Masi A T, Da Silva J A, Cutolo M
Department of Medicine, University of Illinois College of Medicine at Peoria 61656, USA.
Baillieres Clin Rheumatol. 1996 May;10(2):295-332. doi: 10.1016/s0950-3579(96)80019-7.
The available evidence reviewed does not allow definitive response to the question of a primary versus secondary role of sex hormone perturbations in RA. However, this conclusion should not be discouraging in view of the relatively recent focus upon this facet of the physiopathogenesis of RA and the enormous complexities of sex hormone biology and this disease. Specifically, data on the incidence of RA as well as life cycle changes in serum androgenic-anabolic (A-A) and sex hormone levels suggest important risk correlations. Furthermore, HLA-susceptibility markers for RA, gender, menopause and older age are all factors which significantly relate to the risk of developing RA and each has been shown to associate with sex hormone status. Whether or not HPG-AA hormonal status may modulate RA risk (or its course) primarily and independently or merely be predictive markers of other biological mechanisms was critically considered and requires further study. Sex hormone influences on cellular and humoral immunological reactivity and vascular pathogenetic mechanisms in RA were summarized. Androgens generally suppress immunoreactivity and cartilage responses to inflammation-mediated injury processes and may enhance synovial macrophage-like lining cell apoptosis. Oestrogens generally enhance immunoreactivity, offer some protection to inflammation-mediated cartilage damage (but less than androgens) and may inhibit apoptosis in certain in vitro cell models. Scant information is available on the balance of sex hormones (and glucocorticoids) in RA or its presumed pathogenetic mechanisms. Data were reviewed which support the concept of a spectrum of androgenicity in the normal population, particularly among women. A simplified schema of trophic and tropic steroidogenic mechanisms was proposed which could influence androgenic-anabolic (A-A) status and might relate to RA. Serum concentrations of DHAS (mumol/l), T (nmol/l) and O2 (pmol/l) span several orders of magnitude in normal physiology. The effects of alterations in the individual levels of these sex hormones and deviations from their normal physiological balance are not well understood. Critical attention to their biological functions is needed in RA as well as in health and disease generally. Such focused clinical and experimental investigations of HPG-AA functions promise to clarify the complex physiopathology of RA and contribute to its improved long-term management.
所审查的现有证据无法对性激素紊乱在类风湿关节炎中是起主要作用还是次要作用这一问题给出明确答复。然而，鉴于类风湿关节炎发病机制的这一方面是相对较新的研究重点，且性激素生物学和这种疾病极为复杂，这一结论不应令人气馁。具体而言，关于类风湿关节炎发病率以及血清雄激素 - 合成代谢（A - A）和性激素水平的生命周期变化的数据表明存在重要的风险关联。此外，类风湿关节炎的HLA易感性标志物、性别、绝经和老年都是与患类风湿关节炎风险显著相关的因素，并且每个因素都已被证明与性激素状态有关。促性腺激素 - 雄激素 - 合成代谢（HPG - AA）激素状态是否主要且独立地调节类风湿关节炎风险（或其病程），或者仅仅是其他生物学机制的预测标志物，这一问题经过了严格考量，还需要进一步研究。总结了性激素对类风湿关节炎中细胞和体液免疫反应性以及血管发病机制的影响。雄激素通常会抑制免疫反应性以及软骨对炎症介导损伤过程的反应，并可能增强滑膜巨噬细胞样衬里细胞凋亡。雌激素通常会增强免疫反应性，对炎症介导的软骨损伤提供一定保护（但不如雄激素），并且在某些体外细胞模型中可能抑制凋亡。关于类风湿关节炎中（以及糖皮质激素）性激素平衡或其假定发病机制的信息很少。审查了支持正常人群中存在雄激素谱概念的数据，特别是在女性中。提出了一个简化的营养和促激素类固醇生成机制模式，该模式可能影响雄激素 - 合成代谢（A - A）状态，并且可能与类风湿关节炎有关。在正常生理状态下，硫酸脱氢表雄酮（DHAS，μmol/L）、睾酮（T，nmol/L）和雌二醇（E2，pmol/L）的血清浓度跨越几个数量级。这些性激素个体水平的改变及其偏离正常生理平衡的影响尚未得到充分理解。在类风湿关节炎以及一般的健康和疾病中，都需要密切关注它们的生物学功能。对HPG - AA功能进行如此有针对性的临床和实验研究有望阐明类风湿关节炎复杂的发病机制，并有助于改善其长期管理。
