{
    "abstract": "Understanding the hypothalamic-pituitary-gonadal (HPG) axis is essential for grasping human responses under extreme physiological and pathological conditions. The HPG axis regulates reproductive and gonadal hormone activities and significantly impacts the body's response to acute and chronic illnesses. This review explores the fundamental functions of the HPG axis, modifications under critical conditions, and impacts on disease progression and treatment outcomes. In addition, it examines interactions between sex hormones and biomolecules like cytokines and gastrointestinal microorganisms, highlighting their roles in immune response regulation. Clinically, this knowledge can enhance patient prognoses. The review aims to provide a comprehensive framework, based on existing research, for understanding and applying the functions of the HPG axis in managing critical diseases, thereby broadening clinical applications and guiding future research.\nThe response and effects of the hypothalamic-pituitary-gonadal axis during critical illness Our review systematically analyzes the alterations in sex hormone levels during critical illness, delves into the underlying mechanisms, and evaluates the current clinical applications of sex hormone therapies in critical care. In females, critical illness is associated with the reduction of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels, alongside the increase in testosterone, estradiol, and progesterone levels. This elevation in estrogen is attributed to two primary factors: (1) a by-product of adrenal activation, and (2) increased aromatization, which is a chemical structural change that converts testosterone into estradiol. The rise in testosterone and progesterone is predominantly due to adrenal and peripheral tissue activity. In males, there is the decrease in FSH, LH, and testosterone levels, coupled with increased levels of estradiol and progesterone. The decline in testosterone is primarily due to: (1) chronic low-level endotoxin exposure and inflammation impairing androgen synthesis, and (2) increased aromatization in peripheral tissues. The rise in progesterone is attributed to stress-induced stimulation of the adrenal glands. These hormonal changes are closely linked to the patient\u2019s critical condition, with hormone levels generally returning to reference ranges as the condition improves.",
    "authors": [
        {
            "affiliation": "Department of Endocrinology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China.\nKey Laboratory of Endocrine Glucose and Lipids Metabolism and Brain Aging, Ministry of Education, Jinan, Shandong, China.\nDepartment of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.\nShandong Clinical Research Center of Diabetes and Metabolic Diseases, Jinan, Shandong, China.\nShandong Institute of Endocrine and Metabolic Diseases, Jinan, Shandong, China.\nShandong Engineering Laboratory of Prevention and Control for Endocrine and Metabolic Diseases, Jinan, Shandong, China.",
            "firstname": "Yicheng",
            "initials": "Y",
            "lastname": "Ma"
        },
        {
            "affiliation": "Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.\nShandong Clinical Research Center of Diabetes and Metabolic Diseases, Jinan, Shandong, China.\nShandong Institute of Endocrine and Metabolic Diseases, Jinan, Shandong, China.\nShandong Engineering Laboratory of Prevention and Control for Endocrine and Metabolic Diseases, Jinan, Shandong, China.",
            "firstname": "Xiude",
            "initials": "X",
            "lastname": "Fan"
        },
        {
            "affiliation": "Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.\nShandong Clinical Research Center of Diabetes and Metabolic Diseases, Jinan, Shandong, China.\nShandong Institute of Endocrine and Metabolic Diseases, Jinan, Shandong, China.\nShandong Engineering Laboratory of Prevention and Control for Endocrine and Metabolic Diseases, Jinan, Shandong, China.",
            "firstname": "Junming",
            "initials": "J",
            "lastname": "Han"
        },
        {
            "affiliation": "Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.\nShandong Clinical Research Center of Diabetes and Metabolic Diseases, Jinan, Shandong, China.\nShandong Institute of Endocrine and Metabolic Diseases, Jinan, Shandong, China.\nShandong Engineering Laboratory of Prevention and Control for Endocrine and Metabolic Diseases, Jinan, Shandong, China.",
            "firstname": "Yiping",
            "initials": "Y",
            "lastname": "Cheng"
        },
        {
            "affiliation": "Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.\nShandong Clinical Research Center of Diabetes and Metabolic Diseases, Jinan, Shandong, China.\nShandong Institute of Endocrine and Metabolic Diseases, Jinan, Shandong, China.\nShandong Engineering Laboratory of Prevention and Control for Endocrine and Metabolic Diseases, Jinan, Shandong, China.",
            "firstname": "Jiajun",
            "initials": "J",
            "lastname": "Zhao"
        },
        {
            "affiliation": "Department of Critical-Care Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Shandong First Medical University, Jinan, No. 9677, Jingshi Road, Lixia District, Jinan, Shandong 250000, China.",
            "firstname": "Wei",
            "initials": "W",
            "lastname": "Fang"
        },
        {
            "affiliation": "Department of Endocrinology, Shandong Provincial Hospital, Shandong University, No. 544, Jingsi Road, Xishichang Subdistrict, Huaiyin District, Jinan, Shandong 250000, China.\nKey Laboratory of Endocrine Glucose and Lipids Metabolism and Brain Aging, Ministry of Education, Jinan, Shandong, China.\nDepartment of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.\nShandong Clinical Research Center of Diabetes and Metabolic Diseases, Jinan, Shandong, China.\nShandong Institute of Endocrine and Metabolic Diseases, Jinan, Shandong, China.\nShandong Engineering Laboratory of Prevention and Control for Endocrine and Metabolic Diseases, No. 544, Jingsi Road, Xishichang Subdistrict, Huaiyin District, Jinan, Shandong 250000, China.",
            "firstname": "Ling",
            "initials": "L",
            "lastname": "Gao"
        }
    ],
    "conclusions": null,
    "copyrights": "\u00a9 The Author(s), 2025.\n\u00a9 The Author(s), 2025.",
    "doi": "10.1177/20420188251328192",
    "journal": "Therapeutic advances in endocrinology and metabolism",
    "keywords": [
        "critical illness",
        "estrogen",
        "follicle-stimulating hormone",
        "hypothalamic\u2013pituitary\u2013gonadal axis",
        "luteinizing hormone",
        "testosterone"
    ],
    "methods": null,
    "publication_date": "2025-04-04",
    "pubmed_id": "40183031\n23601250\n16670151\n3919042\n20214417\n15569941\n31147553\n25222843\n27756855\n11800519\n35642779\n26884301\n20673032\n8501163\n18363467\n18332796\n18090358\n21488721\n29531449\n27765072\n26997016\n28989885\n21291516\n8501162\n7969774\n1464665\n11443192\n1424172\n7895322\n2500904\n10634385\n16352961\n24936547\n6682119\n1831739\n34402750\n31812658\n20333354\n18413673\n3003907\n7828343\n1117911\n2651094\n12398784\n11800521\n8923461\n7895904\n29183872\n23956762\n26600270\n22028450\n11091120\n14576178\n15288182\n15512855\n8797634\n35420889\n39166923\n35236988\n30320621\n35486387\n19436016\n16675850\n15194467\n20554954\n16428820\n29257783\n25249279\n38212826\n30329017\n34295779\n25956531\n30424806\n32951609\n29558207\n32991827\n29469650\n27700135\n22018233\n27723080\n28778332\n23772041\n23328391\n27546235\n11683373\n18097065\n29946321\n37572114\n24737458\n11044445\n26440402\n10579258\n19609117\n16115495\n21164406\n15785230\n15358759\n26384003\n34618728\n25796471\n29151229\n23158459\n22925127\n17170211\n16772530\n21770760\n15901745\n17011666\n6430018\n26112314\n16039652\n16797538\n10794300\n7925843\n21551677\n8481809\n10208142\n16235407\n18240063\n1621483\n3692444\n11303139\n33909503\n22511747\n20888520\n361300\n20525906\n11205891\n11744660\n11861539\n11585509\n21463817\n18167405\n26358173\n16399021\n16712908\n34066289\n12030918\n35277675\n28538730",
    "results": null,
    "title": "Critical illness and sex hormones: response and impact of the hypothalamic-pituitary-gonadal axis.",
    "xml": "<Element 'PubmedArticle' at 0x7885049af650>"
}