bims-simsho Biomed News
on Systems immunology and sex hormones
Issue of 2025–06–15
fourteen papers selected by
Chun-Chi Chang, Lunds universitet



  1. Int J Mol Sci. 2025 May 24. pii: 5078. [Epub ahead of print]26(11):
      Sex-related differences are found not only in the reproductive system but also across various biological systems, such as the cardiovascular system. Compared with premenopausal women, cardiovascular disease (CVD) tends to occur more frequently in adult men and postmenopausal women (Post-MW). Also, during the reproductive years, sex hormones synthesized and released into the blood stream affect vascular function in a sex-dependent fashion. Estrogen (E2) interacts with estrogen receptors (ERs) in endothelial cells, vascular smooth muscle, and the extracellular matrix, causing both genomic and non-genomic effects, including vasodilation, decreased blood pressure, and cardiovascular protection. These observations have suggested beneficial effects of female sex hormones on cardiovascular function. In addition, the clear advantages of E2 supplementation in alleviating vasomotor symptoms during menopause have led to clinical investigations of the effects of menopausal hormone therapy (MHT) in CVD. However, the findings from these clinical trials have been variable and often contradictory. The lack of benefits of MHT in CVD has been related to the MHT preparation (type, dose, and route), vascular ERs (number, variants, distribution, and sensitivity), menopausal stage (MHT timing, initiation, and duration), hormonal environment (progesterone, testosterone (T), gonadotropins, and sex hormone binding globulin), and preexisting cardiovascular health and other disorders. The vascular effects of sex hormones have also prompted further examination of the use of anabolic drugs among athletes and the long-term effects of E2 and T supplements on cardiovascular health in cis- and transgender individuals seeking gender-affirming therapy. Further analysis of the effects of sex hormones and their receptors on vascular function should enhance our understanding of the sex differences and menopause-related changes in vascular signaling and provide better guidance for the management of CVD in a gender-specific fashion and in Post-MW.
    Keywords:  endothelium; estrogen; progesterone; testosterone; vascular smooth muscle
    DOI:  https://doi.org/10.3390/ijms26115078
  2. Dev Psychobiol. 2025 Jul;67(4): e70053
      Adolescence is marked by changes in affect-related processing that allow individuals to learn from, and adapt to, their socioemotional environments. Although this flexibility allows for greater adaptation, it also confers unique vulnerability, marked by a rise in emotion dysregulation and risk for psychopathology. Mounting evidence implicates adolescent changes in pubertal hormones in the emergence of emotion dysregulation and sex differences therein. Specifically, the literature suggests that pubertal hormones influence brain regions relevant to emotion regulation. Despite evidence that these hormones do not operate in isolation (i.e., they can have a modulatory impact on one another), their interactive effects remain largely unexamined in the context of emotion dysregulation. This marks a critical gap in the literature, as examining hormones in isolation overlooks their interdependent effects, thus limiting our ability to interpret their individual contributions. To address this gap, we examined the interactive impact of two key hormones-dehydroepiandrosterone (DHEA) and testosterone-on self-reported emotion dysregulation in adolescents, along with biological sex differences in these relationships. Participants were 73 community adolescents (aged 11-14; 50.7% assigned male at birth, 68.5% White). Analyses revealed a three-way interaction between DHEA, testosterone, and sex (p = 0.010). Probing revealed that higher testosterone was associated with decreased dysregulation but only among female adolescents with higher relative DHEA (p = 0.039). Thus, exposure to relatively higher DHEA may dampen the impact of testosterone on emotion dysregulation. This has implications for understanding the role of hormonal context and sex differences in the onset and maintenance of emotion dysregulation and related psychopathology in adolescence.
    Keywords:  adolescence; dehydroepiandrosterone (DHEA); emotion regulation; testosterone
    DOI:  https://doi.org/10.1002/dev.70053
  3. Am J Reprod Immunol. 2025 Jun;93(6): e70104
       PROBLEM: Endometritis is an inflammatory disorder often associated with microbial imbalance. Common treatments, such as antibiotics, may lead to drug resistance and do not ensure long-term microbial stability.
    METHOD OF STUDY: This mini review examines vaginal microbiota transplantation (VMT) as a novel approach to the management of endometritis. VMT involves the transfer of healthy microbiota from a donor to restore microbial balance in the recipient.
    RESULTS: VMT helps maintain vaginal acidity and inhibit pathogenic bacteria by restoring the dominant Lactobacillus spp. One of its key mechanisms is inhibiting the NF-κB signaling pathway, which leads to a decrease in inflammatory cytokines such as IL-6, IL-1β, and TNF-α. This reduces tissue inflammation and improves healing. VMT is also more biocompatible than antibiotics and can be more effective in combination with other treatments.
    CONCLUSIONS: VMT is a promising noninvasive approach to the treatment of endometritis, with safety and microbial benefits. However, further studies and standardization of methods are needed to confirm its clinical utility.
    Keywords:  NF‐ κB; endometritis; inflammation; microbiota; vaginal microbiota transplantation
    DOI:  https://doi.org/10.1111/aji.70104
  4. Ann Med Surg (Lond). 2025 Jun;87(6): 3268-3278
      Leukocytes are critical mediators of immune responses and play multifaceted roles in female reproductive health, influencing processes such as menstruation, ovulation, implantation, pregnancy, and parturition. This review examines the dynamic involvement of key leukocyte populations, including neutrophils, macrophages, T lymphocytes, natural killer (NK) cells, and dendritic cells, across reproductive processes. Leukocytes contribute to tissue remodeling, hormonal regulation, immune tolerance, and pathogen defense. Dysregulation in their functions is implicated in reproductive disorders such as endometriosis, recurrent pregnancy loss (RPL), and complications arising from infections. The review integrates emerging insights into the molecular mechanisms governing leukocyte behavior, emphasizing the roles of cytokines, hormones, and chemokines in guiding their recruitment and activity. Key findings underscore the significance of leukocyte-mediated cytokine networks in maintaining immune homeostasis during pregnancy and their critical roles in spiral artery remodeling for fetal-maternal exchange. Neutrophils and macrophages support menstrual shedding and repair, while NK cells facilitate trophoblast invasion and placental development. Dysregulated leukocyte activity contributes to chronic inflammation in endometriosis and impaired immune tolerance in RPL. Additionally, leukocytes are central to immune defenses against infections, but excessive inflammation can lead to infertility or adverse pregnancy outcomes. Therapeutic strategies targeting these immune cells hold promise for managing reproductive health disorders by modulating inflammation, enhancing immune tolerance, and developing biomarkers for early diagnosis. In conclusion, leukocyte dynamics are integral to reproductive physiology and pathology, with significant potential for translational research to optimize reproductive health outcomes.
    Keywords:  female reproductive health; immune cells; leukocytes; menstrual cycle; pregnancy
    DOI:  https://doi.org/10.1097/MS9.0000000000002926
  5. Biol Sex Differ. 2025 Jun 10. 16(1): 40
      Neuropsychiatric and behavioral disorders impact over 15% of U.S. children, with sex differences in manifestation. Prenatal exposure to psychosocial stress predicts adverse neurodevelopmental outcomes, particularly during gestation. Mechanisms remain poorly understood. Research links prenatal stress exposures with placental mitochondrial DNA (mtDNA) mutational load, suggesting that disrupted mitochondrial placental function may play a role. We conceptualize that placental mitochondrial biomarkers reflect environmentally-induced oxidation that may contribute to mechanisms influencing neurodevelopment. Furthermore, as maternal stress can impact female and male children differently, this may in part explain sex differences in early childhood neurobehavioral outcomes. This study explores the association between placental mtDNA mutational load and negative affectivity in infants, and whether these associations are modified by maternal lifetime stress and fetal sex. Placenta samples (N = 394) were collected at delivery and whole mtDNA sequencing was performed to identify gene-specific mutational loads. Mothers completed the Infant Behavior Questionnaire-Revised (IBQ-R) when children were 6.69 ± 1.61 months of age and the Negative Affectivity factor was derived. Multivariable regression analyses were performed to model Negative Affectivity in relation to placental mtDNA mutational load, first adjusting for child sex and maternal age, self-reported race, and education. Lastly, we examined effect modification by maternal stress and fetal sex using cross-product terms and contrast statements. Results showed that higher mutational load in the MT_CYB region was positively associated with increased negative affectivity. Notably, interactions between mtDNA regions (MT_DLOOP and MT_ND), child sex, and maternal stress revealed that girls with higher mutational loads in these regions were at greater risk for increased negative affectivity, particularly under high maternal stress. These findings suggest that placental mtDNA mutational load could serve as a biomarker for neurodevelopmental risk, with sex-specific vulnerabilities influenced by maternal stress. This study underscores the importance of considering both environmental factors and sex differences in understanding early neurodevelopmental trajectories, and the potential of the placenta as a tool for early detection and intervention. Further research is needed to validate these findings and explore their implications for long-term child development. Highlights Increased mutational load in the cytochrome B region of placental mtDNA is associated with higher infant negative affectivity. Girls exhibited greater sensitivity to mutations in the mitochondrial D-loop and NADH dehydrogenase regions, showing stronger links to negative affectivity compared to boys. Higher maternal lifetime stress amplified the impact of mitochondrial NADH dehydrogenase mutational load on negative affectivity in girls, highlighting gene-environment interactions. Findings underscore the placenta's role in integrating environmental and genetic factors that influence early temperament, and its potential role as a future biomarker. This is the first study connecting placental mitochondrial DNA mutations with infant temperament in a diverse population, revealing sex-specific and stress-modulated effects.
    Keywords:  Maternal stress; Mitochondria; Negative affectivity; Neurodevelopment; Placenta
    DOI:  https://doi.org/10.1186/s13293-025-00717-4
  6. Syst Biol Reprod Med. 2025 Dec;71(1): 229-245
      Advancements in next generation sequencing technologies, including 16S rRNA amplicon sequencing, have vastly expanded our understanding of reproductive microbiota and its role in fertility. For example, in humans, the bacterial genus of Lactobacillus is the overwhelmingly dominant commensal bacterium within reproductive tissues and fluids, such as the vagina, and is an indicator of fertility in women. Shifts away from Lactobacillus allow for opportunistic pathogenic bacteria to inhabit the reproductive tract and result in dysbiosis and infertility. The goal of this review is to explore human reproductive microbiota including bacteria that commensally inhabit reproductive tissues and fluids as well as opportunistic pathogenic bacteria that can result in dysbiosis, infertility, and disease. Continued exploration of the microbiome and its association with reproductive health will aid in the development of targeted therapeutic strategies to positively modulate bacteria and improve fertility.
    Keywords:  Dysbiosis; human; infertility; microbiota; reproduction
    DOI:  https://doi.org/10.1080/19396368.2025.2511323
  7. BMC Med. 2025 Jun 09. 23(1): 338
       BACKGROUND: Adenomyosis is associated with lower implantation and higher miscarriage rates. Studies on recurrent pregnancy loss (RPL) and recurrent implantation failure (RIF) have shown that endometrial immune cell populations play a crucial role during implantation and early pregnancy. In women with adenomyosis, improved pregnancy outcomes following assisted reproductive technologies (ART) and pre-treatment with GnRH-agonists (GnRH-a) prior to frozen embryo transfer (FET) have been reported. We aimed to compare the endometrial immune cell populations of women with adenomyosis to those of women with RPL and RIF, and to characterise endometrial leucocyte subpopulations within the adenomyosis group before and after GnRH-a.
    METHODS: We conducted a prospective study between 2021 and 2024. Women with infertility and adenomyosis undergoing ART underwent one endometrial biopsy 6-9 days after oocyte retrieval and a second biopsy after 3 months of GnRH-a prior to FET. Women in the RPL and RIF groups underwent one endometrial biopsy in the midluteal phase. We performed flow cytometry (FC) to characterise immune cell populations and immunohistochemistry (IHC) to analyse uterine natural killer cells (uNKs) and plasma cells (PC). The Kruskal-Wallis test was used for comparisons between the study groups, and the Wilcoxon signed rank tests were used for paired samples before and after GnRH-a.
    RESULTS: Endometrial leucocyte subpopulations at baseline showed no significant differences between the adenomyosis (n = 20), the RPL (n = 40) and RIF (n = 15) group. In the adenomyosis group, following GnRH-a, we observed a significant decrease in the percentage of monocytes, from 77% (IQR 71, 82) to 71% (IQR 65, 75) (adj. p = 0.030). Baseline IHC showed elevated plasma cell concentrations (≥ 5/mm2) in 1/20 adenomyosis patients (5%), 4/40 RPL patients (10%) and 1/15 RIF patients (6.7%) while uNK cells were elevated (≥ 300/mm2) in 8/20 adenomyosis patients (40%), 11/40 RPL patients (27.5%) and 1/15 RIF patients (6.7%).
    CONCLUSIONS: Women with infertility and adenomyosis showed a similar endometrial immune profile as women with RPL and RIF. The beneficial effect of GnRH-a prior to FET in women with adenomyosis may be mediated through effects on monocyte subpopulations. Based on the high prevalence of elevated uNK cells in patients with adenomyosis, we suggest testing women with adenomyosis undergoing ART before FET.
    Keywords:  Adenomyosis; Endometrial immune cells; GnRH-agonists; Infertility; Recurrent implantation failure; Recurrent pregnancy loss; Uterine natural killer cells
    DOI:  https://doi.org/10.1186/s12916-025-04162-3
  8. Int J Mol Sci. 2025 May 30. pii: 5288. [Epub ahead of print]26(11):
      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.
    Keywords:  FEV1; FeNO; IL-13; IL-4; TLR7; TLR8; asthma; estrogens; female; hormones; male; miRNA; obesity; progesterone; severe asthma; sex; women
    DOI:  https://doi.org/10.3390/ijms26115288
  9. Hum Reprod. 2025 Jun 07. pii: deaf103. [Epub ahead of print]
       STUDY QUESTION: Which spermatogonial differentiation states are present in prepubertal testes under normal conditions and following chemotherapy-induced depletion of spermatogonia in paediatric patients with cancer?
    SUMMARY ANSWER: Single-cell transcriptomic analysis reveals that only undifferentiated spermatogonia are present in prepubertal boys, while differentiated states emerge during puberty, with reduced protein expression of advanced spermatogonial markers observed in younger patients, those treated with alkylating agents, or those with a diminished spermatogonial pool.
    WHAT IS KNOWN ALREADY: Paediatric oncology treatments often involve gonadotoxic therapies that can impair spermatogonial stem cells, increasing the risk of subfertility. While five distinct spermatogonial subpopulations have been identified in adult testes via single-cell RNA sequencing, their presence in prepubertal testes of childhood cancer patients remains to be confirmed through marker protein expression.
    STUDY DESIGN, SIZE, DURATION: Gene expression profiles of spermatogonial subpopulations were investigated using single-cell RNA sequencing data from six testicular samples of healthy boys aged 0-17 years. Protein expression patterns were examined via immunofluorescence staining in 14 biobank control samples (median age: 4.9 years; range: 0.6-13.1 years) and in 31 prepubertal testicular tissue samples of paediatric patients with cancer (median age: 6.8 years; range: 0.7-13.1 years).
    PARTICIPANTS/MATERIALS, SETTING, METHODS: Gene expression profiles of UTF1 (states 0-1), ID4 (states 0-1), PIWIL4 (states 0-1), FGFR3 (states 0-2), and KIT (state 4), were analysed in testicular cells of paediatric origin obtained from our previously published open-access data source (GSE134144 and GSE120508). The protein expression of these spermatogonial subpopulation markers was evaluated by counting immunofluorescence-positive cells per analysed area. Marker expression was correlated with prior chemotherapy exposure and spermatogonia numbers. Exposure to alkylating agents was quantified as the cumulative cyclophosphamide equivalent dose (CED), and anthracycline exposure as the cumulative doxorubicin isoequivalent dose equivalents (DIE). A depleted spermatogonia pool was defined as having S/T Z-scores lower than -7 SD.
    MAIN RESULTS AND THE ROLE OF CHANCE: Transcriptomic analysis confirmed that germ cells in the prepubertal testis consist solely of undifferentiated spermatogonia. The expression of KIT protein, defining differentiated spermatogonia, was positively correlated with age (P < 0.001). A reduction in the number of spermatogonia expressing ID4 protein was associated with higher CED (P = 0.001), and spermatogonia expressing KIT protein with higher CED and DIE exposure (P = 0.005, and P = 0.035, respectively). A depleted spermatogonia pool (S/T Z-score <-7 SD) correlated with fewer spermatogonia expressing ID4 (P = 0.033), FGFR3 (P = 0.050), and KIT (P = 0.051) proteins. These results indicate that distinct protein expression patterns were observed following chemotherapy-induced reduction of the spermatogonial pool, with reduced expression of ID4, FGFR3, and KIT proteins. Numbers of spermatogonia positive for markers indicating more naïve, undifferentiated states, such as UTF1 and PIWIL4, did not correlate with spermatogonial pool reduction.
    LIMITATIONS, REASONS FOR CAUTION: The study population was heterogeneous in terms of age and treatment exposure. Moreover, the impact of specific cancer treatments could not be individually assessed. Limited tissue availability reduced the statistical power of the study, and repeated double or triple immunofluorescence staining could not be performed. As a result, the correlations between the expression of different spermatogonial markers can only be considered indicative trends. Child testicular control tissue samples were considered normal for inclusion if no testicular pathology was reported. However, detailed information on prior medical treatments or testicular volumes for the patients in this biobank was unavailable.
    WIDER IMPLICATIONS OF THE FINDINGS: Our observations suggest that alkylating agents have dose-dependent effects on all spermatogonial subpopulations. However, spermatogonial subtypes expressing the protein markers UTF1 and PIWIL4 were more resistant to chemotherapy-induced depletion of the spermatogonial pool, potentially representing true reserve stem cells. The identification of reserve stem cells could provide a valuable method for evaluating the fertility potential of testicular tissue collected for fertility preservation in prepubertal and peripubertal boys.
    STUDY FUNDING/COMPETING INTEREST(S): This study was supported by grants from the Swedish Childhood Cancer Fund (PR2019-0123; PR2022-0115; TJ2020-0023) (J.-B.S.), Finnish Cancer Society (K.J.), Finnish Foundation for Paediatric Research (K.J.), Swedish Research Council (2018-03094; 2021-02107) (J.-B.S.), and Birgitta and Carl-Axel Rydbeck's Research Grant for Paediatric Research (2020-00348; 2020-00335; 2021-00073; 2022-00317, 2024-00255) (J.-B.S., K.J.). Y.C. and Y.Y. received a scholarship from the Chinese Scholarship Council. J.S. was supported by a grant from Mary Béves Foundation for Childhood Cancer Research. H.B.O. was supported by the Sultan Qaboos University in Oman. The authors declare no competing interests.
    TRIAL REGISTRATION NUMBER: N/A.
    Keywords:  immunohistochemistry; prepubertal; single-cell gene expression analysis; spermatogonia; testis
    DOI:  https://doi.org/10.1093/humrep/deaf103
  10. Int J Mol Sci. 2025 May 28. pii: 5193. [Epub ahead of print]26(11):
      Endometriosis, a complex inflammatory disease, affects a significant proportion of women of reproductive age, approximately 10-15%. The disease involves the growth of endometrial glands and stroma outside the uterine cavity, leading to tissue remodeling and fibrosis. Hormonal imbalances, accompanied by local and general inflammation and pain, are key features of endometriosis. Endometriotic lesions are associated with the overproduction of cytokines, metalloproteinases, prostaglandins, reactive oxygen radicals, and extracellular vesicles. Genetic predisposition and cytokine gene polymorphisms have been documented. Macrophages, dendritic cells, mast cells, Th1 in the early phase, Th2 in the late phase, and T regulatory cells play a crucial role in endometriosis. Reduced NK cell function and impaired immune vigilance contribute to endometrial growth. The strong inflammatory condition of the endometrium poses a barrier to the proper implantation of the zygote, contributing to the infertility of these patients. Cytokines from various cell types vary with the severity of the disease. The role of microbiota in endometriosis is still under study. Endometriosis is associated with autoimmunity and ovarian cancer. Hormonal treatments and surgery are commonly used; however, recent interest focuses on anti-inflammatory and immunomodulatory therapies, including cytokine and anti-cytokine antibodies. Modulating the immune response has proven critical; however, more research is needed to optimize treatment for these patients.
    Keywords:  autoimmunity; cancer; cytokines; endometriosis; inflammation; therapy
    DOI:  https://doi.org/10.3390/ijms26115193
  11. Clin Exp Immunol. 2025 Jan 21. pii: uxaf013. [Epub ahead of print]219(1):
      Spindlin-1, a multivalent epigenetic reader, is a new target for cancer therapy. Beside the anticancer effect, modulation of the recognition of methyl marks of histones may impact the immune system, which plays an important role in the anticancer strategy of the human organism. Two Spindlin-1 inhibitors (A366, MS31) were characterized to differentiate between drug and target-specific effects. We performed a comprehensive study regarding the influence of Spindlin-1 inhibition on various immune cells. A366 and MS31 showed immune cell type-dependent cytotoxicity with IC50 values in the ranges of 37-143 µM and 11-3122 µM, respectively, macrophages tending to be less susceptible than lymphocytes. A366 had only minor effects on M1 polarization, whereas MS31 shifted the M1 to a M2 phenotype, as shown by regulated cytokines and surface marker expression. Both A366 and MS31 weakened the polarization of predifferentiated M2 macrophages by reducing surface marker expression, cytokines, and inflammatory markers. A366 and MS31 had no effect on activation and energy metabolism of CD4+ T cells. Interestingly, 5 µM A366 and 2.5 µM MS31 clearly prevented B cell activation, as shown by reduced proliferation, plasmablast formation, and release of immunoglobulins A and G. Additionally, A366 increased energy metabolism in B cells. In conclusion, the inhibition of Spindlin-1 had only minor effects on polarization of macrophages and T cell proliferation but profoundly prevented B cell activation at low concentrations. This suggests that Spindlin-1 inhibitors, while mediating anticancerogenic effects, may also suppress the humoral immune response and increase infection risk.
    Keywords:  A366; MS31; Spindlin-1; cytokines; energy metabolism; immune modulation
    DOI:  https://doi.org/10.1093/cei/uxaf013
  12. Br J Psychiatry. 2025 Jun 09. 1-14
       BACKGROUND: Menopause is an inflection point in the ageing trajectory. Independent of chronological age, menopause is associated with the biological ageing of several body systems. In this review, we highlight the importance of considering the influence of menopause - its types, symptoms and interventions - on brain health. Supplementing the loss of ovarian hormones with menopausal hormone therapy (MHT) may be key for supporting the healthy brain ageing of females. MHT has been associated with reduced risk of several neurodegenerative diseases; however, its benefits are not always observed on brain health.
    AIMS: This narrative review highlights often overlooked MHT factors that influence its effects to produce positive or negative effects on brain health, cognition and neurodegenerative disease risk. These factors include the many varieties of MHT, including formulation, administration route and dosing schedule, as well as individual characteristics, particularly the presence of vasomotor symptoms and apolipoprotein ε4 (APOE4) genotype.
    METHOD: PubMed and Scopus were used to identify articles with relevant search terms.
    RESULTS: Menopause factors, including age, abruptness and symptoms, influence brain ageing. MHT influences brain health, with transdermal MHT showing more positive effects on brain ageing, but its effectiveness may depend on individual factors such as genotype, reproductive and lifestyle factors.
    CONCLUSIONS: To develop effective and individualised MHT treatments, further research is needed. Preclinical models must consider the type of human menopause and MHT. To achieve the greatest dementia prevention in females, more menopause education and care is needed that extends beyond 60 years of age, or 10 years postmenopause.
    Keywords:  Menopausal hormone therapy; ageing; dementias/neurodegenerative diseases; oestradiol; vasomotor symptoms
    DOI:  https://doi.org/10.1192/bjp.2025.52
  13. Clin Exp Med. 2025 Jun 09. 25(1): 194
      Multiple myeloma (MM), a plasma cell malignancy, despite the progress in treatment, is still a challenge for both clinicians and affected patients. Modern treatment regimens including monoclonal antibodies, bispecific antibodies, CAR-T cell therapy as well as new generations of immunomodulatory drugs and proteasome inhibitors significantly improved clinical outcomes. Nonetheless, there is still a room for improvement and novel therapeutic strategies. IL-17-related signaling is a relatively undiscovered area in MM research. It was established that IL-17 is the growth factor for plasma cells including their malignant counterparts, is associated with myelomagenesis and disease progression. Furthermore, IL-17 axis can be pharmacologically targeted by monoclonal antibodies currently being used in different indications. In this narrative review we summarized the role of IL-17 axis in MM. Specifically, we focused on the role of IL-17 in MM development and progression with a particular emphasis upon clinical implications. Moreover, we have briefly summarized the potential role of therapeutic interference with IL-17-related singling and have outlined future research directions.
    Keywords:  Adjuvant therapy; Bone marrow microenvironment; IL-17; Immunotherapy; MM progression; Multiple myeloma
    DOI:  https://doi.org/10.1007/s10238-025-01728-6
  14. Adipocyte. 2025 Dec;14(1): 2508885
      Adipose tissue (AT), one of the largest endocrine tissues in the human body, is an important site for the storage and production of steroid hormones. In particular, AT's capacity to produce androgens could enable it to have a regulatory role in local or general hormone homoeostasis. The links between obesity, polycystic ovary syndrome (PCOS), metabolic disorders, and hormonal balance emphasise the importance of understanding the intricate relationships between AT and androgen dynamics within AT. This review, focusing on androgen metabolism, summarises the androgen profile in white adipose tissue (WAT) and brown adipose tissue (BAT) of humans and animal models, along with the androgen-metabolising enzymes present in WAT, and explores the role of androgens on AT physiology.
    Keywords:  Adipose tissue; androgens; metabolism; obesity; sex steroids
    DOI:  https://doi.org/10.1080/21623945.2025.2508885