Search Results (192)

Background/Objectives: The effect of metformin on the secretory function of thyrotropic cells is sex-dependent. The current study aimed to investigate whether the impact of this drug on activity of the hypothalamic–pituitary–thyroid axis in women is impacted by the androgen status of patients. Methods: The study population included 48 levothyroxine-naïve reproductive-aged women with subclinical hypothyroidism and prediabetes receiving 3.0 g of metformin daily. Women with (n = 24) and without (n = 24) polycystic ovary syndrome were matched for age, insulin sensitivity, TSH, and reasons for thyroid hypofunction. Circulating levels of glucose, glycated hemoglobin, insulin, TSH, thyroid hormones, gonadotropins, androgens, estradiol, SHBG, prolactin, ACTH, and IGF-1 were measured before metformin treatment and six months later. Results: At entry, women with and without polycystic ovary syndrome differed in LH, LH/FSH ratio, androgens, and estradiol. The decrease in TSH, fasting glucose and glycated hemoglobin, and the improvement in insulin sensitivity were less pronounced in women with than in women without polycystic ovary syndrome. In each group, there were no differences in the impact on TSH and thyroid hormones between patients with subclinical hypothyroidism of autoimmune and non-autoimmune origin. The changes in TSH inversely correlated with total testosterone and free androgen index. Only in women with coexisting polycystic ovary syndrome, did metformin slightly reduce LH, LH/FSH ratio, testosterone, and free androgen index. Conclusions: The results suggest that concurrent polycystic ovary syndrome attenuates metformin action on TSH secretion, which can be explained by increased androgen production. Moreover, the drug seems to alleviate PCOS-associated changes in the activity of the reproductive axis. Full article

Background: Resistance training (RT) promotes muscle hypertrophy and strength gains in both men and women. However, sex differences in neuromuscular performance, muscle fiber composition, and the hormonal environment influence strength and power adaptations. While men generally exhibit greater absolute and relative strength, it remains unclear to what extent these differences persist across various load intensities. A better understanding of sex-specific strength and power profiles may help optimize training strategies. The aim of this study was to compare strength and power performance during the bench press exercise in physically active males and females, relative to body mass and fat-free mass (FFM). Methods: Twenty-nine physically active individuals (16 men: 21.3 ± 4.1 years, 13 women: 22.6 ± 4.9 years) performed a one-repetition maximum (1RM) test and an incremental velocity-based assessment at 45%, 55%, 65%, 75%, and 85% of the 1RM using a Smith machine. The barbell velocity was measured via a linear transducer, with the mean propulsive velocity (MPV) recorded for each load. Power-related variables (e.g., peak force [F0], maximal velocity [V0], and maximal power [Pmax]) were analyzed. To account for differences in body composition, data were adjusted for body mass and FFM. Results: Men exhibited significantly greater strength and power than women across most loads when adjusted for both body mass and fat-free mass (FFM) (p < 0.05). These differences were particularly pronounced when normalized to FFM (45–75%1RM; p = 0.001–0.031), with large effect sizes observed (ηp² = 0.185–0.383). Notably, sex differences in mean propulsive velocity (MPV) disappeared at 85%1RM (p = 0.208; ηp² = 0.06), suggesting that maximal neuromuscular recruitment may minimize sex-related disparities at higher intensities. Furthermore, men demonstrated significantly higher values in six of the seven power-related variables, with no significant differences in the %1RM required to achieve an optimal power output. Conclusions: These findings confirm that men exhibit greater strength and power than women, even after adjusting for body composition. However, at high relative loads (≥85%1RM), sex differences in movement velocity appear to diminish, likely due to similar recruitment patterns of high-threshold motor units. These results highlight the importance of sex-specific resistance training programs, particularly in relation to load prescription and the application of velocity-based training methods. Full article

This study investigated the effects of dietary Gonadotropin-releasing hormone (GnRH) and domperidone on the reproductive performance of Devario devario during a 40-day trial. Five treatment groups received varying doses of GnRH (100, 50, 25, 12.5 µg/kg body weight) in combination with domperidone (50, 25, 12.5, 6.25 mg/kg body weight), embossed in a gel-based diet alongside a control group without the exogenous hormones. Reproductive performance was examined by measuring the gonadosomatic index, fecundity, reproductive hormone levels, and histological features of the gonads, blood parameters, and antioxidant enzyme activity. The T1 group (100 µg GnRH + 50 mg domperidone) exhibited the highest GSI in both sexes. The histological analysis of testes from T1, T2 (50 µg GnRH + 25 mg domperidone), and T3 (25 µg GnRH + 12.5 mg domperidone) groups revealed an increased presence of late-stage spermatids and spermatozoa. In females, the T2 group produced the highest proportion of advanced-stage oocytes and demonstrated the greatest absolute fecundity (1300 ± 23 eggs). However, the control group showed the highest fertilization and hatching rates. Testosterone levels were significantly elevated in the T3 group, while vitellogenin levels increased in the T1 and T2 groups. Antioxidant enzyme activity varied, with the T1 group displaying higher superoxide dismutase activity in gills and liver, and the T2 group showing increased SOD activity in muscle and brain. Improvements in haematological parameters were observed across all treatments. These results suggest that an optimal dose of 50 µg GnRH + 25 mg domperidone can enhance reproductive performance in D. devario. Full article

Exercise interventions are increasingly recognized as effective non-pharmacological strategies to improve clinical outcomes in patients with breast cancer. This review provides a comprehensive framework linking physical activity with breast cancer risk reduction, disease progression, and survivorship. We first outline the robust epidemiological evidence demonstrating that regular exercise significantly reduces breast cancer incidence, recurrence, and disease-specific mortality. The review then delves into the molecular mechanisms by which exercise exerts its protective effects, including modulation of sex hormones, metabolic hormones, systemic inflammation, oxidative stress, circulating microRNAs, and breast cancer-related DNA methylation. Furthermore, we summarize findings from clinical trials evaluating the effects of exercise on cardiorespiratory fitness, functional capacity, and quality of life in breast cancer patients. Emerging research on the synergistic potential of exercise with conventional cancer treatments and bioactive dietary components, particularly polyphenols such as saffron and curcumin, is also discussed. Finally, we present evidence-based exercise recommendations tailored to breast cancer patients, emphasizing the importance of individualized prescriptions to optimize safety and therapeutic benefit. Collectively, this review highlights the multifaceted role of exercise in breast cancer prevention, treatment, and survivorship. Full article

Alzheimer’s disease (AD), the most common form of dementia, is a progressive neurodegenerative disorder characterized by memory loss and cognitive decline. In addition to its two major pathological hallmarks, extracellular amyloid beta (Aβ) plaques and intracellular neurofibrillary tangles (NFTs), recent evidence highlights the critical roles of mitochondrial dysfunction and neuroinflammation in disease progression. Aβ impairs mitochondrial function, which, in part, can subsequently trigger inflammatory cascades, creating a vicious cycle of neuronal damage. Estrogen receptors (ERs) are widely expressed throughout the brain, and the sex hormone 17β-estradiol (E2) exerts neuroprotection through both anti-inflammatory and mitochondrial mechanisms. While E2 exhibits neuroprotective properties, its mechanisms against Aβ toxicity remain incompletely understood. In this study, we investigated the neuroprotective effects of E2 against Aβ-induced mitochondrial dysfunction and neuroinflammation in primary cortical neurons, with a particular focus on the role of AMP-activated protein kinase (AMPK). We found that E2 treatment significantly increased phosphorylated AMPK and upregulated the expression of mitochondrial biogenesis regulator peroxisome proliferator-activated receptor gamma coactivator-1 α (PGC-1α), leading to improved mitochondrial respiration. In contrast, Aβ suppressed AMPK and PGC-1α signaling, impaired mitochondrial function, activated the pro-inflammatory nuclear factor kappa-light-chain enhancer of activated B cells (NF-κB), and reduced neuronal viability. E2 pretreatment also rescued Aβ-induced mitochondrial dysfunction, suppressed NF-κB activation, and, importantly, prevented the decline in neuronal viability. However, the pharmacological inhibition of AMPK using Compound C (CC) abolished these protective effects, resulting in mitochondrial collapse, elevated inflammation, and cell death, highlighting AMPK’s critical role in mediating E2’s actions. Interestingly, while NF-κB inhibition using BAY 11-7082 partially restored mitochondrial respiration, it failed to prevent Aβ-induced cytotoxicity, suggesting that E2’s full neuroprotective effects rely on broader AMPK-dependent mechanisms beyond NF-κB suppression alone. Together, these findings establish AMPK as a key mediator of E2’s protective effects against Aβ-driven mitochondrial dysfunction and neuroinflammation, providing new insights into estrogen-based therapeutic strategies for AD. Full article

The heart rate variability (HRV), influenced by female sex hormone fluctuations, is an indicator of athletes’ adaptation. This case study explores HRV responses over 18 months across a natural menstrual cycle (MC) and during oral contraceptive (OC) use in two Olympic female swimmers. HRV measurements—including mean heart rate (HR); root mean square of successive differences (RMSSD); and frequency-domain indices—were collected at rest in supine (SU) and standing (ST) positions across two competitive seasons. Nocturnal HR and RMSSD were assessed using the Ōura^® ring. MC and OC phases were identified through specific tracking, and training load was controlled. In both athletes, resting HR was lower during bleeding phases, increasing from menstruation to the luteal phase (MC) and from withdrawal to active pill phases (OC). In the ST position, RMSSD was higher but decreased throughout the phases. Nocturnal measurements confirmed these trends. Overall, findings suggest a phase-related parasympathetic overactivity shift. This study provides novel insights into HRV responses across hormonal cycles in elite female athletes, which present unique characteristics. Such monitoring tools may support a data-informed approach to guide and periodize training more effectively. Full article

Mini-puberty refers to the transient activation of the hypothalamic–pituitary–gonadal (HPG) axis during early infancy, lasting up to six months in boys and 12–24 months in girls. This phase represents the second activation of the HPG axis, following its initial activation during the second half of fetal life. At birth, the removal of the suppressive effect of placental estrogens on the HPG axis prompts a rise in both gonadotropins and sex steroid hormones, resulting in distinct clinical and laboratory markers of mini-puberty. While the clinical significance of mini-puberty remains partially understood, emerging evidence underscores its essential role in several aspects of human growth and development. In boys, testosterone influences penile growth, increases Sertoli cell numbers in the testes, and lays the foundation for future spermatogenesis. In girls, the increase in estradiol levels promotes follicular maturation and stimulates breast and uterine growth. Beyond the gonadal effects, mini-puberty appears to impact body composition, affecting body weight and promoting accelerated growth. Additionally, it may affect early psychosomatic and neural maturation, playing a role in several key aspects of the infantile brain. This narrative review examines recent findings on the physiology of the activation of the HPG axis before and after birth along with its significance in various aspects of human growth and development. In addition, mini-puberty-unique features in specific groups, such as preterm and small-for-gestational-age infants, are presented. Full article

Asthma is a chronic inflammatory disease characterized by airway hyperresponsiveness, variable airflow obstruction, and persistent inflammation. While its pathophysiology is well established, growing evidence highlights significant sex-based differences in its prevalence, severity, and treatment response. Epidemiological studies indicate that asthma is more common in prepubertal boys but shifts toward a female predominance after puberty, with adult women experiencing higher morbidity and greater healthcare utilization. These disparities suggest a crucial role for sex hormones, genetic predisposition, and epigenetic regulation in asthma pathogenesis. Sex hormones modulate immune responses, contributing to disease progression. Estrogen enhances type 2 inflammation, increases eosinophilic infiltration, and upregulates IL-4 and IL-13 expression, leading to greater airway hyperreactivity in women. Additionally, progesterone fluctuations correlate with perimenstrual asthma exacerbations, while testosterone appears to exert a protective effect by dampening Th2-driven inflammation and airway remodeling. These hormonal influences contribute to sex-specific asthma phenotypes and treatment responses. Genetic and epigenetic factors further shape sex-related differences in asthma. The X chromosome harbors immune-regulatory genes, including TLR7 and TLR8, which amplify inflammatory responses in females. The sex-dependent expression of IL13 and ORMDL3 influences eosinophilic inflammation and airway remodeling. Epigenetic modifications, such as DNA methylation and microRNA regulation, further impact immune activation and corticosteroid responsiveness. For instance, Let-7 miRNAs modulate IL-13 expression, contributing to sex-specific inflammatory profiles. Environmental factors, including air pollution, obesity, and diet, interact with hormonal and genetic influences, exacerbating sex disparities in asthma severity. Obesity-related metabolic dysfunction promotes systemic inflammation, airway remodeling, and steroid resistance, disproportionately affecting women. Given these complex interactions, sex-specific approaches to asthma management are essential. Personalized treatment strategies targeting hormonal pathways, immune regulation, and metabolic health may improve outcomes for both men and women with asthma. Future research should focus on sex-based therapeutic interventions to optimize disease control and mitigate healthcare disparities. Full article

Polyunsaturated fatty acids (PUFAs) play roles in several physiological and pathophysiological processes, but their effects on reproductive function are controversial. The aim of the study was to investigate the effect of n-3 PUFA-rich fish oil and n-6-rich sunflower oil on sex hormone status, in vivo and in vitro uterine contractility, and endometrial remodeling. Female Sprague Dawley, Lister hooded, and Wistar rats were treated orally for 20 days with 1 mL of tap water, sunflower oil, or fish oil. Blood samples were taken for gonadotropic and sex hormone analysis. In vivo smooth muscle contractions were measured weekly by electromyography. Isolated uterine and cecal contractions were measured after sacrificing the animals. Endometrial remodeling was detected based on the presence of αvβ3 integrin by optical imaging. In Sprague Dawley rats, fish oil increased the LH level and progesterone/estradiol (P4/E2) ratio compared to the sunflower oil-treated group. Uterine contractions were reduced both in vitro and in vivo. Endometrial αvβ3 integrin activity was increased in the fish oil group. In Lister hooded rats, neither sunflower nor fish oil treatments modified the investigated parameters. However, in Wistar rats, both oils increased only the in vivo contractions and reduced the P4/E2 ratio, along with αvβ3 integrin fluorescence. n-3 PUFA-rich fish oil induces a breed-dependent effect on sex hormone status and uterine contractions in rats. The response to PUFA intake may vary significantly within a given species, which may have importance both in animal feeding and human nutrition. Full article

Cardiovascular diseases such as coronary heart disease, heart failure, or stroke are the most common cause of death worldwide and are regularly based on risk factors like diabetes mellitus, hypertension, or obesity. At the same time, both diseases and risk factors are significantly influenced by sex hormones. In order to better understand this influence and also specifically improve the therapy of female patients, medical research has recently focused increasingly on gender-specific differences. The goal is to develop personalized, gender-specific therapy concepts for these diseases to further enhance health outcomes. The enzyme adenosine monophosphate-activated protein kinase (AMPK) is a central regulator of energy metabolism, protecting the cardiovascular system from energy depletion, thereby promoting vascular health and preventing cellular damage. AMPK confers cardioprotective effects by preventing endothelial and vascular dysfunction, and by controlling or regulating oxidative stress and inflammatory processes. For AMPK, sex-specific effects were reported, influencing metabolic and cardiovascular responses. Exercise and metabolic stress generally cause higher AMPK activity in males. At the same time, females exhibit protective mechanisms against insulin resistance or oxidative stress, particularly in conditions like obesity. Additionally, males subject to AMPK deficiency seem to experience greater cardiac and mitochondrial dysfunction. In contrast, females show improvement in cardiovascular function after pharmacological AMPK activation. These differences, influenced by hormones, body composition, and gene expression, highlight the potential to develop personalized, sex-specific AMPK-targeted therapeutic strategies for cardiovascular diseases in the future. Here, we discuss the most actual scientific background, focusing on the protective, gender-specific effects of AMPK, and highlight potential clinical applications. Full article

The hypothalamic-pituitary-adrenal (HPA) axis is a neuroendocrine system involved in the coping response to stressful challenges during exercise stimuli. Exercise represents a significant disruptor of homeostasis, inducing an ACTH-cortisol co-secretion, based on different characteristics of exercise in sport horses. Based on this statement, the aim of this study is to evaluate the circulating adrenocorticotropin and cortisol changes in Standardbred trotters, after training and racing sessions, considering the different age and sex. In particular, the aim is to determine to what extent the level of ACTH and cortisol increases during maximum effort in competition conditions (racing), and to compare two exercise conditions of different intensity, training and racing sessions, and effects on ACTH and cortisol responses. Ten Standardbreds, three females and seven males, clinically healthy, were enrolled and subjected to two exercise conditions: a non-competitive session (training) and then a competitive event (racing). Four of them were 2-year-olds and a further six were 3-year-olds. Training and racing effects on both ACTH (p < 0.01) and cortisol (p < 0.01) values were obtained. Compared to the training session, horses showed greater ACTH concentrations at rest (p < 0.001), at 5 (p < 0.01) and 30 min (p < 0.001), and lower cortisol concentrations only at rest (p < 0.01) after racing; 2- and 3-year-old horses showed the greater ACTH concentrations at 5 and 30 min (p < 0.01) post-racing; males showed the greater ACTH concentrations at 5 min and 30 min (p < 0.01) post-racing. The different stimuli of the two contexts, and differences in exercise intensity, such as training and competitive event, may have affected the direction of hypothalamic-pituitary-adrenal (HPA) axis response, both as an ability to adapt to physical stress of different intensity and as a preparatory activity for coping with stimuli. In conclusion, training and racing events induced a different HPA axis response in which both emotional experience and physical maturity could induce a significant adaptive response. As ACTH and cortisol concentrations in adult equids are extremely heterogeneous, further investigation is required to explore how different variables can influence the hormonal dynamics and their role as expressions of adaptive strategies to stress in horses. Full article

This study evaluates the health of a captive colony of Hamadryas baboons at Ravenna Zoo Safari (Italy), focusing on oxidative stress markers and biometric data. Forty-eight individuals were assessed during routine veterinary procedures: males underwent vasectomy, and females were checked for pregnancy. Biometric data collected included body weight, body length, and genital measurements in males, while females were evaluated for reproductive status. Oxidative stress was measured using two tests that assess both harmful pro-oxidant levels and the body’s antioxidant defenses. Results showed no significant differences in oxidative stress levels between sexes, although males and females differed in body weight. Pregnant and postpartum females exhibited higher oxidative stress, likely due to the metabolic and hormonal demands of reproduction. This supports the idea that reproductive activity increases the production of reactive oxygen species, requiring stronger antioxidant responses. In males, correlations between body weight and genital measurements suggest these could help estimate age in the absence of birth records. No link was found between oxidative stress and body weight, indicating limited age-related effects on these markers. Overall, the study highlights the importance of monitoring oxidative stress in captive primates to better understand the effects of reproduction and aging, and to improve welfare and management practices. Full article

The protective potentials of Tribulus terrestris (TT) and L-arginine (L-Arg) against reproductive toxicity induced by fipronil (FPN) in male rats were investigated. A total of 36 male rats were allocated into six groups: control, TT, L-Arg, FPN, FPN + TT, and FPN + L-Arg groups. The body and sex organ weights, semen criteria, serum testosterone levels, and testicular oxidative stress were determined. Sexual behavior, testicular and penile androgen receptor (AR), penile nitric oxide synthase (NOS), immunohistochemistry of proliferating cell nuclear antigen (PCNA), and histopathology were also assessed. FPN disrupted reproductive health by influencing the expression and activity of NOS and AR, leading to compromised erectile function, sexual dysfunction, and hormonal imbalance. Significant improvements in body weight, reproductive organ weights, the expression of NOS and AR, and testosterone levels were observed in the TT- and L-Arg-treated groups. Behavioral assessments indicated improved sexual performance in the TT- and L-Arg-treated groups. Histopathological studies of the testes and penis tissue, immunohistochemical expression of PCNA in testicular tissues, and biochemical analyses further confirmed the protective effects of TT and L-Arg. Collectively, these findings highlighted the potential of TT and L-Arg in counteracting FPN-induced reproductive impairments. Full article

Objectives: There is strong evidence that not enough physical activity is among the most critical risk factors for cancer disease and premature mortality. The literature on the benefits of regular physical activity regarding cancer disease has grown in the last decades. This review aimed to present the current findings on the effect of prediagnosis physical activity on cancer incidence and mortality published between January 2019 and October 2024; this study summarizes the previous evidence, as well as the literature underlying biological mechanisms operating in the exercise–cancer relationship. The review also highlights gaps in the existing research and identifies future research directions. Methods: Medline/PubMed, ScienceDirect, and Google Scholar were searched with the search terms “physical activity” and “physical exercise” in conjunction with the MeSH terms for “cancer” and “carcinoma”. Primary, review, and meta-analysis studies published in English were included if they reported a measure of the effect size of prediagnosis physical activity on cancer incidence and/or cancer mortality. Results: Evidence from 37 observational studies and 10 reviews were included in this systematic review; 22 studies reported the effect of physical activity on cancer incidence, and 15 studies on cancer mortality. Of the 37 included observational studies, 19 confirmed the previous evidence that physical activity significantly decreased all-cancer-combined and cancer-specific site incidences, and 10 studies focused on cancer mortality. However, the molecular mechanisms involved in this process require future studies. The most convincing evidence maintains the effects of physical activity on body weight and fat, insulin resistance, sex hormones, regulation of redox homeostasis, enhancing the antioxidant defense system, and reducing oxidative stress. Conclusions: These data demonstrate substantial prevention against several cancer incidences and mortality among patients who performed regular physical activity, of which dose meets at least the WHO’s guidelines. Further prospective cohort studies and long-term RCT studies are warranted to address a safe and personalized activity dose for cancer-site prevention, identify more precisely the biological mechanisms operating in the physical activity–cancer relationship, and promote the benefits of being physically active. Full article

Testosterone has been shown to enhance hippocampal neurogenesis through increased cell survival, but which stages of new neuron development are influenced by testosterone remains unclear. Therefore, we tested the effects of sex steroids administered during three different periods after cell division in the dentate gyrus of adult male rats to determine when they influence the survival of new neurons. Adult male rats were bilaterally castrated. After 7 days of recovery, a single injection of bromodeoxyuridine (BrdU) was given on the first day of the experiment (Day 0) to label actively dividing cells. All subjects received five consecutive days of hormone injections during one of three stages of new neuron development (days 1–5, 6–10, or 11–15) after BrdU labeling. Subjects were injected during these time periods with either testosterone propionate (0.250 or 0.500 mg/rat), dihydrotestosterone (0.250 or 0.500 mg/rat), or estradiol benzoate (1.0 or 10 µg/rat). All subjects were euthanized sixteen days later to assess the effects of these hormones on the number of BrdU-labeled cells. The high dose of testosterone caused a significant increase in the number of BrdU-labeled cells in the hippocampus compared to all other groups, with the strongest effect caused by later injections (11-15 days old). In contrast, neither DHT nor estradiol injections had any significant effects on number of BrdU-labeled cells. Fluorescent double-labeling and confocal microscopy reveal that the majority of BrdU-labeled cells were neurons. Our results add to past evidence that testosterone increases neurogenesis, but whether this involves an androgenic or estrogenic pathway remains unclear. Full article