Frontiers in Neuroendocrinology最新文献

The importance of ovary-immune interactions in the context of age and disease. 卵巢免疫相互作用在年龄和疾病背景下的重要性。

IF 6.7 1区医学 Q1 ENDOCRINOLOGY & METABOLISM

Frontiers in Neuroendocrinology

Pub Date : 2026-01-29 DOI: 10.1016/j.yfrne.2026.101234

Macy E Zardeneta, Kaylin A Pickle, Farida Sohrabji

The ovary, a dynamic endocrine organ, plays a central role in female reproductive function through the secretion of hormones such as 17β-estradiol, progesterone, testosterone, and inhibin. Beyond its endocrine activity, the ovary serves as a critical site of immune modulation, with tissue-resident and circulating immune cells contributing to folliculogenesis, ovulation, implantation, and pregnancy. This review explores the reciprocal interactions between the ovarian and immune systems across health, disease, and aging. We highlight the diverse functions of ovarian immune cell types in maintaining reproductive homeostasis and their dysregulation in conditions such as polycystic ovary syndrome (PCOS), premature ovarian insufficiency (POI), ovarian hyperstimulation syndrome, and autoimmune diseases. Additionally, we discuss how ovarian removal or dysfunction influences systemic inflammation and increases susceptibility to cardiovascular and neurologic disorders. Together, these findings underscore the ovary's dual role as an endocrine and immune organ, highlighting its significance in female health and disease beyond reproduction.

卵巢是一个动态的内分泌器官，通过分泌17β-雌二醇、黄体酮、睾酮、抑制素等激素，在女性生殖功能中起着核心作用。除了内分泌活动外，卵巢还是免疫调节的关键部位，组织驻留和循环免疫细胞参与卵泡形成、排卵、着床和妊娠。这篇综述探讨了卵巢和免疫系统在健康、疾病和衰老过程中的相互作用。我们强调卵巢免疫细胞类型在维持生殖稳态中的不同功能及其在多囊卵巢综合征（PCOS）、卵巢早衰（POI）、卵巢过度刺激综合征和自身免疫性疾病等疾病中的失调。此外，我们讨论卵巢切除或功能障碍如何影响全身性炎症，增加心血管和神经系统疾病的易感性。总之，这些发现强调了卵巢作为内分泌和免疫器官的双重作用，突出了它在女性健康和生殖以外的疾病中的重要性。

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引用次数: 0

Pathogenesis and potential therapies for perimenopausal depression: Insights from the estrogen-gut microbiota axis 围绝经期抑郁症的发病机制和潜在治疗方法：来自雌激素-肠道微生物群轴的见解。

IF 6.7 1区医学 Q1 ENDOCRINOLOGY & METABOLISM

Frontiers in Neuroendocrinology

Pub Date : 2026-01-01 DOI: 10.1016/j.yfrne.2026.101233

Xuli Wang , Yudong Lin , Mingmei Zhou

Perimenopause represents a critical phase during which women are particularly susceptible to depression. Although fluctuations in estrogen levels resulting from ovarian aging and imbalances in the gut microbiota have been identified as contributing factors to the onset of depression, the interplay among these elements is frequently overlooked. Fluctuations in estrogen levels can further influence neurogenesis or apoptosis through effects on neurotransmitter balance, neuroinflammation, neuroendocrine regulation, and mitochondrial function. Meanwhile, dramatic shifts in estrogen levels can diminish microbial diversity and stability, thereby disrupting the homeostasis of metabolites and neurotransmitters via the gut-brain axis (GBA). Such disturbances may induce neuroinflammation, potentially leading to or exacerbating depressive symptoms. Additionally, the estrobolome (gut bacterial genes encoding estrogen-metabolizing enzymes) plays a regulatory role in the reabsorption, excretion, and systemic levels of estrogen through the modulation of β-glucuronidase activity, thereby affecting estrogen homeostasis. This review first examines the influence of fluctuations in estrogen levels on the composition and function of the gut microbiota, as well as the role of the gut microbiota in estrogen metabolism. It then discusses how estrogen deficiency and dysbiosis of the gut microbiota contribute to the pathogenesis of perimenopausal depression, discussing the potential for a vicious cycle mediated by the estrogen-gut microbiota axis that increases susceptibility to this condition. Finally, this review presents bioactive compounds derived from dietary sources or medicinal plants that exhibit estrogenic and prebiotic properties, which may offer diverse strategies for the prevention and management of perimenopausal depression through modulation of the estrogen-gut microbiota axis.

围绝经期是女性特别容易患抑郁症的关键阶段。虽然卵巢老化和肠道微生物群失衡导致的雌激素水平波动已被确定为抑郁症发病的因素，但这些因素之间的相互作用经常被忽视。雌激素水平的波动可通过影响神经递质平衡、神经炎症、神经内分泌调节和线粒体功能进一步影响神经发生或凋亡。同时，雌激素水平的急剧变化会降低微生物的多样性和稳定性，从而通过肠脑轴（GBA）破坏代谢物和神经递质的稳态。这种干扰可能诱发神经炎症，潜在地导致或加重抑郁症状。此外，雌激素组（编码雌激素代谢酶的肠道细菌基因）通过调节β-葡萄糖醛酸酶活性，在雌激素的重吸收、排泄和全身水平中发挥调节作用，从而影响雌激素的稳态。本文首先探讨了雌激素水平波动对肠道菌群组成和功能的影响，以及肠道菌群在雌激素代谢中的作用。然后讨论了雌激素缺乏和肠道微生物群失调如何导致围绝经期抑郁症的发病机制，讨论了雌激素-肠道微生物群轴介导的恶性循环的可能性，从而增加了对这种疾病的易感性。最后，本文综述了从膳食来源或药用植物中提取的具有雌激素和益生元特性的生物活性化合物，它们可能通过调节雌激素-肠道微生物群轴为预防和管理围绝经期抑郁症提供多种策略。

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引用次数: 0

We must look beyond primary reinforcement to understand nicotine use in women 我们必须超越初级强化来理解女性对尼古丁的使用。

IF 6.7 1区医学 Q1 ENDOCRINOLOGY & METABOLISM

Frontiers in Neuroendocrinology

Pub Date : 2026-01-01 DOI: 10.1016/j.yfrne.2026.101231

Kathleen R. McNealy , Scott T. Barrett , Rick A. Bevins

Women exhibit greater nicotine use vulnerability than men. Common cessation treatments are less effective for women, suggesting unique contributors to women’s smoking that are not fully characterized or targeted by available treatments. High estradiol is associated with enhanced smoking and cessation difficulty, whereas high progesterone is associated with reduced smoking and better cessation success. Hormonal contraceptives can produce similar or even outsized alterations in nicotine use outcomes. Despite clear effects of natural and synthetic sex steroid hormones on nicotine intake, the behavioral pathways by which hormones alter nicotine use outcomes remain unmapped. In this review paper, we propose that uncovering such mechanisms requires examining sex steroid hormone modulation of non-primary reinforcement factors in our animal models. Parallel effects of natural and synthetic sex steroid hormones on nicotine self-administration occur in animal models. Further, women’s smoking is more influenced by environmental stimuli, such as the smell, taste, and visual cues associated with nicotine use than by the reinforcing effects of nicotine. In building our case, we first summarize research supporting the import of environmental factors in nicotine intake for women and translation to female rats. We also synthesize findings on how biological sex and sex steroid hormones influence these mechanisms in humans and rats. Lastly, we will detail promising directions for future research.

女性比男性更容易受到尼古丁的影响。常见的戒烟治疗对女性的效果较差，这表明女性吸烟的独特因素并没有被现有的治疗方法完全描述或针对。高雌二醇与增加吸烟和戒烟困难有关，而高黄体酮与减少吸烟和更好的戒烟成功有关。激素避孕药可以对尼古丁的使用结果产生类似甚至更大的改变。尽管天然和合成的性类固醇激素对尼古丁的摄入有明显的影响，但激素改变尼古丁使用结果的行为途径仍未明确。在这篇综述文章中，我们建议揭示这种机制需要在我们的动物模型中检查性类固醇激素对非原发性强化因子的调节。天然和合成性类固醇激素对尼古丁自我给药的平行效应在动物模型中出现。此外，女性吸烟更多地受到环境刺激的影响，如与尼古丁使用有关的气味、味道和视觉线索，而不是尼古丁的强化作用。在构建我们的案例中，我们首先总结了支持环境因素在女性尼古丁摄入中的重要性的研究，并将其转化为雌性大鼠。我们还综合研究了生物性别和性类固醇激素如何影响人类和大鼠的这些机制。最后，对未来的研究方向进行了展望。

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引用次数: 0

From menarche to menopause: estrogenic influences on stroke-related depression in women 从月经初潮到更年期：雌激素对女性卒中相关抑郁的影响。

IF 6.7 1区医学 Q1 ENDOCRINOLOGY & METABOLISM

Frontiers in Neuroendocrinology

Pub Date : 2026-01-01 DOI: 10.1016/j.yfrne.2026.101232

Lauren Kelly Tierney , Indy Cabeda Diaz , Shahil H. Patel , Ami P. Raval

Post-stroke depression (PSD) is a common and debilitating complication that disproportionately affects women, yet the underlying risk factors remain incompletely understood. Hormonal fluctuations across a woman’s lifespan, including those naturally occurring during puberty, pregnancy, and menopause, as well as exposures to exogenous hormones, such as oral contraceptives, assisted reproductive technologies, and hormonal replacement therapies, profoundly influence neurobiological pathways, potentially modulating both stroke risk and subsequent depressive disorders. Female-specific or female-predominant patient factors, including polycystic ovary syndrome, migraine, autoimmune disease, and breast cancer may exacerbate susceptibility to depression after stroke. Behavioral factors, such as smoking, substance use, and stress, further interact with biological predispositions to impact PSD outcomes. Our review presents current evidence on the intersection of hormonal fluctuations, patient factors, and behavioral influences in shaping the stroke risk and manifestation of PSD in women. Addressing the intersecting influences on PSD offers a promising pathway to improve post-stroke mental health outcomes and enhance quality of life for women.

中风后抑郁（PSD）是一种常见的使人衰弱的并发症，对女性的影响尤为严重，但潜在的危险因素仍未完全了解。女性一生中激素的波动，包括青春期、孕期和更年期自然发生的波动，以及暴露于外源性激素（如口服避孕药、辅助生殖技术和激素替代疗法）的波动，都会深刻影响神经生物学途径，潜在地调节中风风险和随后的抑郁症。女性特异性或以女性为主的患者因素，包括多囊卵巢综合征、偏头痛、自身免疫性疾病和乳腺癌，可能加剧中风后抑郁的易感性。行为因素，如吸烟、物质使用和压力，进一步与生物倾向相互作用，影响PSD的结果。我们的综述提供了目前的证据，表明激素波动、患者因素和行为影响在塑造女性卒中风险和PSD表现方面的交叉作用。解决对PSD的交叉影响为改善中风后心理健康结果和提高妇女的生活质量提供了一条有希望的途径。

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引用次数: 0

The genetic architecture of reproductive subtypes of depression in females 女性抑郁症生殖亚型的遗传结构。

IF 6.7 1区医学 Q1 ENDOCRINOLOGY & METABOLISM

Frontiers in Neuroendocrinology

Pub Date : 2025-12-16 DOI: 10.1016/j.yfrne.2025.101230

Arielle Crestol , Hannah Oppenheimer , Carina J. Koeppel , Claudia Barth

Reproductive subtypes of depression, including premenstrual dysphoric disorder, postpartum depression, and perimenopausal depression are tightly linked to hormonal fluctuations, presenting as windows of vulnerability in females. While it is suggested that these reproductive subtypes present as a stable trait, it remains unclear whether they share an underlying genetic architecture. In this review, we summarize the known genetic etiology of each reproductive subtype of depression, contrast the findings between subtypes, and highlight existing knowledge gaps, challenges, and ways forward. We found that while postpartum depression has been comparatively more studied, genetic studies on premenstrual dysphoric disorder and perimenopausal depression are scarce. Candidate genes commonly studied in major depressive disorder (5-HTT, COMT, MAO-A, and TPH1) as well as ESR1 have been studied across the reproductive subtypes, however, showing inconsistent patterns. No genome-wide association studies currently exist for premenstrual dysphoric disorder or perimenopausal depression. Genome-wide association studies on postpartum depression, although underpowered, point to unique and shared genetic components with other psychiatric disorders, which should be further explored across all reproductive subtypes of depression. To advance this field, well-powered studies with consistent diagnostic criteria across diverse ancestry groups are needed. Identifying whether overlap exists in the genetic architecture of premenstrual dysphoric disorder, postpartum depression, and perimenopausal depression could enhance our understanding of their pathogenesis and foster the development of new therapeutic targets.

生殖抑郁症亚型，包括经前焦虑症、产后抑郁症和围绝经期抑郁症与激素波动密切相关，是女性的脆弱性窗口。虽然有人认为这些生殖亚型作为一种稳定的特征存在，但尚不清楚它们是否共享潜在的遗传结构。在这篇综述中，我们总结了已知的每种生殖亚型抑郁症的遗传病因，对比了不同亚型之间的发现，并强调了现有的知识差距、挑战和前进的方向。我们发现，虽然对产后抑郁症的研究相对较多，但对经前焦虑症和围绝经期抑郁症的遗传研究却很少。在重性抑郁症（5-HTT， COMT， MAO-A和TPH1）中常见的候选基因以及ESR1已经在生殖亚型中进行了研究，然而，显示出不一致的模式。目前还没有关于经前焦虑症或围绝经期抑郁症的全基因组关联研究。产后抑郁症的全基因组关联研究，虽然力度不够，但指出了与其他精神疾病的独特和共享的遗传成分，这应该在所有生殖型抑郁症中进一步探索。为了推进这一领域，需要在不同的祖先群体中进行具有一致诊断标准的有力研究。确定经前烦躁不安、产后抑郁和围绝经期抑郁的遗传结构是否存在重叠，可以增强我们对其发病机制的理解，并促进新的治疗靶点的开发。

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引用次数: 0

Disproportionate mental health risks in autistic females: A rapid review with quantitative and narrative syntheses 自闭症女性不成比例的心理健康风险：定量和叙事综合的快速回顾。

IF 6.7 1区医学 Q1 ENDOCRINOLOGY & METABOLISM

Frontiers in Neuroendocrinology

Pub Date : 2025-12-14 DOI: 10.1016/j.yfrne.2025.101229

Adeline Lacroix , Chih-Chen Tzang , Jennifer Xiaofan Yu , Benjamin Koshy Jacob , Mishel Alexandrovsky , Anna Winge-Breen , Terri Rodak , Meng-Chuan Lai

Mental health conditions are highly prevalent among autistic people, but an updated synthesis of sex-stratified prevalence data, contributing factors, and support strategies is lacking. To address this knowledge gap, we conducted a rapid review utilizing PRISMA-ScR guidelines. MEDLINE, CINAHL, and PsycINFO databases were searched for studies (2004–2024) including female participants with a clinical autism diagnosis, and with a focus on mental health. Of 8,420 records screened, 218 met inclusion criteria. An exploratory quantitative synthesis of population-based and registry-based studies revealed higher rates of mental health conditions in autistic females than males for anxiety, mood, eating, obsessive–compulsive, psychotic, and personality disorders. Narrative synthesis identified moderating factors, including sex-related physiology, gendered experiences, age, age at autism diagnosis, autism characteristics, and co-occurring conditions. Biological and social mechanisms likely interact as contributing factors. Severe consequences of poor mental health underscore the need for tailored approaches accounting for the specific profiles of autistic females.

心理健康状况在自闭症患者中非常普遍，但缺乏对按性别分层的患病率数据、影响因素和支持策略的最新综合。为了解决这一知识差距，我们利用PRISMA-ScR指南进行了快速审查。MEDLINE， CINAHL和PsycINFO数据库检索了2004-2024年的研究，包括临床诊断为自闭症的女性参与者，并以心理健康为重点。在筛选的8,420条记录中，218条符合纳入标准。一项基于人口和登记的探索性定量综合研究显示，自闭症女性在焦虑、情绪、饮食、强迫症、精神病和人格障碍方面的心理健康状况高于男性。叙事综合确定了调节因素，包括性相关生理、性别经历、年龄、自闭症诊断年龄、自闭症特征和共存条件。生物和社会机制可能作为促成因素相互作用。心理健康状况不佳的严重后果突出表明，需要针对自闭症女性的具体情况采取有针对性的办法。

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引用次数: 0

From significant to meaningful: ATOMizing the study of sex differences and similarities 从重要到有意义：性别差异和相似性的原子化研究

IF 6.7 1区医学 Q1 ENDOCRINOLOGY & METABOLISM

Frontiers in Neuroendocrinology

Pub Date : 2025-12-08 DOI: 10.1016/j.yfrne.2025.101228

Carla Sanchis-Segura , Cristina Forn , Rand R Wilcox

The sex differences field often relies on an implicit and flawed heuristic: defining a “difference” by any statistically significant gap between group averages. This practice yields findings that are often not useful, even counterproductive, for understanding sex-related variation and for advancing personalized healthcare.

Following current statistical consensus, we argue that sex differences should be defined not by significance alone but by context-dependent criteria prioritizing informativeness. Drawing on the American Statistical Association’s ATOM principles (Accept uncertainty, be Thoughtful, be Open, be Modest), we call for explicit, justified definitions and for a shift from group averages to meaningful individual variation.

To illustrate this methodological and philosophical shift, we introduce Thresholded Probability of Superiority (TPS), a method that treats sex differences as probability distributions rather than overgeneralized, fixed abstractions. Thus, TPS allows for a more nuanced, relevant, and actionable understanding of sex-related variation, with greater potential to inform precision medicine.

性别差异领域通常依赖于一种隐含的、有缺陷的启发式：通过群体平均水平之间的任何统计上显著的差距来定义“差异”。这种做法产生的结果往往没有用处，甚至适得其反，对于理解与性别相关的变异和推进个性化医疗保健。根据目前的统计共识，我们认为性别差异不应该仅仅通过重要性来定义，而是通过上下文相关的标准来优先考虑信息性。根据美国统计协会的ATOM原则（接受不确定性、深思熟虑、开放、谦虚），我们呼吁明确、合理的定义，并从群体平均转向有意义的个体差异。为了说明这种方法论和哲学上的转变，我们引入了优势阈值概率（TPS），这是一种将性别差异视为概率分布而不是过度概括的固定抽象的方法。因此，TPS允许对性别相关变异进行更细致、相关和可操作的理解，具有更大的潜力为精准医学提供信息。

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引用次数: 0

Impact of statins on mortality and disease progression in patients with Alzheimer’s disease: a nationwide cohort study 他汀类药物对阿尔茨海默病患者死亡率和疾病进展的影响：一项全国性队列研究

IF 6.7 1区医学 Q1 ENDOCRINOLOGY & METABOLISM

Frontiers in Neuroendocrinology

Pub Date : 2025-10-01 DOI: 10.1016/j.yfrne.2025.101218

Yoonjung Park , Hyun Woo Lee , Byoung Seok Ye , Seungyeon Kim , Yun Mi Yu

Recent studies have investigated the neuroprotective potential of statins; however, clinical evidence for delayed Alzheimer’s disease (AD) progression remains scarce. This study investigated the association between statin use and AD progression, as assessed by mortality and memantine initiation. Using data from the Korean National Health Insurance Database, we retrospectively analyzed a cohort of patients aged 60–79 years diagnosed with AD in 2010. After 1:1 propensity score matching, 7,086 patients were included in the study. Statin use was associated with a reduced risk of mortality (HR, 0.84; 95 % CI = 0.74–0.97), notably among previous users (HR, 0.82; 95 % CI = 0.70–0.97), while no delay in memantine initiation was observed (HR, 1.04; 95 % CI = 0.86–1.26). Results were consistent across sensitivity analyses, with no significant interactions by age, sex, or comorbidities. These findings suggest a potential mortality benefit of statins in AD, warranting further investigation into their therapeutic role.

最近的研究调查了他汀类药物的神经保护潜力；然而，迟发性阿尔茨海默病（AD）进展的临床证据仍然很少。本研究调查了他汀类药物使用与AD进展之间的关系，通过死亡率和美金刚启动来评估。使用韩国国民健康保险数据库的数据，我们回顾性分析了2010年诊断为AD的年龄在60-79 岁的患者队列。经1:1倾向评分匹配后，7086例患者纳入研究。他汀类药物的使用与死亡风险降低相关（HR, 0.84; 95 % CI = 0.74-0.97），特别是在以前的使用者中（HR, 0.82; 95 % CI = 0.70-0.97），而未观察到美金刚开始治疗的延迟（HR, 1.04; 95 % CI = 0.86-1.26）。敏感性分析的结果是一致的，年龄、性别或合并症之间没有显著的相互作用。这些发现表明他汀类药物对阿尔茨海默病有潜在的死亡率益处，值得进一步研究其治疗作用。

引用次数: 0

Semaglutide and the pathogenesis of progressive neurodegenerative disease: the central role of mitochondria Semaglutide与进行性神经退行性疾病的发病机制：线粒体的核心作用

IF 6.7 1区医学 Q1 ENDOCRINOLOGY & METABOLISM

Frontiers in Neuroendocrinology

Pub Date : 2025-10-01 DOI: 10.1016/j.yfrne.2025.101217

George B. Stefano , Pascal Büttiker , Simon Weissenberger , Jiri Raboch , Martin Anders

While mitochondria provide critical energy resources, mitochondrial dysfunction can lead to both metabolic and neurodegenerative disorders. Primary mitochondrial disorders (e.g., Leigh syndrome) are uniformly associated with profound neurodegeneration. Recent studies have also implicated mitochondrial dysfunction as a central feature of progressive neurodegenerative diseases, notably Alzheimer’s disease, Parkinson’s disease, Amyotrophic Lateral Sclerosis, and Huntington’s Disease. In addition to its profound impact on metabolic disease, the glucagon-like peptide-1 receptor agonist, semaglutide, has significant neuroprotective features and may limit the progression of one or more of these disorders. These observations might be explained at least in part by the impact of this drug on mitochondrial function and energy production. Collectively, these observations highlight disrupted energy homeostasis as a critical feature of neurodegenerative disease and suggest novel targets for the development of much-needed new neuropharmaceutical strategies.

虽然线粒体提供关键的能量资源，但线粒体功能障碍可导致代谢和神经退行性疾病。原发性线粒体疾病（如Leigh综合征）均与深度神经退行性变相关。最近的研究还表明，线粒体功能障碍是进行性神经退行性疾病的核心特征，特别是阿尔茨海默病、帕金森病、肌萎缩侧索硬化症和亨廷顿病。胰高血糖素样肽-1受体激动剂semaglutide除了对代谢性疾病有深远的影响外，还具有显著的神经保护功能，并可能限制一种或多种代谢性疾病的进展。这些观察结果至少可以部分解释为这种药物对线粒体功能和能量产生的影响。总的来说，这些观察结果强调了能量稳态破坏是神经退行性疾病的一个关键特征，并为开发急需的新神经药物策略提供了新的靶点。

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引用次数: 0

Corrigendum to “A scoping review of functional genomics in perinatal depression”. [Front. Neuroendocrinol. 78 (2025) 101202] “围产期抑郁症功能基因组学范围综述”的勘误表。(前面。[j].中国生物医学工程学报，2016,32(1):1 - 2。

IF 6.7 1区医学 Q1 ENDOCRINOLOGY & METABOLISM

Frontiers in Neuroendocrinology

Pub Date : 2025-10-01 DOI: 10.1016/j.yfrne.2025.101219

Silvia Elisabetta Portis Bruzzone , Victoria Frederikke S. Garre , Stinne Høgh , Vibe G. Frokjaer , Kieran J. O’Donnell , Rand S. Eid

引用次数: 0