RT, and there was no difference between the C/RT and IF/RT groups. CONCLUSION: It appears that intermittent fasting may enhance the efficacy of RT in obese males and is unlikely to have any detrimental effects on muscular strength or the anabolic index. Trial Registration: Iranian Registry of Clinical Trials (IRCT): IRCT20190213042702N4.

OBJECTIVE: Weight loss in older men with obesity and hypogonadism accelerates musculoskeletal decline, yet the underlying metabolic mechanisms remain unclear. Testosterone replacement therapy (TRT), when added to lifestyle therapy (LT), mitigates this decline, but its metabolic basis has not been defined. We examined skeletal muscle metabolomic adaptations to LT with or without TRT, focusing on glycolysis, the pentose phosphate pathway (PPP), the tricarboxylic acid (TCA) cycle, and carnitine metabolism to identify dominant pathways of metabolic adaptation. DESIGN: Randomized, double-blind, placebo-controlled trial (LITROS). METHODS: Eighty-three men aged 65 years or older with obesity (BMI ≥30 kg/m2), hypogonadism (testosterone <10.4 nmol/L), and frailty (Physical Performance Test score ≤31) were randomized to 26 weeks of LT plus TRT (LT+TRT) or LT plus placebo (LT+Pbo). A metabolomic substudy was performed in 44 participants, who underwent serial biopsies of the vastus lateralis for targeted LC-MS/MS analysis of intermediates in glycolysis, PPP, TCA cycle, and carnitine metabolism. RESULTS: Among the pathways examined, only glycolysis showed a consistent and significant response to LT+TRT versus LT+Pbo (between-group p = 0.005). This response was characterized by increases in preparatory (G6P/F6P, FBP) and payoff (3PG, 2PG, PEP) intermediates, along with higher lactate concentrations, whereas pyruvate remained stable. The PPP showed limited changes, and neither the TCA cycle nor carnitine metabolites exhibited consistent patterns. In LT+TRT, the glycolysis factor score was positively correlated with VO2peak (r=0.47, p = 0.04) and inversely correlated with triglycerides (r=-0.52, P = 0.01) and the metabolic syndrome score (r=-0.48, p = 0.02). No significant correlations were observed in LT+Pbo. CONCLUSIONS: TRT during LT selectively enhances skeletal muscle glycolysis, identifying glycolic activation as the dominant metabolic adaptation in this mechanistic study. By increasing glycolytic flux under calorie restriction, TRT may produce efficient ATP generation while conserving amino acids, supporting muscle and bone preservation and improving aerobic and cardiome

BACKGROUND: Psoroptic mange caused by Psoroptes ovis is the most common dermatological disease in rabbits; despite being an ectoparasite, in male rabbits P. ovis alters characteristic hormone-dependent behaviors like chinning and sexual behavior, also inducing a decrease in serum testosterone. Our goal was to evaluate the effect of P. ovis infestation on the histomorphology of testicular and submandibular (chinning) gland tissues of infected rabbits. METHODS: Glands were obtained from experimentally infested and healthy rabbits, processed for inclusion in paraffin and stained with hematoxylin-eosin. RESULTS: Testicular degeneration and submandibular gland hypertrophy were observed. In the testes of infested rabbits, lumen area and perimeter, seminiferous tubule area, tubule perimeter and diameter, increased. Conversely, germinal epithelium thickness and Johnsen scores of spermatogenic scale decreased, indicating impaired spermatogenesis. In the submandibular gland, lumen area and perimeter, and the total duct area and perimeter were increased. In addition, the area and perimeter of the acini also increased, while the number of acini decreased, consistent with glandular hypertrophy. CONCLUSIONS: The acarosis markedly alters the morphometric characteristics of both tissues, highlighting that psoroptic mange exerts a systemic effect on reproduction of the host altering non-dermal tissues with key roles in male reproductive function and chemical communication.

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

Epilepsy is associated with impaired reproductive function and testicular pathologies. Intermittent fasting (IF) is a nonpharmacological metabolic intervention with anti-inflammatory and antioxidant effects. This study investigated the protective effects of IF on testicular damage in a genetic absence epilepsy rat model (GAERS), focusing on histomorphology, oxidative stress parameters, and hormonal profiles. Testicular tissues from Wistar control (WC), Wistar + IF (WIF), GAERS control (GC), and GAERS + IF (GIF) groups (total n = 20; 5 rats per group) were evaluated using hematoxylin and eosin and Periodic Acid-Schiff staining. Apoptosis and spermatogenic cell integrity were assessed using caspase-3, P-element-induced wimpy testis (PIWI), and Deleted in Azoospermia-Like (DAZL) immunohistochemistry. Johnsen's score, seminiferous tubule diameter, and epithelial thickness were quantified. Oxidative stress markers, including catalase, malondialdehyde, glutathione, myeloperoxidase, and superoxide dismutase, were measured using spectrophotometric methods, and serum testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) levels were determined using ELISA kits. The GC group showed significantly reduced Johnsen scores, tubular diameters, and epithelial thickness, along with disrupted basement membrane integrity and increased caspase-3 immunoreactivity. IF significantly improved histological parameters, restored basement membrane integrity, reduced apoptosis, and increased PIWI and DAZL expression in the GIF group. IF also ameliorated oxidative stress and elevated reproductive hormone levels, indicating positive modulation of the hypothalamic-pituitary-gonadal axis. In conclusion, IF reduces oxidative stress and preserves seminiferous tubules and hormonal function in genetic absence epilepsy, highlighting its potential as a supportive nonpharmacological approach to protect male reproductive health.

Ferroptosis, a type of iron overload-induced cell death, is involved in diabetes-induced testicular dysfunction. Hence, this study was designed to investigate, for the first time, the impact of lipoxin A4 (LXA4) administration on testicular tissue in diabetic rats and explore its probable role in regulating ferroptosis in comparison with the standard ferroptosis inhibitor (ferrostatin-1, Fer-1). Albino rats of Wistar strain were divided into a control group, a type II diabetes mellitus (DM) group, a DM + Fer-1group, and a DM + LXA4 group. Serum levels of iron, insulin, glucose, total cholesterol, triglycerides, and testosterone were assayed. Testicular tissue markers of oxidative stress, ferroptosis, and inflammation were also assessed by different methods. Our results confirmed diabetes-induced testicular injury and disruption of its function via inducement of ferroptosis, but this was ameliorated with LXA4 and Fer-1 administration. However, Fer-1 showed a greater protective effect compared to LXA4 under the conditions of this study. We concluded that LXA4 partially secured the testicular tissue of diabetic rats against ferroptosis via augmenting the antioxidant Nrf2/SLC7A11/GPX4 pathway. Therefore, LXA4 may have a possible protective effect on the testicular tissue of diabetic patients.

Testicular tumors are the most common neoplasms of the canine male reproductive tract, corresponding to approximately 25% of all tumors in intact males. A large percentage of cases are characterized by one of three main tumor types: seminomas, interstitial Leydig cell tumors, or Sertoli cell tumors. Clinical importance is primarily associated with endocrine activity rather than malignant behavior; orchiectomy is the treatment of choice for most canine testicular cancers. Endocrine activity, particularly estrogen secretion, may result in feminization syndrome and, in severe cases, bone marrow suppression. The diagnostic approach combines physical examination, ultrasonography with hormonal assessment using endocrine testing (testosterone, estradiol, and T:E ratio), and/or tissue level evidence of the estrogen effect (preputial cytology). Management is centered on orchiectomy; unilateral surgery may be considered when the contralateral testis is clinically and ultrasonographically normal and when preservation of reproductive capacity or working ability is still a priority. Dogs with hormonally active tumors benefit from postoperative hematologic and endocrine monitoring. Recent advances in immunohistochemistry (IHC), such as Ki-67 and inhibin-α markers, and imaging techniques are improving tumor characterization and individualized clinical decision making.

This research aimed to examine the effects of different dietary levels of nano-selenium (NSE) on the reproductive performance, gonad hormones, histopathology, growth performance, feed utilization, and body indices in adult Nile tilapia, Oreochromis niloticus, broodstock for 90 days. The initial weights of the fish were 278.6 ± 5.5 (males) and 178.4 ± 1.6 (females). They were distributed randomly to 15 tanks with 20 fish in each tank (15 females and 5 males, sex ratio 3:1), with each treatment conducted with three replicates. The contents of NSE in five isocaloric and isonitrogenous practical feeds were 0 mg/kg (control), 1 mg/kg (T1), 2 mg/kg (T2), 3 mg/kg (T3), and 4 mg/kg (T4). Results show that the final weight (FW), weight gain (WG), specific growth rate (SGR), protein efficiency ratio (PER), and feed conversion ratio (FCR) were significantly better in T2 and T1, followed by the control, in comparison with others. On the other hand, growth efficiency was decreased in T3 and T4 of both males and females. Referring to body indices and reproductive performance, females were higher than males in the hepatosomatic index (HSI), where the lowest treatment was the control and T4 for both males and females. Female Nile tilapia brood fish given NSE improved reproductive performance indicators (egg number, total egg, and fry number) when compared with the control. With increasing levels of NSE in the feed, the levels of testosterone and progesterone hormones were increased. The highest values for testosterone were in T4, followed by T3, then T2, T1, and the control. The same trend was observed across the progesterone treatments. Additionally, the results of histopathological examination indicate differences in tissues between different treatments as a result of the addition of NSE. These results indicate that NSE supplementation at low levels could lead to improved growth and reproductive efficiency of Nile tilapia.

Testosterone (TST) deficiency and systemic inflammation may both contribute to osteoporosis, yet their joint effects remain underexplored. The platelet-to-lymphocyte ratio (PLR), a readily measurable marker of inflammation, may interact with TST to influence osteoporosis risk. To assess the independent and interactive associations between serum TST and PLR with osteoporosis in U.S. adults using National Health and Nutrition Examination Survey 2011 to 2016 data. We analyzed adults aged ≥20 years with complete data on bone mineral density, TST, and PLR. Osteoporosis was defined per World Health Organization criteria based on dual-energy X-ray absorptiometry bone mineral density. Low TST in men was defined as <300 ng/dL; PLR quartiles were derived from survey data, and cutoff points identified using restricted cubic spline analysis. Weighted logistic regression, restricted cubic spline modeling, and multiplicative interaction analysis were performed. Sensitivity analysis was conducted in participants ≥50 years. Weighted mean age was 39.5 years; 33.2% were male. Osteoporosis prevalence was 5.9%. Higher PLR showed a nonlinear positive association with osteoporosis risk (P for nonlinearity < .05), characterized by a steep increase in risk above the upper quartile. Lower TST was associated with increased odds of osteoporosis in men. A significant multiplicative interaction between low TST and high PLR was observed (P-interaction < .05). Results were consistent in adults ≥50 years. In U.S. adults, elevated PLR and lower TST were independently associated with greater odds of osteoporosis, with evidence of synergistic interaction. Prospective studies are warranted to validate these findings.

Microplastics (MPs) are increasingly recognized as emerging endocrine disrupting chemicals with significant implications for male reproductive health. Despite of well documentation on widespread presence in the environment, their specific effects on testosterone synthesis in humans remain insufficiently characterized. Current in vivo studies demonstrate that MPs impair androgen regulation through several interconnected mechanisms. These include oxidative stress-induced damage to Leydig cells, downregulation of antioxidant enzymes such as GPX1, disruption of the LH/cAMP/PKA/StAR signaling cascade essential for steroidogenesis, activation of NF-κB and inflammatory pathways, and induction of endoplasmic reticulum stress that accelerates testosterone metabolism. Additionally, MPs and their chemical additives interfere with steroidogenic enzymes and hormone receptors. Our review consolidates mechanistic insights linking MPs to testosterone disruption, underscores the dose-dependent nature of these effects. We also highlight critical knowledge gaps particularly the paucity of human data, the physicochemical diversity of MPs, and the long-term reversibility of endocrine disruption.

Emerging pollutants such as polystyrene-nanoplastics (PS-NPs) and polybrominated diphenyl ethers (PBDEs) are a threat to human health and ecological safety. However, NP-mediated PBDE exposure and toxicity remain poorly understood. Herein, male frogs (Pelophylax nigromaculatus) were exposed to 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) and 6‑hydroxy-2,2',4,4'-tetrabromodiphenyl ether (6-OH-BDE-47) alone or in combination with PS-NPs for 30 days to explore the carrier toxicity effect and mechanism of co-exposure. Transcriptome data verified that both BDE-47 and 6-OH-BDE-47 could mediate the steroid hormone synthesis signaling pathway to induce reproductive toxicity. The presence of PS-NPs increased the bioconcentration of BDE-47 and 6-OH-BDE-47 by 54.36 % and 51.49 %, respectively, and aggravate the damage of the testes. To investigate the mechanism underlying the disrupted steroidogenesis, changes in hormones of the hypothalamic-pituitary-gonadal (HPG) axis and gene expression involved in synthesis and transformation of sex hormones were assessed. AR, StAR, CYP11A1 and HSD3B1 were all downregulated, while mRNA expression levels of CYP19A1 and ESR1 were upregulated, accompanied by a decrease in testosterone and an increase in oestradiol. The results demonstrated that PS-NPs can exacerbate the estrogen-like effects of BDE-47 and 6-OH-BDE-47 in male frogs, highlighting the potential risks posed by these pollutants in aquatic ecosystems.

Comment on Prostate. 2025 Jul;85(10):919-931. doi: 10.1002/pros.24899. The article by Pae et al., titled "LHRH Antagonists Restore Serum Testosterone Faster Than LHRH Agonists in Prostate Cancer Patients After Radiotherapy," provides valuable insights into the differential effects of LHRH antagonists and agonists on testosterone recovery in prostate cancer patients undergoing androgen deprivation therapy. While the study highlights the statistically significant accelerated recovery of testosterone with LHRH antagonists, several limitations warrant further discussion. Notably, the study does not adequately address the variability in the duration and formulations of LHRH agents (e.g., 1-month, 3-month, and 6-month formulations), which may influence recovery times. Existing evidence suggests that long-acting formulations are associated with prolonged recovery, raising questions about whether the observed differences are due to pharmacological properties or formulation duration. The clinical relevance of faster testosterone recovery remains uncertain, as the study does not evaluate its impact on patient-reported outcomes such as quality of life, sexual function, or metabolic health. Future research should focus on stratifying analyses by formulation type and duration and assessing the clinical implications of testosterone recovery on patient-centered outcomes to enhance the applicability of these findings to clinical practice. © 2025 Wiley Periodicals LLC.