Department of Rheumatology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands; Struttura Complessa di Reumatologia, Rheumatology Unit, Azienda Policlinico of Modena, University of Modena and Reggio Emilia, Largo del Pozzo 71, 41125 Modena, Italy; Medicine and Rheumatology Unit, IRCCS Istituto Ortopedico Rizzoli, via Pupilli 1, 40136 Bologna, Italy.
Department of Rheumatology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.
Semin Arthritis Rheum. 2020 Feb;50(1):140-148. doi: 10.1016/j.semarthrit.2019.07.007. Epub 2019 Jul 20.
The pathophysiology of systemic sclerosis (SSc) is complex and elusive, however, considering the strong female preponderance and different clinical characteristics between men and women, a contribution of sex hormones has been proposed.
We undertook this systematic literature review to investigate: (1) the role played by male and female sex hormones in the pathogenesis of SSc; (2) how sex hormone levels change in SSc patients and how hormonal variations modify the progression of SSc; (3) the effect of therapies targeting sex hormones on the disease course.
A literature search was performed in Pubmed, Embase, Web of Science, and Cochrane library databases. Given the heterogeneity in study design, different quality assessment tools were applied where appropriate.
We retrieved 300 articles and 30 were included in the review. The available evidence points to a fibrogenic, but also a vasodilatory, role of estrogens in SSc. With the limitation of small sample sizes, women with SSc tend to have lower levels of androgens and non-significantly higher levels of estradiol compared to healthy controls, while in men we found increased levels of estradiol and discordant results for androgens. After menopause the skin score seems to decrease and prevalence of pulmonary artery hypertension seems to rise, which might be prevented by the use of hormone replacement therapy. No recent high-quality trial evaluated the efficacy of hormone-targeting therapies in SSc.
Few translational studies of varying quality evaluated the role of sex hormones in SSc showing possible profibrotic and vasodilatatory effects of estrogens, but more research is needed to elucidate the extent of this contribution. Insights on the influence of sex hormones, along with the availability of new compounds acting on estrogen pathways, might provide ideas for additional studies on the application of sex hormone-targeting therapies in SSc.
系统性硬化症（SSc）的病理生理学复杂且难以捉摸，然而，鉴于女性发病率明显高于男性且男女之间存在不同的临床特征，因此提出了性激素的作用。
我们进行了这项系统文献综述，以探讨：（1）男性和女性性激素在 SSc 发病机制中的作用；（2）SSc 患者的性激素水平如何变化以及激素变化如何影响 SSc 的进展；（3）针对性激素的治疗方法对疾病进程的影响。
在 Pubmed、Embase、Web of Science 和 Cochrane 图书馆数据库中进行文献检索。由于研究设计的异质性，在适当的情况下应用了不同的质量评估工具。
我们检索到 300 篇文章，其中 30 篇文章被纳入综述。现有证据表明，雌激素在 SSc 中具有纤维生成作用，但也具有血管扩张作用。由于样本量较小的限制，与健康对照组相比，患有 SSc 的女性往往具有较低水平的雄激素和非显著较高水平的雌二醇，而男性中发现雌二醇水平升高且雄激素结果不一致。绝经后，皮肤评分似乎下降，肺动脉高压的患病率似乎上升，而激素替代疗法可能预防这种情况。最近没有高质量的试验评估激素靶向治疗在 SSc 中的疗效。
少数质量不同的转化研究评估了性激素在 SSc 中的作用，表明雌激素具有潜在的促纤维化和血管扩张作用，但需要进一步研究来阐明其作用的程度。关于性激素影响的深入了解，以及新的作用于雌激素途径的化合物的出现，可能为在 SSc 中应用性激素靶向治疗的进一步研究提供思路。
