Kotini-Shah Pavitra, Khosla Shaveta, Almeida Felipe Borges, Santovito Luca Spiro, Prendergast Heather, Pinna Graziano
Department of Emergency Medicine, College of Medicine, University of Illinois Chicago, 808 S. Wood St., MC 724, Chicago, IL 60612, USA.
The Psychiatric Institute, Department of Psychiatry, College of Medicine, University of Illinois Chicago, 1601 W. Taylor Street, Chicago, IL 60612, USA.
Int J Mol Sci. 2025 Sep 15;26(18):8976. doi: 10.3390/ijms26188976.
Sex and gender disparities have emerged as critical determinants of COVID-19 outcomes, with males exhibiting higher hospitalization and mortality rates than females. Sex steroids such as estradiol, progesterone, and testosterone have been proposed as modulators of these differences, given their known roles in inflammation, immune function, and vascular health. However, the precise hormonal mechanisms underlying COVID-19 severity, particularly among individuals with comorbid hypertension-a major risk factor for adverse outcomes-remain unclear. In this study, we investigated circulating levels of key sex hormones and their neuroactive metabolites in 116 hypertensive COVID-19 patients enrolled through an urban academic emergency department. Our findings revealed distinct sex-based hormonal profiles and associations with disease severity. Males exhibited higher serum estradiol and testosterone levels, while progesterone levels were significantly higher in postmenopausal females. Notably, hospitalized patients showed elevated estradiol and progesterone levels compared to non-hospitalized individuals, whereas ICU-admitted patients had significantly lower concentrations of all three hormones. A unique exception was ICU-admitted postmenopausal females, who exhibited increased serum testosterone levels relative to non-ICU females. Additionally, in males, elevated 3α-diol was associated with hospitalization and ICU admission, while lower allopregnanolone and estradiol levels correlated with hypoxia in males and females, respectively. These results highlight a dynamic, sex-specific hormonal response to COVID-19 progression in hypertensive individuals, suggesting early upregulation and late depletion of protective sex steroids. Understanding these patterns may improve clinical risk stratification and inform the development of sex-targeted therapeutic interventions for COVID-19 and related inflammatory conditions.
性别差异已成为新冠病毒疾病（COVID-19）预后的关键决定因素，男性的住院率和死亡率高于女性。鉴于雌二醇、孕酮和睾酮等性激素在炎症、免疫功能和血管健康方面的已知作用，它们被认为是这些差异的调节因子。然而，COVID-19严重程度背后的确切激素机制仍不清楚，尤其是在患有合并症高血压（不良预后的主要风险因素）的个体中。在本研究中，我们调查了通过城市学术急诊科招募的116例高血压COVID-19患者的关键性激素及其神经活性代谢物的循环水平。我们的研究结果揭示了基于性别的不同激素谱及其与疾病严重程度的关联。男性的血清雌二醇和睾酮水平较高，而绝经后女性的孕酮水平显著较高。值得注意的是，与未住院患者相比，住院患者的雌二醇和孕酮水平升高，而入住重症监护病房（ICU）的患者所有三种激素的浓度均显著降低。一个独特的例外是入住ICU的绝经后女性，相对于未入住ICU的女性，她们的血清睾酮水平升高。此外，在男性中，3α-二醇升高与住院和入住ICU相关，而别孕烷醇酮和雌二醇水平降低分别与男性和女性的缺氧相关。这些结果突出了高血压个体对COVID-19进展的动态、性别特异性激素反应，表明保护性性激素早期上调和后期耗竭。了解这些模式可能会改善临床风险分层，并为针对COVID-19和相关炎症性疾病的性别针对性治疗干预措施的开发提供信息。
